%0 Journal Article
%T Production and Purification of 165Er from Pressed Ho2O3:Al Targets on a 16.5 MeV Cyclotron
%V 10
%N 1
%I Multidisciplinary Digital Publishing Institute
%P 14
%W https://orbit.dtu.dk/en/publications/production-and-purification-of-sup165super-from-pressed-hosub2sub/
%* http://creativecommons.org/licenses/by/3.0/
%U https://www.mdpi.com/2410-390X/10/1/14
%X Erbium-165 (165Er) is an Auger electron emitter with 7.2 electrons per decay and very few other emissions, making it an interesting candidate for Auger electron therapy. We present here a procedure for producing 165Er by the natHo(p,n)165Er nuclear reaction on a 16.5 MeV medical cyclotron. The target was prepared by pressing a Ho2O3:Al 1:1 (w/w) powder mixture on a Ag disc with a cylindrical depression in the center. With a 0.1 mm Nb foil in front, degrading the energy to 15 MeV, and water cooling at the back of the Ag disc, the target could withstand irradiation at currents up to 45 µA without showing any signs of damage. The beam tolerance of the target was also estimated by calculating the temperature and heat dissipation in the target via the numerical solution of the heat transport equations. For a 180 mg target, the production yield was 12.3 ± 1.9 MBq/µAh. The separation of two neighboring lanthanides is challenging, which led us to study the distribution coefficients for Er and Ho on commercially available LN2 resin for both HNO3 and HCl eluents. Based on these values, we propose a purification procedure involving two successive LN2 columns for separating the 165Er from Ho and Al, followed by a small TK221 column to concentrate the final eluate. No radionuclidic impurities were detected, and the chemical impurities found in the final formulation were traces of Ho, Er, Ca, Pb, and Fe. For three different chelators (DOTA, DTPA, and CHX-A″-DTPA), the effective molar activity of the final formulation was measured. The stability of the three complexes formed was also assessed upon incubation in mouse serum for 28 h.
%G en
%J Instruments
%A Søborg Pedersen, Kristina
%A Deville, Claire
%A Borre, Trine
%A Torabi, Ghazal
%A Naidoo, Clive
%A Jensen, Mikael
%D 2026/3
%K Auger electron emitter
chemical separation
radiolanthanides
radionuclide production
scientific-publication

%0 Journal Article
%T Comparative theranostic efficacy of 177Lu- and 161Tb-labeled A1K2 SdAb in mesothelin-positive tumors
%W https://pubmed.ncbi.nlm.nih.gov/41454065/
%U https://doi.org/10.1007/s00259-025-07723-z
%X Mesothelin (MSLN), a 40 kDa glycoprotein normally confined to mesothelial cells, is overexpressed in several malignancies, including triple-negative breast cancer (TNBC). The anti-mesothelin single-domain antibody (sdAb, or “nanobody®”) DOTA-A1K2, previously validated for positron emission tomography (PET) imaging using site-specific 68Ga radiolabeling, may also serve as a radio-theranostic agent when labeled with 177Lu. Moreover, 161Tb has recently been proposed as an alternative to 177Lu that might provide additional efficacy due to the emission of Auger electrons. The aim of this study was to evaluate in vitro and in vivo the therapeutic effect of [177Lu]Lu-DOTA-A1K2 and [161Tb]Tb-DOTA-A1K2.
%G en
%J European Journal of Nuclear Medicine and Molecular Imaging
%A N’Guessan, Émilien
%A Raes, Florian
%A Ahmadi, Mitra
%A Bacot, Sandrine
%A Dumas, Laurent
%A Leenhardt, Julien
%A du Moulinet d’Hardemare, Amaury
%A Debiossat, Marlène
%A André, Clémence
%A Boutonnat, Jean
%A Durivault, Jérôme
%A Montemagno, Christopher
%A Lenormand, Jean-Luc
%A Djaïleb, Loïc
%A Köster, Ulli
%A Van de Voorde, Michiel
%A Ramaekers, Stijn
%A Verguts, Ken
%A Ghezzi, Catherine
%A Perret, Pascale
%A Lombardi, Charlotte
%A Broisat, Alexis
%D 2025-12-27
%K Lutetium-177
Mesothelin
Radio-ligand therapy
SdAb
Terbium-161
Triple negative breast cancer
user-project

%0 Journal Article
%T First laser-ionized europium collection at CERN-MEDICIS
%V 569
%P 165872
%W https://kuleuven.limo.libis.be/discovery/search?query=any,contains,LIRIAS4268539&tab=LIRIAS&search_scope=lirias_profile&vid=32KUL_KUL:Lirias&offset=0%3F
%U https://www.sciencedirect.com/science/article/pii/S0168583X25002629
%X The MEDICIS facility at CERN aims to produce non-conventional radionuclides towards medical applications. In this work, the first collection of europium-145 (Eu-145) at CERN-MEDICIS is presented, focusing on the development and optimization of a resonance laser ionization scheme to improve isotope extraction efficiency. A two-step ionization scheme was developed and implemented, ensuring compatibility with the available laser infrastructure. The collection campaign in October 2024 successfully delivered Eu-145 for metrology studies, demonstrating the feasibility of laser-enhanced Eu ionization. The results indicate a collection efficiency of 1.85% ± 0.09%, although further development is in progress to optimize the ionization scheme and ion source parameters and operating conditions.
%J Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms
%A Mancheva, R.
%A Bernerd, C.
%A Chrysalidis, K.
%A Cocolios, T. E.
%A Duchemin, C.
%A Elle, M.
%A Rossel, R.
%A Van Dingenen, B.
%D 2025-12-01
%K CERN-MEDICIS
Europium
Mass separation
Medical isotopes
Resonance laser ionization
Scheme development
scientific-publication

%0 Thesis
%T Activity Determination in Nuclear Medicine Using Radionuclide Calibrators
%I Zenodo
%U https://zenodo.org/records/18458894
%X In recent years, the treatment of patients in nuclear medicine using exotic radionuclides (particles that send out ionizing radiation) formulated in pharmaceuticals for patient administration has gained a lot of attention. With that, the need for better assessments of treatment effectiveness has increased as well. At the root of these challenges lies the accuracy with which the radioactive pharmaceuticals are measured. Inaccuracies could lead to treatment failures, adverse effects or misinterpretations of effectiveness in preclinical studies and should be avoided. In this study, a solution of a particularly interesting radionuclide (terbium-161) has been put in various vials, syringes and tubes to see how well the amount of radioactivity that is measured coincided with the amount of radioactivity that was put in the container. The amount of radioactivity was measured using a device commonly referred to the ”radionuclide calibrator” or (”activity meter”). For two vials, the concentration of radioactivity (i.e. amount of activity per 1 gram of solution) has been verified using a second device referred to as the ”gamma counter”. The results are striking. For the syringes and tubes, the amount of radioactivity that was measured is up to 30% higher than what was actually present. The vials, on the other hand, had the measured radioactivity be much closer to what was in the vial. It was also found that for most containers, the items that were used to perform the measurements (to hold the container in the detector, for example) caused the measured radioactivity to deviate from the actual amount as well. The measurements using the gamma counter are promising. The amount of radioactivity per 1 gram of solution was the same as was expected. This means that this second device may proof useful in the future as a tool to verify the amount of radioactivity that was present in a container. However, there were some obstacles observed due to (unavoidable) contaminants present in the solution that make it harder to conduct the measurements. To conclude, the results indicate that the old ”one-size-fits-all” approach that is the dominant approach in nuclear medicine is outdated. Special care and attention must be brought to how to accurately measure the novel radionuclides that are coined to be the (cancer) treatments of the future. Not doing so may lead to large errors that could have been avoided.
%A Jason, Noben
%A Kristof, Baete
%D 2025
%K thesis

%0 Journal Article
%T CERN-MEDICIS: A unique facility for the production of radionuclides for medical research
%I JACoW Publishing
%P 1071-1074 pages, 0.73 MB
%* Creative Commons Attribution 4.0 International
%U https://jacow.org/ipac2025/doi/jacow-ipac2025-tupb047
%X The MEDICIS facility is a unique facility located at CERN, dedicated to the production of non-conventional radionuclides for research and development in imaging, diagnostics and radiation therapy, and based on offline mass separation. It exploits a classified area for handling of highly radioactive open sources, a dedicated isotope separator beam line, a target irradiation station at the 1.4 GeV Proton Synchroton Booster (PSB) and receives activated targets from external institutes during CERN Long Shut-Downs. After collection, the batch is prepared to be dispatched to a research center. Since its commissioning in December 2017, the facility has provided novel radionuclides such as Ba-128, Tb-155, Sm-153, Tm-165 Ra-224/Pb-212 and Ra-225/Ac-225 with high specific activity, some for the first time, to research institutes part of the collaboration. CERN-MEDICIS has advanced significantly to reach mature processes to translate into clinical application for the most promising radionuclides.
%G en
%A Bernerd,Cyril
%A Crepieux,Bernard
%A Duchemin,Charlotte
%A Elle,Manikanta
%A Gilardoni,Simone
%A Heinke,Reinhard
%A Kalnina,Patricija
%A Lambert,Laura
%A Mamis,Edgars
%A Mancheva,Ralitsa
%A Rossel,Ralf
%A Rothe,Sebastian
%A Stora,Thierry
%A Thiboud,Julien
%A Vollaire,Joachim
%E Lin,Ming-Chyuan
%E Sato,Yoichi
%E Huang,Jui-Che
%E Button,David
%E Chuang,Ping-Shun
%D 05 November 2025
%K Accelerator Physics
MC8.U04 - MC8.U04 Isotope Production
mc8-applications-of-accelerators-and-engagement-for-industry-and-society - MC8: Applications of Accelerators, and Engagement for Industry and Society
scientific-publication

%0 Conference Paper
%T Nanolayer of Monocrystalline Si Towards Nanodosimetry of Electron Radiation
%C Cham
%I Springer Nature Switzerland
%P 267-277
%@ 978-3-031-96538-8
%X Nanodosimetry aims to measure the ionizing radiation dose absorbed in nanosized volumes. For that, photothermostimulated exoelectron emission (PTSE) of monocrystalline silicon (Si) nanolayer might be used to detect weak electrons, because their mean free path in the solid is around 100 nm. The current work aims to explore the possibility of using monocrystalline Si for nanodosimetry of high energy electron radiation. It is demonstrated that the PTSE of monocrystalline Si can be used for the identification of 6 MeV electron radiation doses 35–60 Gy. The total emitted charge of PTSE is connected with the delivered dose. The near-threshold photoelectric emission spectroscopy and Fourier-transform infrared spectroscopy (FTIR) indicate that PTSE is influenced by radiation-induced reconstructions.
%G en
%B Joint 20th Nordic-Baltic Conference on Biomedical Engineering & 24th Polish Conference on Biocybernetics and Biomedical Engineering
%A Boka, Gaļina
%A Dekhtyar, Yuri
%A Rocca, Mirko
%A Skrebele, Elizabete
%A Sorokins, Hermanis
%E Ladyzynski, Piotr
%E Pijanowska, Dorota G.
%E Liebert, Adam
%D 2025
%K Exoelectron emission
High energy electron radiation
Monocrystalline silicon
Nanodosimetry
scientific-publication

%0 Journal Article
%T Scandium-47 as a radionuclide precursor: Feasibility of production in a 47Ca/47Sc generator-like system
%V 152-153
%P 109595
%W https://pubmed.ncbi.nlm.nih.gov/41391246/
%U https://www.sciencedirect.com/science/article/pii/S0969805125006043
%X Background
Scandium-47 (47Sc), a medium-energy β− emitter with a half-life of 3.35 days and associated γ emission (159 keV, 68.1 %), is an attractive radionuclide for targeted radionuclide therapy and theranostics. Production of 47Sc via neutron irradiation of enriched 46Ca targets through the 46Ca(n,γ)47Ca → 47Sc decay pathway offers advantages such as thermal neutron utilisation and minimised contaminant co-production. Efficient separation and repeated recovery of 47Sc in a quasi-generator system are crucial for enabling its medical application.
Results
Neutron irradiations of calcium carbonate targets 46Ca-enriched (5.2 % and 10.5 %) at the Maria research reactor yielded up to 5.18 GBq 47Sc and 5.60 GBq 47Ca at the end of bombardment. Separation of 47Sc from 47Ca was performed using DGA resin with recovery efficiencies of 81–97 % for 47Sc and 98–99 % for 47Ca in up to five consecutive elutions within 18 days. Radiochemical purity of eluted [47Sc]ScCl3 exceeded 95 % in initial separations. Radiolabelling studies with DOTA-TATE demonstrated effective molar activities up to 20 MBq/nmol and radiochemical purities >98 %. Stability tests confirmed that the [47Sc]ScCl3 eluate remained suitable for radiolabelling for the entire testing period of up to 4 days post-elution. Trace metal analysis showed predominantly low contamination levels, with sporadic impurities attributed to handling conditions.
Conclusions
The 47Ca/47Sc quasi-generator system based on neutron irradiation of enriched 46Ca targets offers a reliable source of high-quality 47Sc for radiopharmaceutical applications. Multiple elutions from a single target enable sustained production of 47Sc with excellent radionuclidic and radiochemical purity. These results support further development of 47Sc as a theranostic radionuclide for larger-scale production. A preliminary specification for 47Sc as a radionuclide precursor was proposed following the European Pharmacopoeia guidelines, providing a groundwork for future standardisation.
%J Nuclear Medicine and Biology
%A Cieszykowska, Izabela
%A Żółtowska, Małgorzata
%A Pawlak, Dariusz
%A Sochaczewski, Łukasz
%A Tymiński, Zbigniew
%A Marganiec-Gałązka, Justyna
%A Mikołajczak, Renata
%D 2026-01-01
%K Calcium-46
DGA resin
Quality assessment
Radionuclide generator
Radionuclide precursor
Scandium-47
scientific-publication

%0 Journal Article
%T Gamma-ray spectrometry measurements for quality assessment of scandium-47 produced by neutron irradiation of calcium-46
%V 229
%P 112408
%W https://pubmed.ncbi.nlm.nih.gov/41494435/
%U https://www.sciencedirect.com/science/article/pii/S0969804325007535
%X Scandium-47 can be produced indirectly via the 46Ca(n,γ)47Ca→47Sc nuclear reaction by neutron irradiation of calcium targets, either natural or, preferably, enriched in calcium-46. Two target materials differing in the enrichment in calcium-46 and the elemental and isotopic composition were irradiated in the MARIA research reactor. Radioactive concentration of scandium-47 and the radionuclidic purity of the solution obtained after irradiated target dissolution were assessed by gamma-spectrometry using a high-purity germanium (HPGe) detector in the Laboratory of Radioactivity Standards in the Radioisotope Centre POLATOM, NCBJ. The radioactive concentration of scandium-47 was in the range of 0.20–1.48 GBq/mL, and the content of calcium-47 was determined at the level ranging from 0.006 % to 0.055 % of scandium-47 in the final products. The profile of radionuclide impurities and their minimum detectable activities are discussed.
%J Applied Radiation and Isotopes
%A Tymiński, Zbigniew
%A Saganowski, Paweł
%A Żółtowska, Małgorzata
%A Cieszykowska, Izabela
%A Kołakowska, Ewa
%A Marganiec-Gałązka, Justyna
%A Lisowska, Natalia
%A Kamiński, Aleksander
%A Czudek, Marek
%A Cacko, Daniel
%A Broda, Ryszard
%D 2026-03-01
%K Gamma-ray spectrometry
Quality assessment
Radionuclidic purity
Radiopharmaceuticals
Scandium-47
scientific-publication

%0 Journal Article
%T Lead radionuclides for theranostic applications in nuclear medicine: from atom to bedside
%V 16
%N 6
%I Ivyspring International Publisher
%P 2887-2917
%W https://kuleuven.limo.libis.be/discovery/fulldisplay?docid=lirias4391773&context=SearchWebhook&vid=32KUL_KUL:Lirias&lang=en&search_scope=lirias_profile&adaptor=SearchWebhook&tab=LIRIAS&query=any,contains,LIRIAS4391773&offset=0
%U https://www.thno.org/v16p2887.htm
%G en
%J Theranostics
%A Berckmans, Yani
%A Kleynhans, Janke
%A Van Mechelen, Sara
%A Goffin, Karolien
%A Baete, Kristof
%A Koole, Michel
%A Coosemans, An
%A Cocolios, Thomas Elias
%A Deroose, Christophe M.
%A Seimbille, Yann
%A Cleeren, Frederik
%D 2026/1/1
%K scientific-publication

%0 Journal Article
%T Combination of PSMA targeting alpha-emitting radioligand [212Pb]Pb-AB001 with BET bromodomain inhibitors in in vitro prostate cancer models
%V 42
%N 8
%P 362
%W https://trepo.tuni.fi/handle/10024/230131
%U https://doi.org/10.1007/s12032-025-02925-9
%X The alpha-emitting radioligand [212Pb]Pb-AB001, targeting prostate-specific membrane antigen (PSMA), is a promising therapy approach for prostate cancer. Bromodomain and extra-terminal (BET) protein inhibitors, such as AZD5153 and JQ1, disrupt oncogenic transcriptional programs by altering chromatin structure. This study evaluated whether BET inhibition enhances the efficacy of radioligand therapy. Cytotoxic effects of [212Pb]Pb-AB001 alone and in combination with BET inhibitors were assessed in 2D monolayers and a 3D spheroid model of PSMA-positive C4-2 prostate cancer cells. Cell viability, cell cycle alterations, and DNA damage were assessed using viability assays and flow cytometry. Spheroid growth and viability were assessed by fluorescence microscopy. AZD5153 was more potent than JQ1 in reducing cell proliferation. [212Pb]Pb-AB001 induced activity- and time-dependent cytotoxicity with a delayed apoptotic response. BET inhibitors induced G1 arrest, while [212Pb]Pb-AB001 caused G2 arrest. Combination treatment reduced cell viability in an additive manner but did not further affect cell cycle distribution or increase apoptosis compared with [212Pb]Pb-AB001 alone. γH2AX staining in 2D models showed an activity- and time-dependent increase in DNA damage at 1, 3 and 6 days post-treatment with [212Pb]Pb-AB001. BET inhibitors alone induced minimal γH2AX, and combination treatments did not enhance DNA damage beyond [212Pb]Pb-AB001 alone. In 3D spheroids, combination treatment led to synergistic growth suppression. In conclusion, these findings indicate that therapeutic inhibition of BET bromodomain in combination with the alpha-emitting radioligand [212Pb]Pb-AB001 could significantly enhance tumour control and should be further evaluated in metastatic prostate cancer models.
%G en
%J Medical Oncology
%A Liukaityte, Rugile
%A Stenberg, Vilde Yuli
%A Kleinauskas, Andrius
%A Juzenas, Petras
%A Urbanucci, Alfonso
%A Juzeniene, Asta
%D 2025-07-22
%K Bromodomain and extra-terminal proteins
Cell cycle
Combination treatment
Targeted alpha therapy
Targeted radionuclide therapy
scientific-publication

%0 Journal Article
%T Radiobiological investigations of a [212Pb]Pb-carbonic anhydrase IX-targeting small-molecule ligand in renal cell carcinoma and colorectal cancer models
%V 102
%N 2
%I Taylor & Francis
%P 127-137
%W https://pubmed.ncbi.nlm.nih.gov/41481374/
%U https://doi.org/10.1080/09553002.2025.2595630
%X Carbonic anhydrase IX (CAIX), overexpressed in multiple cancers but limited in normal tissue, is a promising target for radionuclide therapy. This study evaluates [212Pb]Pb-MKV-509, a novel DOTA-conjugated small-molecule ligand, for CAIX-targeted alpha therapy in preclinical renal carcinoma (SK-RC-52) and colorectal (HT-29) cancer models. [212Pb]Pb-MKV-509 was assessed for radiochemical purity and stability. Binding assays determined receptor density and dissociation constants. Clonogenic survival, flow cytometry (viability, DNA damage, cell cycle), and spheroid assays (cross-sectional area, doubling time) evaluated biological responses. An in vivo biodistribution study was performed in SK-RC-52 xenograft-bearing mice, with and without carbonic anhydrase pre-blocking using acetazolamide. [212Pb]Pb-MKV-509 exhibited high radiochemical purity (>96%) and stability for up to 48 h. Specific binding was higher in SK-RC-52 than in HT-29 cells. Treatment induced activity-dependent clonogenic inhibition, G2/M arrest, and DNA damage, with greater sensitivity observed in SK-RC-52 cells. Clonogenic survival was reduced by 50% at 3.4 kBq/mL (SK-RC-52) and 7.1 kBq/mL (HT-29). In spheroid models, 2.5–5.0 kBq/mL delayed growth and prolonged doubling time, indicating cross-fire effects. The biodistribution study revealed significant tumor uptake (4.7%IA/g at 2 h), along with high gastrointestinal accumulation. Pretreatment with acetazolamide partially reduced uptake in the stomach and intestines as well as in the tumor. These findings highlight the potential of CAIX-targeted alpha therapy. CAIX expression and receptor density impact binding affinity and therapeutic response. The study demonstrates the importance of 3D tumor models in evaluating alpha-particle cross-fire effects. Further ligand optimization is warranted to enhance tumor specificity and minimize off-target uptake.
%J International Journal of Radiation Biology
%A Kristiansen, Sandra K.
%A Shubin, Kirill
%A Zubrienė, Asta
%A Matulis, Daumantas
%A Dernjani, Nurtene
%A Juzenas, Petras
%A Bruland, Øyvind S.
%A Juzeniene, Asta
%D 2026-02-01
%K Carbonic anhydrase IX
hypoxia
lead-212
radiobiology
scientific-publication
targeted alpha-therapy

%0 Journal Article
%T Scandium thermal release from activated nat<math><msup is="true"><mrow is="true"></mrow><mrow is="true"><mi is="true">n</mi><mi is="true">a</mi><mi is="true">t</mi></mrow></msup></math>Ti and nat<math><msup is="true"><mrow is="true"></mrow><mrow is="true"><mi is="true">n</mi><mi is="true">a</mi><mi is="true">t</mi></mrow></msup></math>V target materials in mixed particle fields: Investigation of parameters relevant for isotope mass separation
%V 553
%P 165400
%W https://cds.cern.ch/record/2903214
%U https://www.sciencedirect.com/science/article/pii/S0168583X24001708
%X Scandium (Sc) has gained significant interest in nuclear medicine due to its 43Sc, 44g/mSc, and 47Sc radioactive isotopes being suitable for cancer diagnostics and therapy, offering a promising avenue for theranostics. Various production methods, including irradiation of enriched or naturally abundant calcium (Ca), titanium (Ti), and vanadium (V) materials with different particle beams, have been investigated to produce 43Sc, 44g/mSc, and 47Sc. However, challenges persist in achieving high molar activity and radiochemical purity for medical applications. The physical isotope mass separation technique presents an alternative, obviating the need for enriched target materials by inherently isolating Sc isotopes during the separation process. Despite recent advancements in Sc mass separation at different facilities, efficiency and yield remain sub-optimal for medical dose production. This study aims to systematically investigate the thermal release kinetics of Sc radionuclides from activated natural titanium foils in tantalum (Ta) environments of ISOL (Isotope Separation On-Line) target units. By elucidating the combination of target material structure and temperature conditions, enhanced release parameters were identified. Maximum Sc release from a non-embossed natTi foil samples was achieved at 1200 °C, for embossed natTi foil samples at 1450 °C and for natV foil samples at 1600 °C, within an hour of reaching the set temperature. These findings offer insights into optimizing the mass separation process to improve the efficiency in Sc radionuclide production for medical applications.
%J Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms
%A Mamis, E.
%A Kalnina, P.
%A Duchemin, C.
%A Lambert, L.
%A Conan, N.
%A Deschamps, M.
%A Dorsival, A.
%A Froeschl, R.
%A Ruiz, F. Ogallar
%A Theis, C.
%A Vincke, H.
%A Crepieux, B.
%A Rothe, S.
%A Pajuste, E.
%A Stora, T.
%D 2024-08-01
%K Diffusion
Mass separation
Sc radionuclides
Thermal release
Ti and V target materials
scientific-publication

%0 Thesis
%T Towards efficient terbium extraction: molecular beams of TbFx for ISOL and nuclear medicine
%U https://zenodo.org/records/18086803
%X The production of radioactive ion beams (RIBs) of terbium (Tb) is of growing interest for both fundamental nuclear-physics studies and nuclear-medicine applications. Four of its radioisotopes, Tb-149, Tb-152, Tb-155 and Tb-161, show particular promise for molecular imagining and targeted cancer therapies, enabling a true theragnostic approach. However, the production of these isotopes, aside from reactor-produced Tb-161, remains challenging, with current methods unable to meet the demands of sustained preclinical research. Among existing methods, the Isotope Separation On-Line (ISOL) technique is currently the only one capable of producing samples of Tb-149, Tb-152 and Tb-155 with high enough radioisotopic purity for development of terbium-based radiopharmaceuticals.

The direct extraction of terbium from irradiated tantalum targets at ISOL facilities is hindered by terbium’s low volatility and strong surface adsorption to tantalum. These properties render it "sticky" and lead to poor extraction efficiencies. Consequently, current approaches rely on indirect production routes, such as the extraction of laser ionised precursor dysprosium (Dy), limiting the fundamental research on exotic terbium isotopes and the translation of protocols for offline mass separation. 

This thesis addresses the bottleneck in terbium production by exploring molecular extraction of‘ terbium as a strategy to enhance its volatility and production efficiency. The development of isotope extraction via molecular sidebands offers a promising pathway to access non-volatile elements, such as terbium, that are otherwise difficult to extract directly from the target. Building on the advances in molecular extraction of actinides, in this work terbium fluoride behaviour is systematically investigated using a combination of online and offline studies. A series of experiments were conducted at five different mass separators at CERN associated with the CERN-ISOLDE facility, including CERN-MEDICIS. The initial investigation was performed using stable compounds at ISOLDE’s offline facilities under simulated ISOL conditions to establish the behaviour of the molecules in the extreme conditions of the ISOL method. Subsequent experiments using irradiated tantalum targets and FEBIAD-type ion sources, with CF4 injection to promote fluoride formation, examined terbium release as a function of different experimental parameters. The ion beams were analysed using Multi Reflection Time-of-Flight Mass Spectrometry (MR-ToF MS), supported by gamma and alpha spectrometry.

This thesis demonstrates the feasibility of extracting terbium as its molecular sidebands, providing insights into best operating conditions and underlying physical mechanisms. It also highlights the limitations of this method and other current production routes. Moreover, it offers a benchmark for extending molecular extraction to other lanthanides of interest. The findings not only enhance our understanding of terbium and terbium fluoride chemistry in extreme ISOL conditions but also provides a pathway for future work. Aside from answers, this thesis also raises questions on what’s the best way forward.

The future of large-scale terbium isotope production lies in the optimisation of extraction techniques which can be applied at emerging facilities such as ISOL@MYRRHA and TATTOOS@PSI. The presented work is a part of ongoing effort to optimise production of terbium radionuclides for clinical and preclinical applications, necessary for advancements in nuclear medicine.
%G eng
%A Wojtaczka, Wiktoria
%D 2025-09-01
%K ion sources
radioactive ion beams
radioactive molecules
thesis

%0 Thesis
%T Isotope separation of Ac-225 and Ra-225 for medical purposes
%U https://zenodo.org/records/18086727
%X At the time of writing, global efforts are underway to produce the medical radionuclide Ac-225 from high-energy accelerator-based methods to support the growing demand for targeted alpha therapy drugs. Almost all known approaches rely on radiochemical separation of Ac-225 and its beta-decay parent Ra-225 from metallic Th-232 targets irradiated with protons. Although the method is efficient, the Ac-225 produced by this method contains the isotopic contaminant Ac-227 that could preclude safe handling in clinical environments. Furthermore, radiochemical extraction of Ac-225 necessarily requires the dissolution of the Th target and produces high levels of liquid radioactive waste. In this thesis, studies on the extraction of Ac-225 and its beta-decay parent Ra-225 as mass-separated ion beams from proton-irradiated thick ThCx targets are presented. This technique allows the nuclear targets to be used multiple times, and importantly is the only current potential purification method with isotope selectivity. As a results of these studies, clinically-relevant quantities of pure Ac-225 have been produced at CERN-MEDICIS from 100 g ThCx targets irradiated with 1.4 GeV protons for the order of 1 d. Several experiments were performed to understand the conditions necessary for the beam production, and to characterize the produced samples. Firstly, the Ac-225 ionization efficiency with surface ionization and a dual resonance laser ionization scheme was determined to be an encouraging 15%. During these tests, the temperature regime required for Ac to reach a vapor pressure sufficient to form ion beams at picoamp currents when heated from its nitrate salt were determined. The experiment was repeated for Ac-225 heated and dried on a mimic ThO2 matrix, that enabled the understanding that chemical interactions between Ac-225 and the ThO2 target material meant that higher, but still attainable target temperatures were required for efficient Ac-225 extraction. Extensive nuclear decay spectrometry campaigns were then performed on several mass-separated Ac-225 samples produced from both mimic target material spiked with Ac-225 and Ac-227 radiotracers, as well as development- and production-scale irradiated Th-based targets. A spectrometry technique was developed specifically for the detection of trace Ac-227 activity that could not be measured by standard nuclear-decay spectrometry techniques. Using this technique, the Ac-227-content of Ac-225 samples was quantified. Finally, through analysis of four production-scale ThCx irradiations, extraction efficiencies and extraction rates of both Ac-225 and Ra-225 ion beams have been determined. The optimum range of target temperatures and ion source temperatures required for efficient collection of ion beams of these radionuclides have been quantified through these studies. The interpretation of the results has led to the conclusion that most Ac-225 is produced due to decay filiation by R-225a, while the extraction efficiency of Ac-225 is release limited. The thesis discusses these results in the context of the contribution of Ac-225 and Ra-225 produced by mass-separation techniques to the potential future Ac-225 supply for medical applications.
%G eng
%A Johnson, Jake
%D 2024-11-18
%K ion sources
radioactive ion beams
thesis

%0 Thesis
%T De la cible de ¹⁵⁵Gd au ¹⁵⁵Tb, un radionucléide pour la santé
%I Université Paris-Saclay
%U https://theses.hal.science/tel-05299673
%X The need for new medical radionuclides continues to grow as treatments become more personalised. The diversity of their decay modes and the variety of their half-lives make them valuable tools for both medical imaging and therapy. An important criterion for their development is the possibility of producing them in sufficient quantities with a high degree of chemical purity (optimisation of chelation chemistry and isotope delivery to target organs) and isotopic purity (minimisation of unnecessary radiation emitted by the radiopharmaceutical). This work has enabled us to propose an alternative method, based on the isotopic separation of a stable precursor of the radionuclide of interest, Terbium-155, with a view to its production by proton irradiation. A number of experiments were carried out, enabling us for the first time to measure the effective production cross-sections of ¹⁵⁵Tb and its contaminants, ¹⁵³Tb, ¹⁵⁴Tb, and ¹⁵⁶Tb, over an energy range compatible with that accessible with most medical cyclotrons. We have thus been able to propose some of the production parameters that will enable us to find the best compromise between a high production rate and a ¹⁵⁵Tb purity compatible with medical needs. The work is carried out within a collaboration that explores the entire production process, from the stable precursor of the radionuclide to the design of a ¹⁵⁵Tb radio-labelled molecule. In addition, comparisons with two theoretical models, TALYS and EMPIRE, have shown the need to complete the nuclear databases, at least for the production of ¹⁵⁴Tb and ¹⁵⁶Tb, in order to make them more predictive.
%A Bouteculet, Morgane
%D 2025-09
%K Activation par protons
Nuclear physics
Physics for health
Physique nucléaire
Physique pour la santé
Production de radioisotopes
Proton activation
Radioisotope production
Theragnostics
Théranostique
user-project-thesis
¹⁵⁵Tb

%0 Thesis
%T Développement d'un agent théranostique ciblant la mésothéline
%I Université Grenoble Alpes
%U https://theses.fr/s417048
%X En médecine nucléaire, le théranostic repose sur l'utilisation d'un agent radiopharmaceutique unique pouvant être couplé à différents isotopes radioactifs, permettant d'effectuer soit un diagnostic précis par imagerie médicale soit un traitement ciblé par radiothérapie interne vectorisée. Ce principe a notamment été illustré en clinique avec l'autorisation du Lutathera pour le traitement des tumeurs neuroendocrines. C'est dans ce contexte que s'inscrit cette thèse, avec comme objectif le développement d'un nouvel agent théranostique ciblant spécifiquement la mésothéline. Il s'agit d'une protéine membranaire fortement surexprimée dans divers cancers agressifs, tels que les carcinomes pancréatiques, ovariens ou encore le cancer du sein triple négatif, tout en étant faiblement exprimée dans les tissus sains, ce qui en fait une cible particulièrement attractive pour des thérapies ciblées. Initialement, le laboratoire LRB UMRS_1039 avait développé l'anticorps à domaine unique (sdAb, ou nanobody) appelé A1-his, radiomarqué au technétium-99m (99mTc-A1-his) et l'avait validé en préclinique pour l'imagerie des tumeurs par imagerie SPECT. L'objectif principal de ce projet de thèse est de poursuivre le développement du sdAb A1-his, afin d'en obtenir un dérivé dédié à une application théranostique. Ainsi, par ingénierie moléculaire, quatre mutants d'A1 ont été générés ne conservant qu'une seule de leurs quatre lysines, permettant une conjugaison site-spécifique précise sur cette unique lysine avec le chélate DOTA. Ces mutants ont été produits en système bactérien puis purifiés avant d'être évalués. L'évaluation comprenait la mesure de leur affinité envers la mésothéline, leur rendement de conjugaison au DOTA ainsi que leur pureté radiochimique et stabilité après radiomarquage au Gallium-68 (68Ga). De plus, l'ensemble de ces mutants ont été évalué in vivo par imagerie PET chez des souris porteuses de tumeurs du sein triple négatif HCC70. Parmi ces candidats, le sdAb 68Ga-DOTA-A1K2-his a été retenu comme le meilleur candidat. Il présente en particulier le meilleur profil de biodistribution. Afin de réduire sa recapture rénale, caractéristique des sdAbs et non spécifique, deux stratégies complémentaires ont été mises en œuvre avec succès : le clivage de l'étiquette histidine via l'utilisation de la TEV protease, ainsi que la co-injection avec la gélofusine, un agent reconnu pour inhiber la recapture rénale des sdAb. Après avoir validé ces stratégies, l'efficacité thérapeutique de DOTA-A1K2 a pu être évaluée sur des modèles tumoraux de souris porteuses de tumeurs MDA-MB-231 surexprimant la mésothéline. Deux isotopes émetteurs de rayonnement β- adaptés à la radiothérapie interne vectorisée ont été sélectionnés pour cette étude : le Lutétium-177 (177Lu), couramment utilisé en clinique, et le Terbium-161 (161Tb), un radioisotope innovant, caractérisé par des propriétés radiophysiques proche de celle du 177Lu, mais ayant une supériorité potentielle sur celui-ci de par l'émission additionnelle d'électrons Auger susceptible d'améliorer l'efficacité thérapeutique. Les résultats obtenus ont montré une réduction significative du volume tumoral associée à une bonne tolérabilité du traitement, confirmant l'intérêt thérapeutique de 177Lu-DOTA-A1K2 ou 161Tb-DOTA-A1K2, sans cependant permettre de conclure la supériorité de l'un sur l'autre. En conclusion, les travaux réalisés au cours de cette thèse démontrent la pertinence et l'efficacité d'un sdAb conjugué de manière site-spécifique au DOTA, et radiomarqué avec les couples isotopiques 68Ga/177Lu ou 68Ga/161Tb. Ces résultats ouvrent des perspectives prometteuses pour le développement d'un agent radiopharmaceutique théranostique innovant, optimisé pour une application clinique en médecine nucléaire, dans le traitement personnalisé des cancers mésothéline-positifs.
%G fr
%A Nguessan, Emilien
%D 24/06/2025
%K user-project-thesis

%0 Thesis
%T Synthesis and radiolabeling studies with 68Ga, 99mTc, 177Lu and 161Tb of new oxine-derived chelating agents for theranostics application
%C Université Grenoble Alpes
%U https://theses.fr/2024GRALS009
%G English
%A Leenhardt, Julien
%D 10/04/2024
%K user-project-thesis

%0 Thesis
%T Study of the proton-induced production of the theranostic radionuclide 47Sc
%I University of Padova
%U https://hdl.handle.net/11577/3512959
%A De Dominicis, Lucia
%D 2024-04-18
%K thesis

%0 Thesis
%T Investigating 225Ac Production at CERN-MEDICIS: Extraction Yield Estimation and Sample Purity
%C Leuven, BE
%I KU Leuven
%U https://cds.cern.ch/record/2910109/files/CERN-THESIS-2024-149.pdf
%G English
%A Keppens, Max
%D 2024-09-14
%K thesis

%0 Thesis
%T Development of enriched gadolinium target for cross section measurement and future production of terbium for nuclear medicine
%I Nantes Université
%R phdthesis
%U https://theses.hal.science/tel-04047001
%X Radionuclides of terbium have attracted much attention for their potential applications in nuclear medicine. However, the short supply of terbium isotopes has limited their applications. This work proposes to use enriched gadolinium targets to produce terbium radioisotopes in biomedical cyclotrons via light-particle-induced reactions. The Auger and gamma emitter 155Tb is taken as a study case using the reaction 155Gd(d,2n)155Tb. To estimate the production yield, thin Gd- containing targets have been firstly developped to measure the cross sections. To this end, the co-electrodeposition method has been chosen to manufacture Ni-Gd2O3 composite targets. Several process parameters that have an impact on deposit quality are stutied to increase the Gd content (up to 3 mg in the deposit). The cross section measurement of natGd(d,2n)Tb, as a proof-of-conception experiment, has been carried out at GIP ARRONAX cyclotron facility using natural Ni-Gd2O3 targets. The production yield is estimated using these results. Thick targets have also been developped via pelletizing method for mass production. The optimal experimental conditions and pellet properties under these conditions have been investigated. An enriched 155Gd2O3 target was irradiated with an incident energy of 15 MeV. The production yield of 155Tb was found to be 10 MBq/μAh and the purity was 89%, which are consistent with the estimation. The coproduction of other Tb isotopes and the recycle of Gd are also involved in this thesis.
%G en
%A Wang, Yizheng
%D 2022-12-06
%K thesis

%0 Thesis
%T Development of a time-of-flight mass spectrometer with a laser desorption-ionization ion source for SMILES (Séparation en Masse couplée à l’Ionisation Laser pour des applications Environnementales et en Santé) project
%I Nantes Université
%R phdthesis
%U https://theses.hal.science/tel-05293795
%X The SMILES (Séparation en Masse couplée à l’Ionisation Laser pour des applications Environnementales et en Santé) mass separator is currently in development at the SUBATECH laboratory. It aims to analyze isotopes for environmental and medical purposes, using laser ionization. Two types of mass separators will be built: one with a dipole magnet and a hot cavity ion source, and the other, a Time-of-Flight Mass Spectrometer (TOF-MS) with a laser desorption- ionization (LDI) source. This thesis focuses on developing a TOF-MS, mainly for analyzing environmental contaminants. TOF-MS differentiates elements based on their time of flight, proportional to √��/�� ratio. A TOF-reflectron (TOF-R) will be developed for the SMILES project, with a linear TOF (TOF-L) serving as a pilot prototype. SIMION software assists in studying ion trajectories in electric and magnetic fields during the design process.
%G en
%A Kamalakannan, Keerthana
%D 2023-12-12
%K thesis

%0 Thesis
%T Ag-111 radiopharmaceutical development in the context of the ISOLPHARM project: from radionuclides production to preclinical studies
%U https://zenodo.org/records/18093541
%X Ag-111 is a radionuclide with promising features for nuclear medicine, particularly as a precursor for theranostic radiopharmaceuticals intended for Targeted Radionuclide Therapy. Preclinical studies, which are essential to assess the suitability of a radiopharmaceutical for its intended clinical application, are being conducted within the framework of the ISOLPHARM project. This project involves a wide collaboration of institutes and researchers, coordinated by the National Laboratories of Legnaro of the National Institute for Nuclear Physics (INFN-LNL). At this site, the SPES facility will host the production of Ag-111 via the ISOL technique. Thanks to a resonant ionisation laser ion source and a mass separation stage, the produced radionuclides can be collected with high specific activity. The work described in this thesis contributed to the development and installation of the experimental setup for the collection of the radionuclide. In parallel with the production activities, preclinical studies on Ag-111 were also carried out. To support these studies, two custom imaging devices were designed and built: one is sensitive to beta radiation and the other one to gamma radiation. These instruments were specifically tailored to the decay characteristics of Ag-111, to fully exploit its imaging potential. Their development was further supported by the creation of corresponding digital twins using the Geant4 simulation toolkit.
%G eng
%A Serafini, Davide
%D 2025-12-22
%K Geant4
ISOL
ISOLPHARM
Laser photo-ionization
Monte Carlo simulation
imaging
nuclear medicine
radiopharmaceutical
targeted radionuclide therapy
thesis

%0 Thesis
%T Scandium radionuclide production and mass separation at CERN-MEDICIS
%U https://zenodo.org/records/18151897
%X In this thesis the metallic foil $^{nat}$Ti, $^{nat}$V and micrometric powder $^{nat}$TiC target materials were investigated and used for medically applicable $^{43}$Sc, $^{44g/m}$Sc and $^{47}$Sc radionuclide production and mass separation at The European Organization for Nuclear Research (CERN)-Medical Isotopes Collected from ISOLDE (MEDICIS). Theoretical activity yields of Sc radionuclide production in Isotope Separation OnLine (ISOL) and cyclotron thick targets were estimated with Monte-Carlo codes and experimental cross sections.

Thermal Sc radionuclide release from irradiated metallic $^{nat}$Ti and $^{nat}$V foils was investigated to determine the impact of diffusion and adsorption processes during the mass separation and collection of radionuclides. Full Sc release from the metallic foil target materials was achieved within an hour at temperature $\sim$70-85 % of their corresponding material melting points. 

Nevertheless, the collected Sc radionuclide activity was low (<100 kBq) even at higher target material temperatures. This led to a large program of target and ion source system (TISS) developments reported in this thesis to overcome the limiting factors associated with the gaseous particle interaction with the ISOL TISS structures. Operation parameters, various configurations and modifications of the ISOL TISS and their impact on the collection efficiency were investigated.

The aspects of Sc volatilization, molecule formation and release from ISOL target and ion source system, as well as atomic and molecular gas species ionization were analyzed. The released Sc radionuclides were mass-separated as atomic and molecular ion beams and collected for subsequent radiochemical purification.Various theoretical models were used to describe the different limiting factors of radionuclide collection efficiency, such as diffusion, molecule formation, desorption, effusion, ionization and radionuclide collection rate.
%G eng
%A Mamis, Edgars
%D 2024-12-06
%K Mass Separation
Molecular Ion Beams
Radiochemistry
Scandium Radionuclides
Target and Ion Source System
Thermal Release
thesis

%0 Thesis
%T Tumor Absorbed Dose-Response Relationships in Targeted Radionuclide Therapy. A Preclinical Investigation of Lutetium-177 and Terbium-161 Radiolabeled Peptides
%U https://zenodo.org/records/18086931
%X Neuroendocrine tumors (NETs) are a heterogeneous group of neoplasms that originate from cells of the neuroendocrine system. Targeted radionuclide therapy (TRT) has become the standard treatment in the management of patients with inoperable or metastasized well-differentiated NETs (up to 90% of symptomatic patients). Peptide receptor radionuclide therapy (PRRT) employs an exclusive feature of well-differentiated NETs that is the overexpression of somatostatin receptors (SST, subtype 2 or 5). This allows for the treatment with somatostatin analogs such as octreotide as well as radiolabeled somatostatin analogs (SSAs) such as 90Y-DOTATOC and 177Lu-DOTATATE. The basic principle of a radiopharmaceutical such as 177-Lu-DOTATATE is to chelate a vector molecule ((Tyr3)octreotate), which specifically targets the cancerous tissue, with a radionuclide (L-177u), which emits ionizing radiation, damaging the DNA of the cancer cells, thereby killing the cancerous cells, but not the surrounding healthy tissue. As an alternative to Lu-177, the recently introduced radiolanthanide Tb-161 has been proposed for NET therapeutic applications. It has a similar half-life (6.89 days) and chemical properties while emitting β- particles (Eβ-av=154 keV) for therapeutic purposes and γ-irradiation (Eγ=49 keV, I=17.0%; Eγ=75 keV, I=10.2%) suitable for SPECT imaging. Tb-161 also emits a substantial number of low-energy conversion and Auger electrons (≤ 50 keV; about 10x higher emission yield than Lu-177), which makes this radionuclide exceptionally interesting for the treatment of disseminated cancers, such as metastasized NETs, with multiple metastases ranging from a single cell (diameter: ~10 μm) to micro cell clusters (diameter: < 1 mm). Since the very beginning, researchers attempted to understand the radiobiologic effects of external beam radiotherapy (EBRT) and how this could be optimized to maximize therapeutic benefit. To correctly evaluate efficacy and safety of therapy modalities and in the framework of individualized treatment, for which prediction of outcome is important, appropriate biological/biophysical models are needed. The probability that a given therapy may eradicate or control the tumor, is indicated by the formalism 'tumor control probability' (TCP). Originally, TCP models have been developed to predict external beam radiotherapy outcomes, both across populations and on a patient-specific level. TRT however is highly different from conventional external beam radiotherapy since it is a form of protracted radiation delivery during which the dose-rate is variable (e.g. due to physical half-life of the radionuclide, its specific activity and vector pharmacokinetics) and the spatial activity distribution is often non-uniform on both cellular and tissue level. Thereby, vectors can be coupled to an abundance of radionuclides that emit beta, alpha or Auger electrons, associated or not with X or gamma rays. Consequently, commonly used assumptions for modeling of EBRT dose response cannot be generalized towards TRT as well. Despite frequent and successful use of Lu-177-DOTATATE in the clinic, little or no radiobiologic considerations are made at the time of treatment planning or delivery, nor is there an abundance of data from preclinical studies. Currently, treatment is usually administered as a standard dose and number of cycles without adjustment for peptide uptake, dosimetry or radiobiological and DNA damage effects in the tumor. Moreover, data on the influence of absorbed doses on the response and toxicity of treatment with radiopharmaceuticals, which are actually a prerequisite for evidence-based individualized therapy, are also still lacking. The aim of this PhD is to develop a framework for improved modeling of the dose-response, i.e. the tumor control probability, for specific TRT scenarios. We will determine the different parameters within the TCP model based on extensive experimental data, gained from well designed experimental studies, representing the specific TRT exposure characteristics. The radiopharmaceuticals of interest consist of the clinically relevant DOTATATE vector, combined with the Lu-177 or Tb-161 radionuclide, tested in well-characterized in vitro and in vivo NET models. Due to the fact that Tb-161 emits a higher percentage of internal conversion and Auger electrons, Tb-161-DOTATATE is expected to deliver a higher absorbed dose to the bound tumor cell and immediate neighboring cells. We aim with our established TCP model to illustrate the expected improved therapeutic efficacy of Tb-161 DOTATATE compared to Lu-177 DOTATATE.
%G eng
%A Spoormans, Kaat
%D 2025-11-04
%K targeted radionuclide therapy

%0 Thesis
%T High intensity surface ion source towards long-term irradiation for ISOL@MYRRHA
%U https://zenodo.org/records/18086646
%X This thesis presents the development and experimental testing of a novel surface ion source for ISOL@MYRRHA at the Belgian Nuclear Research Centre SCK CEN. The MYRRHA project is an industrial-scale prototype of a subcritical lead-bismuth cooled reactor driven by a linear particle accelerator. Part of the beam coming from the accelerator will be extracted towards an ISOL facility, ISOL@MYRRHA, for radioactive ion beam production. The research focuses on enhancing the efficiency and reliability of ion sources under the unique conditions of this facility, which include a primary beam of 100 MeV protons with up to 0.5 mA beam intensity driven by a linear particle accelerator.

Due to its simplicity and robustness, a surface ion source was selected for ISOL@MYRRHA as a first source, with the capability to function as a laser ion source cavity. The thesis explores the surface ionisation principle, examining the interactions at the heated material surface, the formation of plasma sheath potential, and the impact of these phenomena on ionisation efficiency.

The importance and impact of the surface ion source’s heating system were studied: electron-bombardment and Ohmic heating. The former was used during the development of surface ionisation theory and the latter is the typical form used nowadays in ISOL facilities. The implications of Ohmic heating on temperature and potential distributions within the ion source are discussed. An active thermal screen concept to mitigate cold spots, identified in Ohmic heating systems, has been developed. This concept, along with its variations for different manufacturing methods – Welded, 3D printed, and Assembled designs – were explored, resulting in a prototype of the Assembled design constructed at SCK CEN, then successfully tested at CERN.

Experimental results from initial tests are detailed, including the prototype’s thermal-electric behaviour and its performance under various operational conditions.

The thesis concludes with insights into the ionisation efficiency of different elements, the impact of ion load and temperature on ion origin, and the prototype’s durability over extended operation and under stress conditions. The findings and their consequences for the understanding of the surface ion source are then summarised. Finally, practical solutions and advancements for the future ISOL@MYRRHA facility and the development of a next surface ion source are discussed.
%G eng
%A Hurier, Sophie
%D 2024-10-03
%K ion sources
radioactive ion beams
thesis

%0 Journal Article
%T Sustainability plan
%I Zenodo
%* Creative Commons Attribution 4.0 International
%U https://zenodo.org/doi/10.5281/zenodo.18034767
%X Sustainability aspects were taken into account from the outset of the PRISMAP project, with the overall objective being to establish the European medical radionuclides programme on a long-term. After approximately five years of implementing and developing PRISMAP, the European and international landscape, as well as that of nuclear medicine and radiopharmaceuticals, has evolved to a degree that far exceeds the most optimistic forecasts made when PRISMAP was first developed. 

In this document, we present the various aspects taken into account in the sustainability of PRISMAP, with an important milestone being the submission of a new PRISMAP+ project proposal aimed at providing a structure for the period 2026-2029, as a new phase of the European medical radionuclides programme, in order to connect with the evolving landscape of cutting-edge European research in nuclear medicine.
%A Köster, Ulli
%A Stora, Thierry
%D 2025-12-23
%K deliverable

%0 Journal Article
%T User projects
%I Zenodo
%U https://zenodo.org/records/17898315
%X This document summarises the user projects carried out as part of the PRISMAP project.

During its lifetime, the PRISMAP project published five calls for proposals. Of the 67 proposals submitted, 47 were selected for funding and 43 were actually carried out until the final report.

This document contains descriptions of the funded projects and some related statistics, a list of scientific publications and other dissemination activities resulting from these projects, and feedback received from users after completion, including suggestions for future projects. We also draw conclusions from the lessons learned on the consortium side.

Finally, the deliverable includes an appendix with summaries of all selected projects and a link to the final reports of the user projects on a dedicated page of the PRISMAP website.
%G eng
%A Duchemin, Charlotte
%A Haddad, Ferid
%D 2025-12-11
%K deliverable

%0 Journal Article
%T Standards for clinical translation
%I Zenodo
%* Creative Commons Attribution 4.0 International, Open Access
%U https://zenodo.org/record/6599181
%X Radiopharmaceuticals are considered Medicinal Products, thereby they must be prepared and applied within the regulated area of pharmaceuticals. This includes radionuclides, which have seen extraordinary advancements in research and development over the last decade in regards to theranostics. The governing EU directives and regulations, including regulatory guidance, cannot keep pace with this development. PRISMAP, the European Medical Radionuclide Program, brings together key nuclear research centres and leading clinical translational research facilities across Europe to provide a sustainable source of high purity grade new radionuclides for the starting research community. One of PRISMAP`s paramount aims is to standardise and harmonise research and development activities with novel radionuclides to cope with pharmaceutical regulatory requirements and provide guidance for clinical translation. The PRISMAP workshop: “Radionuclide Production to Nuclear Medicine Clinical Applications: Regulatory Standards and Harmonisation of Quality and Safety”, held in February 2022, provided the basis for this document, which gives guidance for the early phase clinical research with novel radionuclides. It describes the current standards and a harmonised view of the European regulatory framework. The document complements the existing regulatory framework and is not considered legally binding.<br> Six chapters cover different aspects in radiopharmaceutical development. Each chapter includes dedicated guidelines and guidance documents from regulatory authorities and professional organisations, as well as references to scientific publications on the respective topic.<br> An introduction of PRISMAP and the project scope is followed by a definition of terms and nomenclature for specification of novel radionuclides within PRISMAP. The following chapter focuses on the production of radionuclides and implementation of GMP in the radiopharmaceutical development process. It provides relevant definitions and gives recommendations where GMP compliant processes should be introduced in the production of novel radionuclides. Guidance for controls of radionuclides including starting materials, process validation, in-process controls, chemical precursors and production of radiopharmaceuticals are briefly addressed. The subsequent chapter covers quality specifications and quality control. It includes details on relevant European Pharmacopoeia texts and guidance for compliance, summarises other regulatory texts from the EMA and ICH, giving general considerations on specifications and specific guidance for validation of analytical methods. It provides definitions on drug substance and drug product and addresses all relevant specific quality criteria for novel radionuclides. The next chapter deals with metrology and medical physics aspects in clinical translation. The relation to the Basic Safety Standards of the Council Directive 2013/59/Euratom is described, which includes aspects of therapy planning and dosimetry for novel radionuclides. Standardisation in relation to traceability is addressed in a dedicated part on Metrology. The role of Medical Physics in the context of standardisation and harmonisation of the clinical use of novel radionuclides for imaging equipment, image acquisition, processing parameters, and quality control implementation of new technologies is summarised.<br> The final chapter covers Non-Clinical Safety and Pharmacology aspects and provides an overview of the current guidance documents to assess preclinical dosimetry, toxicity (new EMA guideline specific for radiopharmaceuticals), and pharmacology of radiopharmaceuticals, which are developed with the aim to be used in human clinical trials. Recent specific guidance documents on this topic, particularly from the IAEA are summarised and included.<br> This guidance document serves as an essential and comprehensive guide for radionuclide producers, radiopharmaceutical translational scientists, clinical and hospital based radiopharmaceutical development researchers through the complex jungle of pharmaceutical regulations and guidelines. It provides a harmonised view to standardise data required for clinical translation of novel radionuclides.
%G en
%A Decristoforo, Clemens
%A Hayashi, Sason Feldkamp
%A Bordeau, Cecile
%A Haddad, Ferid
%A Viertl, David
%A Deville, Claire
%A Naidoo, Clive
%A Pedersen, Kristina Søborg
%A Jensen, Mikael
%A Köster, Ulli
%A Correia, João Galamba
%A Gano, Lurdes
%A Bruchertseifer, Frank
%A Baete, Kristof
%A Mikolajczak, Renata
%A Collins, Sean
%A Geistlich, Susanne
%A Van Der Meulen, Nick
%A Ponsard, Bernard
%A Van De Voorde, Michiel
%A Campillos, Monica
%D 2022-05-31
%K PRISMAP, radionuclides, pharmaceutical, standardization and harmonization
deliverable

%0 Journal Article
%T Quality data collection for clinical translation
%I Zenodo
%* Creative Commons Attribution 4.0 International
%U https://zenodo.org/doi/10.5281/zenodo.16612998
%A Decristoforo, Clemens
%D 2025-07-30
%K deliverable

%0 Journal Article
%T Cytotoxicity and cell cycle changes in prostate cancer cells with differing PSMA expression and p53 status after treatment with PSMA-targeting radioligand [212Pb]Pb-AB001
%I Nature Publishing Group
%W https://pubmed.ncbi.nlm.nih.gov/41318731/
%* 2025 The Author(s)
%U https://www.nature.com/articles/s41598-025-29785-7
%X Targeted alpha therapy holds promise for treating advanced prostate cancer, but the interplay between prostate-specific membrane antigen (PSMA) expression, p53 status, and downstream cell fate remains poorly defined. This study evaluates the cytotoxic and cell cycle effects of the alpha-emitting radioligand [212Pb]Pb-AB001 in prostate cancer cell lines with differing PSMA expression and p53 status: C4-2 (PSMA+/TP53-wild-type) and PC-3 PIP (PSMA+++/ TP53-null). [212Pb]Pb-AB001 significantly inhibited proliferation and clonogenic survival in both cell lines in an activity-dependent manner. At 95% clonogenic inhibition, both cell lines exhibited G2-phase arrest, S-phase suppression and reduced mitotic entry on day 1. At higher activities, PC-3 PIP cells showed polyploidy, and features consistent with mitotic catastrophe and senescence. Cytotoxicity was more pronounced in C4-2 3D spheroid models than in 2D monolayers, suggesting contribution of crossfire and bystander effects. Total cell-bound activity, rather than added activity, better predicted radiotoxicity in both TP53-wild-type and TP53-null cell lines, indicating that its therapeutic effect is primarily governed by PSMA-mediated uptake rather than p53 status. These results support the therapeutic potential of [212Pb]Pb-AB001 across cells with varying TP53 status and suggest that combining [212Pb]Pb-AB001 with DNA repair or checkpoint inhibitors may enhance treatment efficacy.
%G en
%J Scientific Reports
%A Stenberg, Vilde Yuli
%A Liukaityte, Rugile
%A Kristiansen, Sandra Kvarsvik
%A Wangen-Riise, Rina
%A Kleinauskas, Andrius
%A Dunne, Victoria
%A Juzeniene, Asta
%D 2025-11-29
%K Cancer
Cell biology
Oncology
scientific-publication

%0 Journal Article
%T Optimised solid-phase extraction of 211At: Activity balance of 211At, 210At and 210Po after wet chemistry target dissolution
%V 225
%P 112146
%U https://linkinghub.elsevier.com/retrieve/pii/S0969806X24006388
%G en
%J Radiation Physics and Chemistry
%A Sevenois, Matthijs Bart
%A Jensen, Holger Jan
%A Haddad, Ferid
%A Bäck, Tom
%A D'Huyvetter, Matthias
%A Navarro, Laurent
%A Covens, Peter
%D 12/2024
%K user-project

%0 Journal Article
%T Preclinical Evaluation of Gastrin-Releasing Peptide Receptor Antagonists Labeled with <sup>161</sup> Tb and <sup>177</sup> Lu: A Comparative Study
%P jnumed.123.266233
%U http://jnm.snmjournals.org/lookup/doi/10.2967/jnumed.123.266233
%G en
%J Journal of Nuclear Medicine
%A Holzleitner, Nadine
%A Cwojdzinski, Tatjana
%A Beck, Roswitha
%A Urtz-Urban, Nicole
%A Hillhouse, Colin C.
%A Grundler, Pascal V.
%A Van Der Meulen, Nicholas P.
%A Talip, Zeynep
%A Ramaekers, Stijn
%A Van De Voorde, Michiel
%A Ponsard, Bernard
%A Casini, Angela
%A Günther, Thomas
%D 2023-12-14
%K user-project

%0 Journal Article
%T A true theranostic pair – 44/47Sc-labeled GRPR antagonist shows great promise for managing prostate and breast cancer
%U https://doi.org/10.1007/s00259-025-07651-y
%X This study investigates the theranostic potential of a 44/47Sc-labeled antagonist targeting the gastrin-releasing peptide receptor (GRPR) in prostate and breast tumors.
%G en
%J European Journal of Nuclear Medicine and Molecular Imaging
%A Kumar, Naveen
%A Bilinska, Adrianna
%A Menéndez, Elena
%A Läppchen, Tilman
%A Moon, Euy Sung
%A Zoltowska, Malgorzata
%A Pawlak, Dariusz
%A Cieszykowska, Izabela
%A Mikolajczak, Renata
%A Rösch, Frank
%A Rominger, Axel
%A Gourni, Eleni
%D 2025-11-11
%K 44/47Sc
Everolimus
Fractionated dose
GRPR antagonist
mTOR inhibitor
user-project

%0 Journal Article
%T Different 212Pb Generators and Its Radiation Safety Concerning 220Rn (Thoron) Emanation
%V 13
%N 6
%P 462
%U https://www.mdpi.com/2305-6304/13/6/462
%X (1) Background: As the demand for 212Pb for clinical theranostics rises, empirical studies that examine the radiation safety implications of different 224Ra sources are needed to facilitate discussions with local authorities for the translation of 203/212Pb theranostics routine clinical practice. (2) Methods: Environmental 220Rn (Thoron) emanation was detected by a RAD7 detector in the vicinity of respective 212Pb sources and additional alpha-dosimeters to detect 220Rn during generator elution, radiosynthesis, and quality control. Personnel gamma exposure was measured using whole-body and ring dosimeters. Generators included those based on wet-chemical-process- and emanation-based technology. (3) Results: During generator handling, varying levels of 220Rn were observed in the vicinity of generators. An additional monthly whole-body dose must be considered when handling different sources of 212Pb generators, and this depends upon local shielding and the handling approaches toward use of the technology. (4) Conclusions: 224Ra in any form (including radionuclide generators) should always be handled within a fume hood to keep potential contamination and exposure to personnel as low as reasonably achievable. Following standard practices of radiation safety, generators of 212Pb can be used safely for theranostic applications.
%G en
%J Toxics
%A Pretze, Marc
%A Hartmann, Holger
%A Duchemin, Charlotte
%A Stora, Thierry
%A Inzamam, Muhammad
%A Kästner, David
%A Sagastume, Edwin A.
%A Schultz, Michael K.
%A Kotzerke, Jörg
%A Bundschuh, Ralph A.
%A Freudenberg, Robert
%D 2025-05-30
%K user-project

%0 Journal Article
%T Navigating the safety profile of Actinium-225 targeted alpha therapy: a comprehensive review
%W https://zenodo.org/records/16986225
%U https://doi.org/10.1007/s40336-025-00733-9
%X This review aims to collect the available documents on the clinical safety of Ac-225 radiopharmaceuticals targeted alpha radionuclide therapy and summarize practical safety data recommended for clinical development of Ac-225 radiopharmaceuticals.
%G en
%J Clinical and Translational Imaging
%A Roustaei, Hessamoddin
%A D’Alessandria, Calogero
%A Decristoforo, Clemens
%D 2025-11-04
%K Actinium-225
Review
Safety
TAT
Targeted alpha therapy
Targeted radionuclide therapy
Toxicity
scientific-publication

%0 Journal Article
%T User Meetings
%I Zenodo
%* Creative Commons Attribution 4.0 International
%U https://zenodo.org/doi/10.5281/zenodo.16871555
%A Gander, Filippo
%D 2025-08-14
%K deliverable

%0 Journal Article
%T Workshops for senior researchers
%I Zenodo
%* Creative Commons Attribution 4.0 International
%X The multidisciplinary nature of the PRISMAP consortium and PRISMAP community is a challenge to engage with a common language. Through its Training Office, and together with its Dissemination Team, PRISMAP engages towards senior and established researchers to provide educational content that promotes enhanced mutual understanding between the different fields.

In this report, we present all the activities that have been carried in the last 3 years within PRISMAP. From these, we have drawn conclusions on how to adjust our approach to reach to a broader audience and further promote the mutual understandings of the different parts of the PRISMAP community.
%G en
%A Cocolios, Thomas Elias
%D 2024-05-03
%K deliverable

%0 Journal Article
%T Standardised access procedures
%I Zenodo
%* Creative Commons Attribution 4.0 International
%U https://zenodo.org/doi/10.5281/zenodo.11109550
%X The objective of the deliverable D1.2.’Standardised access procedures’ is to establish a common PRISMAP accessprocess by standardising the access procedures for all PRISMAP production facilities (TNA2) and biomedicalfacilities (TNA2), ensuring a smooth and efficient user experience.
%G en
%A Vreys, Ruth
%A Duchemin, Charlotte
%A Haddad, Ferid
%A Viertl, David
%A D'Alessandria, Calogero
%A Talip, Zeynep
%A Köster, Ulli
%D 2024-04-30
%K deliverable

%0 Journal Article
%T Safety data collection for clinical translation
%I Zenodo
%U https://zenodo.org/records/17253347
%A Decristoforo, Clemens
%D 2025-10-02
%K deliverable

%0 Journal Article
%T Report on precursor synthesis and related infrared spectroscopy measurements
%I Zenodo
%* Creative Commons Attribution 4.0 International
%U https://zenodo.org/doi/10.5281/zenodo.10091918
%X According to the PRISMAP Description of Action, D10.6 is dedicated to the "Synthesis of the appropriate molecular precursors containing Ca and Ti and the related FTIR spectra measurements", towards the application of laser-enhanced isotopically selective condensation for the enrichment of Ca and Ti radionuclides.
As calcium hexafluoroacetylacetonate (C10H2CaF12O4) is commercially available, it has been procured externally for this purpose and characterised towards its planned use.
Gas-phase infrared spectroscopy was employed to investigate the vibrational modes of calcium hexafluoroacetylacetonate (C10H2CaF12O4) in the wide wavenumber range from 550 to 1700 cm-1. The measured spectrum agrees well with previous density functional theory calculations, allowing a targeted laser excitation within PRISMAP at 490 cm-1, in order to resonantly excite a Ca isotope sensitive vibration.
This demonstrates that this commercially available compound is appropriate for the sought-out application and that dedicated synthesis is thus not required.
A similar approach may now be followed for Ti-containing molecules, where we need first to identify a suitable stable molecule, then perform the associated DFT calculations, perform the synthesis if no commercial compound can be identified, and finally verify those with infrared light spectroscopy.
%G en
%A Cocolios, Thomas Elias
%A Duchemin, Charlotte
%A Mamis, Edgars
%A Stora, Thierry
%D 2023-11-09
%K deliverable

%0 Journal Article
%T Report on Gd target production
%I Zenodo
%* Creative Commons Attribution 4.0 International
%X Short-lived radionuclides of the terbium (Tb) family show great interest for application in nuclear medicine. Different production routes exist to produce these radionuclides, but the most obvious ones use gadolinium as target material. Within the WP10 of PRISMAP, INFN and ARRONAX have worked on Gd target preparation for both cross section measurements (thin targets) and radionuclide production (thick targets). This work used the preparation of gadolinium targets for Tb-155 production as a case study as developed techniques can easily be adapted to other enriched Gd isotopes. Thin target preparation using different electrochemical techniques has been explored as well as different methods to prepare pellets from Gd2O3 powder including sintering. Targets of both types were prepared and irradiated both in France and Italy.
%A Cisternino, S.
%A Haddad, F.
%A Kotliarenko, A.
%A Sounalet, T.
%A Wang, Y.
%D 2024-05-03
%K deliverable

%0 Journal Article
%T Proceedings book workshop 1
%I Zenodo
%* Creative Commons Attribution 4.0 International, Open Access
%U https://zenodo.org/record/7913190
%X This deliverable is the Proceedings book of the PRISMAP workshop 1 “PRISMAP workshop on emerging infrastructures and technical developments”. The Workshop on Emerging Infrastructures and Technical Developments was organised at Legnaro National Laboratories on 21-24 November 2022. The Workshop gave a general update on international facilities producing radionuclides, identified the most promising radionuclides on which production R&amp;D shall focus in the near future, and presented the latest technical developments on targets, ion sources and mass separation techniques. This is one of the two events organised within the WP8: Involvement of Emerging Infrastructures. The workshop was organised in a hybrid format, registering 76 participants, out of which 39 in person and 37 remotely. The first day of the workshop included 15 talks dedicated to infrastructures and radionuclides programmes. The second day was dedicated to more technical topics, including 9 technical talks covering the major activities performed within WP10: on targets, ion sources and isotopes purification. The on-site participants could join a visit to SPES facilities, enjoying a unique opportunity to enter all sections of this ISOL facility which is getting ready to start the beam commissioning. Furthermore, a poster session has been organised, where 9 posters have been presented. Proceedings contributions from some of the posters are included in this Book of Proceedings.
%G en
%A Manzolaro, Mattia
%A Corradetti, Stefano
%A Pupillo, Gaia
%A Popescu, Lucia
%D 2023-05-09
%K biomedical research facilities
deliverable
high power cyclotrons
high purity isotopes
high purity radionuclides
isotope mass separation facilities
mass separation
nuclear reactors
radiopharmaceuticals

%0 Journal Article
%T PRISMAP workshops
%I Zenodo
%U https://zenodo.org/records/17458154
%X We have organised five events for the broad scientific community throughout the duration of the PRISMAP project, including two at the international congress of EANM. Those events have been very successful, resulting in increased membership to the PRISMAP Community and shaping future collaborations, some of which have been concretised in the PRISMAP+ proposal.
%G eng
%A Cocolios, Thomas Elias
%D 2025-10-27
%K deliverable

%0 Journal Article
%T Precision nuclear data for extended radionuclide offer
%I Zenodo
%U https://zenodo.org/records/15348568
%X Nuclear decay data are fundamental constants of a radionuclide’s decay process and are unique to that radionuclide. Nuclear decay data are of importance to a wide range of activities in nuclear medicine, from the production of radionuclides to their use in nuclear medicine clinics. Thus, accurate and precise nuclear decay data are vital to ensure confidence in the activities undertaken across the end-to-end process of radiopharmaceutical use.

During the progress of PRISMAP the number of radionuclides has increased from an original offering of 18 radionuclides to an extensive portfolio of 28 radionuclides. In a previous report the status of the nuclear decay data of these original 18 radionuclides was reviewed and recommendations given where future measurement campaigns were needed to improve this data. This same undertaking has been performed for the extended offering of radionuclides, adding reviews of the radionuclides of Sc-43, Mn-52, Pd-103, Rh-103m, Ba-138, Cs-128, Sm-153, Au-199, Pb-203, Ra-223 (and its six-decay progeny), Ra-224 (and its six-decay progeny) and Th-227.

A summary of the current state of nuclear decay data of these radionuclides have been covered in this report using the latest evaluations published by the Nuclear Data Sheets or the Decay Data Evaluation Project. Where recent studies have been published since the last evaluation a comparison to these new values have been included. Based on these reviews, recommendations have been proposed throughout the report for new nuclear decay data studies, where the current literature is lacking or there is room for improvement.
%G eng
%A Collins, Sean
%D 2025-05-06
%K Gamma ray
Half-Life
Nuclear Decay Data
Nuclear Medicine
PRISMAP
Radioactivity
Radionuclide
Targeted Radionuclide Therapy
deliverable

%0 Journal Article
%T Database of packages, documents, approvals
%* Creative Commons Attribution 4.0 International
%U https://zenodo.org/doi/10.5281/zenodo.11109988
%X The PRISMAP Database of packages, documents, approvals  

A public deliverable D9.3 under the PRISMAP project
%G en
%A Jensen, Mikael
%D 2024-05-03
%K deliverable
radioactivity transport

%0 Journal Article
%T Compliant and efficient transportation
%* Creative Commons Attribution 4.0 International
%U https://zenodo.org/doi/10.5281/zenodo.10069352
%G en
%A Jensen, Mikael
%A Duchemin, Charlotte
%A Talip, Zeynep
%D 2023-11-03
%K deliverable

%0 Journal Article
%T Academia meets industry events
%U https://zenodo.org/records/17457553
%A Radzina, Maija
%D 27.05.2025
%K deliverable

%0 Journal Article
%T White Paper on Emerging Facilities for Production of Novel Radionuclides for Use in Nuclear Medicine
%I Zenodo
%U https://zenodo.org/records/17553316
%X The key objective of PRISMAP is to establish a European infrastructure for researchers and physicians, providing a sustainable source of highly pure non-conventional radionuclides for development in medicine as well as protocols and services for the pharmaceutical industry and the healthcare sector. It is composed of a consortium of European facilities for radionuclide production, including high-flux neutron sources, mass separator facilities, and high-power accelerators, with biomedical research institutes and hospitals dedicated to translating emerging radionuclides into medical diagnosis and treatment. PRISMAP focuses on the development and study of non-conventional radionuclides for translational medical research.

This work is part of WP8 of PRISMAP on “Involvement of Emerging Infrastructures”. The goals of this White Paper are: First, to provide a comprehensive list of the emerging facilities which are part of the PRISMAP consortium. These emerging facilities are at different stages of maturity, some are already operating, some are in the design or construction phases, and finally, some are just on paper. Second, to provide results on production capabilities for some of the innovative radionuclides that are part of the PRISMAP portfolio. During the project, two workshops, the first one at INFN in Legnaro, Italy, in 2022, and the second at SCK CEN in 2025, were held as part of the same work package. In the second workshop, preliminary results on calculations for six innovative radionuclides were presented. The final results are summarized in this white paper.



The six radionuclides with high potential in nuclear medicine are Sc-47, Cu-67, Tb-152, Tb-155, Pt-195m and Ac-225. They were selected from the list in the PRISMAP portfolio (Pt-195m while not yet in the PRISMAP portfolio, but had been requested by PRISMAP users) because their production routes at existing facilities are particularly challenging, and it is of vital interest to consider alternative ways at emerging facilities, considering production at particle accelerators, γ-ray beams, and neutron sources, with the possible use of mass separation. As it is shown in the report, the results are extremely encouraging in terms of production capabilities, and all of the emerging facilities can, in one way or the other, contribute to the development and production of these innovative radionuclides. Some challenges remain, and these are discussed in the individual sections dedicated to the radionuclides and in the conclusions.
%A Zanini, Luca
%D 2025-11-07
%K deliverable

%0 Journal Article
%T Traceability for radionuclides
%I Zenodo
%* Creative Commons Attribution 4.0 International
%U https://zenodo.org/doi/10.5281/zenodo.11093646
%X Radionuclides play an important role in the diagnosis of a range of key diseases or for the delivery of targeted cancer therapies. This unique capability has been utilised for decades and drives the development of new radiopharmaceuticals using well known radionuclides and the search for novel radionuclides that can expand the pool of treatments available and lead to improvements in patient outcomes. The development and manufacture of these radiopharmaceuticals and use in a patient requires the accurate measurement of the activity of the radionuclide to provide the efficient and safe use of the drug.

To achieve this, regulators look to radiopharmaceutical manufacturers and radiopharmacies to be capable of accurately measuring the activity of the radionuclide present in a manner traceable to national or international standards of activity. Traceability provides the best route to ensure that the measurement devices being used, and their calibrations are providing accurate results, through a documented unbroken chain of calibrations.

As new radionuclides are identified and developed for use in nuclear medicine National Metrology Institutes (NMIs) play a crucial role in developing these national and international standards through the realisation of primary standards of activity of the radionuclide. The NMIs are responsible for providing a method for disseminating these standards to the radiopharmaceutical manufacturers, radiopharmacies and clinics to provide the link to the SI unit of the becquerel and give confidence in the activity measurements.

Through the well-established comparison systems of the International Reference System (SIR) at the Bureau International Des Poids et Mesures (BIPM) the NMIs can compare their national standards against those of other nations and show their equivalence and provide confidence in the standards being provided. Over the years many primary standards for radionuclides with applications in medicine have been developed and compared, with some of PRISMAP radionuclides already having been compared by NMIs. With many new radionuclides being proposed for nuclear medicine applications, there is still a substantial amount of work for the NMIs and the BIPM to perform to provide traceability.
%A Collins, Sean
%D 2024-05-01
%K deliverable

%0 Journal Article
%T First public report from the PRISMAP work package 9 (WP9, transport and logistics)
%* Creative Commons Attribution 4.0 International, Open Access
%U https://zenodo.org/record/6606494
%X This report is the first public output from the PRISMAP work package 9 (WP9, transport and logistics). The report describes in outline the existing rules and means of transport (primarily air and road) and how these rules and their implementation induce important constraints on the optimal distribution of novel radionuclides within the network. Based on input from the project partners and the analysis of the most urgent transportation needs arising from the first round of user projects, the report describes important bottlenecks for the efficient and reliable transport of novel radionuclides.
%G en
%A Jensen, Mikael
%A Naidoo, Clive
%A Bertreix, Philippe
%A Frosio, Thomas
%A Viertel, David
%A Köster, Ulli
%A Cocolios, Thomas Elias
%D 2022-06-02
%K Novel Radionuclides
Transportation Radioactive Materials
deliverable

%0 Journal Article
%T MOOC on the basis of In the Heart of Medical Radioactivity
%I Zenodo
%* Creative Commons Attribution 4.0 International
%U https://zenodo.org/doi/10.5281/zenodo.10057649
%A Le Pennec, Anne
%D 2023-10-31
%K deliverable

%0 Journal Article
%T Questionnaire on industrial and clinical key players and needs
%I Zenodo
%* Creative Commons Attribution 4.0 International, Open Access
%U https://zenodo.org/record/7154340
%X This document is a summary of responses received from the public known European industrial manufacturing and research institution and clinical facility representatives. The responses were given to the PRISMAP Consortium questionnaire disseminated in January-August 2022, approaching radionuclides and radiopharmaceutical manufacturers, research institutions and clinical end users in nuclear medicine, with the aim to identify potential stakeholders in the industrial and clinical communities interested by a coordinated approach in Europe such as PRISMAP. The summary from PRISMAP questionnaire stratifies the feedback from 114 respondents: radionuclide and radiopharmaceutical producers, research facilities and preclinical/clinical end users. In addition, it gives an insight into the location and capabilities of the main isotope-producing cyclotron facilities, many of which are known from the IAEA cyclotron database [2]). The questionnaire was offered with an opportunity to make new research and international collaboration partners, where all parties could benefit from harmonised supply and legislation procedures, expanding network and distribution routes, and subsequently gain visibility within the PRISMAP User Forum map at www.prismap.eu. The questionnaire was focused on the radionuclide use in medicine with emphasis on future needs for specific radionuclides and possible research developments with awareness of legislation, logistics and involved personnel education challenges and future perspectives.
%G en
%A Radzina, Maija
%A Mamis, Edgars
%A Saule, Laura
%A Pajuste, Elina
%A Kalnina, Marika
%A Cocolios, Thomas
%A Talip, Zeynep
%A Stora, Thierry
%D 2022-09-30
%K Clinical End Users
Radiopharmaceutical Manufacturers
Research Institutions
deliverable
nuclear medicine
questionnaire

%0 Journal Article
%T Validation of ICP-OES and γ-spectrometry methodologies for quality assessment of 67Cu from cyclotron production via the 70Zn(p,α)67Cu nuclear reaction
%V 334
%N 8
%P 5637-5648
%W https://orbit.dtu.dk/en/publications/validation-of-icp-oes-and-%CE%B3-spectrometry-methodologies-for-qualit/
%U https://doi.org/10.1007/s10967-025-10270-4
%X Increasing interest in 67Cu for targeted radionuclide therapy necessitates development of robust and validated analytical methods to ensure compliance with regulatory standards for clinical translation. We validated methods based on inductively coupled plasma optical emission spectroscopy (ICP-OES) and high-purity germanium (HPGe) γ-spectrometry. For ICP-OES, criteria were met for most elements, with Al and Ca, suffering matrix effects. Apparent molar activity calculated by ICP-OES was congruent with DOTA-titration-based effective molar activity when Al and Ca were excluded. HPGe γ-spectrometry was shown to enable accurate discrimination and quantification of co-produced radionuclides (67Ga, 66Ga, 69mZn) from 67Cu at 99.5% radionuclidic purity.
%G en
%J Journal of Radioanalytical and Nuclear Chemistry
%A Søndergaard, Ursula
%A Thomas, Kolle E.
%A Sundset, Rune
%A Deville, Claire
%A Jensen, Mikael
%A Pedersen, Kristina S.
%A Moldes-Anaya, Angel
%D 2025-08-01
%K 67Cu
ICP-OES
Quality control
Validation of radioanalytical methods
scientific-publication
γ spectrometry

%0 Journal Article
%T Two-step extraction chromatography separation of 161Tb from 160Gd-enriched irradiated target material and verification of the [161Tb]TbCl3 suitability for radiolabelling
%V 226
%P 112144
%W https://pubmed.ncbi.nlm.nih.gov/40907080/
%U https://linkinghub.elsevier.com/retrieve/pii/S0969804325004890
%G en
%J Applied Radiation and Isotopes
%A Żółtowska, Małgorzata
%A Pawlak, Dariusz
%A Cieszykowska, Izabela
%A Saganowski, Paweł
%A Lisowska, Natalia
%A Filiks, Anna
%A Mikołajczak, Renata
%D 12/2025
%K scientific-publication

%0 Journal Article
%T Activity standardization of 47Sc by LS methods
%V 226
%P 112213
%W https://pubmed.ncbi.nlm.nih.gov/41038005/
%U https://linkinghub.elsevier.com/retrieve/pii/S0969804325005585
%G en
%J Applied Radiation and Isotopes
%A Marganiec-Gałązka, J.
%A Lisowska, N.
%A Kamiński, A.
%A Saganowski, P.
%A Tymiński, Z.
%A Cieszykowska, I.
%A Żółtowska, M.
%D 12/2025

%0 Journal Article
%T Production study of Fr, Ra and Ac radioactive ion beams at ISOLDE, CERN
%V 14
%N 1
%P 11033
%W https://cds.cern.ch/record/2900414?ln=en
%U https://www.nature.com/articles/s41598-024-60331-z
%X Abstract
            
              The presented paper discusses the production of radioactive ion beams of francium, radium, and actinium from thick uranium carbide (UC
              
                
                  $$_{x}$$
                  
                    
                      
                      x
                    
                  
                
              
              ) targets at ISOLDE, CERN. This study focuses on the release curves and extractable yields of francium, radium and actinium isotopes. The ion source temperature was varied in order to study the relative contributions of surface and laser ionization to the production of the actinium ion beams. The experimental results are presented in the form of release parameters. Representative extractable yields per
              
                
                  $$\mu$$
                  
                    μ
                  
                
              
              C are presented for
              
                
                  $$^{222-231}$$
                  
                    
                      
                      
                        222
                        -
                        231
                      
                    
                  
                
              
              Ac, several Ra and Fr isotopes in the mass ranges 214
              
                
                  $$\le$$
                  
                    ≤
                  
                
              
              A
              
                
                  $$\le$$
                  
                    ≤
                  
                
              
              233 and 205
              
                
                  $$\le$$
                  
                    ≤
                  
                
              
              A
              
                
                  $$\le$$
                  
                    ≤
                  
                
              
              231 respectively. The release efficiency for several isotopes of each of the studied elements was calculated by comparing their yields to the estimated in-target production rates modeled by CERN-FLUKA. The maximal extraction efficiency of actinium was calculated to be 2.1(6)% for a combination of surface ionization using a Ta ion source and resonant laser ionization using the two-step 438.58 nm, and 424.69 nm scheme.
%G en
%J Scientific Reports
%A Jajčišinová, E.
%A Dockx, K.
%A Au, M.
%A Bara, S.
%A Cocolios, T. E.
%A Chrysalidis, K.
%A Farooq-Smith, G. J.
%A Fedorov, D. V.
%A Fedosseev, V. N.
%A Flanagan, K. T.
%A Heines, M.
%A Houngbo, D.
%A Johnson, J. D.
%A Kellerbauer, A.
%A Kraemer, S.
%A Marsh, B. A.
%A Popescu, L.
%A Ramos, J. P.
%A Rothe, S.
%A Seliverstov, M. D.
%A Sels, S.
%A Stegemann, S.
%A Stryjczyk, M.
%A Verelst, V.
%D 2024-05-14

%0 Journal Article
%T First ion source at ISOL@MYRRHA with an improved thermal profile - Theoretical considerations
%V 2743
%N 1
%P 012065
%W https://lirias.kuleuven.be/4163533&lang=en
%U https://iopscience.iop.org/article/10.1088/1742-6596/2743/1/012065
%X Abstract
            ISOL@MYRRHA will be a new Radioactive Ion Beam (RIB) facility in Belgium based on the Isotope Separation On-Line (ISOL) technique, and established within the framework of MYRRHA, the world’s first large-scale accelerator driven system project at power levels scalable to industrial systems. The surface ion source, or hot cavity, is chosen as initial source for its reliability and simple design. To account for the higher flux of atoms through this cavity, a theoretical study of the processes within the ion source is discussed here, based on theoretical equations and thermal-electric simulations. In the past, the temperature was clearly identified as a key element to this source, but with the assumption that it remains constant throughout the cavity. Nonetheless, more recent thermal-electric simulations have revealed that the source Ohmic heating leads to temperature gradients along the cavity tube. The temperature profile impact on ionisation in the hot cavity will be reviewed here.
%J Journal of Physics: Conference Series
%A Hurier, S
%A Rijpstra, K
%A Ramos, J P
%A Popescu, L
%A Cocolios, T E
%A Mancheva, R
%A Chrysalidis, K
%A Rothe, S
%A Au, M
%A Koliatos, A
%D 2024-05-01
%K scientific-publication

%0 Journal Article
%T Rapporteurs avant soutenance :
%X Radionuclides of terbium have attracted much attention for their potential applications in nuclear medicine. However, the short supply of terbium isotopes has limited their applications. This work proposes to use enriched gadolinium targets to produce terbium radioisotopes in biomedical cyclotrons via light-particle-induced reactions. The Auger and gamma emitter 155Tb is taken as a study case, the involved production reaction is 155Gd(d,2n)155Tb.
%G en
%A Lebeda, Ondřej
%A Braccini, Saverio

%0 Journal Article
%T Report on ion source with increased throughput
%I Zenodo
%* Creative Commons Attribution 4.0 International
%U https://zenodo.org/doi/10.5281/zenodo.16616807
%X This report describes the limitations of existing laser and surface ion sources in terms of ion throughput and the developments towards high-throughput ion sources for long-lived radionuclides carried out within the PRISMAP network. This work is built upon first principles through a theoretical understanding of the processes inside the ion source coupled with advanced thermo-mechanical, electrical, and Particle-In-Cell simulations of ion sources, validated by experimental tests. Two new hot-cavity ion sources developed by INFN and SCK CEN are benchmarked against the state-of-the-art ion source from CERN using their offline front end and mass separator. The new developments show promising features that will be further explored in subsequent research. Additional developments on other sources, such as the forced electron beam induced arc discharge (FEBIAD) are presented for completeness of the ongoing activities.
%G en
%A Cocolios, Thomas Elias
%A Mancheva, Ralitsa
%A Ballan, Michele
%A Khwairakpam, Omorjit Singh
%A Scarpa, Daniele
%A Voltan, Giacomo
%A Rijpstra, Kim
%A Quanjel, Lennert
%A Manzolaro, Mattia
%A Rothe, Sebastian
%D 2025-07-30
%K deliverable
ion source
medical radionuclides
radioactive ion beam

%0 Journal Article
%T Training events for young researchers
%I Zenodo
%* Creative Commons Attribution 4.0 International
%U https://zenodo.org/doi/10.5281/zenodo.15410805
%X The PRISMAP Training Office has been responsible for the organisation of 5 schools across different topics of relevance to the PRISMAP Community. Those events have been organised by SCK CEN, DTU, IST-ID, KULeuven, and LU, with strong input from other members from the consortium, such as ARRONAX and PSI. Furthermore, PRISMAP has supported the ISINucMed school organised by ARRONAX, which topic very strongly aligns with the aims of the PRISMAP Training Office. All these events were organised free of charge for the participants. They featured lectures by renowned speakers in the field, laboratory activities, and site visits.

In this deliverable, the different events are reviewed systematically, demonstrating their success and impact. Based on the feedback received, conclusions are drawn. In particular, the oversubscription of the events indicates the need for these events and suggests that such activities need to be continued in the future. Some of those events have already been repeated in the context of other networks or projects. Each organising committee stands ready to reproduce that event, should the opportunity arise.
%A Cocolios, Thomas Elias
%A Cortés Ortega, Francisco
%D 2025-05-01
%K deliverable

%0 Journal Article
%T CERN-MEDICIS: Operational indicators to support the production of new medical radionuclides by mass-separation
%V 2687
%N 8
%P 082039
%W https://lirias.kuleuven.be/4140773
%U https://iopscience.iop.org/article/10.1088/1742-6596/2687/8/082039
%X Abstract
            CERN-MEDICIS is an isotope mass separation facility dedicated to biomedical research located in a type A work sector, receiving on average 50% of the 1.4 GeV protons delivered by the Proton Synchrotron Booster (PSB). It was commissioned with Radioactive Ion Beams (RIB’s) in 2017. MEDICIS has operated for the past 5 years in batch mode, with targets irradiated in a station located at the HRS beam dump, and with external sources provided by MEDICIS cyclotrons and nuclear reactors partners, notably during the Long Shutdown (LS2). Additional features of the facility include the MELISSA laser ion source, radiochemistry on implanted radionuclides and an online gamma-ray spectroscopy implantation monitoring. In 2022, we introduced Key Performance Indicators (KPI’s) to monitor the operation of the facility for collected efficiencies, the optimisation of the radiological risks and evaluate impact of possible modifications of the station, paralleling for instance LHC’s integrated luminosity. Defined KPI’s cover aspects in the operation cycle, e.g. planning in CERN schedule, target irradiations, duration of the process, radiological risk mitigation, facility up-time, developments and maintenance. MEDICIS KPI’s can help distinguish which of the operation and infrastructure life cycle requires immediate intervention, developments or consolidation. Those are related to the irradiation stations and irradiation possibilities, the beamlines (parallel collections), target and ion sources (reliability), robot handling and infrastructure, or the separation process itself.
%J Journal of Physics: Conference Series
%A Stora, T
%A Duchemin, C
%A Andreazza, W
%A Aubert, E
%A Bernerd, C
%A Cocolios, T
%A Deschamps, M
%A Dorsival, A
%A Duraffourg, M
%A Fedosseev, V
%A Somoza, J Ferreira
%A Gilardoni, S
%A Grenard, J L
%A Heinke, R
%A Johnson, J
%A Koliatos, A
%A Khan, Q
%A Lambert, L
%A Mamis, E
%A Marsh, B
%A Marzari, S
%A Mitifiot, C
%A Pozzi, F
%A Prvakova, S
%A Rinchet, J Y
%A Rodriguez, J Rodriguez
%A Roesler, S
%A Rossel, R
%A Rothe, S
%A Vollaire, J
%A Widorski, M
%D 2024-01-01
%K scientific-publication

%0 Journal Article
%T To be GMP or not to be– a radionuclide’s question
%V 10
%N 1
%I Springer Science and Business Media LLC
%W https://pubmed.ncbi.nlm.nih.gov/40637991/
%* https://creativecommons.org/licenses/by-nc-nd/4.0
%U https://ejnmmipharmchem.springeropen.com/articles/10.1186/s41181-025-00369-0
%G en
%J EJNMMI Radiopharmacy and Chemistry
%A Decristoforo, Clemens
%A Mikolajczak, Renata
%A Naidoo, Clive
%A Lapi, Suzanne
%A Haddad, Ferid
%A Schmid, David Emmanuel
%A Gano, Lurdes
%A Köster, Ulli
%A Stora, Thierry
%D 2025-07-10
%K scientific-publication

%0 Journal Article
%T Diamond detectors’ response to intense high-energy electron pulses
%V 1047
%I Elsevier BV
%P 167801
%W https://arts.units.it/handle/11368/3040118
%* https://www.elsevier.com/tdm/userlicense/1.0/
%U https://linkinghub.elsevier.com/retrieve/pii/S0168900222010932
%G en
%J Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment
%A Bassanese, S.
%A Bosisio, L.
%A Cautero, G.
%A Cristaudo, P.
%A Di Mitri, S.
%A Ferianis, M.
%A Gabrielli, A.
%A Giuressi, D.
%A Jin, Y.
%A Lanceri, L.
%A Marich, M.
%A Vitale, L.
%D 02/2023

%0 Journal Article
%T Quantification of trace 227Ac and other radionuclidic impurities in mass-separated 225Ac samples produced at CERN-MEDICIS
%V 15
%N 1
%I Springer Science and Business Media LLC
%W https://pmc.ncbi.nlm.nih.gov/articles/PMC12222749/
%* https://creativecommons.org/licenses/by/4.0
%U https://www.nature.com/articles/s41598-025-02277-4
%X Abstract                      225Ac is a promising candidate medical radionuclide for targeted alpha therapy of advanced stage cancers. One of the main production pathways is the high-energy proton spallation of thorium-based targets, that requires an efficient, nuclide-selective separation method to recover 225Ac from hundreds of co-produced spallation and fission products. The main radioactive contaminant of concern is 227Ac  (T1/2 = 21.8 years), that could preclude extensive medical use if not significantly suppressed. In this work, 225Ac samples were produced by mass separation of radioactive ion beams extracted from proton-irradiated thorium-based targets. The activity of 225Ac and other possible contaminants of the samples were measured using complementary gamma- and alpha-decay spectrometry methods, while 227Ac activity was calculated by performing alpha-decay spectrometry of recoiled progeny from the sample. Using this novel method, accurate measurement of trace 227Ac activity in 225Ac samples was performed much faster than with conventional spectrometry techniques, thanks to its 10,000-fold increase in relative sensitivity. The end of collection activity ratio of 227Ac to 225Ac in two samples from irradiated targets were determined to be               $$2.00(10) \times 10^{-6}$$             and               $$2.7(4) \times 10^{-6}$$             respectively, three orders of magnitude below the 227Ac activity in 225Ac products obtained through radiochemical separation. The high separation factor of 225Ac over 227Ac suggests the suitability of mass-separated accelerator-based 225Ac for medical use.
%G en
%J Scientific Reports
%A Johnson, Jake D.
%A Bernerd, Cyril
%A Bruchertseifer, Frank
%A Cocolios, Thomas E.
%A Deseyn, Marie
%A Duchemin, Charlotte
%A Heines, Michael
%A Keppens, Max
%A Lambert, Laura
%A Meurrens, Nathan
%A Rossel, Ralf E.
%A Stora, Thierry
%A Bergh, Viktor Van Den
%D 2025-07-02
%K scientific-publication

%0 Journal Article
%T Production of 67Cu at a biomedical cyclotron via 70Zn(p,α)67Cu reaction and its evaluation in a preclinical study using small animal SPECT/CT
%V 215
%P 111551
%W https://orbit.dtu.dk/en/publications/production-of-sup67supcu-at-a-biomedical-cyclotron-via-sup70supzn
%U https://linkinghub.elsevier.com/retrieve/pii/S0969804324003798
%G en
%J Applied Radiation and Isotopes
%A Søndergaard, Ursula
%A Thomas, Kolle E.
%A Søborg Pedersen, Kristina
%A Kranz, Mathias
%A Sundset, Rune
%A Moldes-Anaya, Angel
%A Jensen, Mikael
%D 01/2025
%K scientific-publication

%0 Journal Article
%T Electron-gamma decay spectroscopy of<sup>152</sup> Tb
%V 100
%N 6
%P 065308
%W https://zenodo.org/records/15631070
%U https://iopscience.iop.org/article/10.1088/1402-4896/add812
%X Abstract
            
              Terbium-152, decaying by electron capture and
              β
              +
              emission to
              152
              Gd with
              Q
              
                EC
              
              = 3990(40) keV and
              T
              1/2
              = 17.8784(95) h, shows promise in nuclear medicine. First-in-human trials have demonstrated its suitability for positron emission tomography (PET) imaging, with potential applications in personalised cancer treatments through its membership of the terbium theragnostic quartet. A source of
              152
              Tb was produced at CERN-ISOLDE, using spallation of a tantalum target induced by a 1.4 GeV proton beam and mass separation with the ISOL method. The source was then shipped to ILL Grenoble for measurement. This paper details the electron-gamma spectroscopy of the decay using the PN1/LOHENGRIN setup, supporting the gamma-gamma spectroscopy of
              152
              Tb sources produced in the same ISOLDE run. Preliminary measurements of the relative intensity of internal conversion electrons are presented, validating theoretical predictions of internal conversion coefficients for several transitions and confirming their assigned multipolarity. The final analysis will support the gamma-gamma spectroscopy in establishing a revised level scheme for the decay, leading to an updated beta strength function and a corresponding change in dosimetry calculations.
%J Physica Scripta
%A O’Sullivan, E B
%A Collins, S M
%A Daugas, J-M
%A Domenichetti, L
%A Heery, J
%A Henderson, J
%A Köster, U
%A Michelagnoli, C
%A Parry, T
%A Pascu, S
%A Regan, P H
%A Shearman, R
%D 2025-06-01
%K scientific-publication

%0 Journal Article
%T Mitochondria-tropic radioconjugates to enhance the therapeutic potential of terbium-161
%V 10
%N 1
%P 18
%W https://pubmed.ncbi.nlm.nih.gov/40214871/
%U https://ejnmmipharmchem.springeropen.com/articles/10.1186/s41181-025-00339-6
%G en
%J EJNMMI Radiopharmacy and Chemistry
%A Santos, Joana F.
%A Laere, Camille Van
%A Silva, Catarina D.
%A Cassells, Irwin
%A Fernandes, Célia
%A Raposinho, Paula
%A Belchior, Ana
%A Pinto, Catarina I. G.
%A Mendes, Filipa
%A Cawthorne, Christopher
%A Ooms, Maarten
%A Voorde, Michiel Van De
%A Cleeren, Frederik
%A Paulo, António
%D 2025-04-11
%K scientific-publication

%0 Journal Article
%T Alpha Atlas: Mapping global production of α-emitting radionuclides for targeted alpha therapy
%P 108990
%W https://zenodo.org/records/14636782
%U https://linkinghub.elsevier.com/retrieve/pii/S0969805124001161
%G en
%J Nuclear Medicine and Biology
%A Tosato, Marianna
%A Favaretto, Chiara
%A Kleynhans, Janke
%A Burgoyne, Andrew R.
%A Gestin, Jean-François
%A Van Der Meulen, Nicholas P.
%A Jalilian, Amirreza
%A Köster, Ulli
%A Asti, Mattia
%A Radchenko, Valery
%D 12/2024
%K scientific-publication

%0 Journal Article
%T Novel radionuclides: demand, production and distribution for translational research in Europe
%V 9
%N 1
%P 85
%W https://pubmed.ncbi.nlm.nih.gov/39692851/
%U https://ejnmmipharmchem.springeropen.com/articles/10.1186/s41181-024-00318-3
%G en
%J EJNMMI Radiopharmacy and Chemistry
%A Radzina, Maija
%A Saule, Laura
%A Mamis, Edgars
%A Pajuste, Elina
%A Koester, Ulli
%A Cocolios, Thomas Elias
%A Proskurins, Jevgenijs
%A Kalnina, Patricija
%A Zabolockis, Rudolfs Janis
%A Palskis, Kristaps
%A Talip, Zeynep
%A Jensen, Mikael
%A Duchemin, Charlotte
%A Baatout, Sarah
%A Leufgen, Kirsten
%A Stora, Thierry
%D 2024-12-18
%K scientific-publication

%0 Journal Article
%T Comparative analysis of positron emitters for theranostic applications based on small bioconjugates highlighting 43Sc, 61Cu and 45Ti
%V 11
%N 1
%P 98
%W https://pmc.ncbi.nlm.nih.gov/articles/PMC11582248/
%U https://ejnmmiphys.springeropen.com/articles/10.1186/s40658-024-00699-z
%G en
%J EJNMMI Physics
%A Hindié, Elif
%A Köster, Ulli
%A Champion, Christophe
%A Zanotti-Fregonara, Paolo
%A Morgat, Clément
%D 2024-11-22
%K scientific-publication

%0 Journal Article
%T Towards complete decay spectroscopy of 152Tb
%V 232
%P 112641
%W https://zenodo.org/records/15000604
%U https://linkinghub.elsevier.com/retrieve/pii/S0969806X25001331
%G en
%J Radiation Physics and Chemistry
%A O’Sullivan, E.B.
%A Collins, S.M.
%A Daugas, J.-M.
%A Domenichetti, L.
%A Heery, J.
%A Henderson, J.
%A Köster, U.
%A Michelagnoli, C.
%A Parry, T.
%A Pascu, S.
%A Regan, P.H.
%A Shearman, R.
%D 07/2025
%K scientific-publication

%0 Journal Article
%T Synthesis and Preclinical Evaluation of PSMA-Targeted <sup>111</sup> In-Radioconjugates Containing a Mitochondria-Tropic Triphenylphosphonium Carrier
%V 21
%N 1
%P 216-233
%W https://scholar.tecnico.ulisboa.pt/records/ibUNhdb0b2Dy5OGcri83d8yGCP-w_FOLub7F
%* https://doi.org/10.15223/policy-029
%U https://pubs.acs.org/doi/10.1021/acs.molpharmaceut.3c00787
%G en
%J Molecular Pharmaceutics
%A Santos, Joana F.
%A Braz, Maria T.
%A Raposinho, Paula
%A Cleeren, Frederik
%A Cassells, Irwin
%A Leekens, Simon
%A Cawthorne, Christopher
%A Mendes, Filipa
%A Fernandes, Célia
%A Paulo, António
%D 2024-01-01
%K scientific-publication

%0 Journal Article
%T Position paper to facilitate patient access to radiopharmaceuticals: considerations for a suitable pharmaceutical regulatory framework
%V 9
%N 1
%P 2
%W https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10761641/
%U https://ejnmmipharmchem.springeropen.com/articles/10.1186/s41181-023-00230-2
%X Abstract
            
              Background
              Nuclear medicine has made enormous progress in the past decades. However, there are still significant inequalities in patient access among different countries, which could be mitigated by improving access to and availability of radiopharmaceuticals.
            
            
              Main body
              This paper summarises major considerations for a suitable pharmaceutical regulatory framework to facilitate patient access to radiopharmaceuticals. These include the distinct characteristics of radiopharmaceuticals which require dedicated regulations, considering the impact of the variable complexity of radiopharmaceutical preparation, personnel requirements, manufacturing practices and quality assurance, regulatory authority interfaces, communication and training, as well as marketing authorisation procedures to ensure availability of radiopharmaceuticals. Finally, domestic and regional supply to ensure patient access via alternative regulatory pathways, including in-house production of radiopharmaceuticals, is described, and an outlook on regulatory challenges faced by new developments, such as the use of alpha emitters, is provided.
            
            
              Conclusions
              All these considerations are an outcome of a dedicated Technical Meeting organised by the IAEA in 2023 and represent the views and opinions of experts in the field, not those of any regulatory authorities.
%G en
%J EJNMMI Radiopharmacy and Chemistry
%A Korde, Aruna
%A Patt, Marianne
%A Selivanova, Svetlana V.
%A Scott, Andrew M.
%A Hesselmann, Rolf
%A Kiss, Oliver
%A Ramamoorthy, Natesan
%A Todde, Sergio
%A Rubow, Sietske M.
%A Gwaza, Luther
%A Lyashchenko, Serge
%A Andersson, Jan
%A Hockley, Brian
%A Kaslival, Ravindra
%A Decristoforo, Clemens
%D 2024-01-02
%K scientific-publication

%0 Journal Article
%T On the feasibility of online terbium extraction at ISOL@MYRRHA
%V 541
%P 249-252
%U https://linkinghub.elsevier.com/retrieve/pii/S0168583X23002306
%G en
%J Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms
%A Leenders, Benji
%A Aerts, Alexander
%A Cocolios, Thomas E.
%A Cottenier, Stefaan
%A Houngbo, Donald
%A Popescu, Lucia
%D 08/2023
%K scientific-publication

%0 Book Section
%T Weak Electron Emission of Nanodiamond Irradiated with High Energy Electrons
%V 89
%C Cham
%I Springer Nature Switzerland
%P 293-303
%@ 978-3-031-37131-8 978-3-031-37132-5
%U https://link.springer.com/10.1007/978-3-031-37132-5_37
%G en
%B 19th Nordic-Baltic Conference on Biomedical Engineering and Medical Physics
%E Dekhtyar, Yuri
%E Saknite, Inga
%A Boka, Galina
%A Dekhtyar, Yuri
%A Rocca, Mirko
%A Sokolov, Artur
%A Sorokins, Hermanis
%D 2023
%K scientific-publication

%0 Journal Article
%T The SPES laser ion source: Time structure, laser enhancement and efficiency measurements with gallium at ISOLDE Offline 2
%V 548
%P 165249
%W https://cds.cern.ch/record/2888522
%U https://linkinghub.elsevier.com/retrieve/pii/S0168583X24000181
%G en
%J Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms
%A Khwairakpam, O.S.
%A Mancheva, R.
%A Au, M.
%A Bernerd, C.
%A Centofante, L.
%A Chrysalidis, K.
%A Crepieux, B.
%A Fedosseev, V.N.
%A Heinke, R.
%A Marchi, T.
%A Mariotti, E.
%A Marsh, B.A.
%A Monetti, A.
%A Nicolosi, P.
%A Rothe, S.
%A Scarpa, D.
%A Schuett, M.
%A Stora, T.
%A Andrighetto, A.
%A Manzolaro, M.
%D 03/2024
%K scientific-publication

%0 Journal Article
%T Target Development towards First Production of High-Molar- Activity 44gSc and 47Sc by Mass Separation at CERN-MEDICIS
%V 17
%N 3
%P 390
%W https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10974744/
%* https://creativecommons.org/licenses/by/4.0/
%U https://www.mdpi.com/1424-8247/17/3/390
%X The radionuclides 43Sc,  44g/mSc, and 47Sc can be produced cost-effectively in sufficient yield for medical research and applications by irradiating  natTi and  natV target materials with protons. Maximizing the production yield of the therapeutic 47Sc in the highest cross section energy range of 24–70 MeV results in the co-production of long-lived, high-γ-ray-energy 46Sc and 48Sc contaminants if one does not use enriched target materials. Mass separation can be used to obtain high molar activity and isotopically pure Sc radionuclides from natural target materials; however, suitable operational conditions to obtain relevant activity released from irradiated  natTi and  natV have not yet been established at CERN-MEDICIS and ISOLDE. The objective of this work was to develop target units for the production, release, and purification of Sc radionuclides by mass separation as well as to investigate target materials for the mass separation that are compatible with high-yield Sc radionuclide production in the 9–70 MeV proton energy range. In this study, the in-target production yield obtained at MEDICIS with 1.4 GeV protons is compared with the production yield that can be reached with commercially available cyclotrons. The thick-target materials were irradiated at MEDICIS and comprised of metallic  natTi,  natV metallic foils, and  natTiC pellets. The produced radionuclides were subsequently released, ionized, and extracted from various target and ion source units and mass separated. Mono-atomic Sc laser and molecule ionization with forced-electron-beam-induced arc-discharge ion sources were investigated. Sc radionuclide production in thick  natTi and  natV targets at MEDICIS is equivalent to low- to medium-energy cyclotron-irradiated targets at medically relevant yields, furthermore benefiting from the mass separation possibility. A two-step laser resonance ionization scheme was used to obtain mono-atomic Sc ion beams. Sc radionuclide release from irradiated target units most effectively could be promoted by volatile scandium fluoride formation. Thus, isotopically pure  44g/mSc, 46Sc, and 47Sc were obtained as mono-atomic and molecular ScF 2+ ion beams and collected for the first time at CERN-MEDICIS. Among all the investigated target materials,  natTiC is the most suitable target material for Sc mass separation as molecular halide beams, due to high possible operating temperatures and sustained release.
%G en
%J Pharmaceuticals
%A Mamis, Edgars
%A Duchemin, Charlotte
%A Berlin, Valentina
%A Bernerd, Cyril
%A Bovigny, Mathieu
%A Chevallay, Eric
%A Crepieux, Bernard
%A Gadelshin, Vadim Maratovich
%A Heinke, Reinhard
%A Hernandez, Ronaldo Mendez
%A Johnson, Jake David
%A Kalniņa, Patrīcija
%A Koliatos, Alexandros
%A Lambert, Laura
%A Rossel, Ralf Erik
%A Rothe, Sebastian
%A Thiboud, Julien
%A Weber, Felix
%A Wendt, Klaus
%A Zabolockis, Rudolfs Jānis
%A Pajuste, Elīna
%A Stora, Thierry
%D 2024-03-18
%K scientific-publication

%0 Journal Article
%T Terbium radionuclides for theranostic applications in nuclear medicine: from atom to bedside
%V 14
%N 4
%P 1720-1743
%W https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10879862/
%U https://www.thno.org/v14p1720.htm
%G en
%J Theranostics
%A Van Laere, Camille
%A Koole, Michel
%A Deroose, Christophe M.
%A De Voorde, Michiel Van
%A Baete, Kristof
%A Cocolios, Thomas E.
%A Duchemin, Charlotte
%A Ooms, Maarten
%A Cleeren, Frederik
%D 2024
%K scientific-publication

%0 Journal Article
%T Thermal and Structural Characterization of a Titanium Carbide/Carbon Composite for Nuclear Applications
%V 15
%N 23
%P 8358
%W https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9739871/
%U https://www.mdpi.com/1996-1944/15/23/8358
%X In the framework of ISOL (isotope separation on-line) facilities, porous carbides are among the most employed target materials for the production of radioactive ion beams for research. As foreseen by the ISOL technique, a production target is impinged by an energetic particle beam, inducing nuclear reactions from such an interaction. The resulting radionuclides are subsequently released, thanks to the high target working temperature (1600–2000 °C); ionized; and extracted into a beam. Since the target microstructure and porosity play a fundamental role in the radionuclide release efficiency, custom-made target materials are often specifically produced, resulting in unknown thermal and structural properties. Considering that such targets might undergo intense thermal stresses during operation, a thermal and structural characterization is necessary to avoid target failure under irradiation. In the presented work, a custom-made porous titanium carbide that was specifically designed for application as an ISOL target was produced and characterized. The thermal characterization was focused on the evaluation of the material emissivity and thermal conductivity in the 600–1400 °C temperature range. For the estimation of a reference material tensile stress limit, the virtual thermoelastic parameter approach was adopted. In particular, for the aforementioned temperature range, an emissivity between 0.7 and 0.8 was measured, whereas a thermal conductivity between 8 and 10 W/mK was estimated.
%G en
%J Materials
%A Ballan, Michele
%A Corradetti, Stefano
%A Manzolaro, Mattia
%A Meneghetti, Giovanni
%A Andrighetto, Alberto
%D 2022-11-24
%K scientific-publication

%0 Journal Article
%T Study of thulium-167 cyclotron production: a potential medically-relevant radionuclide
%V 11
%P 1288588
%W https://boris.unibe.ch/188616/1/fchem-11-1288588.pdf
%U https://www.frontiersin.org/articles/10.3389/fchem.2023.1288588/full
%X Introduction:
              Targeted Radionuclide Therapy is used for the treatment of tumors in nuclear medicine, while sparing healthy tissues. Its application to cancer treatment is expanding. In particular, Auger-electron emitters potentially exhibit high efficacy in treating either small metastases or single tumor cells due to their short range in tissue. The aim of this paper is to study the feasibility of a large-scale production of thulium-167, an Auger-electron emitter radionuclide, in view of eventual systematic preclinical studies.
            
            
              Methods:
              Proton-irradiated enriched erbium-167 and erbium-168 oxides were used to measure the production cross sections of thulium-165, thulium-166, thulium-167, and thulium-168 utilizing an 18-MeV medical cyclotron equipped with a Beam Transport Line (BTL) at the Bern medical cyclotron laboratory. The comparison between the experimental and the TENDL 2021 theoretical cross-section results were in good agreement. Additional experiments were performed to assess the production yields of thulium radioisotopes in the BTL. Thulium-167 production yield was also measured irradiating five different target materials (
              167
              Er
              2
              O
              3
              ,
              168
              Er
              2
              O
              3
              ,
              
                nat
              
              Tm
              2
              O
              3
              ,
              
                nat
              
              Yb
              2
              O
              3
              ,
              171
              Yb
              2
              O
              3
              ) with proton beams up to 63 MeV at the Injector II cyclotron of Paul Scherrer Institute.
            
            
              Results and Discussion:
              Our experiments showed that an 8-h irradiation of enriched ytterbium-171 oxide produced about 420 MBq of thulium-167 with a radionuclidic purity of 99.95% after 5 days of cooling time with a proton beam of about 53 MeV. Larger activities of thulium-167 can be achieved using enriched erbium-168 oxide with a 23-MeV proton beam, obtaining about 1 GBq after 8-h irradiation with a radionuclidic purity of
              
                
                  <
                
              
              99.5% 5 days post end of bombardment.
%J Frontiers in Chemistry
%A Renaldin, Edoardo
%A Dellepiane, Gaia
%A Braccini, Saverio
%A Sommerhalder, Alexander
%A Zhang, Hui
%A Van Der Meulen, Nicholas P.
%A Eichler, Robert
%A Talip, Zeynep
%D 2023-10-19
%K scientific-publication

%0 Journal Article
%T Study of terbium production from enriched Gd targets via the reaction 155Gd(d,2n)155Tb
%V 201
%P 110996
%W https://hal.science/hal-04197419
%U https://linkinghub.elsevier.com/retrieve/pii/S0969804323003494
%G en
%J Applied Radiation and Isotopes
%A Wang, Yizheng
%A Sounalet, Thomas
%A Guertin, Arnaud
%A Nigron, Etienne
%A Michel, Nathalie
%A Haddad, Férid
%D 11/2023
%K scientific-publication

%0 Journal Article
%T Resonant laser ionization and mass separation of 225Ac
%V 13
%N 1
%P 1347
%W https://cds.cern.ch/record/2848111
%U https://www.nature.com/articles/s41598-023-28299-4
%X Abstract
            
              
                
                  $$^{225}$$
                  
                    
                      
                      225
                    
                  
                
              
              Ac is a radio-isotope that can be linked to biological vector molecules to treat certain distributed cancers using targeted alpha therapy. However, developing
              
                
                  $$^{225}$$
                  
                    
                      
                      225
                    
                  
                
              
              Ac-labelled radiopharmaceuticals remains a challenge due to the supply shortage of pure
              
                
                  $$^{225}$$
                  
                    
                      
                      225
                    
                  
                
              
              Ac itself. Several techniques to obtain pure
              
                
                  $$^{225}$$
                  
                    
                      
                      225
                    
                  
                
              
              Ac are being investigated, amongst which is the high-energy proton spallation of thorium or uranium combined with resonant laser ionization and mass separation. As a proof-of-principle, we perform off-line resonant ionization mass spectrometry on two samples of
              
                
                  $$^{225}$$
                  
                    
                      
                      225
                    
                  
                
              
              Ac, each with a known activity, in different chemical environments. We report overall operational collection efficiencies of 10.1(2)% and 9.9(8)% for the cases in which the
              
                
                  $$^{225}$$
                  
                    
                      
                      225
                    
                  
                
              
              Ac was deposited on a rhenium surface and a ThO
              
                
                  $$_{2}$$
                  
                    
                      
                      2
                    
                  
                
              
              mimic target matrix respectively. The bottleneck of the technique was the laser ionization efficiency, which was deduced to be 15.1(6)%.
%G en
%J Scientific Reports
%A Johnson, Jake D.
%A Heines, Michael
%A Bruchertseifer, Frank
%A Chevallay, Eric
%A Cocolios, Thomas E.
%A Dockx, Kristof
%A Duchemin, Charlotte
%A Heinitz, Stephan
%A Heinke, Reinhard
%A Hurier, Sophie
%A Lambert, Laura
%A Leenders, Benji
%A Skliarova, Hanna
%A Stora, Thierry
%A Wojtaczka, Wiktoria
%D 2023-01-24
%K scientific-publication

%0 Journal Article
%T Recurrent Prostate Cancer Diagnostics with 18F-PSMA-1007 PET/CT: A Systematic Review of the Current State
%V 12
%N 12
%P 3176
%W https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9777208/
%U https://www.mdpi.com/2075-4418/12/12/3176
%X Background: Early diagnosis of recurrent prostate cancer is a cornerstone for further adequate therapy planning. Therefore, clinical practice and research still focuses on diagnostic tools that can detect prostate cancer in early recurrence when it is undetectable in conventional diagnostic imaging. 18F-PSMA-1007 PET/CT is a novel method to evaluate patients with biochemical recurrent PCa. The aim of this review was to evaluate the role of 18F-PSMA-1007 PET/CT in prostate cancer local recurrence, lymph node metastases and bone metastases detection. Methods: Original studies, reviews and five meta-analyses were included in this article. A total of 70 studies were retrieved, 31 were included in the study. Results: All patients described in the studies underwent 18F-PSMA-1007 PET/CT. The administered 18F-PSMA-1007 individual dose ranged from 159 ± 31 MBq to 363.93 ± 69.40 MBq. Results showed that 18F-PSMA-1007 PET/CT demonstrates a good detection rate in recurrent prostate cancer. Conclusions: 18F-PSMA-1007 PET/CT appears to achieve reliable performance in detecting recurrent prostate cancer. The high detection rate of 18F-PSMA-1007 PET/CT in recurrent prostate cancer was confirmed, especially in local recurrence and small lymph nodes with non-specific characteristics on conventional diagnostic imaging methods. However, several authors emphasize some limitations for this tracer—for example, non-specific uptake in bone lesions that can mimic bone metastases.
%G en
%J Diagnostics
%A Saule, Laura
%A Radzina, Maija
%A Liepa, Mara
%A Roznere, Lilita
%A Lioznovs, Andrejs
%A Ratniece, Madara
%A Mamis, Edgars
%A Vjaters, Egils
%D 2022-12-15
%K scientific-publication

%0 Journal Article
%T Production of innovative radionuclides for medical applications at the CERN-MEDICIS facility
%V 542
%P 137-143
%W https://cds.cern.ch/record/2866075?ln=en
%U https://linkinghub.elsevier.com/retrieve/pii/S0168583X2300201X
%G en
%J Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms
%A Bernerd, C.
%A Johnson, J.D.
%A Aubert, E.
%A Au, M.
%A Barozier, V.
%A Bernardes, A.-P.
%A Bertreix, P.
%A Bruchertseifer, F.
%A Catherall, R.
%A Chevallay, E.
%A Chrysalidis, K.
%A Christodoulou, P.
%A Cocolios, T.E.
%A Crepieux, B.
%A Deschamps, M.
%A Dorsival, A.
%A Duchemin, C.
%A Fedosseev, V.
%A Fernier, P.
%A Heines, M.
%A Heinke, R.
%A Khalid, U.
%A Khan, M.
%A Khan, Q.
%A Lambert, L.
%A Mamis, E.
%A Marsh, B.A.
%A Marzari, S.
%A Menaa, N.
%A Munos, M.
%A Pozzi, F.
%A Prvakova, S.
%A Ramos, J.P.
%A Riccardi, F.
%A Rinchet, J.-Y.
%A Rossel, R.E.
%A Stora, T.
%A Thiboud, J.
%A Vollaire, J.
%A Van Den Bergh, V.
%A Wojtaczka, W.
%D 09/2023
%K scientific-publication

%0 Journal Article
%T Production and Supply of α-Particle–Emitting Radionuclides for Targeted α-Therapy
%V 62
%N 11
%P 1495-1503
%W https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8612335/
%U http://jnm.snmjournals.org/lookup/doi/10.2967/jnumed.120.261016
%G en
%J Journal of Nuclear Medicine
%A Radchenko, Valery
%A Morgenstern, Alfred
%A Jalilian, Amir R.
%A Ramogida, Caterina F.
%A Cutler, Cathy
%A Duchemin, Charlotte
%A Hoehr, Cornelia
%A Haddad, Ferrid
%A Bruchertseifer, Frank
%A Gausemel, Haavar
%A Yang, Hua
%A Osso, Joao Alberto
%A Washiyama, Kohshin
%A Czerwinski, Kenneth
%A Leufgen, Kirsten
%A Pruszyński, Marek
%A Valzdorf, Olga
%A Causey, Patrick
%A Schaffer, Paul
%A Perron, Randy
%A Maxim, Samsonov
%A Wilbur, D. Scott
%A Stora, Thierry
%A Li, Yawen
%D 11/2021
%K scientific-publication

%0 Journal Article
%T Novel radionuclides for use in Nuclear Medicine in Europe: where do we stand and where do we go?
%V 8
%N 1
%P 27
%W https://pubmed.ncbi.nlm.nih.gov/37823964/
%U https://ejnmmipharmchem.springeropen.com/articles/10.1186/s41181-023-00211-5
%X Abstract
            
              Background
              In order to support the ongoing research across Europe to facilitate access to novel radionuclides, the PRISMAP consortium (European medical radionuclides programme) was established to offer the broadest catalog of non-conventional radionuclides for medical and translational research. The aim of this article is to introduce readers with current status of novel radionuclides in Europe.
            
            
              Main body
              
                A consortium questionnaire was disseminated through the PRISMAP consortium and user community, professional associations and preclinical/clinical end users in Europe and the current status of clinical end-users in nuclear medicine were identified. A total of 40 preclinical/clinical users institutions took part in the survey. Clinical end users currently use the following radionuclides in their studies:
                177
                Lu,
                68
                 Ga,
                111
                In,
                90
                Y, other alpha emitters,
                225
                Ac,
                64
                Cu and Terbium isotopes. Radionuclides that would be of interest for users within the next 2–5 years are
                64
                Cu, Terbium radionuclide “family” and alpha emitters, such as
                225
                Ac.
              
            
            
              Conclusions
              Thanks to a questionnaire distributed by the PRISMAP consortium, the current status and needs of clinical end-users in nuclear medicine were identified.
%G en
%J EJNMMI Radiopharmacy and Chemistry
%A Radzina, Maija
%A Saule, Laura
%A Mamis, Edgars
%A Koester, Ulli
%A Cocolios, Thomas Elias
%A Pajuste, Elina
%A Kalnina, Marika
%A Palskis, Kristaps
%A Sawitzki, Zoe
%A Talip, Zeynep
%A Jensen, Mikael
%A Duchemin, Charlotte
%A Leufgen, Kirsten
%A Stora, Thierry
%D 2023-10-12
%K scientific-publication

%0 Journal Article
%T Improved procedures for production and purification of 135La from enriched [135Ba]BaCO3 on a 16.5 MeV cyclotron
%V 192
%P 110612
%W https://orbit.dtu.dk/en/publications/improved-procedures-for-production-and-purification-of-sup135supl
%U https://linkinghub.elsevier.com/retrieve/pii/S0969804322004973
%G en
%J Applied Radiation and Isotopes
%A Pedersen, Kristina Søborg
%A Deville, Claire
%A Søndergaard, Ursula
%A Jensen, Mikael
%A Jensen, Andreas I.
%D 02/2023
%K scientific-publication

%0 Journal Article
%T Half-life determination of 155Tb from mass-separated samples produced at CERN-MEDICIS
%V 190
%P 110480
%W https://cds.cern.ch/record/2837180
%U https://linkinghub.elsevier.com/retrieve/pii/S0969804322003657
%G en
%J Applied Radiation and Isotopes
%A Collins, S.M.
%A Robinson, A.P.
%A Ivanov, P.
%A Köster, U.
%A Cocolios, T.E.
%A Russell, B.
%A Webster, B.
%A Fenwick, A.J.
%A Duchemin, C.
%A Ramos, J.P.
%A Chevallay, E.
%A Jakobsson, U.
%A Stegemann, S.
%A Regan, P.H.
%A Stora, T.
%D 12/2022
%K scientific-publication

%0 Journal Article
%T First on-line application of the high-resolution spectroscopy laser ion source PI-LIST at ISOLDE
%V 541
%P 8-12
%U https://linkinghub.elsevier.com/retrieve/pii/S0168583X23001945
%G en
%J Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms
%A Heinke, Reinhard
%A Au, Mia
%A Bernerd, Cyril
%A Chrysalidis, Katerina
%A Cocolios, Thomas E.
%A Fedosseev, Valentin N.
%A Hendriks, Isabel
%A Jaradat, Asar A.H.
%A Kaja, Magdalena
%A Kieck, Tom
%A Kron, Tobias
%A Mancheva, Ralitsa
%A Marsh, Bruce A.
%A Marzari, Stefano
%A Raeder, Sebastian
%A Rothe, Sebastian
%A Studer, Dominik
%A Weber, Felix
%A Wendt, Klaus
%D 08/2023
%K scientific-publication

%0 Journal Article
%T Exploring the Potential of High-Molar-Activity Samarium-153 for Targeted Radionuclide Therapy with [153Sm]Sm-DOTA-TATE
%V 14
%N 12
%P 2566
%W https://researchportal.sckcen.be/en/publications/exploring-the-potential-of-high-molar-activity-samarium-153-for-t
%U https://www.mdpi.com/1999-4923/14/12/2566
%X Samarium-153 is a promising theranostic radionuclide, but low molar activities (Am) resulting from its current production route render it unsuitable for targeted radionuclide therapy (TRNT). Recent efforts combining neutron activation of 152Sm in the SCK CEN BR2 reactor with mass separation at CERN/MEDICIS yielded high-Am 153Sm. In this proof-of-concept study, we further evaluated the potential of high-Am 153Sm for TRNT by radiolabeling to DOTA-TATE, a well-established carrier molecule binding the somatostatin receptor 2 (SSTR2) that is highly expressed in gastroenteropancreatic neuroendocrine tumors. DOTA-TATE was labeled with 153Sm and remained stable up to 7 days in relevant media. The binding specificity and high internalization rate were validated on SSTR2-expressing CA20948 cells. In vitro biological evaluation showed that [153Sm]Sm-DOTA-TATE was able to reduce CA20948 cell viability and clonogenic potential in an activity-dependent manner. Biodistribution studies in healthy and CA20948 xenografted mice revealed that [153Sm]Sm-DOTA-TATE was rapidly cleared and profound tumor uptake and retention was observed whilst these were limited in normal tissues. This proof-of-concept study showed the potential of mass-separated 153Sm for TRNT and could open doors towards wider applications of mass separation in medical isotope production.
%G en
%J Pharmaceutics
%A Vermeulen, Koen
%A Van de Voorde, Michiel
%A Segers, Charlotte
%A Coolkens, Amelie
%A Rodriguez Pérez, Sunay
%A Daems, Noami
%A Duchemin, Charlotte
%A Crabbé, Melissa
%A Opsomer, Tomas
%A Saldarriaga Vargas, Clarita
%A Heinke, Reinhard
%A Lambert, Laura
%A Bernerd, Cyril
%A Burgoyne, Andrew R.
%A Cocolios, Thomas Elias
%A Stora, Thierry
%A Ooms, Maarten
%D 2022-11-23
%K scientific-publication

%0 Journal Article
%T Excitation functions of deuteron induced nuclear reactions on dysprosium targets for the production of the theranostic relevant isotopes of terbium
%V 137
%N 10
%P 1180
%W https://hal.archives-ouvertes.fr/hal-03838611
%U https://link.springer.com/10.1140/epjp/s13360-022-03378-z
%X Abstract
            
              The physical properties of
              
                
                  $${}^{149,152,155,161}$$
                  
                    
                      
                      
                        149
                        ,
                        152
                        ,
                        155
                        ,
                        161
                      
                    
                  
                
              
              Tb enable their use in both diagnostic and therapeutic applications in the field of nuclear medicine. For this reason the optimization of the production routes of these radionuclides is of widespread interest in research. In this work, the feasibility of the production of
              
                
                  $${}^{155}$$
                  
                    
                      
                      155
                    
                  
                
              
              Tb and
              
                
                  $${}^{161}$$
                  
                    
                      
                      161
                    
                  
                
              
              Tb via the nuclear reactions induced by deuterons on dysprosium target with natural isotopic abundances has been discussed. The cross sections of
              
                
                  $${}^{nat}$$
                  
                    
                      
                      
                        nat
                      
                    
                  
                
              
              Dy(d,x) reactions have been studied in the 12.5–32 MeV energetic range with the stacked-foil technique and the corresponding Thick Target Yields have been obtained. The presence of terbium and dysprosium contaminants (
              
                
                  $${}^{156,160}$$
                  
                    
                      
                      
                        156
                        ,
                        160
                      
                    
                  
                
              
              Tb,
              
                
                  $${}^{155,157,159}$$
                  
                    
                      
                      
                        155
                        ,
                        157
                        ,
                        159
                      
                    
                  
                
              
              Dy) has been evaluated too.
%G en
%J The European Physical Journal Plus
%A Colucci, Michele
%A Carminati, Stefano
%A Haddad, Ferid
%A Nigron, Etienne
%A Groppi, Flavia
%A Manenti, Simone
%D 2022-10-26
%K scientific-publication

%0 Journal Article
%T Emerging Radionuclides in a Regulatory Framework for Medicinal Products – How Do They Fit?
%V 8
%P 678452
%W https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192700/
%U https://www.frontiersin.org/articles/10.3389/fmed.2021.678452/full
%X Recent years have seen the establishment of several radionuclides as medicinal products in particular in the setting of theranostics and PET. [
              177
              Lu]Lutetium Chloride or [
              64
              Cu]Copper Chloride have received marketing authorization as radionuclide precursor, [
              68
              Ga]Gallium Chloride has received regulatory approval in the form of different
              68
              Ge/
              68
              Ga generators. This is a formal requirement by the EU directive 2001/83, even though for some of these radionuclide precursors no licensed kit is available that can be combined to obtain a final radiopharmaceuticals, as it is the case for Technetium-99m. In view of several highly promising, especially metallic radionuclides for theranostic applications in a wider sense, the strict regulatory environment poses the risk of slowing down development, in particular for radionuclide producers that want to provide innovative radionuclides for clinical research purposes, which is the basis for their further establishment. In this paper we address the regulatory framework for novel radionuclides within the EU, the current challenges in particular related to clinical translation and potential options to support translational development within Europe and worldwide.
%J Frontiers in Medicine
%A Decristoforo, Clemens
%A Neels, Oliver
%A Patt, Marianne
%D 2021-5-28
%K scientific-publication

%0 Journal Article
%T Efficient Production of High Specific Activity Thulium-167 at Paul Scherrer Institute and CERN-MEDICIS
%V 8
%P 712374
%W https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8546370/
%U https://www.frontiersin.org/articles/10.3389/fmed.2021.712374/full
%X Thulium-167 is a promising radionuclide for nuclear medicine applications with potential use for both diagnosis and therapy (“theragnostics”) in disseminated tumor cells and small metastases, due to suitable gamma-line as well as conversion/Auger electron energies. However, adequate delivery methods are yet to be developed and accompanying radiobiological effects to be investigated, demanding the availability of
              167
              Tm in appropriate activities and quality. We report herein on the production of radionuclidically pure
              167
              Tm from proton-irradiated natural erbium oxide targets at a cyclotron and subsequent ion beam mass separation at the CERN-MEDICIS facility, with a particular focus on the process efficiency. Development of the mass separation process with studies on stable
              169
              Tm yielded 65 and 60% for pure and erbium-excess samples. An enhancement factor of thulium ion beam over that of erbium of up to several 10
              4
              was shown by utilizing laser resonance ionization and exploiting differences in their vapor pressures. Three
              167
              Tm samples produced at the IP2 irradiation station, receiving 22.8 MeV protons from Injector II at Paul Scherrer Institute (PSI), were mass separated with collected radionuclide efficiencies between 11 and 20%. Ion beam sputtering from the collection foils was identified as a limiting factor.
              In-situ
              gamma-measurements showed that up to 45% separation efficiency could be fully collected if these limits are overcome. Comparative analyses show possible neighboring mass suppression factors of more than 1,000, and overall
              167
              Tm/Er purity increase in the same range. Both the actual achieved collection and separation efficiencies present the highest values for the mass separation of external radionuclide sources at MEDICIS to date.
%J Frontiers in Medicine
%A Heinke, Reinhard
%A Chevallay, Eric
%A Chrysalidis, Katerina
%A Cocolios, Thomas E.
%A Duchemin, Charlotte
%A Fedosseev, Valentin N.
%A Hurier, Sophie
%A Lambert, Laura
%A Leenders, Benji
%A Marsh, Bruce A.
%A van der Meulen, Nicholas P.
%A Sprung, Peter
%A Stora, Thierry
%A Tosato, Marianna
%A Wilkins, Shane G.
%A Zhang, Hui
%A Talip, Zeynep
%D 2021-10-12
%K scientific-publication

%0 Journal Article
%T DFT calculations of Ti-based molecules clustering with Ar for laser-based enrichment of stable isotopes
%V 541
%P 141-143
%W https://cds.cern.ch/record/2859805?ln=en
%U https://linkinghub.elsevier.com/retrieve/pii/S0168583X23002513
%G en
%J Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms
%A Bernerd, Cyril
%A Cocolios, Thomas Elias
%A Dooms, Lucas
%A Ferrari, Piero
%A Payne, Oliver
%D 08/2023
%K scientific-publication

%0 Journal Article
%T Determination of the Terbium-152 half-life from mass-separated samples from CERN-ISOLDE and assessment of the radionuclide purity
%V 202
%P 111044
%W https://pubmed.ncbi.nlm.nih.gov/37797447/
%U https://linkinghub.elsevier.com/retrieve/pii/S0969804323003974
%G en
%J Applied Radiation and Isotopes
%A Collins, S.M.
%A Köster, U.
%A Robinson, A.P.
%A Ivanov, P.
%A Cocolios, T.E.
%A Russell, B.
%A Fenwick, A.J.
%A Bernerd, C.
%A Stegemann, S.
%A Johnston, K.
%A Gerami, A.M.
%A Chrysalidis, K.
%A Mohamud, H.
%A Ramirez, N.
%A Bhaisare, A.
%A Mewburn-Crook, J.
%A Cullen, D.M.
%A Pietras, B.
%A Pells, S.
%A Dockx, K.
%A Stucki, N.
%A Regan, P.H.
%D 12/2023
%K scientific-publication

%0 Journal Article
%T Can we reach suitable 161Tb purity for medical applications using the 160Gd(d,n) reaction?
%V 200
%P 110927
%W https://hal.science/hal-04170236
%U https://linkinghub.elsevier.com/retrieve/pii/S0969804323002804
%G en
%J Applied Radiation and Isotopes
%A Nigron, Etienne
%A Guertin, Arnaud
%A Haddad, Férid
%A Granger, Lucas
%A Rayer, Maxence
%A Rintaud, Alexandre
%D 10/2023
%K scientific-publication

%0 Journal Article
%T 67Cu Production Capabilities: A Mini Review
%V 27
%N 5
%P 1501
%W https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8912090/
%U https://www.mdpi.com/1420-3049/27/5/1501
%X Is the 67Cu production worldwide feasible for expanding preclinical and clinical studies? How can we face the ingrowing demands of this emerging and promising theranostic radionuclide for personalized therapies? This review looks at the different production routes, including the accelerator- and reactor-based ones, providing a comprehensive overview of the actual 67Cu supply, with brief insight into its use in non-clinical and clinical studies. In addition to the most often explored nuclear reactions, this work focuses on the 67Cu separation and purification techniques, as well as the target material recovery procedures that are mandatory for the economic sustainability of the production cycle. The quality aspects, such as radiochemical, chemical, and radionuclidic purity, with particular attention to the coproduction of the counterpart 64Cu, are also taken into account, with detailed comparisons among the different production routes. Future possibilities related to new infrastructures are included in this work, as well as new developments on the radiopharmaceuticals aspects.
%G en
%J Molecules
%A Mou, Liliana
%A Martini, Petra
%A Pupillo, Gaia
%A Cieszykowska, Izabela
%A Cutler, Cathy S.
%A Mikołajczak, Renata
%D 2022-02-23
%K scientific-publication

%0 Journal Article
%T Nuclear data for day-1 radionuclides
%I Zenodo
%* Creative Commons Attribution 4.0 International, Open Access
%U https://zenodo.org/record/8247129
%X Nuclear decay data are fundamental constants of a radionuclide’s decay process and are unique to that radionuclide. Nuclear decay data have been identified as being of importance to a wide range of activities in nuclear medicine, from the production of radionuclides to their use in nuclear medicine clinics. Accurate and precise data on nuclear decay is therefore necessary to ensure confidence in all activities undertaken throughout the process of using radiopharmaceutical products. This report provides a review of the status of the nuclear decay data of the diagnostic or therapeutic radionuclides in the PRISMAP catalogue available at the start of the project in May 2021. There were eighteen original radionuclides available at the commencement of the project, which were identified as Sc-44, Sc-47, Cu-64, Cu-67, Ag-111, La-135, Tb-149, Tb-152, Tb-155, Tb-161, Er-165, Ho-166, Er-169, Yb-175, Pt-195m, Bi-213, At-211 and Ac-225. This review does not include a review of the radionuclides Dy-166 and Tm-165 that are used as generators to produce Ho-166 and Er-165 and has focused on these progenies instead. Whilst PRISMAP has extended their radionuclide catalogue since the initiation of the project to now encompass a total of twenty-six radionuclides at the time of publishing this report, these additional radionuclides have not been covered by this review. These may be included in a future review. A summary of the current state of nuclear decay data of the initial eighteen radionuclides have been covered using the latest evaluations published by the Nuclear Data Sheets or the Decay Data Evaluation Project. Where recent studies have been published since the last evaluation a comparison to these new values have been included. Based on these reviews’ recommendations, where the current literature is lacking or there is room for improvement, new nuclear decay data studies are needed or have been proposed.
%G en
%A Collins, Sean
%D 2023-08-14
%K Gamma-ray emission intensities
Half-life
Nuclear Decay Data
Nuclear Medicine
PRISMAP
deliverable

%0 Journal Article
%T DFT calculations for Ca and Ti containing molecules
%I Zenodo
%* Creative Commons Attribution 4.0 International, Open Access
%U https://zenodo.org/record/6607408
%X Density Functional Theory (DFT) calculations have been performed on simple Ti containing molecules, namely TiF, TiF<sub>2</sub>, TiF<sub>3</sub>, and TiF<sub>4</sub>, to establish the methodology (benchmark of the appropriate level of theory) and determine basic properties of these simple molecules, such as geometry, vibration frequencies, and binding to Ar atoms for clusterization (at room temperature and at 15 K). The frequencies identified are in the far infrared and thus are not practical for laser-based Fourier Transform Infrared (FTIR) spectroscopy.<br> This method is then applied on more complex molecules, namely Ti[OEt]<sub>4</sub> and Ti[OPr]<sub>4</sub>, which have been identified within PRISMAP as potential candidates for enrichment applications. Preliminary results reproduce the experimental spectrum known for Ti[OEt]<sub>4</sub> and identify at which wavelength range the vibrational modes that are sensitive to the Ti isotope are located. This suggests that more complex molecules might not provide better separation than the simple TiF<sub>x</sub> molecules.
%G en
%A Cocolios, Thomas Elias
%A Dooms, Lucas
%A Ferrari, Piero
%A Payne, Oliver
%A Bernerd, Cyril
%D 2022-05-13
%K Clusters
Density functional theory
deliverable