Our 6th newsletter shows all PRISMAP activities that have been successfully carried out in the last months and also gives an outlook on the future, including the last PRISMAP period with the last meeting of the consortium and the continuation of our activities in PRISMAP+.

Consortium Meeting 8 (CM8) was held in early April 2-4, 2025 in Mol, Belgium. This consortium meeting included a public event, "PRISMAP Meets Industry," where collaboration and engagement with stakeholders in the radiopharmaceutical industry were fostered, also with Belgian companies active in the field of medical radionuclides. Traditionally, these days were full of project news, exciting reports from user projects and plans for the final project phase and beyond.

Just before the Consortium meeting, a PRISMAP workshop on emerging infrastructures was held also in Mol. The workshop included two intensive days of presentations, poster exhibition and discussions, as well as a half-day visit to the SCK CEN infrastructures MYRRHA, BR2 and CRF. The programme included sessions on the assessment of emerging infrastructures for specific radionuclides, isotope separation for isotope enrichment and technical developments for radionuclide production. A round table discussion on innovative radionuclides and user needs rounded off the workshop.

Last period activities included such events as the PRISMAP session at Norwegian Workshop on radionuclide production and medical application (Oslo, Norway, 12-16 May 2025), organised by the Norwegian Nuclear Research Centre at University of Oslo. This session included a discussion on the preparation of the PRISMAP+ successor project and a Scandinavian node.

About upcoming events - don't miss the International Day of Women in Radiopharmaceutical Sciences webinar Monday, 18th August, 14:00-15:00 CE(S)T, celebrating women’s contributions to the field, https://www.linkedin.com/feed/update/urn:li:activity:7348621752752586752

We also have upcoming international conferences where PRISMAP will be represented, including EANM 2025 (Barcelona, Spain) on 4-8 October, 2025. Further details on PRISMAP involvement will follow. EANM 2025 Annual Congress I October 4-8, 2025

And finally, the last PRISMAP consortium meeting 9 (CM9) will take place on 18-21 November 2025 in Warsaw, Poland and online. The meeting will start with a one day and a half public event in Warsaw from Tuesday, 18 November 2025 mid-day followed by a full-day on Wednesday, 19 November 2025. On Thursday, 20 November and Friday, 21 November 2025, internal meetings will be held until the early afternoon dedicated to the final reporting and closure of the project, Final PRISMAP public event

Dear readers, enjoy this PRISMAP newsletter, feel free to share it and give us your feedback; and let this last PRISMAP period be successful for you and our entire community!

PRISMAP's Workshop and Consortium Meeting 8 was hosted by SCK CEN at Sunparks Kempense Meren, Mol, Belgium

Workshop on Emerging Infrastructures

The Workshop gave a general introduction to infrastructures producing radionuclides, which were subject to a large study developed by the PRISMAP partners to explore and optimize production of key isotopes for the user community. The assessments of the PRISMAP labs were presented and discussed. The last session of the workshop was dedicated to the realization of a White Paper, presenting the infrastructures, the results and conclusions of the study.

To ensure sustainability and a good geographical coverage, emerging infrastructures received special attention in PRISMAP. The organization of this workshop was one of the activities in support of the emerging facilities. The aim was to explore and develop their radionuclide-production capacity, to discuss radionuclides of interest to the user community and current/future R&D efforts towards the realization of new infrastructures and improved performances. The programme included sessions on the following topics:

• Emerging Infrastructures - assessment for specific radionuclides
• Mass separation for isotopic enrichment
• Technical developments for radionuclide production
• Round-table discussion on innovative radionuclides and user needs

Consortium Meeting 8 (CM8)

CM8 combined internal reporting and strategy sessions and public engagement:

“PRISMAP Meets Industries” event where Industry guests shared insights on radiopharmaceutical development, logistics, and the path to clinical application

Bringing together leading voices from across the radiopharmaceutical value chain, the event offered an interesting dive into the opportunities and challenges shaping the future of NuclearMedicine in Europe for the benefit of patients. From cutting-edge alpha theranostics to industrial-scale isotope production and logistics, our speakers highlighted the power of collaboration between research, industry and healthcare to accelerate innovation in cancer care.

Highlights included: Thierry Stora (CERN) – setting the scene with PRISMAP’s mission; Bernard Ponsard (SCKCEN) – giving NuclearMedicineEurope (NMEU)’s perspective; Anne Royer Moës Moes (IBA) – on alpha theranostics and the AccelerateEU project; Grégory Saive (TRASIS) – accelerating adoption of radiopharmaceuticals; Samy Bertrand (PANTERA) – on Ac-225 production at scale; Raphaël (Raph) ORTIZ (Telix EMEA) – navigating theranostic opportunities; Jean-Michel Luyckx - the Belgian perspective; D'Huyvetter, Matthias (PRECIRIX) – bridging R&D and industrial translation; Frank Vanderlinden (SCKCEN) – enabling secure PRISMAP transports; Claude Poliart (Life Couriers) – insights on medical isotope logistics.

Grateful to all the speakers, moderators, and participants for their openness and inspiring contributions. A big thank you to the PRISMAP community for facilitating these important exchanges and to SCKCEN (and in particular Lucia Popescu) for hosting and organizing the event.

• Public Event: PRISMAP users presented their research, including theranostic tools, targeted therapies, and imaging.
• Internal Discussions: The consortium reviewed project progress, discussed sustainability, and prepared for the final phase of the project.

The meeting concluded with a General Assembly presenting and discussing the roadmap toward Consortium Meeting 9.

Meeting atmosphere and discussions at CM8

Discussing project news and PRISMAP meets industry event

The goal of the Consortium Meeting (CM8) was to prepare the last months of the project. Our public event, which has already become a tradition at our consortium meetings, rounded off the meeting with our project news and exciting reports from our user projects. Many, many thanks to SCK-CEN, our host, especially Lucia Anna Popescu and her team, for a beautiful experience in the Lake District near Mol/Belgium!

You can find all our scientific outcomes on the PRISMAP website and on Zenodo. Here are some highlights from our recent publications:

1.Ursula Søndergaard et al. Production of 67Cu at a biomedical cyclotron via 70Zn(p,alpha)67Cu reaction and its evaluation in a preclinical study using small animal SPECT/CT (2025), 10.1016/j.apradiso.2024.111551

Clinical advancements in nuclear medicine theranostics have excited a research interest in exploring novel radionuclides for medical use. The duo of the β−emitter 67Cu and the positron emitter 64Cu, has advantages over the well-established clinical pair 68Ga and 177Lu in terms of capability for high-precision therapy. Low availability has hindered the use of 67Cu, whereas 64Cu has become established at a limited number of sites through production in low-to-medium energy biomedical cyclotrons. Via the reaction 70Zn(p,α)67Cu, 67Cu can also be cyclotron-produced, although data on the cross sections of this reaction are sparse. Our aim in this study was three-fold: 1) to establish cross sections for relevant beam energies (14–16 MeV) of the 70Zn(p,α)67Cu reaction; 2) determine experimentally the thick target yield for 16.5 MeV proton beam; 3) establish a routine production of 67Cu for radiochemical and preclinical research. Additionally, our work aims to explore the feasibility of using biomedical cyclotrons for development of novel therapeutic radionuclides.

Thin layers of enriched 70Zn were electrodeposited onto silver foils to employ the stacked foils technique for assessing the cross-section at six energies. The thick target yield was measured experimentally using a pressed [70Zn]ZnO target. Methods were developed for solid phase extraction separation of 67Cu from the target material, as well as quality control of the product with regard to radionuclidic and radiochemical purity. Radiolabelling of PSMA-617 precursor was performed, and the end product was injected into a healthy mouse for a kinetic study. As a proof of concept for preclinical applications, the animal was then SPECT imaged using the 185 keV gamma emission line.

Summarizing, our data confirm that biomedical cyclotrons can contribute in developing novel radionuclides, even of low cross section, for preclinical research.

2. E B O'Sullivan et al, Electron-gamma decay spectroscopy of 152Tb (2025), 10.1088/1402-4896/add812

Electron-gamma spectroscopy of the decay of 152Tb supports the gamma-gamma spectroscopy of the same decay. Preliminary measurements of conversion electrons and E0 transitions have been used to validate the transition intensities recommended in the evaluated nuclear data for the 433 keV and 615 keV transitions. Further measurements of the K/(L+M) ratio of the 271 keV and 344 keV transitions have been compared to theoretical predictions based on BrIcc calculations, confirming the pure E2 multipole character of these transitions. Discrepancies between the measured and predicted K/(L+M) ratios for the 586 keV transition indicate the need for further analysis of these data.

These electrons are not measurable with the HPGe array used in the gamma-gamma spectroscopy experiment, and have an important role in mapping the level scheme of the decay. Accurate internal conversion coefficients are vital in balancing the feeding in and out of excited states in 152Gd, in turn allowing the feeding of these states in the beta decay to be calculated. The determination of the beta strength function, and therefore the beta dose to patients, is a key aim of the gamma-gamma spectroscopy which this parallel experiment supports.

Internal conversion electrons are also an important contribution to the patient dose in their own right, depositing a higher proportion of the transition energy into the patient's body than gamma rays due to the short range of electrons. Auger electrons emitted following internal conversion may have ranges less than the size of an individual cell, with a strongly localised biological effect.

While this experiment is limited in its ability to detect low intensity transitions, the completed analysis will provide confirmation of predicted internal conversion coefficients and E0 transition strengths, supporting the decay spectroscopy of 152Tb and the goal of providing accurate nuclear data for its clinical use.

3. Joana F. Santos, Mitochondria-tropic radioconjugates to enhance the therapeutic potential of terbium-161 (2025), https://doi.org/10.1186/s41181-025-00339-6

Strategies that focus on delivering Auger electron emitters to highly radiosensitive intracellular targets—such as the nucleus, cell membrane, or mitochondria—are gaining attention. Targeting these organelles could enhance therapeutic efficacy while minimizing off-target toxicity by allowing lower administered doses. In this context, this study explores the therapeutic potential of 161Tb-labeled radiocomplexes that integrate the mitochondria-targeting triphenylphosphonium (TPP) moiety with a prostate-specific membrane antigen (PSMA) targeting vector. The goal is to assess these dual-targeted radiocomplexes for their ability to deliver conversion electrons (CE) and Auger electrons (AEs) to prostate cancer (PCa) cells, specifically targeting the mitochondria to enhance therapeutic efficacy.

The TPP-modified 161Tb-radiocomplexes effectively targeted the mitochondria of PSMA-positive PCa cells, leading to increased DNA damage and reduced cell viability compared to single-targeted radiocomplexes. These findings suggest that dual-targeting strategies, which combine PSMA and mitochondrial targeting, can enhance the therapeutic potential of radiopharmaceuticals for prostate cancer treatment.

4. Collins, S. et al. Deliverable D11.3 - Precision nuclear data for extended radionuclide offer. (2025). https://zenodo.org/records/15348568.

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. 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.

5.Cocolios, T. E. et al. Deliverable D6.3 - Training events for young researchers. (2025). https://zenodo.org/records/15410805.

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.

The latest PRISMAP Call 5 was again a success, with 24 proposals submitted! These proposals highlighted a wide range of innovative approaches in radiopharmaceutical development for cancer therapy and imaging, as well as advancements in radioisotope production.

In parallel, under the leadership of Belgium, the Council of the European Union approved a resolution on June 17, 2024, emphasizing Europe’s need to maintain autonomy and leadership in the medical radioisotope field.This is especially important given that production is concentrated in only a few member states, and some isotopes have a very short half-life, posing challenges for availability and transport. The resolution calls for collaboration among the European Commission, Euratom Supply Agency, member states, and industry stakeholders to secure source materials, sustain research, and improve transport logistics. This initiative builds on previous EU strategies, like the 2021 SAMIRA strategy, to strengthen nuclear medicine and support Europe's Beating Cancer Plan.

The Economic and Social Committee's report on “Europe's Beating Cancer Plan” highlights the life-saving impact of nuclear medicine and the need for equal access to cancer treatment across Europe. It stresses the importance of prioritising radionuclide-targeted therapies due to their precision and reduced harm, and calls for investment in workforce education, training, and mobility.

This edition features several exciting events and opportunities for the PRISMAP community. Notably, we will have a PRISMAP session at the Workshop on Radionuclide Production and Medical Application in Oslo (May 12-16, 2025), organised by the Norwegian Nuclear Research Centre. Additionally, the ISOLPHARM group of PRISMAP partner INFN will organize a thematic workshop at the FisMat 2025 conference in Venice (July 7-11, 2025), focusing on the ISOL technique for medical radionuclide production. Mark also your calendars for the International Day of Women in Radiopharmaceutical Sciences webinar on August 18, 2025, celebrating women’s contributions to the field.

We also have a number of upcoming international conferences where PRISMAP will be represented, including ECR 2025 (Vienna), EMIS 2025 (Whistler, BC, Canada) and INPC 2025 (Daejeon, Korea). Further details on participation and submission opportunities are included.

We are very much looking forward to welcoming you in Mol, Belgium for the upcoming Consortium Meeting 8 organised by Lucia Popescu, early April. This consortium meeting will include a public event, "PRISMAP Meets Industry," where we aim to foster further collaboration and engagement with stakeholders in the radiopharmaceutical industry.

Finally, as a last focus of this newsletter, we would like to highlight the Nuclear Medical Applications infrastructures at SCK CEN, which are depicted at the end of the newsletter. These groundbreaking efforts are shaping the future of radiopharmaceuticals in the fight against cancer.

We look forward to continued engagement and collaboration in these exciting initiatives, which are driving the future of radiopharmaceutical research and its application in cancer therapy in Europe and beyond.

Introduction: Pioneering nuclear research for nuclear medical applications

Since its establishment in 1952, the Belgian Nuclear Research Centre (SCK CEN) has been at the forefront of nuclear research and the advancement of nuclear medical applications.

SCK CEN’s research strength lies in its integrated ecosystem, which unites a diverse array of scientific disciplines within its Institute of Nuclear Medical Applications (NMA). This collaborative environment plays a pivotal role in advancing the development of radiopharmaceuticals, underpinned by comprehensive expertise in radiobiology, radiochemistry, radiopharmacy, and dosimetry. This multidisciplinary approach fosters an advanced research platform that accelerates the progression of innovative preclinical-stage nuclear medicine solutions.

With a dedicated team of over 100 professionals, NMA focuses on advancing the application of nuclear medical applications in the treatment of diseases, particularly cancer through the development of new radiopharmaceuticals.

Research areas and technological advancements

SCK CEN's research encompasses several critical areas in the development of radiopharmaceuticals and their application in targeted therapies:

• Development of carrier molecules for radioligand therapy with various potential therapeutic applications.
• Separation chemistry plays a central role in the production of high-purity radioisotopes for medical use, along with the recycling of raw materials. This expertise ensures that isotopes meet the stringent purity requirements necessary for medical applications.
• Decades of research into the radiation effects on the human body are now being leveraged to optimize radioligand therapies.

NMA has established a strong foundation in preclinical research, with a focus on optimizing the development pipeline from laboratory experiments to clinical studies. The integration of radiobiological principles and dosimetry ensures that radiopharmaceuticals are not only effective but also safe when applied in clinical settings.

Targeted cancer therapies: Radioligands and high-affinity ligands

A core focus of SCK CEN NMA's work is the development of radioligands—molecules designed to bind selectively to cancer cells and deliver targeted radiation to destroy tumors while minimizing damage to surrounding healthy tissue. The NMA institute's research includes:

• The design and synthesis of high-affinity ligands using peptide or chemical-based platforms that specifically target molecular markers on cancer cells.
• The formulation and validation of radioligands, where radiochemical binding of the ligand, chelator, and radioisotope is carefully tested to ensure precise delivery and prevent premature release of the radioisotope.
• In vitro studies assessing radiopharmaceutical uptake, cell viability, stress responses, and radiotoxicity in non-target areas, as well as radioligand behavior in living organisms to measure absorption, distribution, metabolism, and excretion.

Additionally, rigorous dosimetric analysis is performed to evaluate the radiation doses delivered to various organs and tissues, ensuring that these doses are within safe and effective limits. The overall aim is to translate preclinical data into clinical practice, optimizing radioligand therapies for human patients.

Hot Animal Facility (HAF)

The Hot Animal Facility (HAF) supports the development of radiopharmaceuticals with advanced preclinical studies. Comprising nine specialized laboratories, HAF conducts both in vitro and in vivo testing, ensuring safety and efficacy before clinical trials.

In in vitro tests, we assess radiopharmaceutical uptake, cell viability, and stress responses. For in vivo studies, we map radioisotope distribution in animal models, ensuring radiotoxicity control in non-target areas.

We also evaluate efficacy, dose-response, and survival curves, comparing treatments like radioligand therapy versus standard cancer treatments. This integrated approach helps optimize personalized therapies and advance radioligand therapies toward clinical application.

Translating preclinical research to clinical applications

The research at NMA is structured to provide a seamless transition from preclinical models to clinical applications. Key components include:

• Optimizing dosing protocols based on preclinical findings.
• Validating preclinical models to ensure they accurately represent human biology.
• Ensuring patient safety by conducting thorough radiobiology and dosimetry studies to guarantee the correct radiation dose is delivered to targeted cells while minimizing risks to healthy tissues.

This robust preclinical framework is designed to facilitate the subsequent transition to clinical studies, ensuring that treatments are safe, effective, and reproducible in human patients.

Centralized Radiochemical Facility (CRF)

A significant development in SCK CEN NMA’s infrastructure is the Centralized Radiochemical Facility (CRF), currently under construction, which will be instrumental in the GMP production of radiopharmaceuticals. Scheduled to come online in 2027, the CRF will initially focus on the production of n.c.a. lutetium-177, a critical isotope for radioligand therapies, while also being capable of processing next-generation isotopes.

The CRF will utilize advanced radiochemical separation techniques to produce isotopes that meet the stringent standards of the European Pharmacopoeia,ensuring the highest levels of chemical and radionuclide purity. In the short term, the CRF will support treatments for 15,000 patients per year, with long-term plans to increase production to serve 100,000 patients annually. This facility will be central to ensuring a stable and reliable supply of isotopes for clinical applications, particularly in radioligand therapy.

Collaborative efforts for a robust supply chain

The CRF’s production capabilities are further strengthened by a public-public partnership with the National Institute for Radio Elements (IRE), a Belgian institute with extensive experience in the distribution of medical radioisotopes. Through this collaboration, SCK CEN and IRE aim to establish a reliable and sustainable global supply chain for medical radioisotopes, ensuring that the isotopes produced at CRF can meet the growing global demand for nuclear medicine.

Another key partnership includes the development of terbium 161-based radiopharmaceuticals. In this context, a partnership with Terthera plays a crucial role by ensuring a robust and adaptable production infrastructure to support the next generation of radioligand therapies, further advancing nuclear medicine.

BR2 research reactor: A key component in radiopharmaceutical production

At the core of SCK CEN’s radiopharmaceutical production is the BR2 research reactor, a state-of-the-art facility that is pivotal in the production of essential medical isotopes, including molybdenum-99 and lutetium-177. Operating 203 days per year since 2019, BR2 ensures a continuous, reliable supply of isotopes to meet the needs of the medical community. On average, the reactor supports the diagnosis and treatment of over 11 million patients annually, playing a critical role in the global radiopharmaceutical supply chain.

The BR2 reactor is capable of producing 10 to 15 different radioisotopes per cycle, with a focus on molybdenum-99 and lutetium-177, both of which are crucial for diagnostic imaging and targeted cancer therapies.

Conclusion: Shaping the future of nuclear medicine

SCK CEN remains committed to advancing nuclear medical applications through continuous research, development, and the production of high-quality radiopharmaceuticals. With its integrated approach, state-of-the-art facilities, and deep expertise in the field, SCK CEN is poised to remain a global leader in radioligand therapies, ensuring the delivery of life-saving treatments to cancer patients worldwide.

Through its dedication to innovation and collaboration, SCK CEN is helping shape the future of nuclear medicine, offering hope to millions of patients in need of precision therapies.

Hi Kirsten! Many have seen you at one of our Public Events, but many still wonder: who are you and what does SCIPROM do?

Hello Thomas, thank you very much for inviting me to this interview! I am the Executive Director of SCIPROM. SCIPROM is a small company based near Lausanne, Switzerland. We provide management, dissemination and communication services and are also responsible for these tasks within PRISMAP.

So what is the state of PRISMAP today? How far along are we, literally and in practice?

The third year of PRISMAP is drawing to a close and we are beginning to harvest the results of the project while preparing for future developments.

There were quite a few projects funded through the last 4 calls. Is that much/within expectations/short?

Yes, indeed, already 32 projects have been selected for PRISMAP funding, with the involvement of biomedical facilities increasing over time. That fits in well with our planning.

How are the projects ongoing?

The first projects are now being finalised, while the last ones selected under Call 4 are now starting their activities and receiving their first deliveries after an initial phase of legal and ethical requirements.

When can we expect a next call?

We are currently reviewing previous services, implementing new services and planning a final call for proposals. We hope to launch this call in 2024.

What will happen after PRISMAP?

We hope to receive EC funding for a further four years and are currently preparing for this, including an extension of the current project to close the potential time gap between the two projects.

How can we stay informed?

Join the PRISMAP community and stay tuned via our website, LinkedIn and newsletters.

Thank you so much for your time!

Interview by Thomas Cocolios, Dissemination Manager

From the onset of the PRISMAP consortium, we realised that we were not all talking the same language. The strength of PRISMAP is the bridge that we are building across many communities, from the basics of radionuclide production all the way to the preclinical studies, with all the links in the supply and research chain between. That strength is to be valued but also requires particular attention, and that attention is training.

It starts with having a strong basic understanding of the key concepts that are central to our field: radioactivity, radionuclide production, radiopharmaceuticals, medical imaging & therapy, and radioprotection. Those form the five core themes of the MOOC that PRISMAP is now supporting via ARRONAX with the partnership of Nantes Université.

PRISMAP also offers topical schools to provide advanced training in topics where we believe our community can really benefit. The focus of those trainings is to bring attention towards the state of the art, while also giving participants hands-on opportunities. In 2023, we offered three schools, organised by SCKCEN (Belgium), DTU (Denmark), and IST (Portugal). Meanwhile, we are organising two more in 2024: the PRISMAP school on Radionuclide Production in Leuven (Belgium) in the spring and the PRISMAP school on Medical Imaging in Riga (Latvia) in the autumn. Meanwhile, we also partner with other key events from the field, such as the ISI NucMed school organised in Nantes (France).

We use all those events to also build up a library of material for training and education on the education portal of the PRISMAP website. On that page, you will find the material we offer, as well as an introduction to our PhD Charter: a way to form a community of young researchers crossing our different fields. If you are a PhD student and you are interested in what PRISMAP does, make sure to have a look and sign up!

But training is not only for students and young researchers. Also experienced researchers might have a lot to learn about other fields within our community. As a nuclear physicist, I keep on learning every time I exchange with colleagues in radiopharmacy or in pre-clinical research. And that should also be one of our ambitions: to keep learning and find within PRISMAP the chance to share and exchange. This is why PRISMAP supports transdisciplinary participations in many conferences to promote this exchange of knowledge at all levels, such as during the public lecture of the ARIS conference in Avignon (France) or the PRISMAP participation in the Auger Symposium in Montpellier (France) last year.

Finally, all these developments and all this knowledge should be easily accessible for all. This is why PRISMAP has created an information portal where the state of the art in nuclear decay data, production of radionuclides, preparation of radiopharmaceuticals, quality control and metrology, and radioprotection & logistics are presented.

Developing new radiopharmaceuticals is a long and challenging journey, and finding the right radionuclide supplier is one of the many obstacles researchers face. This is especially true when non-conventional radionuclides are required. To address this problem, PRISMAP aims to be your one-stop partner by centralizing all relevant information on our website, about all the non-conventional radionuclides we offer and their points of supply.

PRISMAP also aims to facilitate the delivery of those radionuclides to the broader scientific community. Therefore, we offer access to five fully equipped biomedical facilities for your research needs. Whether the half-life of your requested radionuclide doesn't allow for delivery to your lab in time or you don't have the right equipment or radioprotection authorization, our biomedical facilities are here to help you achieve your research goals. We can even offer support for conducting your first in-human clinical study. Learn more about our facilities in this newsletter and on our website.

PRISMAP is also about connecting people in our field through events like workshops, consortium meetings, young scientist gatherings, and summer schools. Check out our past and upcoming events in this newsletter and stay informed of the forthcoming meetings.

Our experts at PRISMAP are also producing new scientific outputs relevant for future research involving the PRISMAP radionuclides. For example, read in this issue how our partners are establishing more accurate half-lives of the terbium radionuclides or refining 225Ac production.

At PRISMAP, our priority is helping you to achieve your research objectives in the field of nuclear medicine. Read two testimonies from our users who received their first deliveries of radionuclides in this newsletter.

With the third call for projects starting now, it's the perfect time to see how PRISMAP can help you advance your research for the next generation of medical radiotracers. Visit our website to submit your project or contact the PRISMAP helpdesk for assistance.

By Charlotte Duchemin – Following the evaluation of the first two calls, PRISMAP has now entered a new phase with the first radionuclides being delivered. We have asked two of those projects to let us know about their experience so far.

Project 12 entitled “Added Value using Terbium-161 over Lutetium-177 in Combination with the metabolically more stable GRPR Ligand AMTG for Targeted Radiotherapy of GRPR-expressing Malignancies? – A Preclinical Evaluation” started on the 15 November 2022 with the first delivery of Tb-161 by PSI, followed by two additional deliveries in December 2022 by PSI and SCK CEN. Dr. rer. nat. Thomas Günther (TUM), project leader of project 12, said: “In a project, which involves the preclinical comparison of [161Tb]Tb-RM2 and its analog, [161Tb]Tb-AMTG, with their 177Lu-labeled derivatives, a higher gastrin-releasing peptide receptor (GRPR) affinity and metabolic stability in vivo was found for [161Tb]Tb-AMTG, which resulted in significantly improved activity levels in the PC-3 tumour xenograft at each time point examined (1, 4, 24 and 72 h p.i.). In combination with the higher rate of emitted Auger electrons per decay for Tb-161 as compared to Lu-177, the highest therapeutic efficacy is anticipated for [161Tb]Tb-AMTG, which will be further determined in future studies.”

Dr Alexis Broisat, project leader of project 11, has received a first batch of Tb-161 on 24 January 2023 from SCK CEN. This project aims at studying the “development and preclinical evaluation of a mesothelin-targeting theranostic agent”. Dr Broisat specifies that this first batch of Tb-161 allows his team to, on one side, test the capacity of non-conventional chelates developed at the University of Grenoble (France) to complex Tb and, on the other side, to develop the radiolabelling of nanobodies with this new and promising radionuclide for theranostic applications.

You can find more inspiration by browsing our accepted projects on the PRISMAP website! 

On 11 January 2023, the PRISMAP Executive Board gathered in Leuven for the review of the first periodic report from PRISMAP. Our achievements of the first 18 months were discussed with representatives from the European Commission and an external evaluator.

You can find a publishable summary of the periodic report on the PRISMAP website. The feedback from the European Commission was very positive and encourages us to continue forward and develop our activities further.

On the occasion of World Cancer Day (4 Feb), the Be Aware, Show You Care event was held by Women in Nuclear with a hybrid programme on Monday 6 February 2023 at 4pm CET at the IAEA headquarters in Vienna, Austria.

The event was moderated by Margaret Doane the IAEA Deputy Director General and Head of the Department of Management; Ragdaa Attia IAEA Nuclear Science and Instrumentation Laboratory opened the event featuring the IAEA imPACT programme with Lisa Stevens the IAEA PACT Director for Rays of Hope, followed by WHO Global Breast Cancer initiatives with Ben O. Anderson MD FACS, Cancer Control at WHO, Lisbeth Cordero Mendez Radiation Oncologist IAEA, Sason Feldkamp Hayashi a project manager at Medical University Innsbruck for PRISMAP, Timea Varadi a research scientist from AC²T research GmbH, and Janette Donner WiN IAEA President from the IAEA Department of Safeguards.

“One of the United Nations Sustainable Development Goals targets for 2030 aims to reduce early deaths from non-communicable diseases, including cancer, by one third. Achieving this ambitious target could result in saving at least 40 million lives from cancer. This, however, requires a concerted effort from a broad range of partners in multiple sectors to considerably scale up resources and establish strong political commitment for an effective global response to cancer.” – IAEA PACT programme

The event focused on the many programmes addressing global cancer care initiatives; the IAEA PACT “Rays of Hope: Cancer care for all” ensures the integration of radiotherapy in comprehensive cancer control and of engaging with other international organisations such as the World Health Organisation (WHO) to address cancer control in a comprehensive way. Since then, the Agency has worked closely with WHO, the International Agency for Research on Cancer (IARC), the Union for International Cancer Control (UICC) and many other relevant collaborators to build a coalition of global partners committed to addressing the challenge of cancer in low- and middle-income IAEA Member States. The programme WHO Global Breast Cancer Initiative strives to reduce breast cancer mortality by 2.5 percent per year, which over a 20-year period can save 2.5 million lives. The purpose of this core technical package is to outline a pathway for incremental, sustainable improvements tailored to country-specific needs based on three key strategies and objectives: health promotion for early detection; timely diagnosis; and comprehensive breast cancer management.

Global nuclear medicine programmes were illustrated and PRISMAP was highlighted, which aims to provide access to novel radionuclides and biomedical centres along the translational pathway for the development of radiopharmaceuticals by our starting research community. Gaps to access and availability of nuclear medicine centres and radiopharmaceuticals were identified and a message that a strong coalition of partners is needed to ensure a reliable and robust system for nuclear medicine in disease management of cancer care.

Lastly, the importance of self-care, prevention and early detection, to educate folks to start a dialogue with their healthcare provider was emphasised.

When establishing this User Forum, we first and foremost wanted to make sure that our main stakeholders – the user community – would be kept up to date with our calls, with our progress, and with our news. We reach out to you – hopefully not too frequently – to provide information about our calls, such as the ongoing call 3, or when special events are planned, like the public events at the occasion of the PRISMAP consortium meetings. We also publish this newsletter twice a year, to inform you broadly about what is going on behind the curtain.

We would also like to engage in a bilateral dialogue and provide you, our users with a voice. For this purpose, we have established the PRISMAP helpdesk to collect your feedback and questions. Communications through this channel mostly focus on questions related to ongoing applications, by teams preparing their file for our previous calls.

We also sent around last year a broad consultation in the form of a questionnaire. We would like to thank all those who took the time to provide us with input; outcomes of this survey have been compiled and can be found on the PRISMAP Outcomes page. Should you wish to express your views on the production of medical radionuclides, feel free to fill it yet as we continue to accept input in preparation for a publication on the findings of this survey.

We would also love to hear from you directly, learn what we could do to foster your research.

In order to get more direct feedback from the User Forum, we would like to formalise its structure and give you a way to shape PRISMAP and our communication. For that purpose, we propose three simple steps:

• Nominating 2 to 3 representatives from the User Forum, to be the voice of the users and represent your interest in exchanging with PRISMAP.
• A direct participation of the User Forum in the preparation of the public event, by involving the representatives in preparing the agenda and selecting the content.
• An annual hybrid Town Hall, animated by the representatives, to bring the feedback from the users to the attention of PRISMAP.

Should you be interested to become one of the representatives, you may send your name and a short motivation in two lines to Thomas Cocolios (thomas.cocolios@kuleuven.be; PRISMAP Dissemination Manager) or to Charlotte Duchemin (charlotte.duchemin@cern.ch; Technical Manager).

If you have any question or suggestion, you are always welcome to reach out through our helpdesk or by contacting anyone whom you might know in PRISMAP. You may also find us on Twitter and LinkedIn.

By Jake Johnson – Ac-225 is a medical radionuclide that has attracted significant interest from the oncology community since landmark studies in 2016 demonstrated its in-vivo efficacy in terminal stage metastatic resistant prostate cancer patients. Even before, it was considered a strong candidate for use in targeted alpha therapy of metastatic and distributed cancers. The Ac-225 decay chain has several features making it appropriate for this therapy modality. Not least is the emission of four successive alpha particles, with an energy totalling 28 MeV, meaning there is potential for very high targeted dose per unit activity of Ac-225. Furthermore, its 9.92-day half-life means that it can be produced, separated, and shipped while suffering minimal decay losses, in contrast to shorter lived candidate isotopes for targeted alpha therapy (TAT). This half-life is also well matched to the biological half-life of large targeting vectors such as antibodies, that have high specificity to cell membrane antigens. With respect to radiopharmaceutical synthesis, it has been demonstrated that Ac-225 can be conjugated to targeting molecules using typical chelators including Macropa and DOTA as well as novel macrocyclic chelators such as crown. Aside from these features, Ac-225 can be used as a generator for Bi-213, a TAT candidate itself that can be conjugated to smaller targeting molecules such as peptides or hormone analogues for targeting of different receptors and therefore cancer types.

There is currently a surge in Ac-225 research, including several clinical trials to develop good manufacturing protocols for Ac-based pharmaceuticals. The success of such research programmes relies on a stable and reliable supply of medical-grade Ac-225, which is currently a major issue. Medical Ac-225 can currently only be sourced from Th-229 generators in Oak Ridge National Laboratory (USA), or the Joint Research Centre of the European Commission in Karlsruhe (Germany) whose combined output is limited to approximately 70GBq per year. Research partnerships between accelerator complexes in North America with the capacity to produce Ac-225 through high energy proton irradiation of thorium, and radiopharmaceuticals start-up companies are being developed. Furthermore, accelerator-production of Ac-225 for medical purposes is being pursued in Europe by notably start-up companies such as alfaRim and PANTERA. However, there is no clear time scale on these developments.

Within the PRISMAP consortium, CERN MEDICIS has recently demonstrated that it is able to contribute towards Ac-225 research through the production of isotopically pure samples following the proton irradiation of ThO₂. By using the technique of resonant laser ionisation and mass separation, it has been demonstrated that Ac-225 can be collected with an efficiency of greater than 10%, while suppressing the Ac-227 content that normally contaminates Ac-225 samples produced from irradiated targets to levels well below the exemption limit per patient dose. The separation efficiency has been measured during dedicated experiments and benchmarked using a combination of decay spectroscopy approaches at KU Leuven. Meanwhile the purity, most notably with respect to the Ac-227 activity in a Ac-225 sample from an irradiated ThO₂ target was determined by the sensitive method of alpha-recoil spectroscopy. The production and separation of Ac-225 at CERN MEDICIS is under ongoing investigation to try to even further improve the efficiency of the technique, such that this novel radioisotope can be reliably delivered to partners for pre-clinical research.

You can find our recent publication on the topic on the Outcomes page of the PRISMAP website.

By Séan Collins — One of the missions of PRISMAP is to provide accurate and precise standards and decay data that will underpin the development of the new generation of radionuclides that the consortium is making available for research and development. For any activity determination of a radionuclide, a critical component is the ability to define the activity at a point in time without which we cannot know the activity accurately. This is an important consideration throughout the lifecycle, whether during the production and purification of the radionuclide to when determining the activity of a radiopharmaceutical being administered to a patient. A starting point for providing an accurate standard for a radionuclide is to ensure that the radioactive half-life being used is accurate and precise, without which how can we have confidence in the standard or if any deviations are due to radioactive impurities?

In the ongoing efforts at NPL and CHUV’s Institut de radiophysique (IRA) to provide traceability to the terbium theranostic quartet of Tb-149, Tb-152, Tb-155, Tb-161, and other radionuclides provided by PRISMAP, we have investigated these half-lives. Many of the half-lives for these radionuclides have not been measured since the 1960s or 1970s and their relative uncertainties are not conducive to providing suitably precise traceable standards. Using multiple independent techniques, including ionisation chamber measurements, gamma-ray spectrometry and liquid scintillation counting, the radioactive decay rate has been followed over many half-lives. As radionuclide contaminants can be present in these samples, careful consideration of their influence must be made, along with many other factors that can impose biases in the determined half-life.

In these investigations, we have found large differences between those published in previous studies. For example, in the case of Tb-161 we determined a half-life that was significantly longer than the currently evaluated value whilst for Tb-155 a half-life was determined that was 1.6 % shorter than previous studies. Making use of the high-purity samples being provided PRISMAP we have been able to determine these half-lives with high precision, with improvements of almost an order of magnitude over those found in nuclear data evaluation databases.

These half-lives being determined in PRISMAP provide new accurate and precise data that will underpin standards being produced by NPL and IRA, and provide confidence in the activity measurements made for these radionuclides by all.

Find out more about the published results on Tb-155 and Tb-161 and feel free to browse all our results in the PRISMAP Outcomes page.

Comparison of the uncertainty propagation of the standard uncertainty of the half-life for ¹⁵⁵Tb, and ¹⁶¹Tb to the uncertainty of the activity, over approximately five half-lives, from the evaluated half-lives (black line) and those reported in this work (red line).

By Tom Clarijs – The Belgian Nuclear Research Centre SCK CEN in Mol is one of the largest research institutions in Belgium and is renowned worldwide for its extensive expertise in peaceful applications of ionising radiation. The SCK CEN Academy provides opportunities for Bachelor and Master students, PhD candidates and any professional interested in enriching his or her nuclear competences.

The Belgian Nuclear Research Centre SCK CEN in Mol is one of the largest research institutions in Belgium and is renowned worldwide for its extensive expertise in peaceful applications of ionizing radiation. With its pioneering role and its unique state of the art nuclear experimental facilities, SCK CEN performs breakthrough research in a wide spectrum of topics such as innovative nuclear systems, medical applications, sustainable waste & decommissioning, etc...

Within the SCK CEN Academy, all nuclear expertise and experience gained from our different research projects is collected and transferred. In the interest of maintaining a competent workforce in industry, healthcare, research, and policy organisations, and of transferring nuclear knowledge to the next generations, the SCK CEN Academy takes it as its mission to:

• reach out to pupils, their teachers and the public;
• provide guidance for students (Bachelor, Master and PhD level) and junior researchers;
• contribute to academic courses for students and organise customised training for professionals;
• offer policy support with regard to E&T matters;
• care for critical-intellectual capacities for society.

Guidance for junior researchers

The SCK CEN Academy provides opportunities for Bachelor and Master students, PhD candidates and any professional interested in enriching his or her nuclear competences. About 100 Bachelor and Master students perform an internship or prepare their thesis at SCK CEN on an annual basis. Presently, also about 90 PhD students from numerous countries prepare their thesis at our laboratories.

Applications for current PhD topics are in full swing, including topics relevant to the PRISMAP community. Deadline for application is March 23, 2023.

Education and training

The SCK CEN Academy works together with several Belgian and foreign universities and contributes to academic education. We also offer customised training courses to develop and improve the nuclear competences of employees working in the nuclear industry, the medical sector, research organisations and public authorities engaged in radioactive applications. Within the course programmes, lectures and practical sessions are complemented with visits to several nuclear laboratories and research reactors. These technical visits enable trainees to enrich and illustrate their acquired knowledge with the practice of real-life situations.

The PRISMAP training course on translational research of radiopharmaceuticals will be organised from 20 until 24 March 2023, including topics on the radiobiological, radiochemical and dosimetric aspects of radiopharmaceuticals. Technical visits related to the research of radiopharmaceuticals are foreseen.

Curious about the available research topics and training opportunities? Visit our website on www.sckcen.be/academy, sign up for our newsletter and follow us on LinkedIn.