Newsletter 1 — Editorial by Thierry Stora, PRISMAP Coordinator

Our first Newsletter is starting with the new year of the Tiger, and it is certainly no surprise to most of you as it also coincides with the anniversary for the discovery of isomers in radionuclides, without which the most frequent SPECT scans with 99m-Technetium performed across the globe would not be possible.

With the starting PRISMAP – The European medical radionuclide programme, we indeed hope new isomers will find their way into clinical research and practices. This is precisely the idea behind our consortium and this first Newsletter. We are aiming at reaching out to researchers spread across life sciences and their related technologies at large, in biomedical research and in nuclear medicine. European researchers – maybe you? – will be able to receive non-conventional radionuclides offered through our web portal, and potentially also benefit from your project directly developed in one of our associated biomedical platforms for preclinical and clinical studies.

The portfolio of radionuclides with special research grades offered by the federation of our large-scale facilities, is made available thanks to efforts of our colleagues in charge of developing the tools and the coordination of the consortium, Iris, Thomas, Clemens, Renata and many others. A particular highlight was the recent meeting of the consortium after the severe restrictions imposed to travels, that partially took place at CERN and in Geneva nearby in the now popular hybrid format. This allowed us to physically meet for the first time, exchange on the first milestones that were met, launch the first call for projects, receive feedback from our external advisors, and already project ourselves in the future.

You will find in this first Newsletter insights on institutes in charge of radionuclides delivery and of biomedical research, together with advanced data and developments of techniques required by PRISMAP services. And if you are undertaking graduate studies in a related field of nuclear and radiopharmaceutical science, please consider getting a dedicated PRISMAP label and get in touch with our training office as soon as possible!

Dear reader, enjoy this first PRISMAP Newsletter, don’t hesitate to distribute it further and provide us with feedback; and let this Year of the Tiger be a successful year for yourself and all of our colleagues!

Transport

Transport and logistics is collecting knowledge about the many small and big obstacles to rapid transfer of radioactivity between the PRISMAP partners. At present the focus is on the transport to ARRONAX in France of Cu-64 samples for the intercomparison tests. Negotiations with airlines, transport companies, handling agents and authorities are under way to clarify the possibilities for short-term exceptions and also more general solutions in the future. When off-line mass separation is to be used regularly there is a double pressure on the rapid transfer, as activity first needs to go from reactor/cyclotron to the mass separator, and then from the separator to the end user.

An interim report describing the present transport situation will be delivered within the next few months.

PhD Label — From producing radioisotopes to dosimetry

During my studies in nuclear physics, I learned all about the atomic nucleus. I was stumped when I learned how the nuclear structure could be described completely by quantum mechanical formalisms and how this naturally leads to radioactive decay as it was observed by M. Curie and her husband. Even more fascinating is the fact that this physical phenomenon eventually contributes to the treatment of cancer patients. However, the transition from a radionuclide into a medicinal product is not evident and requires large efforts and excellent collaborations between various disciplines. Until now, I had the opportunity to dig into two different aspects of radionuclide therapy. After studying the production of medical radioisotopes, I am currently investigating the tumour dosimetry of radionuclide therapy.

Read more

Radiolanthanides

The use of radionuclides in nuclear medicine for diagnostics and therapy has significantly increased over the last decay. As a result, there is an urgent need to explore the usage of new radionuclides and relative innovative production methods. Depending on both half-life and decay emission, these radionuclides can be used for imaging, via positron emission tomography (PET) or single-photon emission computed tomography (SPECT), and for therapy via α, β−, or conversion and /or Auger electron emission. Within each of these categories, there are several radiolanthanides with a variety of tissue ranges and half-lives offering attractive decay properties.

Production of sufficient amounts of high quality radiolanthanides requires systematic research in targetry, irradiation, radiochemistry and quality control. In some cases, it is difficult to produce carrier-free and/or radionuclidically pure products with conventional reactor-based or accelerator-driven production routes. Thus, the use of mass separators to produce carrier-free radionuclides for nuclear medicine is becoming an attractive method. In the frame of PRISMAP WP12, together with eleven universities and research laboratories, scientists are going to investigate the potential of novel radiolanthanides for nuclear medicine applications.

The main tasks of this WP are the development of specific radiochemical separation methods and preclinical research studies for novel radiolanthanides (149Tb, 152Tb, 155Tb, 161Tb, 175Yb, 153Sm, 167Tm, 165Er, 169Er, and 135La). In particular, an assessment of the quality control and radiolabelling processes of these radiolanthanides will be established. This information will be of great interest for developing clinical methods using different Tb radionuclides for theragnostic applications. The produced data will also implement the use of conversion/Auger-electron-emitting radionuclides towards the treatment of disseminated tumor cells and small metastases. Enhanced knowledge of these novel radiolanthanides and exploration of their therapeutic effects will be greatly appreciated by the scientific community of nuclear medicine and will pave the way towards more efficient cancer treatments.

Bringing metrology to PRISMAP

As PRISMAP looks to make a new generation of radionuclides easily accessible to researchers, it is vital that any pre-clinical and clinical research is underpinned by accurate and reproducible measurements of activity and dosimetry. In the clinical setting these measurements are typically performed using a radionuclide calibrator before administration to a patient, with traceability to a national metrology institute such as the National Physical Laboratory (UK) or the Institute of Radiation Physics (Switzerland). This traceability comes through the primary standardisation of activity and underpins all clinical use of any radiopharmaceutical. To this end, the translational data generation work package (WP11) will seek to provide this traceability for the novel radionuclides being generated by the PRISMAP consortium and disseminate these standards to the wider community. Alongside this development, accurate nuclear decay data will be determined to provide confidence in this fundamental data. A challenge of molecular radiotherapy is the understanding of the dose delivered at a cellular level and the biological effect of the emissions of a radionuclide to tumour cells. To improve our understanding, Riga Technical University (Lativia) will investigate the doses absorbed from the emissions from the radioactive decay of radionuclides using nano-dosimeters. The University of Oslo will look at developing a traceable link of the activity standards of the PRISMAP radionuclides to their relative biological effectiveness through the dose response. 

Radioisotope production research

Production of medical radionuclides has always benefited from high level technologies developed in the context of nuclear and accelerator physics research. In particular, some important ISOL technologies adopted for targets, ion sources, and isotope separation demonstrated an enormous potential for medical radionuclides. WP10-JRA2 is organised in three different tasks: target design and characterisation (task 1), ion sources (task 2), and isotope separation techniques (task 3). They are all oriented to improve the scientific instruments and the technologies required for the production of medical radionuclides. This approach will benefit from the collaboration among prestigious international research institutes in the framework of PRISMAP.

Task 1 and task 2 will mainly focus on the optimization of targets and ion sources, respectively, with the aim to increase as much as possible the production rate of specific medical radionuclides. In particular, new high performance materials will be studied and characterized, especially at high temperature ranges. New targets and ion sources will be designed making use of complex multiphysics simulation tools.

The object of task 3 is the strong enrichment of Ca and Ti isotopes from their natural abundance to an abundance useful for radionuclide production in reactors or cyclotrons. Indeed, production of theranostic scandium isotopes (43Sc, 44Sc, 44mSc and 47Sc) relies on the availability of highly enriched Ca or Ti isotopes respectively. With this in mind, task 3 will investigate the enrichment via laser-enhanced isotopically selective condensation, an innovative technique pioneered at EPFL and successfully used in the past for the enrichment of different isotopes.

As a concluding remark, it is clear that WP10-JRA2 will lay the foundations for a structured community of scientists and research engineers deeply focused on the technologies for the production of pure medical radionuclides.

TUM Department of Nuclear Medicine

The TUM Department of Nuclear Medicine is one of the largest Nuclear Medicine Departments in Europe. The Department has a long-standing experience in performing preclinical and clinical research in molecular imaging as well as therapeutic applications of new radiotheranostic tracers.

A specific strength of the department is the rapid translation of novel molecular imaging technologies to the clinic.

It operates radiochemistry facilities as well as preclinical and clinical imaging facilities for the testing and clinical translation of new radiopharmaceuticals. A description of these facilities and the services that the department offers to PRISMAP users can be found below.

Preclinical facilities

For housing animals treated with beta or alpha-emitting radionuclides. They are equipped with small animal imaging facilities (PET/MRI and SPECT/CT) for in vivo and in vitro characterisation of newly developed tracers.

Chemistry facilities

For radiolabelling with a variety of diagnostic and therapeutic radionuclides, including GMP facilities for clinical studies.

Clinical facilities


These are equipped with a dedicated treatment ward for radionuclide therapies of patients. Clinical trials are supported by a team of researchers within the department, that are highly experienced in the regulatory aspects of preforming clinical trials with radionuclides.

Services offered

  • Targeting agent and chelator development
  • Radiolabelling strategy and instrumentation for quality controls
  • Preclinical study
  • Chemical and radiochemical characterization
  • In vitro characterization of new radiotracers
  • In vivo characterization of new radiotracers
  • Toxicity/dosimetry studies
  • Regulatory documents
  • Radiopharmaceutical GMP manufacturing
  • Clinical trial

Radioisotope production at the Paul Scherrer Institute

The Paul Scherrer Institute (PSI) is Switzerland’s largest research insitute for natural and engineering sciences, conducting cutting-edge research in three main fields: matter and materials, energy and the environment and human health. PSI develops, builds and operates complex large research facilities. Every year, more than 2400 scientists from around the world come to PSI to use its unique facilities to perform experiments that are not possible anywhere else.

PSI runs a High Intensity Proton Accelerator (HIPA) amenity as part of its Large Facilities, where three accelerators are connected in series to increase proton beam energy. A Cockcroft-Walton accelerator accelerates protons at 870 keV to the Injector II separated sector cyclotron, where the protons are accelerated to 72 MeV at an intensity of ~2.5 mA to the Ring cyclotron. The Ring cyclotron accelerates the protons further to 590 MeV, which is then sent down the beam line to various experimental vaults, before the remainder of the beam is collected in a Pb beam dump, which serves as a neutron spallation source for the Swiss Neutron Source (SINQ).

Along the beam line between Injector II and the Ring cyclotron, the Radionuclide Development/production irradiation station (known as IP2) gleans ~50 μA protons from Injector II, by means of a beam splitter, into the IP2 target station. These protons irradiate various targets towards the production of exotic radionuclides intended for medical purposes.

Many radiometals currently used in nuclear medicine are for the diagnosis of disease, with the most popular means of detection being Positron Emission Tomography (PET). These positron emitters are easily produced at low proton energies using medical cyclotrons, however, development using such facilities are rare. The irradiation station at IP2 is used for ~8 months of the year and, as a result, is not considered for use in a commercial setting. The system is still put to good use, however, towards the development of novel, non-standard radiometals.

SINQ houses a ‘rabbit’ system for neutron irradiation of materials inserted into a beam tube. Two pairs of rabbit system tubes reach into the volume of the moderator vessel. The pair of tubes closest to the target (PNA) is utilized for radionuclide production and development, which includes the production of radioactive tracers towards developing chemical separation methods (thermal neutron flux: 2x1013 n cm–2s–1mA–1). Over the last decade, PNA has been predominantly used for the development and upscale of 161Tb production.

The Center for Radiopharmaceutical Sciences (CRS) is one of the few research organizations in Europe that is able to produce radiopharmaceuticals not only for research purposes but also for clinical trials. The Radionuclide Development group is a joint group between CRS and the Laboratory of Radiochemistry (LRC). The research focus of the group is on the production and chemical separation of novel radionuclides for innovative radiopharmaceuticals from targetry to preclinical applications. Radionuclide Development collaborates closely with other CRS research groups specializing in preclinical studies using novel radionuclides.

PSI is a partner of the PRISMAP consortium and avails its facilities for projects involving radionuclides such as 44/43Sc, 44Sc, 64Cu and 161Tb. PSI is also a Work Package leader in the development of novel radiolanthanides towards potential medical/preclinical research.

Recently, a large-facility grant proposal was submitted to the ETH Rat and Swiss National Science Foundation (entitled IMPACT -Isotope and Muon Production using Advanced Cyclotron and Target technologies; see https://www.psi.ch/impact). The concept involves the installation of a spallation and mass separation facility (ISOL) to allow production of high activities of radionuclides that are currently difficult to obtain (TATTOOS –TArgeted Tumour Therapy and Other Oncological Solutions). Should this proposal be granted, PSI will be preparing towards its construction and preparation, with the facility expected to be operational in mid-2028. It is aimed to produce desired alpha emitters towards radiopharmaceutical application and Targeted Alpha Therapy (149Tb initially, to be followed by 225Ra/225Ac).

The PRISMAP PhD Label – creating opportunities for young researchers

One of the main goals of PRISMAP is to create a sustainable, well-connected community of people working on all the aspects of medical isotopes from production and research to clinical applications. A key factor in making this community sustainable are the young researchers who are working on their PhD in the field. We are in the process of creating a PRISMAP PhD Label with the aim of establishing a quality label that will be recognised by higher education institutions in the field.

The PRISMAP Label will be awarded to PhD students who completed the requirements listed in the PRISMAP PhD Charter at the end of their PhD in recognition of their research achievements, transdisciplinary training, mobility and networking capacity, and breadth of professional and transferable skills. The PRISMAP PhD Label will thus become a recognisable label ensuring quality of training for the employer and employability for the students beyond their PhD. Get in touch if you think your higher education institution should be the first to sign on to the PRISMAP PhD Charter.

Additionally, as part of completing the requirements to obtaining the PRISMAP PhD Label and in order to create opportunities for students to network, candidates to the PRISMAP PhD Label will contribute short articles about their research or current events in the field to this newsletter. These contributions will form a community-run blog on the PRISMAP website where students can showcase their research. Click here to read the first contribution where Kaat Spoormans (SCK CEN/KU Leuven) is telling us about transitioning from radioisotope production research to modelling organ dosimetry with innovative isotopes.

A blink into the future: The SPES facility

The selective production of exotic species (SPES) facility is now under construction in Italy at the Legnaro National Laboratories of the National Institute for Nuclear Physics (LNL-INFN). The SPES facility will allow the production of Radioactive Isotopes for both Nuclear Physics Research and Nuclear Medicine. In the context of Medical Applications, two important projects have been developed taking as a common basis the SPES 70 MeV cyclotron; these projects are ISOLPHARM and LARAMED, and a brief description is proposed below.

The ISOLPHARM project aims at the production of a wide set of high purity radionuclides for medical use, either for diagnosis or for therapy, according to the Isotope Separation On-Line (ISOL) technique, an accelerator-based method currently being implemented at LNL-INFN. The ISOLPHARM project will, indeed, exploit the SPES Radioactive Ion Beams (RIBs) to produce high quality radioisotopes for radiopharmaceutical applications. The ISOLPHARM project will have the capability of producing a wide set of high purity (carrier-free) radionuclides for the research in the radiopharmaceutical field. Radionuclides of such a purity are highly required for the radiolabeling of ligands for therapy and diagnosis and the discovery of new radiopharmaceuticals. More information can be found at https://isolpharm.pd.infn.it/w....

The LAboratory of RADionuclides for MEDicine (LARAMED) project is one of the so-called “Progetti Premiali” (Awarded Projects) funded by the Italian Government through the Ministry of University and Research (MUR). The aim of LARAMED is the direct production, in good amount, of batches of different, medical-grade, radionuclides and radiopharmaceuticals, by using the proton beam provided by the SPES cyclotron useful for preclinical-clinical applications. Currently the LARAMED facility is under construction in the SPES building at LNL-INFN and it includes two bunkers devoted to the irradiation runs at low and high beam intensity (for nuclear cross section measurements and radionuclides production respectively) and dedicated laboratories aimed at target manufacturing and processing after irradiation (e.g. radiochemistry, γ-spectrometry, quality controls and the labelling of radiopharmaceuticals). LARAMED is also a “box” of scientific projects, funded by the INFN (CSN) and other Institutions, focused on specific radionuclides (99Mo/99mTc, 67Cu, 47Sc, 52/51Mn, 149,152,155,161Tb) and technology aspects (radiochemistry, targetry, etc.). Additional information can be found at https://www.lnl.infn.it/en/spes-laramed-range/.

Both ISOLPHARM and LARAMED will surely enrich the offer of different radioisotopes in the context of PRISMAP. The ISOLPHARM and LARAMED facilities are under construction and the commissioning phase will gradually start within the end of 2022 and will continue in 2023.

PRISMAP Survey

We welcome you to participate in our effort in creating the first European medical radionuclide infrastructure map with well-established distribution routes, expertise, harmonized legislation and research opportunities by filling this survey prepared by the PRISMAP Industrial collaboration team.

Take this opportunity to gain new research and international collaboration partners, benefit from harmonized supply and legislation procedures, expand Your network and distribution routes, and gain visibility within the PRISMAP User Forum map. Active respondents of the survey will be offered to participate in the preparation of the pooled results publication.

The survey consists of 3 branches and the subsequent questions are answer dependent:

  1. Radionuclide/ Radiopharmaceutical manufacturers and distributors;
  2. Research (including semi-academia) and education;
  3. Clinical user (hospitals, clinics, and professional organizations).

This survey is conducted to reach the following aims:

  • Identify key players in the industrial, research and clinical communities in the context of PRISMAP and investigate the needs of industrial, scientific and clinical end-users in nuclear medicine
  • Analyse the current facility profiles, geographic location, capabilities, licensing, logistics, future research and development perspectives, challenges, and needs for collaboration and improvement

Show more posts

PRISMAP newsletter features

The editorial content of our newsletter is available on this page.