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.
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:
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 (firstname.lastname@example.org; PRISMAP Dissemination Manager) or to Charlotte Duchemin (email@example.com; 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:
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.
By Erika Jajcisinova – When I discovered physics at school, it was love at first sight. All these theories explaining everything around us. During my bachelor and master's studies at Comenius University in Bratislava, I developed an interest in nuclear physics. After completing my master thesis in nuclear structure, I noticed that I was missing something. I knew that I wanted to help people and one of the ways was through nuclear medicine. The way how these "invisible" particles can diagnose diseases and treat humans may seem like magic to many.
When I saw the opportunity to collaborate with top institutions, KU Leuven and Joint Research Centre in Karlsruhe, I couldn't resist. This PhD topic was exactly what I was looking for. After starting my PhD, I got introduced to this field. I learned about so many ways how nuclear physics can be used for diagnostics and treatment. What was even more appealing is the space for improvement. The PRIMAP community is a great idea. The research in novel techniques for theragnostic purposes is still ongoing and connecting research centres all across Europe. It supplies radionuclides to all the people that show interest. I am blessed to be a part of such a strong collaboration.
In my research, I am focussing on the production of Ac-225 for applications in nuclear medicine specifically for targeted alpha therapy. In this field, Lu-177 is widely used as radionuclide. As I mentioned before, there is still space for improvement. One of the options is Ac-225. This isotope decays by emitting 4 alpha particles with energies between 5-6 MeV that deposits their energy in a very short range at the end of their path. Because of this, they provide better energy deposition in the cancer cells and the amount of activity used for such treatment was significantly decreased. As expected, Ac-225 showed better efficacy than Lu-177 in the clinical studies. This started an extreme rise in demand which went faster that the current production. Many research facilities are trying to find a way how to increase the production of this isotope.
During my PhD studies, I am trying to find a way how to increase this production. Firstly, by exploring the production way of highly energetic proton interaction with Uranium Carbide target using the ISOL method at CERN-ISOLDE. The aim is to characterise and optimise production and determine the possible contribution to the supply. Another way that I plan to investigate is the production of Ac-255 from the Ra-226 target. This target can provide direct and indirect supply of actinium. This would open many more ways of increasing production and making it available in many medical centres across the world.
Thanks to the support and collaboration of all these institutions, I hope we will help to meet the demand soon and make this treatment available for everyone who needs it.
Erika earned her Master’s degree in Nuclear Physics from Comenius University in Bratislava, Slovakia in 2022. She recently started her PhD studies at KU Leuven, Belgium in the interdisciplinary group of the Institute for Nuclear and Radiation Physics (IKS). To gain even more expertise, she will spend half of her time at the Joint Research Centre of the European Commission in Karlsruhe, Germany. Her graduate work focusses on increasing the supply of Ac-225 radionuclide for use in nuclear medicine.
PRISMAP – The European medical radionuclide programme is now active for more than a year. Tremendous work has been made to set up the whole organisation scheme, which is now effective and working every day to promote the availability of non-conventional radionuclides at the European level, and ease their use in the coming years.
This is a very important achievement as the interest and use of a radionuclide depends in part to its physical and chemical characteristics but mostly on its availability. Availability is a key concern and especially for non-conventional radionuclide that, at the beginning, are produced in a limited number of centres and interest only few end-users.
On one side, to launch the production of a novel radionuclide, as a producer, potential users are contacted. Before joining a programme, those users discuss the future availability to see if it will be compatible with a potential clinical trial in terms of activity and quality. They are also very keen on redundancy and consistency of quality among the limited number of producers. It is then often difficult to raise their interest in novel radionuclides. On the other side, when a user asks to a producer about a novel radionuclide, the latter studies the potential market and, as it is often limited at the beginning, he is reluctant to start developing it.
Thanks to PRISMAP - The European medical radionuclide programme, this chicken and egg situation can be solved. Production centres all over Europe have come together to propose novel radionuclides to interested users through a call for project standing every 6 month during the duration of the project (link to 3.4 PRISMAP’s first call and 3.5PRISMAP’s second call). For most novel radionuclides, several production centres can provide them allowing whole year availability. In parallel, in-depth work is conducted on specifications and product comparisons to ensure quality (link to 3.7 Standards for clinical translation). Having in mind the quality of service, PRISMAP’s team launched a survey to identify the needs of the scientific community through a survey (link to 3.1PRISMAP survey) and also looked to the too often forgotten aspect of transportation (link to radionuclide transport and logistics) that is very important in the case of radioactive material. Finally a strong training programme is being set-up to make researchers from physics, chemistry, biology, pharmacy, and medicine acquainted to the use to these novel radionuclides (link to 6.Training Office).
All these aspects are illustrated in the present newsletter. By working at the same time on all these aspects, we intend to make novel-radionuclides more readily available and expect to strongly support developments of molecular imaging, internal targeted therapy, and the theranostic approach in nuclear medicine.
The PRISMAP consortium meeting 3 was organized by the team from the University of Latvia (LU) and gathered 23 participants in Riga, Latvia on-site at LU Campus (Science building) and 49 participants on-line on June 13-16th, 2022.
This forum brought together existing PRISMAP consortium partners and advisors, as well as industrial partners for best strategies on how to build the united network of available and novel radionuclides/radiopharmaceuticals in Europe.
Four days of discussions included invited speakers from the UK, USA, Austria, and Spain who highlighted the importance of this initiative for the emerging infrastructures, clinical community, and patients.
The first call for innovative and collaborative projects applications was described as very successful with high interest during the public event (attended by more than 100 participants).
The industrial and clinical collaboration is evolving as shown by growing participation in the PRISMAP survey (see map) and more than 75% of respondents confirm the necessity of PRISMAP as the way to unite the radionuclide manufacturing, researcher and end user communities.
A public event was held to also exchange with our users, entitled PRISMAP grows up; the recording is available online. We presented some of the recent achievements of PRISMAP, especially concerning the training resources (detailed below), our first public results, and our online communication platforms.
We invited a few of the applicants from our first call to share their experience and present to all what their research entails, as much to inspire as to show the breadth of fields of research that can be covered within PRISMAP. We concluded the public event with a round table on how to target communities or regions that are not yet involved with PRISMAP. If you feel your colleagues could be interested, feel free to share this newsletter and invite them to join the user forum!
A session titled Science, opportunities without borders was dedicated to the networking importance and impact of global events on the availability of radionuclides, complemented by a discussion on recent efforts on how to ensure the security of supply of radioisotopes.
The social programme was organized by prof. Maija Radzina (radiologist, Latvia) and her team Edgards Mamis and Laura Saule, and included a visit to the Riga Cyclotron/PET centre – NUCLEO (18MeV). Each evening event was a delightful experience with variety of local cuisine and sightseeing opportunities, guided by local organizers, such as an Old Riga walking tour, seaside walk with early summer swimming event, and sunset in the Baltic Sea.
Twelve user proposals from seven different countries, requesting eleven different radionuclides, were received for the first PRISMAP call, thereunder two proposals that requested access to PRISMAP medical facilities and ten that requested delivery of PRISMAP radionuclides to their user laboratory. The eleven-headed PRISMAP user selection panel, led by Cornelia Hoehr (TRIUMF, Canada), analysed the proposals in terms of scientific excellence, project implementation, expected outcome, and competences of the research team.
After a first preselection, nine proposals qualified for the next step. The panel then discussed details with the proposers per email and video conference. In particular, the selection of adequate radionuclides and frequency of delivery was discussed with the proposers to optimize the efficient use of PRISMAP radionuclides. While PRISMAP does propose a wide range of radionuclides, the available activities and frequency of production do vary considerably. E.g., for the quadruplet of terbium isotopes, the longer-lived 161Tb and 155Tb are available more frequently and at higher activities than the shorter-lived 152Tb and 149Tb. It is therefore strongly recommended to structure projects as to perform basic research on Tb radiolabelling or pharmacokinetic studies rather with the longer-lived isotopes, while keeping the shorter-lived ones for a later stage when the individual decay properties are really essential for a given application. If you have any question on how to shape your own project, don’t hesitate to contact our helpdesk!
Eventually all nine preselected proposals were approved, but sometimes only a first part up to a milestone where the feasibility of the full programme can be further assessed. The successful proposers (from BE, DE, ES, FR and IT) were informed of the outcome and user agreements with the supplying or hosting PRISMAP facilities were prepared. You can browse the public summary of the selected projects on our website.
PRISMAP, the European Medical Radionuclide Programme, 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, brought together members of PRISMAP, professionals from industry, regulatory bodies, and overseas experts. It provided the basis for a dedicated document, which gives guidance for the early phase clinical research with novel radionuclides. It describes the current standards and provides a harmonised view of the European regulatory framework thereby complementing the existing regulatory framework without being legally binding.
The document includes terms and nomenclature for quality specifications of novel radionuclides within PRISMAP, followed by major aspects in production of radionuclides and the implementation of good manufacturing practices (GMP). The subsequent chapters cover quality specifications and quality control, with a designated chapter on metrology and medical physics aspects in clinical translation. The final chapter describes non-clinical safety and pharmacology aspects and provides an overview of the current regulatory guidance documents for preclinical testing.
This guidance document from the PRISMAP consortium serves as an essential and comprehensive source 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. The document can be found amongst our published reports.
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!