Novel and upcoming medical radionuclides

In nuclear medicine, a radioactive substance is administered to the patient, which then travels to specific biological targets in the body. Depending on the radioactive properties of the radionuclide, the substance may emit radiation that can be detected with external detectors to visualize the distribution of the nuclide in question (SPECT, PET imaging); alternatively, the substance may emit charged particles such as α- or β-particles that deliver their energy locally (within micrometres to a few millimetres, i.e. from the size of a cell to the size of a metastasis), thereby destroying only cells in the vicinity, for example to treat a cancer with targeted radionuclide therapy (TRNT).

Of the more than 3000 different radionuclides that researchers have synthesized in the laboratory, only a handful are regularly used for medical procedures, mainly for imaging, although interest in TRNT has increased in recent years. One of the main difficulties in developing novel radio-medical products is access to radionuclides during the development and early biomedical research phases. In the context of Prismap - the European Medical Radionuclides Programme - can facilitate this development phase by providing access to novel radionuclides of high purity for medical research.

Generation of radionuclides

The radioactive elements used in nuclear medicine do not exist in nature and must be synthesized in the laboratory. There are two main routes: neutron irradiation in a nuclear research reactor or proton, deuteron or alpha irradiation with a particle accelerator. The size and energy of the particle accelerator determine which radionuclide can be produced: Small, compact devices are available in many hospitals and provide access to the radionuclides in use today. However, for the production of novel radionuclides, which are currently not available, devices with higher energy are needed.

Purification of radionuclides

New challenges arise in the production of these novel radionuclides: the simultaneous production of unwanted radioactivity that could affect the quality of the drug, have adverse effects on the patient and complicate waste management in hospitals. Therefore, novel purification techniques are needed. Within PRISMAP, techniques based on physical mass separation and radiochemistry are being developed to achieve high-purity radionuclide production suitable for pharmaceuticals.

Access and translational research

To support ongoing research across Europe and beyond, Prismap will provide immediate access to new radionuclides. A central access platform has been set up via the website to showcase production and support opportunities.

A network of world-leading European facilities, including nuclear reactors, medium- and high-energy accelerators and radiochemical laboratories, has been formed to offer the broadest possible catalogue of radionuclides for medical research. A mass separation facility is available at the Cern Medicis facility, allowing the physical separation of isotopes of an element. This is complemented by a network of biomedical research facilities that can host external researchers to carry out their research close to the production facility if the radionuclides are not suitable for long transport to their facility or if European approval for novel radionuclides has not yet been granted.

Access to the radionuclides and associated facilities will be granted on the basis of excellence selection. Access to the radionuclides and, where appropriate, to the complementary biomedical facilities will be requested via the Prismap online platform. A selection panel composed of experts in the fields of radionuclide production, molecular imaging and radionuclide therapy will select the best projects among the applicants. The first call for proposals will be launched before the end of 2021 and is expected to be published in the first quarter of 2022. It will be open to all interested parties.

A look into the future

In the rapidly evolving field of nuclear medicine, Prismap is also focused on the future. The European Commission is committed to tackling the societal impact of cancer through Europe's Beating Cancer plan and, in particular, the Samira action plan unveiled earlier this year, which includes the establishment of a European Radionuclide Valley Initiative. Through the Prismap consortium of 23 academic and research institutions across Europe, the development towards upscaling the production of these novel radionuclides is being explored in the form of novel production technologies, new purification methods and proof-of-concept studies. These will demonstrate the development of new treatments from the bench to patient care and feed directly into this Europe-wide plan.

Prismap Consortium

Prisma is a consortium serving a community of early-stage researchers, and aims to establish itself as a community and to host new facilities to extend the capabilities of the programme. New facilities such as the Jules Horowitz reactor at CEA Cadarache (France), the ISOL@MYRRHA mass separator facility at SCK CEN (Belgium), the new SPES accelerator complex at INFN National Laboratories in Legnaro (Italy) are emerging, the European Spallation Source at Lund (Sweden) and finally the new SPIRAL2 facility at GANIL (France), which has recently accelerated its first beams, and the FAIR facility at GSI (Germany), whose construction is progressing. These new facilities will benefit directly from the knowledge gained from Prisma and will help to increase production capacity throughout Europe.

Through the collaboration between research hospitals and metrology institutes, new data will be generated and compiled to allow an immediate and smooth introduction of the novel radionuclides in medicine. All new findings will be used to produce new educational material for professionals in the different fields of this multidisciplinary area, as well as for training the next generation of professionals and advising the European Commission on these novel radionuclides. 

PSI is main partner

The Paul Scherrer Institute is one of the main partners in the Prismap consortium. The researchers use its large-scale research facilities Spallation Neutron Source Switzerland SINQ and Injector 2 as well as the irradiation station IP2 to produce radionuclides for medical purposes. The radionuclides are coupled to a molecular complex, selectively dock onto tumour cells in the body and can destroy them with their particle radiation. The Centre for Radiopharmaceutical Sciences at PSI is one of the few research organisations in Switzerland that is able to develop radiopharmaceuticals not only for research purposes but also for clinical trials. The approval procedure for clinical trials with the promising therapeutic radionuclide terbium-161 is currently underway. In addition, as part of the new BFI project IMPACT (Isotope and Muon Production with Advanced Cyclotron and Target Technology), an upgrade of the high-intensity proton accelerator facility HIPA is planned for the period from 2024 to 2028 to enable the production of new radionuclides for diagnostics and therapy.

Nuclear medicine research is a multidisciplinary approach and progress requires bridges to be built between physicists, engineers, radiochemists, inorganic chemists, structural biologists, clinicians, medical physicists, dosimetrists, pharmacologists and oncologists. Prismap - the European Medical Radionuclides Programme - will support the implementation of a multidisciplinary approach to work in practice.

Source: Paul Scherrer Institute, text based on a communication from the Cern