TF1: Innovative radionuclides
Besides using carbon-11 and fluorine-18, several radionuclides were identified as having potential for the development of radiopharmaceuticals in oncology and neurology. They are copper-64, scandium-44, zirconium-89, gallium-68 for PET imaging and astatine-211, copper-67, scandium-47 for radionuclide therapy. With the exception of gallium-68 available from different companies as a Ge/Ga generator, the availability of other radionuclides is strongly dependent on the ability of the IRON Labex’s partners to produce them in sufficient amounts and adequate qualities.
The objective of TF1 is to develop the production of radionuclides of interest within the constraints associated with the development of radiopharmaceuticals (production under Good Manufacturing Practices - GMP). This requires, as applicable, the measurement of the cross sections of production, the development of targets, the optimization of irradiation parameters, and the development of extraction radiochemistry and characterization of radionuclide produced.
Within the context of the IRON Labex, two cyclotrons will produce these radionuclides: ARRONAX in Nantes and CYRCé in Strasbourg. Regular exchanges on GMP will be held with other biomedical cyclotrons involved in the project (Caen, Tours, Toulouse).
TF2: From chemistry to drug formulation
Access to radiopharmaceutical is an essential prerequisite for molecular imaging and targeted radionuclide therapy. TF2 is interested in the development of these drugs, from their conception to formulation for in vivo injection, in order to exploit them later on in imaging or therapy in the IRON Labex’s WPs.
A key objective of this TF is to develop and optimize the synthesis and radiochemistry of radionuclides available or in development within the consortium (11C, 18F, 47Sc, 64Cu, 67Cu, 68Ga, 89Zr, 188Re, 211At …). Radiolabeling, which is a major focus of TF2 is coupled to multiple scientific fields that use synthetic chemistry (of various structures: aromatic, heterocyclic, peptides, carbohydrates, nucleoside or complexing, used as radiolabeling precursors), coordination chemistry (metals and lanthanides), bioconjugation and vectorization. Studies on structure-activity relationship and modeling, analytical chemistry and radiosynthesis automation are also crucial disciplines of this TF. All of the innovations from the TF2 should contribute to the development of innovative radiopharmaceuticals for diagnostic applications and therapy.
In general, TF2 is based on methodological and technological research for fundamental studies as well as industrial transfers. It also takes into account the regulatory aspects of radiopharmacy for GMP production of radiopharmaceuticals for clinical trials.
TF3: Preclinical assessment
The new radioactive molecules generated in TF1 and TF2 must be validated in preclinical models, at both cellular and animal levels. These preclinical models are required to demonstrate the effectiveness of new radiopharmaceuticals, evaluate their distribution and toxicity, and compare them with the reference molecules. The rodents immunocompetent or not are frequently used because they allow to work on substantial cohorts in a limited time. Teams of the IRON Labex also develop models of dogs and primates which are more closer to phase I/II clinical trials.
The objective of this TF is to develop a common strategy to analyze radiopharmaceutical candidates dedicated to imaging (PET, SPECT or multimodal) and therapy in oncology and neuroscience.
Specific models are set up: Alzheimer’s disease, neuroinflammation, cerebral ischaemia, hypoxia models. In oncology, the IRON Labex has many tumor models (prostate, breast, lung, liver, bone marrow thyroid cancer, multiple myeloma). A particular objective is the development of models of glioblastoma in different species.
TF4: Clinical transfer
The objective of TF4 is to ensure the transition from preclinical to clinical work from the WP1 (functional imaging of neurological diseases), WP2 (functional and phenotype imaging in neurology and oncology) and WP3 (nanomedicine and radionuclide therapy). To this aim, TF4 combines not only administrative skills (Radiopharmacy, correspondence with ASN (Nuclear Safety Authority) and ANSM (National Security Agency of Pharmaceuticals)), but also medical technology competences (PET acquisition and therapy platforms) and clinical expertises (clinical investigation centers, hospital services). The clinical transfer of TF4 involves both clinical pilot studies of first administration in man (Phase 1) and multicenter clinical protocols in order to answer to specific clinical questions in neuroscience and oncology.
In neuroscience, the main ongoing issues relate to dementia (clinical trials on amyloid plaques, development of tracers for tau protein and vesicular acetylcholine transporter), and stroke (neuroinflammation, ischemia, development of tracers to explore neuronal death).
In oncology, several clinical trials are already underway for different cancers (breast, lung, thyroid, myeloma and carcinoma …).
TF5: Social and human sciences
Since several years, nuclear medicine is undergoing strong development related to medical innovations in this area. Related research plays an important role by providing new knowledge for the purpose of diagnosis and therapy in the field of production of new radionuclides and imaging techniques. These innovations are very sensitive because they are structured in an environment of beliefs and representations associated with radioactivity, heavy regulatory burden and a health care system undergoing profound change (new public management). Thus, nuclear medicine covers important issues that arise at different levels: societal, organizational and individual.
TF5 has two approaches of analysis:
- The first is to characterize and understand the risks associated with the production and administration of radiopharmaceuticals for all stakeholders of nuclear medicine.
- For health professionals, what is their relation to the risks associated with low doses, what are the effects on their professional practices and modalities of cooperation?
- For the patient, what are the risk representations and perceptions regarding nuclear medicine and its characteristics, and what is the impact of these dimensions on the experience of nuclear imaging in the pathway of care?
- The second concerns the innovation process. It aims at providing a research on:
- The process of hybridization of the ARRONAX cyclotron, identification of tensions and effects on innovation.
- The establishment of an imaging collaborative platform between the teams of the IRON Labex.