The development of a new radiopharmaceutical is a long process, and several years are required for its introduction in clinical trials. Considering both the relevance of 111Ag as radiopharmaceutical precursor for its nuclear and chemical properties, and the promising results obtained with the previous two-years ISOLPHARM_Ag experiment, a new three-years proposal is presented, ISOLPHARM-EIRA aiming not only at strengthening the already achieved results, but also to go beyond them, by working towards the first in vitro and in vivo tests with radioactive silver.
Production of 111Ag
Radioactive silver nuclides were already successfully produced using a SPES UCx target prototype and delivered to experimental areas in dedicated experiments. However, since the SPES facility is not yet ready for the irradiation of fissile targets, the ISOL production of 111Ag will not be shortly possible. Traditional techniques are not suitable for the production of amounts of high purity 111Ag, except when enriched 110Pd target is irradiated in a nuclear reactor. Thus, to allow the performance of radiolabeling tests small quantities of 111Ag will be produced using the LENA reactor in Pavia.
Since the first batches of 111Ag for ISOLPHARM could be produced in a nuclear reactor through the 110Pd(n,γ)111Pd→111Ag reaction, a purification method for the extraction of Ag from a Pd target will be studied. Furthermore, being 110Pd isotopically-enriched targets very costly, the possibility to recycle the irradiated targets should be kept into consideration when designing the purification method.
Experiment with fluorescent probe and 111Ag
Small amount of 111Ag produced with the traditional method (i.e. with a nuclear reactor starting from enriched 110Pd), will be purified and will be exploited for studying the performance of the most promising chelators. Reaction conditions (pH, time, temperature and amount of chelators) will be studied and optimized. Stability of the complexes over time and in different physiological media will be assessed as well. Finally, the results obtained in tests with fluorescent probes as prescreening CCK2R targeting molecules and in vivo imaging with 111Ag radiolabeled compound will be merged in order to design an optimized compound.