Cyclotron-Production of 51/52Mn Isotopes: the METRICS Project Final Report

The METRICS (Multimodal PET/mRi Imaging with Cyclotron-produced 52/51Mn and stable paramagnetic Mn iSotopes) has been a 3+1 years (2018-2021) research project, funded by INFN-CSN5 and led by the Legnaro National Laboratories, which goal was to develop the R&D technology to get a cyclotron-driven 52/51Mn radionuclide production aimed at the so-called Multi-Modality Imaging (MMI), in the framework of LARAMED project at LNL [1]. We briefly recall here that MMI is the modern diagnostic approach in clinics which combines the different imaging modalities, due to different physical processes, to collect a better diagnostic information. As an exemplum giving, when combining PET (Positron Emission Tomography) or SPECT (Single Photon Emission Computed Tomography) with CT (Computed Tomography) or MRI (Magnetic Resonance Imaging), MMI allows to pair functional and molecular information, obtained by PET or SPECT, with anatomical information got by using imaging techniques, such as CT and MRI. While functional imaging through PET or SPECT always requires the administration of a radiolabeled tracer, anatomical imaging through MRI or CT involves the administration of a contrast agent to achieve the highest signal to noise ratio. However, so far radiolabeled tracer and contrast agent have always different chemical nature and therefore follow different biological pathways, which lead to an unavoidable mismatch about the content of the diagnostic information. The only way to achieve a genuine molecular fusion between PET/SPECT and MRI information, collected by both the contrast and the radioactive probe, is that they should be chemically identical. It is therefore interesting to seek for an element having paramagnetic properties, useful as an MRI contrast agent, and providing some radioactive isotopes as well, suitable for PET/SPECT scans. These requirements are met by the transition element manganese, having both paramagnetic properties and some β+-emitting radioisotopes, such as 52Mn (t1/2=5.591d, I=29.6%, E(β+)avg= 244.6 keV), 52mMn (t1/2= 21.1 min, I=96.6%, E(β+)avg = 1179 keV) and 51Mn (t1/2= 45.59 min, I=97.1%, E(β+)avg = 970.2 keV). Aim of METRICS project, has been therefore to seek for physics/chemistry/radiopharmaceutical conditions able to develop a perfect molecular matching between PET and MRI by using paramagnetic and radioactive manganese isotopes, to afford an unprecedented type of PET/MRI hybrid imaging modality. Moreover, to develop all the needed technology, i.e., dedicated targets, optimization of the proper radiochemical separation methods and, at last, the development of new Mn(II)-complexes, with the aim to get a cyclotron-based 52Mn production. What follows is a concise summary of the project main outcomes achieved. Specific details of the METRICS project may be found in former editions of the Annual Report.