The production and chemistry development of new radioisotopes are important steps in designing radiopharmaceuticals for nuclear imaging applications. Titanium-45 (45Ti) is a novel radionuclide with desired physical characteristics for use in PET imaging including a moderate half-life (3.08 hour), decay by positron emission (85%) and low mean positron energy of 0.439MeV. Despite these promising characteristics, the radiochemistry for 45Ti including the development of suitable bifunctional chelators is relatively unexplored. Building on our prior work on optimized production techniques for 45Ti, we aimed to explore chelators which bind efficiently under mild conditions and form complexes which are stable in vivo. Radiolabeling studies of 45Ti were carried with two different chelators (THPMe and TREN-CAM). Radiochemistry optimization was conducted by incubating 500uCi 45Ti with chelators at varying mass and pH conditions. Serum stability studies were performed in mouse serum. In vivo imaging studies were performed with both THP and TRENCAM labeled with 45Ti and free 45Ti. Dynamic PET scans were conducted for 1 hour after injection and biodistribution studies were performed immediately after imaging. Radiolabeling optimization have shown significant binding of THPMe and TRENCAM with 45Ti is possible with high radiolabeling yields (&gt;95%) for both THPMe and TRENCAM achieved within 30 minutes of incubation at 370C. Excellent serum stability of 45Ti with labeled chelators was observed where &gt;95% labeled complex was intact after 6 hours of incubation. Tissue biodistribution studies demonstrated that the complexes showed rapid clearance and significantly lower 45Ti in heart, lung and other key organs compared to free 45Ti. This study has opened new possibilities of establishing 45Ti as a novel radionuclide which hold promise for future investigations.

Titanium-45 radiochemistry with THPMe and TREN-CAM for development of PET radiopharmaceuticals

ACS Spring 2022

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