A new chelator-free multifunctional [64Cu]CuS nanoparticle platform for simultaneous µPET/CT imaging and radiotherapy

410 Objectives The efficacy of 64Cu as a radioisotope for positron emission tomography (PET) imaging and radiotherapy have been recently established. The purpose of this study was to synthesize and evaluate a novel class of chelator-free [64Cu]CuS nanoparticles (NPs) suitable for both PET imaging and as a radiopharmaceutical agent for radiotherapy. Methods [64Cu]CuS NPs were synthesized and characterized with regard to size, radiolabeling efficiency, stability, and imaging properties. For radiotherapy study, nude mice bearing s.c. BT474 breast cancer were injected intratumorally at a dose of 200 µCi/tumor (~3 x 1014 nanoparticles in 50 µL). Results [64Cu]-CuS NPs possessed excellent stability and were simple to make. Compare to the traditional radiolabeling technique, 64Cu was an integral component of CuS NPs, which obviates the need to introduce radiometal chelators to the surface of NPs. High quality in vivo PET images was obtained after intravenous injection of [64Cu]-CuS NPs that passively target tumor. Tumor-growth inhibition was significantly greater in mice injected with a single dose of [64Cu]-CuS NPs than in mice injected with control agents. Conclusions The combination of small size, extremely high labeling efficiency, and integration of 64Cu as one of the structural components of CuS NPs makes [64Cu]CuS NPs ideally suited for multifunctional molecular imaging and radiotherapy applications