Synthesis-free PET imaging of brown adipose tissue and TSPO via combination of disulfiram and (64)CuCl(2)

PET imaging is a widely applicable but a very expensive technology. On-site synthesis is one important contributor to the high cost. In this report, we demonstrated the feasibility of a synthesis-free method for PET imaging of brown adipose tissue (BAT) and translocator protein 18 kDa (TSPO) via a combination of disulfiram, an FDA approved drug for alcoholism, and (64)CuCl(2) (termed (64)Cu-Dis). In this method, a step-wise injection protocol of (64)CuCl(2) and disulfiram was used to accomplish the purpose of synthesis-free. Specifically, disulfiram, an inactive (64)Cu ligand, was first injected to allow it to metabolize into diethyldithiocarbamate (DDC), a strong (64)Cu ligand, which can chelate (64)CuCl(2) from the following injection to form the actual PET tracer in situ. Our blocking studies, western blot, and tissue histological imaging suggested that the observed BAT contrast was due to (64)Cu-Dis binding to TSPO, which was further confirmed as a specific biomarker for BAT imaging using [(18)F]-F-DPA, a TSPO-specific PET tracer. Our studies, for the first time, demonstrated that TSPO could serve as a potential imaging biomarker for BAT. We believe that our strategy could be extended to other targets while significantly reducing the cost of PET imaging.