Synthesis-free PET imaging of brown adipose tissue and TSPO via combination of disulfiram and 64CuCl2

• Type of Material: Article
• Authors: Jing Yang, Massachusetts General Hospital; Jian Yang, Massachusetts General Hospital; Lu Wang, Massachusetts General Hospital; Anna Moore, Massachusetts General Hospital; Steven Huan Liang, Emory University; Chongzhao Ran, Massachusetts General Hospital
• Language: English
• Date: 2017-12-01
• Publisher: Nature
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2017
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41598-017-09018-2
• Title of Journal or Parent Work: Scientific Reports
• Volume: 7
• Issue: 1
• Start Page: 8298
• End Page: 8298
• Grant/Funding Information: This work was supported by NIH/NIDDK R56DK108813 award (C.R.).
• Keywords: Positron-Emission Tomography; Receptors, GABA; Protein Binding; Animals; Molecular Imaging; Biomarkers; Copper Radioisotopes; Mice; Adipose Tissue, Brown; Ligands; Disulfiram
• Research Categories: Chemistry, Organic; Health Sciences, Radiology

Abstract

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 64CuCl2 (termed 64Cu-Dis). In this method, a step-wise injection protocol of 64CuCl2 and disulfiram was used to accomplish the purpose of synthesis-free. Specifically, disulfiram, an inactive 64Cu ligand, was first injected to allow it to metabolize into diethyldithiocarbamate (DDC), a strong 64Cu ligand, which can chelate 64CuCl2 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 64Cu-Dis binding to TSPO, which was further confirmed as a specific biomarker for BAT imaging using [18F]-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.