18 F-Labeled BODIPY Dye: A Potential Prosthetic Group for Brain Hybrid PET/Optical Imaging Agents

There are few hybrid positron emission tomography (PET)/fluorescence imaging agents available for brain imaging. For this purpose, BODIPY dye is very attractive because one of its fluorine atoms can be readily exchanged with F, and it can be modified to produce red-shifted fluorescence. In this study, therefore, we synthesized and investigated a F-labeled red-shifted BODIPY dye as a prosthetic group for brain hybrid PET/optical imaging agents and determined the optimal dose of this radioligand for hybrid imaging. The red-shifted BODIPY dye (1) was synthesized, and one of its fluorine atoms was exchanged with F using SnCl in high yield. Partition coefficients of F-labeled BODIPY dye ([ F]1) and 1 were measured using its radioactivity and fluorescence, respectively, which were shown to be suitable for brain penetration. Optimal dose for hybrid imaging was determined by analysis of PET/CT and optical images of Balb/C nude mice injected with [ F]1 and 1, respectively. Hybrid PET/optical images of mice injected with optimal dose of [ F]1 showed strong radioactivity and fluorescence signal in the brain at 2 min after injection, with rapid clearance by 30 min. Tissue distribution data confirmed the in vivo and ex vivo PET/optical imaging data, indicating desirable brain pharmacokinetics of the radioligand. Taken together, the results of this study suggest that [ F]1 can be widely used as a prosthetic group for brain hybrid PET/optical imaging agents.