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

Abstract

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-18, and it can be modified to produce red shifted fluorescence. In this study, therefore, we synthesized and investigated a F-18-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 '8F using SnCl (4) in high yield. Partition coefficients of BF-labeled BODIPY dye ([F-18]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-18]1 and 1, respectively. Hybrid PET/optical images of mice injected with optimal dose of [F-18]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-18]1 can be widely used as a prosthetic group for brain hybrid PET/optical imaging agents.