Evaluation of ¹⁸F-labeled BODIPY dye as potential PET agents for myocardial perfusion imaging

Despite the great potential of positron emission tomography/computed tomography (PET/CT) in cardiovascular disease imaging, one of the major limitations is the availability of PET probes with desirable half-lives and reasonable cost. In this report, we hypothesized that lipophilic cationic BODIPY dye could be selectively accumulated in cardiac muscle, possibly for the development of novel PET myocardial perfusion imaging (MPI) probes.

A (18)F-labeled BODIPY dye ([(18)F]1) was synthesized efficiently through a fluoride exchange reaction catalyzed by the Lewis acid tin chloride (SnCl₄). The compound was first evaluated by a cellular uptake assay in vitro, followed by biodistribution and microPET imaging studies in vivo.

[(18)F]1 was obtained in more than 90% labeling yield, with >98% radiochemical purity. The HEK-293 cellular uptake assay showed that the preferential uptake of [(18)F]1 could be related to the cell membrane potential. The biodistribution data demonstrated high levels of [(18)F]1 accumulation in the heart. In the biodistribution study in mice, the radioactivity uptake in the heart, blood, liver and lung was 3.01 ± 0.44, 0.39 ± 0.09, 0.69 ± 0.07, 1.71 ± 0.27%ID/g, respectively, at 3h post-injection (p.i.). The heart-to-lung and heart-to-liver ratios are 1.76 ± 0.14 and 4.37 ± 0.51 at 3h p.i., respectively. Volume-of-interest analysis of the microPET images correlated well with the biodistribution studies in mice. The heart was clearly visualized in normal rats, with 0.72 ± 0.18, 0.69 ± 0.18, 0.67 ± 0.20 and 0.59 ± 0.17%ID/g uptake at 0.5, 1, 2 and 4h p.i., respectively.

(18)F-labeled BODIPY dye showed good heart uptake and heart-to-blood and heart-to-lung contrast. A (18)F-labeled BODIPY dyes may represent a new category of cationic PET agents for myocardial perfusion imaging.