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

Objectives PET/CT (positron emission tomography/computed tomography) imaging holds the promise of becoming a key diagnostic modality for cardiovascular diseases by allowing visualization and quantification of biochemical pathways, specific receptor targets, physiology and pathology. Despite its great potential, one of the major limitations is the availability of properly labeled PET probes. In this report, we discovered that ¹⁸F-labeled BODIPY dyes hold the great potential for PET myocardial perfusion imaging (MPI).

Methods ¹⁸F-Labeled BODIPY dyes were synthesized efficiently through a catalyzed fluoride exchange reaction that was developed in our group. The resulting compounds were first evaluated with cellular uptake assay and FACS in vitro, followed by biodistribution and micro-PET imaging studies in vivo.

Results After one step labeling, ¹⁸F-BODIPYs were obtained in more than 90% labeling yield with >95% radiochemical purity. The cellular uptake assay showed preferential uptake of ¹⁸F-BODIPY dye in HEK-293 cells, which was successfully reduced with high concentration of K+ ion. Biodistribution data demonstrated high levels of accumulation of ¹⁸F-BODIPY in the heart. In the biodistribution study, uptake of radioactivity 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 3 h post injection. Region of interest analysis of microPET images correlated well with biodistribution studies. The heart was clearly visualized in normal rat as well.

Conclusions ¹⁸F-BODIPYs showed prominent heart uptake and good heart to blood, heart to liver, and heart to lung ratios. The ¹⁸F-Labeled BODIPY dyes may represent a new category of cationic PET agents for characterizing myocardial blood flow.

Research Support This work has been supported by the National Science Foundation (CHE-0952912), the Welch Foundation (A-1423), the USC Department of Radiology, and the American Cancer Society (121991-MRSG-12-034-01-CCE).