Characterization of uptake of the new PET imaging compound 18F-fluorobenzyl triphenyl phosphonium in dog myocardium.

UNLABELLED 18F-Labeled p-fluorobenzyl triphenyl phosphonium cation (18F-FBnTP) is a member of a new class of positron-emitting lipophilic cations that may act as myocardial perfusion PET tracers. Here, we characterize the 18F-FBnTP uptake and retention kinetics, in vitro and in vivo, as well as the myocardial and whole-body biodistribution in healthy dogs, using PET. METHODS Time-dependent accumulation and retention of 18F-FBnTP in myocytes in vitro was studied. Seven anesthetized, mongrel dogs underwent dynamic PET scans of the heart after intravenous administration of 126-240 MBq 18F-FBnTP. In 4 of the 7 dogs, at the completion of a 60-min dynamic scan, whole-body scans (4 bed positions, 5-min emission and 3-min transmission per bed) were acquired. Arterial blood samples were collected at 0, 5, 10, 20, 30, and 60 min after administration, plasma activity was counted, and high-performance liquid chromatographic analyses for metabolites were performed. The extent of defluorination was assessed by measuring 18F-FBnTP bone uptake in mice, compared with 18F-fluoride. RESULTS The metabolite fraction comprised <5% of total activity in blood at 5 min and gradually increased to 25% at 30 min after injection. In vivo, 18F-FBnTP myocardial concentration reached a plateau level within a few minutes, which was retained throughout the scanning time. In contrast, activity in the blood pool and lungs cleared rapidly (half-life = 19.5 +/- 4.4 and 30.7 +/- 11.6 s, respectively). Liver uptake did not exceed the activity measured in the myocardium. At 60 min, the uptake ratios of left ventricular wall to blood, lung, and liver (mean of 7 dogs) were 16.6, 12.2, and 1.2, respectively. Summation of activity from 5 to 15 min and from 30 to 60 min after injection produced high-quality cardiac images of similar contrast. Circumferential sampling and a polar plot revealed a uniform distribution, near unitary value, throughout the entire myocardium. The mean coefficient of variance, on 30- to 60-min images along the septum-to-anterior wall and the apex-to-base axes was 7.58% +/- 1.04% and 6.11% +/- 0.89% (mean +/- SD; n = 7), respectively, and on 5- to 15-min images was 7.25% +/- 1.43% and 6.12% +/- 1.88%, respectively. 18F-FBnTP whole-body distribution was highly organ specific with the kidney cortex being the major target organ, followed by the heart and the liver. CONCLUSION 18F-FBnTP is a promising new radionuclide for cardiac imaging using PET with rapid kinetics, uniform myocardial distribution, and favorable organ biodistribution.