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Characterization of Uptake of the New PET Imaging Compound ¹⁸F-Fluorobenzyl Triphenyl Phosphonium in Dog Myocardium

¹ Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, Maryland; ² Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland; and ³ Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland

Correspondence: For correspondence or reprints contact: Igal Madar, PhD, JHOC 4230, 601 North Caroline St., Baltimore, MD 21287. E-mail: imadar{at}jhmi.edu

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.

Key Words: ¹⁸F-FBnTP • heart • PET • imaging

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