Radiosynthesis and evaluation of 18F-labeled aliphatic phosphonium cations as a myocardial imaging agent for positron emission tomography

IntroductionLipophilic cations such as phosphonium cations penetrate the hydrophobic barriers of the plasma and mitochondrial membranes and accumulate in the mitochondria in response to negative inner-transmembrane potentials. The present study reports the radiosynthesis and evaluation of F-18-labeled aliphatic triphenylphosphonium cations as a potential agent for myocardial imaging by using PET.Materials and methods(7-[F-18]fluoroheptyl)triphenylphosphonium salt ([F-18]3) and (8-[F-18]fluorooctyl)triphenylphosphonium salt ([F-18]6) were radiolabeled by means of two-step nucleophilic substitution reactions. We measured the log P value of [F-18]3 and [F-18]6 to assess the appropriate range of lipophilicity for their suitability as PET myocardial imaging agents. Normal rats were imaged with microPET after intravenous injection of 37MBq of [F-18]3 and [F-18]6. To determine the pharmacokinetics, a region of interest was drawn around the heart, and time-activity curves of [F-18]3 and [F-18]6 were generated to obtain the counts per pixel per second.ResultsThe radiolabeled compounds [F-18]3 and [F-18]6 were synthesized with 18-25% yield. The radiochemical purity was greater than 98% on the basis of the analytical high-performance liquid chromatography system, and the specific activity was greater than 160-170Ci/mmol. The log P value of the tracers was 2.520.01 ([F-18]3) and 2.91 +/- 0.02 ([F-18]6). Myocardium-to-liver ratios of [F-18]3 and [F-18]6 were 2.59 and 1.07, respectively, 10min after injection, whereas the myocardium-to-lung ratios were 5.57 and 3.35, respectively. In addition, [F-18]3 and [F-18]6 showed intense, homogenous uptake in the myocardium.Conclusion(18)F-labeled aliphatic phosphonium cations [F-18]3 and [F-18]6 might have potential as novel myocardial agents for PET and could prove useful in clinical cardiac PET/computed tomography applications.