Radiosynthesis and preliminary biological evaluation of a new ¹⁸F-labeled triethylene glycol derivative of triphenylphosphonium

Delocalized lipophilic cations such as [¹⁸F]fluorobenzyltriphenylphosphonium ([¹⁸F]FBnTP) can accumulate in mitochondria and have been used in myocardial perfusion imaging (MPI). In this study, we established a simplified method for [¹⁸F]FBnTP synthesis using triphenylphosphine hydrobromide (PPh₃•HBr) without preparing an intermediate that contains benzyl bromide structure. Applying this new method, we synthesized and evaluated a novel ¹⁸F-labeled PEGylated BnTP derivative ([¹⁸F]FPEGBnTP). In vitro cellular uptake study demonstrated that [¹⁸F]FPEGBnTP accumulated in cells in proportion to the relative intensity of mitochondrial membrane potential. Biodistribution study revealed that the heart: Liver uptake ratio of [¹⁸F]FPEGBnTP (4.00 at 60 min) was superior to that of [¹⁸F]FBnTP (1.50 at 60 min). However, [¹⁸F]FPEGBnTP showed slow blood clearance and high radioactivity uptake in bone at 120-min post-injection. These results imply the possibility of [¹⁸F]FPEGBnTP being used as a MPI agent. However, there is a need of further structural optimization and flow-dependent uptake study. A ¹⁸F-PEGylated derivative of benzyltriphenylphosphonium ([¹⁸F]FPEGBnTP) was synthesized through the reaction of the ¹⁸F-PEGylated benzyl alcohol intermediate with triphenylphosphine hydrobromide. [¹⁸F]FPEGBnTP showed higher accumulation in the heart than the organs near the heart.