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

Delocalized lipophilic cations such as [ 18 F]fluorobenzyltriphenylphosphonium ([ 18 F]FBnTP) can accumulate in mitochondria and have been used in myocardial perfusion imaging (MPI). In this study, we established a simplified method for [ 18 F]FBnTP synthesis using triphenylphosphine hydrobromide (PPh 3 •HBr) without preparing an intermediate that contains benzyl bromide structure. Applying this new method, we synthesized and evaluated a novel 18 F‐labeled PEGylated BnTP derivative ([ 18 F]FPEGBnTP). In vitro cellular uptake study demonstrated that [ 18 F]FPEGBnTP accumulated in cells in proportion to the relative intensity of mitochondrial membrane potential. Biodistribution study revealed that the heart : liver uptake ratio of [ 18 F]FPEGBnTP (4.00 at 60 min) was superior to that of [ 18 F]FBnTP (1.50 at 60 min). However, [ 18 F]FPEGBnTP showed slow blood clearance and high radioactivity uptake in bone at 120‐min post‐injection. These results imply the possibility of [ 18 F]FPEGBnTP being used as a MPI agent. However, there is a need of further structural optimization and flow‐dependent uptake study.