Preparation and biological evaluation of radioiodine‐labeled triphenylphosphine derivatives as mitochondrial targeting probes

The positive‐charged lipophilic triphenylphosphonium cations (TPPs+) have been served as mitochondrial targeting vehicles for the delivery of various probes. In this study, we developed a new method for the preparation of radioiodine‐labeled TPPs+. Four 125I‐labeled TPPs+, [125I] 9–[125I] 12, were prepared from the corresponding triphenylphosphine phenylborate precursors of B 5–B 8 via an optimized copper‐catalyzed one‐step procedure in high radiochemical yield (>95%). After radio‐HPLC purification, the final products could be obtained with high specific activity. Their physicochemical properties, in vitro cellular uptake, and ex vivo mice biodistribution were investigated. The results suggested the 125I‐labeled TPPs+ were lipophilic and could specifically accumulate in the mitochondrial‐rich myocardial cells through the mitochondrial membrane potential. Four 125I‐labeled TPPs+, [125I] 9–[125I] 12, were successfully synthesized in high radiochemical yield (>95%) via an optimized copper‐catalyzed one‐step radioiodination method. The results of biological evaluation suggested that the 125I‐labeled TPPs+ could specifically accumulate in the mitochondrial‐rich myocardial cells through the mitochondrial membrane potential.