Radiosynthesis of 11-[¹⁸F]fluoroundecyltriphenylphosphonium (MitoF) as a potential mitochondria-specific positron emission tomography radiotracer

Abstract

Changes in the magnitude of the mitochondrial membrane potential occur in a range of important pathologies. To assess changes in membrane potential in patients, we set out to develop an improved mitochondria-targeted positron emission tomography probe comprising a lipophilic triphenylphosphonium cation attached to a fluorine-18 radionuclide via an 11-carbon alkyl chain, which is well-established to effectively transport to and localise within mitochondria. Here, we describe the radiosynthesis of this probe, 11-[(18) F]fluoroundecyl-triphenylphosphonium (MitoF), from no-carrier-added [(18) F]fluoride and a fully automated synthetic protocol to prepare it in good radiochemical yields (2-3 GBq at end-of-synthesis) and radiochemical purity (97-99%).

Mitochondria-Targeted Triphenylphosphonium-Based Compounds: Syntheses, Mechanisms of Action, and Therapeutic and Diagnostic Applications

“…In a breast carcinoma model in mice, the same compound showed a 45% reduced uptake of the compound after 48 h of injection of Taxotere, with no effect in heart, liver, or kidney uptake . Another 18 F-bearing probe, 4-[ 18 F]­fluorophenyltriphenylphosphonium ([ 18 F]-TPP, Chart ), was synthesized and evaluated as a myocardial blood flow agent for PET. ,, Subsequently, a myriad of other analogues, varying the hydrophobicity of the alkyl linker connecting the fluorine-18 atom and the TPP + , were synthesized and tested in heart models. ,,− Results showed a preferential uptake of the TPP + -based PET agents in the heart with enhanced heart-to-lung ratios in mice 1 h after injection …”