cGMP compliant one-step, one-pot automated [18F]FBnTP production for clinical imaging of mitochondrial activity

Abstract

Abstract Background 4-[18F]fluorobenzyl-triphenylphosphonium ([18F]FBnTP) is a lipophilic cation PET tracer. The cellular uptake of [18F]FBnTP is correlated with oxidative phosphorylation by mitochondria, which has been associated with multiple critical diseases. To date, [18F]FBnTP has been successfully applied for imaging myocardial perfusion, assessment of severity of coronary artery stenosis, delineation of the ischemic area after transient coronary occlusion, and detection/quantification of apoptosis in various animal models. Recent preclinical and clinical studies have also expanded the possibilities of using [18F]FBnTP in oncological diagnosis and therapeutic monitoring. However, [18F]FBnTP is typically prepared through a tediously lengthy four-step, three-pot reaction and required multiple synthesizer modules; Thus, such an approach remains a challenge for this promising radiopharmaceutical to be implemented for routine clinical studies. Herein, we report an optimized one-step, one-pot automated approach to produce [18F]FBnTP through a single standard commercially-available radiosynthesizer that enables centralized production for clinical use. Results The fully automated production of [18F]FBnTP took less than 55 min with radiochemical yields ranging from 28.33 ± 13.92% (non-decay corrected), apparent molar activity of 69.23 ± 45.62 GBq/µmol, and radiochemical purities of 99.79 ± 0.41%. The formulated [18F]FBnTP solution was determined to be sterile and colorless with a pH of 4.0–6.0. Our data has indicated no observable radiolysis after 8 h from the time of final product formulation and maximum assay of 7.88 GBq. Conclusions A simplified and cGMP-compliant radiosynthesis of [18F]FBnTP has been established on the commercially available synthesizer in high activity concentration and radiochemical purity. While the preclinical and clinical studies using [18F]FBnTP PET are currently underway, the automated approaches reported herein facilitate clinical adoption of this radiotracer and warrant centralized production of [18F]FBnTP for imaging multiple patients.