Automated radiosynthesis of mGluR5 PET tracer [¹⁸F]FPEB from aryl-chloro precursor and validation for clinical application

The radioligand [¹⁸F]FPEB, used for PET imaging of the brain's metabotropic glutamate receptor subtype 5 (mGluR5), undergoes a thorough validation process to ensure its safety, efficacy, and quality for clinical use. The process starts by optimizing the synthesis of [¹⁸F]FPEB to achieve high radiochemical yield and purity. This study focuses on optimizing the radiolabeling process using an aryl-chloro precursor and validating the GMP production for clinical applications. Fully automated radiolabeling was achieved via one-step nucleophilic substitution reaction. [¹⁸F]FPEB was produced and isolated in high radioactivity and radiochemical purity. Throughout the validation process, thorough quality control measures are implemented. Radiopharmaceutical batch release criteria are established, including testing for physical appearance, filter integrity, pH, radiochemical purity, molar activity, radiochemical identity, chemical impurity, structural identity, stability, residual solvent, sterility, and endotoxin levels. In conclusion, the validation of [¹⁸F]FPEB involved a comprehensive process of synthesis optimization, quality control, which ensure the safety, efficacy, and quality of [¹⁸F]FPEB, enabling its reliable use in clinical PET. Here, we successfully radiolabeled and validated [¹⁸F]FPEB using aryl-chloro precursor according to GMP production for clinical application.