68Ga-PSMA-11 preparation and radiochemical purity analysis via quality by design (QBD) principles

68Ga-PSMA-11 radiopharmaceuticals have been widely used in recent years for PET/CT imaging of prostate cancer recurrence and metastases. Synthesis conditions may affect radiolabeling quality and in vivo behavior and no standard procedure for the quality control (QC) is available. In this study, it is aimed to determine the critical process parameters of 68Ga-PSMA-11 synthesis via QbD approach, and to optimize 68Ga-PSMA-11 synthesis via experimental design programs. In addition, since European Pharmacopoeia have no respective guidelines on the QC of 68Ga-PSMA-11, it is aimed to develop and validate analytical method for determination of radiochemical and chemical purity. Critical process parameters (CQA) and experimental design (DoE) for 68Ga-PSMA-11 synthesis optimization were identified based on literature review. DoE was statistically designed using Design Expert software version 10.0. Response surface modelling (RSM) was applied to estimate the relationship between the independent factors and CQAs. Validation of the analytical method for the determination of chemical and radiochemical purity of 68Ga-PSMA-11 was carried out according to ICH Q2 (R1) guidelines. As a result a new selective and sensitive high-performance liquid chromatography method for chemical and radiochemical purity testing of 68Ga-PSMA-11 has been developed and validated. The linearity between 0.5-15 μg / mL was found R2 ≥ 0.99 and % RSD value was found <2. As a result of the optimization study carried out by using Design Expert 10.0.0 software, the reaction temperature was 95 C, the reaction time was 220 sec, reaction pH 4.40 and the amount of PSMA-11 was 10 μg / mL. Key Words: 68Ga-PSMA-11, Quality by Design, Optimization,Radiopharmaceutical The present work was supported by the Research Fund of Istanbul University. Project No. TYL-2019-33814