Résumé
Background and Importance: ¹⁷⁷Lu-PSMA-617 is a treatment of progressive, metastatic, castration-resistant prostate cancers expressing PSMA receptors, previously treated with taxane and at least one second-generation hormone therapy. ¹⁷⁷Lu-PSMA-617 is a radiopharmaceutical drug with a marketing authorisation and is manufactured industrially (PLUVICTO®, Novartis). However, it can also be prepared in-house, especially for preclinical applications. Thus, quality control procedures are required to determine radiochemical purity (RCP).Aim and Objectives: To develop and validate a radio-high-performance liquid chromatography (HPLC) analysis method to measure RCP of ¹⁷⁷Lu-PSMA-617. Material and Methods: Radio-HPLC analyses were carried out on an apparatus equipped with a C18 column and a radioactivity detector. Three commercial ¹⁷⁷Lu-PSMA-617 batches were used as samples. The parameters considered for method validation were specificity, linearity, accuracy, precision, robustness, limits of detection (LOD) and limits of quantification (LOQ). Means, standard deviations and coefficient of variation (CV) for RCP, retention time (tr) and recovery were calculated. Linear regression coefficient R² was computed for linearity.Results: Radiochemical identification of ¹⁷⁷Lu-PSMA-617 consisted in 10 analyses of each three commercial batches and showed a consistent tr of 10.07 min (CV% < 0.1). Recovery was excellent, with 12.87 ± 0.06 MBq recovered at column outlet for a 12.2 MBq injected activity. The addition of radio-impurities in known quantities validated the accuracy of the method (differences between measured RCP and theoretical RCP ranging from 101.57% to 105.52%). CV% of RCP and tr values over 12 measures of a single batch were respectively <0.11% and <0.12%, which confirmed the repeatability of the method. Forced degradation conditions in the presence of acid, base, oxidative stress or heating led to the formation in situ of impurities with a tr largely different from the analyte, confirming the specificity of the method. LOQ and LOD were 0.68 and 0.21 MBq/mL, respectively, and the radiodetector response was linear from 2 to 300 MBq/mL (R² = 0.9977). Robustness was found to be limited as the mean tr values varied by -4.8% when the column was heated to 50 °C instead of 25 °C.Conclusion and Relevance: A radio-HPLC method for the quality control of ¹⁷⁷Lu-PSMA-617 was validated and can be used for in-house preparations for preclinical purposes of this radioactive drug.