Features and Practical Aspects of Radiochemical Purity Determination of Receptor-Specific Lu-177 Radiopharmaceuticals as Exemplified by [<sup>177</sup>Lu]Lu–PSMA-617

Abstract

Radiochemical purity (RCP) is one of the key quality criteria for radiopharmaceuticals (RPs) used in clinical practice. The results of RCP measurements depend on the analytical technique, as well as detection parameters, which are specific to a particular analytical system. When reviewing literature data on the synthesis, pharmaceutical development, preclinical and clinical trials of the same radiopharmaceutical by different authors, one may note significant variability in the RCP values obtained. Hence, it is important to carefully select analysis parameters and study their influence on the results. The aim of the study was to compare previously published and self-developed procedures for RCP analysis of 177 Lu-RPs in terms of their efficiency in the detection and quantification of possible radiochemical impurities, as well as to determine the analytical system parameters that have a significant impact on the interpretation of the analysis results, using [ 177 Lu]Lu–PSMA-617 as a case study. Materials and methods : the study used samples of [ 177 Lu]Lu–PSMA-617 with a volume activity of lutetium-177 of 150–4800 MBq/mL, containing 10–100 µmol/L of the PSMA-617 precursor and 30 mmol/L of sodium acetate as a buffering solution (pH 4.5). The samples were tested by high-performance liquid chromatography (HPLC) and thin-layer chromatography in the conditions described in the literature and developed in the course of the work. Results : the study showed a significant influence of the chosen analytical procedure on the results of [ 177 Lu]Lu–PSMA-617 RCP assessment. The profile of possible radiochemical impurities requires the use of high-resolution HPLC techniques. Conclusions : the analytical procedure developed and applied by the authors is quite effective. The results of RCP assessment are influenced by the detection system parameters, such as the length and inner diameter of the flow cell and the means of analytical signal processing (peak extraction parameters, smoothing parameters, and noise subtraction/suppression). This fact necessitates validation considering the characteristics of a particular analytical system and demonstrates the need to assess interlaboratory precision in the framework of the implementation and verification of analytical procedures.