Background. Stability of precursors and reagents are of utmost importance for developing a suitable, fast and routinely reproducible analytical method for the quality control of radiopharmaceuticals, for the validation of the analytical method itself, as well as for radiolabeling procedure. During the validation of the analytical method used for the determination of chemical and radiochemical purity of an injectable solution of 68Ga-PSMA-11, a trend to instability of the PSMA-11 standard, the same used as a precursor in the radiosynthesis of 68Ga-PSMA11, has been found. This instability led to the formation of a secondary compound in a time-dependent manner. The formation of this compound made difficult the validation of the analytical method and influenced the radiolabeling yield, by increasing free 68Ga which, obviously, decreased the final yield.
Results. The nature of this compound was investigated by adding chelators, such as EDTA, to PSMA-11 solutions and by using the combination of UHPLC-HRMS. The results led to the definition of the secondary compound structure, as natFe-PSMA-11, from the combination of the high affinity chelator HBED-CC, present in the molecule of PSMA-11, and environmental Fe(III).
Conclusions. Strategies to reduce the risk of low radiolabeling yields and to increase the stability of the standards were also discussed.