Optimization of Precursor Preparation in PSMA-11 Radiolabeling to Obtain a Highly Reproducible Radiochemical Yield

[Ga-68]Ga-PSMA-11 PET/CT plays a pivotal role in the diagnosis and staging of prostate cancer because of its higher sensitivity and detection rate compared with traditional choline PET/CT. A highly reproducible radiochemical yield of the radiopharmaceutical to be used in the clinical routine is an important parameter for planning and optimization of clinical activity. During radiometallation of PSMA-11, the presence of metal ion contaminants in the peptide precursor may cause a decrease in the [Ga-68]Ga-PSMA-11 radiochemical yield because of metal ion contaminants competition with gallium-68. To optimize the radiochemical yield of [Ga-68]Ga-PSMA-11 radiosynthesis, data obtained by preparing the solution of the PSMA-11 precursor with three different methods (A, B, and C) were compared. Methods A and B consisted of the reconstitution of different quantities of precursor (1000 mu g and 30 mu g, respectively) to obtain a 1 mu g/mL solution. In Method A, the precursor solution was aliquoted and stored frozen, while the precursor solution obtained with Method B was entirely used. Method C consisted of the reconstitution of 1000 mu g of precursor taking into account net peptide content as described in European Pharmacopoeia. Radiosynthesis data demonstrated that reconstitution methods B and C gave a consistently higher and reproducible radiochemical yield, highlighting the role of metals and precursor storage conditions on the synthesis performance.

Automated summary

[Ga-68]Ga-PSMA-11 PET/CT plays a pivotal role in the diagnosis and staging of prostate cancer due to its higher sensitivity and detection rate. Optimizing the radiochemical yield of the radiopharmaceutical is important for clinical activity planning and optimization. The presence of metal ion contaminants in the peptide precursor during radiometallation of PSMA-11 can decrease the radiochemical yield of [Ga-68]Ga-PSMA-11 due to competition with gallium-68.