Optimization of the production of Gallium-68 labeled peptides (PSMA et DOTATOC)
1 October 2025
J. Costes1, A. Pierrot1, K. Casagrande1, J. Masset2, J. Delage1, F. Sadeghipour1,3,4.1 Pharmacy Department, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
2 Research and Development Center, Trasis Radiopharmacy Instruments, Ans, Belgium.
3 Pharmaceutical Sciences, Geneva-Lausanne Pharmacy School, University of Geneva, Switzerland.
4 Centre de Recherche et d’Innovations en Sciences Pharmaceutiques cliniques, University of Lausanne, Switzerland.
Introduction
The increasing demand for PET/CT 68Ga-DOTATOC and 68Ga-PSMA has led to an increase in production. However, availability is limited due to the activity available at the end of synthesis and the time required between two generator elutions. The simultaneous use of two generators increases the final activity. Kits for this type of production are available from our supplier but offer reduced yields, limiting their usefulness. Therefore, it was decided to study the feasibility of the fractionated elution method to increase the available activity. The aim of this work is to ensure that the quality of the preparation is not altered by radiolysis due to the increase in radioactivity.
Material and methods
Each elution was fractionated into three parts. Only the fraction containing the highest activity was retained for labeling. Different profiles of fractionated elutions were tested to identify the one that allows obtaining the highest volumetric activity. Five validation batches were produced for each peptide (DOTATOC and PSMA-11) on the Mini AiO® synthesis modules (Trasis), using the selected elution profile and by mixing the elutions from the two generators. For each batch, the following parameters were evaluated: yields, radiochemical purity (RCP), and stability at 3 hours (measured by HPLC and TLC).
Results
The fractionated elution profile that allowed obtaining the highest volumic activity is: 1 mL – 2.5 mL – 1.5 mL. The activity found in the second fraction represents 82.7 ± 1.2% of the total activity. The validation batches were produced with 2 x 2.5 mL of concentrated eluates. The yields obtained for PSMA-11 and DOTATOC are 78.3 ± 5.2% and 80.6 ± 3.0%, respectively. The RCP obtained at the end of synthesis are 96.6 ± 0.5% and 97.6 ± 0.4% by HPLC and 97.7 ± 1.4% and 99.6 ± 0.1% by TLC, respectively. The stabilities at 3 hours are 96.6 ± 0.7% and 95.7 ± 0.7% by HPLC and 98.0 ± 1.2% and 99.7 ± 0.2% by TLC, respectively.
Discussion and conclusion
The use of the fractionated elution method allows obtaining synthesis yields and production quality similar to that obtained using a single generator. No radiolysis phenomenon has been identified. Thus, this work confirms the possibility of producing 68Ga-DOTATOC and 68Ga-PSMA with higher labeling activities, allowing the inclusion of 4 patients per preparation instead of 2 previously.