Feasibility of a Scale-down Production of [68Ga]Ga-NODAGA-Exendin-4 in a Hospital Based Radiopharmacy

Background: Glucagon-like peptide 1 receptor (GLP-1R) is preferentially expressed in beta-cells, but it is highly expressed in human insulinomas and gastrinomas. Several GLP-1 receptor-avid radioligands have been developed to image insulin-secreting tumors or to provide a quantitative in vivo biomarker of pancreatic beta-cell mass. Exendin-4 is a high affinity ligand of the GLP1-R, which is a candidate for being labeled with a PET isotope and used for imaging purposes. Objective: Here, we report the development and validation results of a semi-manual procedure to label [Lys40,Nle14(Ahx-NODAGA)NH2]exendin-4, with Ga-68. Methods: A(68)Ge/Ga-68 Generator (GalliaPharma (R), Eckert and Ziegler) was eluted with 0.1M HCl on an automated synthesis module (Scintomics GRP (R)). The peptide contained in the kit vial (Radioisotope Center POLATOM) in different amounts (10-20-30 mu g) was reconstituted with 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethansulfonic acid (HEP-ES) solution and (GaCl3)-Ga-68 (400-900 MBq), followed by 10 min incubation at 95 degrees C. The reaction solution was then purified through an Oasis HLB column. The radiopharmaceutical product was tested for quality controls (CQs) in accordance with the European Pharmacopoeia standards. RESULTS: The synthesis of [Ga-68]Ga-NODAGA-Exendin-4 provided optimal results with 10 mu g of peptide, getting the best radiochemical yield (23.53 +/- 2.4%), molar activity (100 GBq/mu mol) and radiochemical purity (91.69%). CONCLUSION: The study developed an imaging tool [Ga-68]Ga-NODAGA-Exendin-4, avoiding pharmacological effects of exendin-4, for the clinical community.

Automated summary

This study developed and validated a semi-manual procedure to label [Ga-68]Ga-NODAGA-Exendin-4 for imaging insulin-secreting tumors. Using 10 μg of the peptide yielded optimal radiochemical yield, molar activity, and radiochemical purity.