Background: Glucagon-like peptide 1 receptor (GLP-1R) is preferentially expressed in β-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 β-cell mass. Exendin-4 is a high affinity ligand of the GLP1R, 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: A68Ge/68Ga Generator (GalliaPharma®, Eckert and Ziegler) was eluted with 0.1M HCl on an automated synthesis module (Scintomics GRP®). The peptide contained in the kit vial (Radioisotope Center POLATOM) in different amounts (10-20-30 μg) was reconstituted with 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethansulfonic acid (HEPES) solution and68GaCl3 (400–900 MBq), followed by 10 min incubation at 95°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 [68Ga]Ga-NODAGA-Exendin-4 provided optimal results with 10 μg of peptide, getting the best radiochemical yield (23.53 ± 2.4%), molar activity (100 GBq/μmol) and radiochemical purity (91.69%). Conclusion: The study developed an imaging tool [68Ga]Ga-NODAGA-Exendin-4, avoiding pharmacological effects of exendin-4, for the clinical community.

Feasibility of a Scale-down Production of [68Ga]Ga-NODAGA-Exendin-4 in a Hospital Based Radiopharmacy / Migliari, S.; Sammartano, A.; Scarlattei, M.; Baldari, G.; Janota, B.; Bonadonna, R. C.; Ruffini, L.. - In: CURRENT RADIOPHARMACEUTICALS. - ISSN 1874-4710. - 15:1(2022), pp. 63-75. [10.2174/1874471014666210309151930]

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

Bonadonna R. C.;
2022

Abstract

Background: Glucagon-like peptide 1 receptor (GLP-1R) is preferentially expressed in β-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 β-cell mass. Exendin-4 is a high affinity ligand of the GLP1R, 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: A68Ge/68Ga Generator (GalliaPharma®, Eckert and Ziegler) was eluted with 0.1M HCl on an automated synthesis module (Scintomics GRP®). The peptide contained in the kit vial (Radioisotope Center POLATOM) in different amounts (10-20-30 μg) was reconstituted with 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethansulfonic acid (HEPES) solution and68GaCl3 (400–900 MBq), followed by 10 min incubation at 95°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 [68Ga]Ga-NODAGA-Exendin-4 provided optimal results with 10 μg of peptide, getting the best radiochemical yield (23.53 ± 2.4%), molar activity (100 GBq/μmol) and radiochemical purity (91.69%). Conclusion: The study developed an imaging tool [68Ga]Ga-NODAGA-Exendin-4, avoiding pharmacological effects of exendin-4, for the clinical community.
Feasibility of a Scale-down Production of [68Ga]Ga-NODAGA-Exendin-4 in a Hospital Based Radiopharmacy / Migliari, S.; Sammartano, A.; Scarlattei, M.; Baldari, G.; Janota, B.; Bonadonna, R. C.; Ruffini, L.. - In: CURRENT RADIOPHARMACEUTICALS. - ISSN 1874-4710. - 15:1(2022), pp. 63-75. [10.2174/1874471014666210309151930]
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11381/2925075
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