Silvia Migliari, Antonino Sammartano, Maura Scarlattei, Giorgio Baldari, Barbara Janota, Riccardo C Bonadonna, Livia Ruffini
{"title":"[68Ga]Ga-NODAGA-Exendin-4在医院放射药房规模化生产的可行性","authors":"Silvia Migliari, Antonino Sammartano, Maura Scarlattei, Giorgio Baldari, Barbara Janota, Riccardo C Bonadonna, Livia Ruffini","doi":"10.2174/1874471014666210309151930","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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 GLP1- R, which is a candidate for being labeled with a PET isotope and used for imaging purposes.</p><p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>A<sup>68</sup>Ge/<sup>68</sup>Ga 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 and <sup>68</sup>GaCl<sub>3</sub> (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.</p><p><strong>Results: </strong>The synthesis of [<sup>68</sup>Ga]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%).</p><p><strong>Conclusion: </strong>The study developed an imaging tool [<sup>68</sup>Ga]Ga-NODAGA-Exendin-4, avoiding pharmacological effects of exendin-4, for the clinical community.</p>","PeriodicalId":10991,"journal":{"name":"Current radiopharmaceuticals","volume":"15 1","pages":"63-75"},"PeriodicalIF":1.5000,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"6","resultStr":"{\"title\":\"Feasibility of a Scale-down Production of [<sup>68</sup>Ga]Ga-NODAGA-Exendin-4 in a Hospital Based Radiopharmacy.\",\"authors\":\"Silvia Migliari, Antonino Sammartano, Maura Scarlattei, Giorgio Baldari, Barbara Janota, Riccardo C Bonadonna, Livia Ruffini\",\"doi\":\"10.2174/1874471014666210309151930\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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 GLP1- R, which is a candidate for being labeled with a PET isotope and used for imaging purposes.</p><p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>A<sup>68</sup>Ge/<sup>68</sup>Ga 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 and <sup>68</sup>GaCl<sub>3</sub> (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.</p><p><strong>Results: </strong>The synthesis of [<sup>68</sup>Ga]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%).</p><p><strong>Conclusion: </strong>The study developed an imaging tool [<sup>68</sup>Ga]Ga-NODAGA-Exendin-4, avoiding pharmacological effects of exendin-4, for the clinical community.</p>\",\"PeriodicalId\":10991,\"journal\":{\"name\":\"Current radiopharmaceuticals\",\"volume\":\"15 1\",\"pages\":\"63-75\"},\"PeriodicalIF\":1.5000,\"publicationDate\":\"2022-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"6\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Current radiopharmaceuticals\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2174/1874471014666210309151930\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current radiopharmaceuticals","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/1874471014666210309151930","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
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 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 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: 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 and 68GaCl3 (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.
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