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GMP-compliant production of [(68)Ga]Ga-NeoB for positron emission tomography imaging of patients with gastrointestinal stromal tumor

BACKGROUND: [(68)Ga]Ga-NeoB is a novel DOTA-coupled Gastrin Releasing Peptide Receptor (GRPR) antagonist with high affinity for GRPR and good in vivo stability. This study aimed at (1) the translation of preclinical results to the clinics and establish the preparation of [(68)Ga]Ga-NeoB using a GMP...

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Autores principales: Pretze, Marc, Reffert, Laura, Diehl, Steffen, Schönberg, Stefan O., Wängler, Carmen, Hohenberger, Peter, Wängler, Björn
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260665/
https://www.ncbi.nlm.nih.gov/pubmed/34228236
http://dx.doi.org/10.1186/s41181-021-00137-w
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author Pretze, Marc
Reffert, Laura
Diehl, Steffen
Schönberg, Stefan O.
Wängler, Carmen
Hohenberger, Peter
Wängler, Björn
author_facet Pretze, Marc
Reffert, Laura
Diehl, Steffen
Schönberg, Stefan O.
Wängler, Carmen
Hohenberger, Peter
Wängler, Björn
author_sort Pretze, Marc
collection PubMed
description BACKGROUND: [(68)Ga]Ga-NeoB is a novel DOTA-coupled Gastrin Releasing Peptide Receptor (GRPR) antagonist with high affinity for GRPR and good in vivo stability. This study aimed at (1) the translation of preclinical results to the clinics and establish the preparation of [(68)Ga]Ga-NeoB using a GMP conform kit approach and a licensed (68)Ge/(68)Ga generator and (2) to explore the application of [(68)Ga]Ga-NeoB in patients with gastrointestinal stromal tumors (GIST) before and/or after interventional treatment (selective internal radiotherapy, irreversible electroporation, microwave ablation). RESULTS: Validation of the production and quality control of [(68)Ga]Ga-NeoB for patient use had to be performed before starting the GMP production. Six independent batches of [(68)Ga]Ga-NeoB were produced, all met the quality and sterility criteria and yielded 712 ± 73 MBq of the radiotracer in a radiochemical purity of > 95% and a molar activity of 14.2 ± 1.5 GBq/μmol within 20 min synthesis time and additional 20 min quality control. Three patients (2 females, 1 male, 51–77 yrs. of age) with progressive gastrointestinal stromal tumor metastases in the liver or peritoneum not responsive to standard tyrosine kinase inhibitor therapy underwent both [(68)Ga]Ga-NeoB scans prior and after interventional therapy. Radiosynthesis of (68)Ga-NeoB was performed using a kit approach under GMP conditions. No specific patient preparation such as fasting or hydration was required for [(68)Ga]Ga-NeoB PET/CT imaging. Contrast-enhanced PET/CT studies were performed. A delayed, second abdominal image after the administration of the of [(68)Ga]Ga-NeoB was acquired at 120 min post injection. CONCLUSIONS: A fully GMP compliant kit preparation of [(68)Ga]Ga-NeoB enabling the routine production of the tracer under GMP conditions was established for clinical routine PET/CT imaging of patients with metastatic GIST and proved to adequately visualize tumor deposits in the abdomen expressing GRPR. Patients could benefit from additional information derived from [(68)Ga]Ga-NeoB diagnosis to assess the presence of GRPR in the tumor tissue and monitor antitumor treatment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s41181-021-00137-w.
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spelling pubmed-82606652021-07-19 GMP-compliant production of [(68)Ga]Ga-NeoB for positron emission tomography imaging of patients with gastrointestinal stromal tumor Pretze, Marc Reffert, Laura Diehl, Steffen Schönberg, Stefan O. Wängler, Carmen Hohenberger, Peter Wängler, Björn EJNMMI Radiopharm Chem Research Article BACKGROUND: [(68)Ga]Ga-NeoB is a novel DOTA-coupled Gastrin Releasing Peptide Receptor (GRPR) antagonist with high affinity for GRPR and good in vivo stability. This study aimed at (1) the translation of preclinical results to the clinics and establish the preparation of [(68)Ga]Ga-NeoB using a GMP conform kit approach and a licensed (68)Ge/(68)Ga generator and (2) to explore the application of [(68)Ga]Ga-NeoB in patients with gastrointestinal stromal tumors (GIST) before and/or after interventional treatment (selective internal radiotherapy, irreversible electroporation, microwave ablation). RESULTS: Validation of the production and quality control of [(68)Ga]Ga-NeoB for patient use had to be performed before starting the GMP production. Six independent batches of [(68)Ga]Ga-NeoB were produced, all met the quality and sterility criteria and yielded 712 ± 73 MBq of the radiotracer in a radiochemical purity of > 95% and a molar activity of 14.2 ± 1.5 GBq/μmol within 20 min synthesis time and additional 20 min quality control. Three patients (2 females, 1 male, 51–77 yrs. of age) with progressive gastrointestinal stromal tumor metastases in the liver or peritoneum not responsive to standard tyrosine kinase inhibitor therapy underwent both [(68)Ga]Ga-NeoB scans prior and after interventional therapy. Radiosynthesis of (68)Ga-NeoB was performed using a kit approach under GMP conditions. No specific patient preparation such as fasting or hydration was required for [(68)Ga]Ga-NeoB PET/CT imaging. Contrast-enhanced PET/CT studies were performed. A delayed, second abdominal image after the administration of the of [(68)Ga]Ga-NeoB was acquired at 120 min post injection. CONCLUSIONS: A fully GMP compliant kit preparation of [(68)Ga]Ga-NeoB enabling the routine production of the tracer under GMP conditions was established for clinical routine PET/CT imaging of patients with metastatic GIST and proved to adequately visualize tumor deposits in the abdomen expressing GRPR. Patients could benefit from additional information derived from [(68)Ga]Ga-NeoB diagnosis to assess the presence of GRPR in the tumor tissue and monitor antitumor treatment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s41181-021-00137-w. Springer International Publishing 2021-07-06 /pmc/articles/PMC8260665/ /pubmed/34228236 http://dx.doi.org/10.1186/s41181-021-00137-w Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Pretze, Marc
Reffert, Laura
Diehl, Steffen
Schönberg, Stefan O.
Wängler, Carmen
Hohenberger, Peter
Wängler, Björn
GMP-compliant production of [(68)Ga]Ga-NeoB for positron emission tomography imaging of patients with gastrointestinal stromal tumor
title GMP-compliant production of [(68)Ga]Ga-NeoB for positron emission tomography imaging of patients with gastrointestinal stromal tumor
title_full GMP-compliant production of [(68)Ga]Ga-NeoB for positron emission tomography imaging of patients with gastrointestinal stromal tumor
title_fullStr GMP-compliant production of [(68)Ga]Ga-NeoB for positron emission tomography imaging of patients with gastrointestinal stromal tumor
title_full_unstemmed GMP-compliant production of [(68)Ga]Ga-NeoB for positron emission tomography imaging of patients with gastrointestinal stromal tumor
title_short GMP-compliant production of [(68)Ga]Ga-NeoB for positron emission tomography imaging of patients with gastrointestinal stromal tumor
title_sort gmp-compliant production of [(68)ga]ga-neob for positron emission tomography imaging of patients with gastrointestinal stromal tumor
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260665/
https://www.ncbi.nlm.nih.gov/pubmed/34228236
http://dx.doi.org/10.1186/s41181-021-00137-w
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