Cargando…
Automated synthesis and quality control of [(68)Ga]Ga-PentixaFor using the Gaia/Luna Elysia-Raytest module for CXCR4 PET imaging
BACKGROUND: [(68)Ga]Ga-PentixaFor is a promising radiotracer for positron emission tomography imaging of several human tumors overexpressing the chemokine receptor-4 (CXCR4). CXCR4 overexpression has been demonstrated in patients with hematologic malignancies, solid cancers, as well as cardiovascula...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9905377/ https://www.ncbi.nlm.nih.gov/pubmed/36749409 http://dx.doi.org/10.1186/s41181-023-00187-2 |
_version_ | 1784883795304906752 |
---|---|
author | Daniel, Thomas Balouzet Ravinet, Clara Clerc, Jérôme Batista, Rui Mouraeff, Yvan |
author_facet | Daniel, Thomas Balouzet Ravinet, Clara Clerc, Jérôme Batista, Rui Mouraeff, Yvan |
author_sort | Daniel, Thomas |
collection | PubMed |
description | BACKGROUND: [(68)Ga]Ga-PentixaFor is a promising radiotracer for positron emission tomography imaging of several human tumors overexpressing the chemokine receptor-4 (CXCR4). CXCR4 overexpression has been demonstrated in patients with hematologic malignancies, solid cancers, as well as cardiovascular pathologies of inflammatory origins. However, its radio synthesis is not yet fully developed in France, and existing methods do not use our type of synthesis module. Therefore, we aimed at developing a [(68)Ga]Ga-PentixaFor synthesis with Gaia/Luna Elysia-Raytest module to use it in clinical purpose. RESULTS: 12 syntheses were carried out by varying the temperature conditions and radiolabeling times, and led to choose specific labelling conditions with the Gaia/Luna Elysia-Raytest module: 97 °C, 4 min. The mean synthesis time of the 3 validation runs under good manufacturing practice (GMP) was 24 min 27 s (± 8 s), and the mean radiochemical yield was 87.0% [standard deviation (SD) 6.67%]. Different quality control parameters were also evaluated in accordance with European Pharmacopeia: radiochemical and radionuclidic purity, pH, sterility, stability and endotoxins levels. The average radiochemical purity was 99.1% (SD 0.25%) assessed by instant thin layer chromatography and 99.8% (SD 0.092%) assessed by high pressure liquid chromatography. average [(68)Ge] breakthrough was 1.48 × 10(–5)%, under the recommended level of 0.001%. We assessed the stability of the radiotracer up to 4 h at room temperature (no augmentation of the [(68)Ga] chloride in the final product, i.e. radiochemical purity (RCP) > 98.5%). The endotoxins levels were < 5 EU/mL, and the pH was 6.5 (same for the three syntheses). CONCLUSION: The [(68)Ga]Ga-PentixaFor synthesis process developed on the Gaia/Luna Elysia-Raytest module has fulfilled all acceptance criteria for injectable radiopharmaceutical products regarding the European Pharmacopeia. The radiochemical purity, stability, efficacy, as well as the microbiological quality of the three GMP batches were found to be good. The robustness of the synthesis process may be suitable for multi-dose application in clinical settings. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s41181-023-00187-2. |
format | Online Article Text |
id | pubmed-9905377 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-99053772023-02-08 Automated synthesis and quality control of [(68)Ga]Ga-PentixaFor using the Gaia/Luna Elysia-Raytest module for CXCR4 PET imaging Daniel, Thomas Balouzet Ravinet, Clara Clerc, Jérôme Batista, Rui Mouraeff, Yvan EJNMMI Radiopharm Chem Research Article BACKGROUND: [(68)Ga]Ga-PentixaFor is a promising radiotracer for positron emission tomography imaging of several human tumors overexpressing the chemokine receptor-4 (CXCR4). CXCR4 overexpression has been demonstrated in patients with hematologic malignancies, solid cancers, as well as cardiovascular pathologies of inflammatory origins. However, its radio synthesis is not yet fully developed in France, and existing methods do not use our type of synthesis module. Therefore, we aimed at developing a [(68)Ga]Ga-PentixaFor synthesis with Gaia/Luna Elysia-Raytest module to use it in clinical purpose. RESULTS: 12 syntheses were carried out by varying the temperature conditions and radiolabeling times, and led to choose specific labelling conditions with the Gaia/Luna Elysia-Raytest module: 97 °C, 4 min. The mean synthesis time of the 3 validation runs under good manufacturing practice (GMP) was 24 min 27 s (± 8 s), and the mean radiochemical yield was 87.0% [standard deviation (SD) 6.67%]. Different quality control parameters were also evaluated in accordance with European Pharmacopeia: radiochemical and radionuclidic purity, pH, sterility, stability and endotoxins levels. The average radiochemical purity was 99.1% (SD 0.25%) assessed by instant thin layer chromatography and 99.8% (SD 0.092%) assessed by high pressure liquid chromatography. average [(68)Ge] breakthrough was 1.48 × 10(–5)%, under the recommended level of 0.001%. We assessed the stability of the radiotracer up to 4 h at room temperature (no augmentation of the [(68)Ga] chloride in the final product, i.e. radiochemical purity (RCP) > 98.5%). The endotoxins levels were < 5 EU/mL, and the pH was 6.5 (same for the three syntheses). CONCLUSION: The [(68)Ga]Ga-PentixaFor synthesis process developed on the Gaia/Luna Elysia-Raytest module has fulfilled all acceptance criteria for injectable radiopharmaceutical products regarding the European Pharmacopeia. The radiochemical purity, stability, efficacy, as well as the microbiological quality of the three GMP batches were found to be good. The robustness of the synthesis process may be suitable for multi-dose application in clinical settings. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s41181-023-00187-2. Springer International Publishing 2023-02-07 /pmc/articles/PMC9905377/ /pubmed/36749409 http://dx.doi.org/10.1186/s41181-023-00187-2 Text en © The Author(s) 2023 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 Daniel, Thomas Balouzet Ravinet, Clara Clerc, Jérôme Batista, Rui Mouraeff, Yvan Automated synthesis and quality control of [(68)Ga]Ga-PentixaFor using the Gaia/Luna Elysia-Raytest module for CXCR4 PET imaging |
title | Automated synthesis and quality control of [(68)Ga]Ga-PentixaFor using the Gaia/Luna Elysia-Raytest module for CXCR4 PET imaging |
title_full | Automated synthesis and quality control of [(68)Ga]Ga-PentixaFor using the Gaia/Luna Elysia-Raytest module for CXCR4 PET imaging |
title_fullStr | Automated synthesis and quality control of [(68)Ga]Ga-PentixaFor using the Gaia/Luna Elysia-Raytest module for CXCR4 PET imaging |
title_full_unstemmed | Automated synthesis and quality control of [(68)Ga]Ga-PentixaFor using the Gaia/Luna Elysia-Raytest module for CXCR4 PET imaging |
title_short | Automated synthesis and quality control of [(68)Ga]Ga-PentixaFor using the Gaia/Luna Elysia-Raytest module for CXCR4 PET imaging |
title_sort | automated synthesis and quality control of [(68)ga]ga-pentixafor using the gaia/luna elysia-raytest module for cxcr4 pet imaging |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9905377/ https://www.ncbi.nlm.nih.gov/pubmed/36749409 http://dx.doi.org/10.1186/s41181-023-00187-2 |
work_keys_str_mv | AT danielthomas automatedsynthesisandqualitycontrolof68gagapentixaforusingthegaialunaelysiaraytestmoduleforcxcr4petimaging AT balouzetravinetclara automatedsynthesisandqualitycontrolof68gagapentixaforusingthegaialunaelysiaraytestmoduleforcxcr4petimaging AT clercjerome automatedsynthesisandqualitycontrolof68gagapentixaforusingthegaialunaelysiaraytestmoduleforcxcr4petimaging AT batistarui automatedsynthesisandqualitycontrolof68gagapentixaforusingthegaialunaelysiaraytestmoduleforcxcr4petimaging AT mouraeffyvan automatedsynthesisandqualitycontrolof68gagapentixaforusingthegaialunaelysiaraytestmoduleforcxcr4petimaging |