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A practical fully automated radiosynthesis of [(18)F]Flurpiridaz on the module modular lab-pharmtracer without external purification
BACKGROUND: [(18)F]Flurpiridaz is a promising novel cardiac PET imaging tracer formed by the radiolabeling of pyridaben derivative with fluorine-18. Clinical studies on [(18)F]Flurpiridaz are currently at the phase III level for the assessment of MPI. Providing high image quality thanks to its relat...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9637077/ https://www.ncbi.nlm.nih.gov/pubmed/36334143 http://dx.doi.org/10.1186/s41181-022-00182-z |
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author | Eryilmaz, Kurtulus Kilbas, Benan |
author_facet | Eryilmaz, Kurtulus Kilbas, Benan |
author_sort | Eryilmaz, Kurtulus |
collection | PubMed |
description | BACKGROUND: [(18)F]Flurpiridaz is a promising novel cardiac PET imaging tracer formed by the radiolabeling of pyridaben derivative with fluorine-18. Clinical studies on [(18)F]Flurpiridaz are currently at the phase III level for the assessment of MPI. Providing high image quality thanks to its relatively long half-life, F-18 is a high-potential radionuclide for the early detection of CAD. In this study, we aimed to develop a fully automated synthesis of [(18)F]Flurpiridaz without further preparative HPLC purification. RESULTS: Precursor 6 was obtained by multi-step synthesis starting from mucochloric acid (1) as a sole product with 35% yield and identified by spectroscopic measurement. Manually cold labeling experiments were performed using the stable isotope [(19)F]F, and TBA-HCO(3) PTC provided desirable fluorinated compound with high yield. A fully automated [(18)F]Flurpiridaz synthesis on the ML-PT device provided 55–65% radiochemical yield with more than 98% radiochemical purity. The final product purification method demonstrated that [(18)F]Flurpiridaz could be obtained without an external preparative HPLC system as a pharmaceutical quality. CONCLUSION: A novel and fascinating strategy was developed for the fully automated synthesis of [(18)F]Flurpiridaz (7) on ML PT. Organic synthesis of precursor 6 was achieved with a desirable yield and characterized by NMR and HR-MS. A detailed set of cold experiments were completed for optimization conditions before hot trials and TBA-HCO(3) increased molar activity with a minimum amount of side products. Radiolabeling showed that our self-designed automated synthesis method enables high radiochemical yield and radiochemical purity for the production of [(18)F]Flurpiridaz. The desirable radiopharmaceutical quality of the product was obtained without using an additional preparative HPLC system. [(18)F]Flurpiridaz (7) preserved its stability within 12 h and final specifications were consistent with the acceptance criteria in Ph. Eur. regulations. |
format | Online Article Text |
id | pubmed-9637077 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-96370772022-11-07 A practical fully automated radiosynthesis of [(18)F]Flurpiridaz on the module modular lab-pharmtracer without external purification Eryilmaz, Kurtulus Kilbas, Benan EJNMMI Radiopharm Chem Research Article BACKGROUND: [(18)F]Flurpiridaz is a promising novel cardiac PET imaging tracer formed by the radiolabeling of pyridaben derivative with fluorine-18. Clinical studies on [(18)F]Flurpiridaz are currently at the phase III level for the assessment of MPI. Providing high image quality thanks to its relatively long half-life, F-18 is a high-potential radionuclide for the early detection of CAD. In this study, we aimed to develop a fully automated synthesis of [(18)F]Flurpiridaz without further preparative HPLC purification. RESULTS: Precursor 6 was obtained by multi-step synthesis starting from mucochloric acid (1) as a sole product with 35% yield and identified by spectroscopic measurement. Manually cold labeling experiments were performed using the stable isotope [(19)F]F, and TBA-HCO(3) PTC provided desirable fluorinated compound with high yield. A fully automated [(18)F]Flurpiridaz synthesis on the ML-PT device provided 55–65% radiochemical yield with more than 98% radiochemical purity. The final product purification method demonstrated that [(18)F]Flurpiridaz could be obtained without an external preparative HPLC system as a pharmaceutical quality. CONCLUSION: A novel and fascinating strategy was developed for the fully automated synthesis of [(18)F]Flurpiridaz (7) on ML PT. Organic synthesis of precursor 6 was achieved with a desirable yield and characterized by NMR and HR-MS. A detailed set of cold experiments were completed for optimization conditions before hot trials and TBA-HCO(3) increased molar activity with a minimum amount of side products. Radiolabeling showed that our self-designed automated synthesis method enables high radiochemical yield and radiochemical purity for the production of [(18)F]Flurpiridaz. The desirable radiopharmaceutical quality of the product was obtained without using an additional preparative HPLC system. [(18)F]Flurpiridaz (7) preserved its stability within 12 h and final specifications were consistent with the acceptance criteria in Ph. Eur. regulations. Springer International Publishing 2022-11-05 /pmc/articles/PMC9637077/ /pubmed/36334143 http://dx.doi.org/10.1186/s41181-022-00182-z Text en © The Author(s) 2022 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 Eryilmaz, Kurtulus Kilbas, Benan A practical fully automated radiosynthesis of [(18)F]Flurpiridaz on the module modular lab-pharmtracer without external purification |
title | A practical fully automated radiosynthesis of [(18)F]Flurpiridaz on the module modular lab-pharmtracer without external purification |
title_full | A practical fully automated radiosynthesis of [(18)F]Flurpiridaz on the module modular lab-pharmtracer without external purification |
title_fullStr | A practical fully automated radiosynthesis of [(18)F]Flurpiridaz on the module modular lab-pharmtracer without external purification |
title_full_unstemmed | A practical fully automated radiosynthesis of [(18)F]Flurpiridaz on the module modular lab-pharmtracer without external purification |
title_short | A practical fully automated radiosynthesis of [(18)F]Flurpiridaz on the module modular lab-pharmtracer without external purification |
title_sort | practical fully automated radiosynthesis of [(18)f]flurpiridaz on the module modular lab-pharmtracer without external purification |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9637077/ https://www.ncbi.nlm.nih.gov/pubmed/36334143 http://dx.doi.org/10.1186/s41181-022-00182-z |
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