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GMP production of 6-[(18)F]Fluoro-l-DOPA for PET/CT imaging by different synthetic routes: a three center experience

BACKGROUND: The radiofluorinated levodopa analogue 6-[(18)F]F-l-DOPA (3,4-dihydroxy-6-(18)F-l-phenylalanine) is a commonly employed radiotracer for PET/CT imaging of multiple oncological and neurological indications. An unusually large number of different radiosyntheses have been published to the po...

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Autores principales: Andersen, Valdemar L., Soerensen, Mikkel A., Dam, Johan Hygum, Langkjaer, Niels, Petersen, Henrik, Bender, Dirk Andreas, Fugloe, Dan, Huynh, Tri Hien Viet
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8197687/
https://www.ncbi.nlm.nih.gov/pubmed/34117961
http://dx.doi.org/10.1186/s41181-021-00135-y
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author Andersen, Valdemar L.
Soerensen, Mikkel A.
Dam, Johan Hygum
Langkjaer, Niels
Petersen, Henrik
Bender, Dirk Andreas
Fugloe, Dan
Huynh, Tri Hien Viet
author_facet Andersen, Valdemar L.
Soerensen, Mikkel A.
Dam, Johan Hygum
Langkjaer, Niels
Petersen, Henrik
Bender, Dirk Andreas
Fugloe, Dan
Huynh, Tri Hien Viet
author_sort Andersen, Valdemar L.
collection PubMed
description BACKGROUND: The radiofluorinated levodopa analogue 6-[(18)F]F-l-DOPA (3,4-dihydroxy-6-(18)F-l-phenylalanine) is a commonly employed radiotracer for PET/CT imaging of multiple oncological and neurological indications. An unusually large number of different radiosyntheses have been published to the point where two different Ph. Eur. monographs exist depending on whether the chemistry relies on electrophilic or nucleophilic radiosubstitution of appropriate chemical precursors. For new PET imaging sites wishing to adopt [(18)F]FDOPA into clinical practice, selecting the appropriate production process may be difficult and dependent on the clinical needs of the site. METHODS: Data from four years of [(18)F]FDOPA production at three different clinical sites are collected and compared. These three sites, Aarhus University Hospital (AUH), Odense University Hospital (OUH), and Herlev University Hospital (HUH), produce the radiotracer by different radiosynthetic routes with AUH adopting an electrophilic strategy, while OUH and HUH employ two different nucleophilic approaches. Production failure rates, radiochemical yields, and molar activities are compared across sites and time. Additionally, the clinical use of the radiotracer over the time period considered at the different sites are presented and discussed. RESULTS: The electrophilic substitution route suffers from being demanding in terms of cyclotron operation and maintenance. This challenge, however, was found to be compensated by a production failure rate significantly below that of both nucleophilic approaches; a result of simpler chemistry. The five-step nucleophilic approach employed at HUH produces superior radiochemical yields compared to the three-step approach adopted at OUH but suffers from the need for more comprehensive synthesis equipment given the multi-step nature of the procedure, including HPLC purification. While the procedure at OUH furnishes the lowest radiochemical yield of the synthetic routes considered, it produces the highest molar activity. This is of importance across the clinical applications of the tracer discussed here, including dopamine synthesis in striatum of subjects with schizophrenia and congenital hyperinsulinism in infants. CONCLUSION: For most sites either of the two nucleophilic substitution strategies should be favored. However, which of the two will depend on whether a given site wishes to optimize the radiochemical yield or the ease of the use. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s41181-021-00135-y.
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spelling pubmed-81976872021-06-28 GMP production of 6-[(18)F]Fluoro-l-DOPA for PET/CT imaging by different synthetic routes: a three center experience Andersen, Valdemar L. Soerensen, Mikkel A. Dam, Johan Hygum Langkjaer, Niels Petersen, Henrik Bender, Dirk Andreas Fugloe, Dan Huynh, Tri Hien Viet EJNMMI Radiopharm Chem Research Article BACKGROUND: The radiofluorinated levodopa analogue 6-[(18)F]F-l-DOPA (3,4-dihydroxy-6-(18)F-l-phenylalanine) is a commonly employed radiotracer for PET/CT imaging of multiple oncological and neurological indications. An unusually large number of different radiosyntheses have been published to the point where two different Ph. Eur. monographs exist depending on whether the chemistry relies on electrophilic or nucleophilic radiosubstitution of appropriate chemical precursors. For new PET imaging sites wishing to adopt [(18)F]FDOPA into clinical practice, selecting the appropriate production process may be difficult and dependent on the clinical needs of the site. METHODS: Data from four years of [(18)F]FDOPA production at three different clinical sites are collected and compared. These three sites, Aarhus University Hospital (AUH), Odense University Hospital (OUH), and Herlev University Hospital (HUH), produce the radiotracer by different radiosynthetic routes with AUH adopting an electrophilic strategy, while OUH and HUH employ two different nucleophilic approaches. Production failure rates, radiochemical yields, and molar activities are compared across sites and time. Additionally, the clinical use of the radiotracer over the time period considered at the different sites are presented and discussed. RESULTS: The electrophilic substitution route suffers from being demanding in terms of cyclotron operation and maintenance. This challenge, however, was found to be compensated by a production failure rate significantly below that of both nucleophilic approaches; a result of simpler chemistry. The five-step nucleophilic approach employed at HUH produces superior radiochemical yields compared to the three-step approach adopted at OUH but suffers from the need for more comprehensive synthesis equipment given the multi-step nature of the procedure, including HPLC purification. While the procedure at OUH furnishes the lowest radiochemical yield of the synthetic routes considered, it produces the highest molar activity. This is of importance across the clinical applications of the tracer discussed here, including dopamine synthesis in striatum of subjects with schizophrenia and congenital hyperinsulinism in infants. CONCLUSION: For most sites either of the two nucleophilic substitution strategies should be favored. However, which of the two will depend on whether a given site wishes to optimize the radiochemical yield or the ease of the use. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s41181-021-00135-y. Springer International Publishing 2021-06-12 /pmc/articles/PMC8197687/ /pubmed/34117961 http://dx.doi.org/10.1186/s41181-021-00135-y 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
Andersen, Valdemar L.
Soerensen, Mikkel A.
Dam, Johan Hygum
Langkjaer, Niels
Petersen, Henrik
Bender, Dirk Andreas
Fugloe, Dan
Huynh, Tri Hien Viet
GMP production of 6-[(18)F]Fluoro-l-DOPA for PET/CT imaging by different synthetic routes: a three center experience
title GMP production of 6-[(18)F]Fluoro-l-DOPA for PET/CT imaging by different synthetic routes: a three center experience
title_full GMP production of 6-[(18)F]Fluoro-l-DOPA for PET/CT imaging by different synthetic routes: a three center experience
title_fullStr GMP production of 6-[(18)F]Fluoro-l-DOPA for PET/CT imaging by different synthetic routes: a three center experience
title_full_unstemmed GMP production of 6-[(18)F]Fluoro-l-DOPA for PET/CT imaging by different synthetic routes: a three center experience
title_short GMP production of 6-[(18)F]Fluoro-l-DOPA for PET/CT imaging by different synthetic routes: a three center experience
title_sort gmp production of 6-[(18)f]fluoro-l-dopa for pet/ct imaging by different synthetic routes: a three center experience
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8197687/
https://www.ncbi.nlm.nih.gov/pubmed/34117961
http://dx.doi.org/10.1186/s41181-021-00135-y
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