Improved automated one-pot two-step radiosynthesis of (S)-[18F]FETrp, a radiotracer for PET imaging of indoleamine 2,3-dioxygenase 1 (IDO1)
Abstract Background (S)-[18F]FETrp is a promising PET radiotracer for imaging IDO1 activity, one of the main enzymes involved in the tryptophan metabolism that plays a key role in several diseases including cancers. To date, the radiosynthesis of this tryptophan analogue remains highly challenging d...
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| Format: | Article |
| Language: | English |
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SpringerOpen
2024-04-01
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| Series: | EJNMMI Radiopharmacy and Chemistry |
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| Online Access: | https://doi.org/10.1186/s41181-024-00256-0 |
| _version_ | 1797219454072913920 |
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| author | Aurélie Maisonial-Besset David Kryza Klaus Kopka Sophie Levesque Emmanuel Moreau Barbara Wenzel Jean-Michel Chezal |
| author_facet | Aurélie Maisonial-Besset David Kryza Klaus Kopka Sophie Levesque Emmanuel Moreau Barbara Wenzel Jean-Michel Chezal |
| author_sort | Aurélie Maisonial-Besset |
| collection | DOAJ |
| description | Abstract Background (S)-[18F]FETrp is a promising PET radiotracer for imaging IDO1 activity, one of the main enzymes involved in the tryptophan metabolism that plays a key role in several diseases including cancers. To date, the radiosynthesis of this tryptophan analogue remains highly challenging due to partial racemization occurring during the nucleophilic radiofluorination step. This work aims to develop a short, epimerization-free and efficient automated procedure of (S)-[18F]FETrp from a corresponding enantiopure tosylate precursor. Results Enantiomerically pure (S)- and (R)-FETrp references as well as tosylate precursors (S)- and (R)-3 were obtained from corresponding N a -Boc-(L and D)-tryptophan in 2 and 4 steps, respectively. Manual optimisation of the radiolabelling conditions resulted in > 90% radiochemical conversion with more than 99% enantiomeric purity. Based on these results, the (S)-[18F]FETrp radiosynthesis was fully automated on a SynChrom R&D EVOI module to produce the radiotracer in 55.2 ± 7.5% radiochemical yield, 99.9% radiochemical purity, 99.1 ± 0.5% enantiomeric excess, and molar activity of 53.2 ± 9.3 GBq/µmol (n = 3). Conclusions To avoid racemisation and complicated purification processes, currently encountered for the radiosynthesis of (S)-[18F]FETrp, we report herein significant improvements, including a versatile synthesis of enantiomerically pure tosylate precursor and reference compound and a convenient one-pot two-step automated procedure for the radiosynthesis of (S)-[18F]FETrp. This optimised and robust production method could facilitate further investigations of this relevant PET radiotracer for imaging IDO1 activity. |
| first_indexed | 2024-04-24T12:33:54Z |
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| id | doaj.art-49b3c42351434cc394f2ac1f88f2ef8f |
| institution | Directory Open Access Journal |
| issn | 2365-421X |
| language | English |
| last_indexed | 2024-04-24T12:33:54Z |
| publishDate | 2024-04-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | EJNMMI Radiopharmacy and Chemistry |
| spelling | doaj.art-49b3c42351434cc394f2ac1f88f2ef8f2024-04-07T11:34:50ZengSpringerOpenEJNMMI Radiopharmacy and Chemistry2365-421X2024-04-019112210.1186/s41181-024-00256-0Improved automated one-pot two-step radiosynthesis of (S)-[18F]FETrp, a radiotracer for PET imaging of indoleamine 2,3-dioxygenase 1 (IDO1)Aurélie Maisonial-Besset0David Kryza1Klaus Kopka2Sophie Levesque3Emmanuel Moreau4Barbara Wenzel5Jean-Michel Chezal6Université Clermont Auvergne, Inserm, Imagerie Moléculaire et Stratégies Théranostiques, UMR 1240Imthernat, LAGEPP, CNRS UMR 5007, Université de Lyon, Hospices Civils de LyonInstitute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Research Site LeipzigUniversité Clermont Auvergne, Inserm, Imagerie Moléculaire et Stratégies Théranostiques, UMR 1240Université Clermont Auvergne, Inserm, Imagerie Moléculaire et Stratégies Théranostiques, UMR 1240Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Research Site LeipzigUniversité Clermont Auvergne, Inserm, Imagerie Moléculaire et Stratégies Théranostiques, UMR 1240Abstract Background (S)-[18F]FETrp is a promising PET radiotracer for imaging IDO1 activity, one of the main enzymes involved in the tryptophan metabolism that plays a key role in several diseases including cancers. To date, the radiosynthesis of this tryptophan analogue remains highly challenging due to partial racemization occurring during the nucleophilic radiofluorination step. This work aims to develop a short, epimerization-free and efficient automated procedure of (S)-[18F]FETrp from a corresponding enantiopure tosylate precursor. Results Enantiomerically pure (S)- and (R)-FETrp references as well as tosylate precursors (S)- and (R)-3 were obtained from corresponding N a -Boc-(L and D)-tryptophan in 2 and 4 steps, respectively. Manual optimisation of the radiolabelling conditions resulted in > 90% radiochemical conversion with more than 99% enantiomeric purity. Based on these results, the (S)-[18F]FETrp radiosynthesis was fully automated on a SynChrom R&D EVOI module to produce the radiotracer in 55.2 ± 7.5% radiochemical yield, 99.9% radiochemical purity, 99.1 ± 0.5% enantiomeric excess, and molar activity of 53.2 ± 9.3 GBq/µmol (n = 3). Conclusions To avoid racemisation and complicated purification processes, currently encountered for the radiosynthesis of (S)-[18F]FETrp, we report herein significant improvements, including a versatile synthesis of enantiomerically pure tosylate precursor and reference compound and a convenient one-pot two-step automated procedure for the radiosynthesis of (S)-[18F]FETrp. This optimised and robust production method could facilitate further investigations of this relevant PET radiotracer for imaging IDO1 activity.https://doi.org/10.1186/s41181-024-00256-0[18F]FETrpIDO1Fluorine-18RadiochemistryRadiofluorinationAutomation |
| spellingShingle | Aurélie Maisonial-Besset David Kryza Klaus Kopka Sophie Levesque Emmanuel Moreau Barbara Wenzel Jean-Michel Chezal Improved automated one-pot two-step radiosynthesis of (S)-[18F]FETrp, a radiotracer for PET imaging of indoleamine 2,3-dioxygenase 1 (IDO1) EJNMMI Radiopharmacy and Chemistry [18F]FETrp IDO1 Fluorine-18 Radiochemistry Radiofluorination Automation |
| title | Improved automated one-pot two-step radiosynthesis of (S)-[18F]FETrp, a radiotracer for PET imaging of indoleamine 2,3-dioxygenase 1 (IDO1) |
| title_full | Improved automated one-pot two-step radiosynthesis of (S)-[18F]FETrp, a radiotracer for PET imaging of indoleamine 2,3-dioxygenase 1 (IDO1) |
| title_fullStr | Improved automated one-pot two-step radiosynthesis of (S)-[18F]FETrp, a radiotracer for PET imaging of indoleamine 2,3-dioxygenase 1 (IDO1) |
| title_full_unstemmed | Improved automated one-pot two-step radiosynthesis of (S)-[18F]FETrp, a radiotracer for PET imaging of indoleamine 2,3-dioxygenase 1 (IDO1) |
| title_short | Improved automated one-pot two-step radiosynthesis of (S)-[18F]FETrp, a radiotracer for PET imaging of indoleamine 2,3-dioxygenase 1 (IDO1) |
| title_sort | improved automated one pot two step radiosynthesis of s 18f fetrp a radiotracer for pet imaging of indoleamine 2 3 dioxygenase 1 ido1 |
| topic | [18F]FETrp IDO1 Fluorine-18 Radiochemistry Radiofluorination Automation |
| url | https://doi.org/10.1186/s41181-024-00256-0 |
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