Manual and automated Cu-mediated radiosynthesis of the PARP inhibitor [18F]olaparib
Positron emission tomography (PET) is a diagnostic nuclear imaging modality that relies on automated protocols to prepare agents labeled with a positron-emitting radionuclide (e.g., 18F). In recent years, new reactions have appeared for the 18F-labeling of agents that are difficult to access by appl...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
Nature Research
2020
|
| _version_ | 1797060106592976896 |
|---|---|
| author | Guibbal, F Isenegger, PG Wilson, TC Pacelli, A Mahaut, D Sap, JBI Taylor, NJ Verhoog, S Preshlock, S Hueting, R Cornelissen, B Gouverneur, V |
| author_facet | Guibbal, F Isenegger, PG Wilson, TC Pacelli, A Mahaut, D Sap, JBI Taylor, NJ Verhoog, S Preshlock, S Hueting, R Cornelissen, B Gouverneur, V |
| author_sort | Guibbal, F |
| collection | OXFORD |
| description | Positron emission tomography (PET) is a diagnostic nuclear imaging modality that relies on automated protocols to prepare agents labeled with a positron-emitting radionuclide (e.g., 18F). In recent years, new reactions have appeared for the 18F-labeling of agents that are difficult to access by applying traditional radiochemistry, for example those requiring 18F incorporation into unactivated (hetero)arenes. However, automation of these new methods for translation to the clinic has progressed slowly because extensive modification of manual protocols is typically required when implementing novel 18F-labeling methodologies within automated modules. Here, we describe the workflow that led to the automated radiosynthesis of the poly(ADP-ribose) polymerase (PARP) inhibitor [18F]olaparib. First, we established a robust manual protocol to prepare [18F]olaparib from the protected N-[2-(trimethylsilyl)ethoxy]methyl (SEM) arylboronate ester precursor in a 17% ± 5% (n = 15; synthesis time, 135 min) non-decay-corrected (NDC) activity yield, with molar activity (Am) up to 34.6 GBq/µmol. Automation of the process, consisting of copper-mediated 18F-fluorodeboronation followed by deprotection, was achieved on an Eckert & Ziegler Modular-Lab radiosynthesis platform, affording [18F]olaparib in a 6% ± 5% (n = 3; synthesis time, 120 min) NDC activity yield with Am up to 319 GBq/µmol. |
| first_indexed | 2024-03-06T20:12:56Z |
| format | Journal article |
| id | oxford-uuid:2b31e33c-e32a-4c16-ba20-350944bbe156 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:12:56Z |
| publishDate | 2020 |
| publisher | Nature Research |
| record_format | dspace |
| spelling | oxford-uuid:2b31e33c-e32a-4c16-ba20-350944bbe1562022-03-26T12:29:34ZManual and automated Cu-mediated radiosynthesis of the PARP inhibitor [18F]olaparibJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:2b31e33c-e32a-4c16-ba20-350944bbe156EnglishSymplectic ElementsNature Research2020Guibbal, FIsenegger, PGWilson, TCPacelli, AMahaut, DSap, JBITaylor, NJVerhoog, SPreshlock, SHueting, RCornelissen, BGouverneur, VPositron emission tomography (PET) is a diagnostic nuclear imaging modality that relies on automated protocols to prepare agents labeled with a positron-emitting radionuclide (e.g., 18F). In recent years, new reactions have appeared for the 18F-labeling of agents that are difficult to access by applying traditional radiochemistry, for example those requiring 18F incorporation into unactivated (hetero)arenes. However, automation of these new methods for translation to the clinic has progressed slowly because extensive modification of manual protocols is typically required when implementing novel 18F-labeling methodologies within automated modules. Here, we describe the workflow that led to the automated radiosynthesis of the poly(ADP-ribose) polymerase (PARP) inhibitor [18F]olaparib. First, we established a robust manual protocol to prepare [18F]olaparib from the protected N-[2-(trimethylsilyl)ethoxy]methyl (SEM) arylboronate ester precursor in a 17% ± 5% (n = 15; synthesis time, 135 min) non-decay-corrected (NDC) activity yield, with molar activity (Am) up to 34.6 GBq/µmol. Automation of the process, consisting of copper-mediated 18F-fluorodeboronation followed by deprotection, was achieved on an Eckert & Ziegler Modular-Lab radiosynthesis platform, affording [18F]olaparib in a 6% ± 5% (n = 3; synthesis time, 120 min) NDC activity yield with Am up to 319 GBq/µmol. |
| spellingShingle | Guibbal, F Isenegger, PG Wilson, TC Pacelli, A Mahaut, D Sap, JBI Taylor, NJ Verhoog, S Preshlock, S Hueting, R Cornelissen, B Gouverneur, V Manual and automated Cu-mediated radiosynthesis of the PARP inhibitor [18F]olaparib |
| title | Manual and automated Cu-mediated radiosynthesis of the PARP inhibitor [18F]olaparib |
| title_full | Manual and automated Cu-mediated radiosynthesis of the PARP inhibitor [18F]olaparib |
| title_fullStr | Manual and automated Cu-mediated radiosynthesis of the PARP inhibitor [18F]olaparib |
| title_full_unstemmed | Manual and automated Cu-mediated radiosynthesis of the PARP inhibitor [18F]olaparib |
| title_short | Manual and automated Cu-mediated radiosynthesis of the PARP inhibitor [18F]olaparib |
| title_sort | manual and automated cu mediated radiosynthesis of the parp inhibitor 18f olaparib |
| work_keys_str_mv | AT guibbalf manualandautomatedcumediatedradiosynthesisoftheparpinhibitor18folaparib AT iseneggerpg manualandautomatedcumediatedradiosynthesisoftheparpinhibitor18folaparib AT wilsontc manualandautomatedcumediatedradiosynthesisoftheparpinhibitor18folaparib AT pacellia manualandautomatedcumediatedradiosynthesisoftheparpinhibitor18folaparib AT mahautd manualandautomatedcumediatedradiosynthesisoftheparpinhibitor18folaparib AT sapjbi manualandautomatedcumediatedradiosynthesisoftheparpinhibitor18folaparib AT taylornj manualandautomatedcumediatedradiosynthesisoftheparpinhibitor18folaparib AT verhoogs manualandautomatedcumediatedradiosynthesisoftheparpinhibitor18folaparib AT preshlocks manualandautomatedcumediatedradiosynthesisoftheparpinhibitor18folaparib AT huetingr manualandautomatedcumediatedradiosynthesisoftheparpinhibitor18folaparib AT cornelissenb manualandautomatedcumediatedradiosynthesisoftheparpinhibitor18folaparib AT gouverneurv manualandautomatedcumediatedradiosynthesisoftheparpinhibitor18folaparib |