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David Nicewicz
University of North Carolina at Chapel Hill
Corresponding Author
ORCiD: https://orcid.org/0000-0003-1199-9879
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Positron emission tomography (PET) is a powerful imaging technology that could visualize and measure metabolic processes in vivo and/or obtain unique information about drug candidates at early stages. Identification of new and improved molecular probes plays a critical role in PET, but its progress is limited in many situations due to the lack of efficient and simple labeling methods to modify biologically active small molecules and/or drugs. Although various approaches have been reported, current methods to radiofluorinate unactivated arenes are still limited. Here we document the discovery of a robust method for constructing C–18F bonds through direct halide/18F conversion in electron-rich halo(hetero)arene substrates. Based on readily available halide precursors and mild photoredox conditions, 18FF- is efficiently introduced into a broad spectrum of organic molecules, including pharmaceutical compounds in a site-selective manner. Notably, the direct 19F/18F conversion method is demonstrated to be a simple and robust protocol for PET probe screening/preparation: this methodology not only identifies a new cancer imaging agent L-61-18F-COOH after a rapid screening of a tyrosine isomer library; but also allows the simple and high-yielding synthesis of the widely used PET agent L-18FFDOPA. Taken together, photoredox-mediated halide/18F interconversion strategies represent an innovative chemical tool to prepare new and clinically significant PET agents that are synthetically inaccessible or cumbersome to achieve by traditional methods.
Keywords
Positron Emission Tomography, Molecular Probes, Drug Candidates, C-18F Bonds, Halide Precursors, Site-selective Introduction
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Yes there is potential Competing Interest. The authors have filed a provisional US patent on the basis of the research in this manuscript.
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See the published version of this preprint at Nature Chemistry.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Article
David Nicewicz
University of North Carolina at Chapel Hill
Corresponding Author
ORCiD: https://orcid.org/0000-0003-1199-9879
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at Nature Chemistry.
Version 1
Posted 04 Dec, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Nature Chemistry.
Positron emission tomography (PET) is a powerful imaging technology that could visualize and measure metabolic processes in vivo and/or obtain unique information about drug candidates at early stages. Identification of new and improved molecular probes plays a critical role in PET, but its progress is limited in many situations due to the lack of efficient and simple labeling methods to modify biologically active small molecules and/or drugs. Although various approaches have been reported, current methods to radiofluorinate unactivated arenes are still limited. Here we document the discovery of a robust method for constructing C–18F bonds through direct halide/18F conversion in electron-rich halo(hetero)arene substrates. Based on readily available halide precursors and mild photoredox conditions, 18FF- is efficiently introduced into a broad spectrum of organic molecules, including pharmaceutical compounds in a site-selective manner. Notably, the direct 19F/18F conversion method is demonstrated to be a simple and robust protocol for PET probe screening/preparation: this methodology not only identifies a new cancer imaging agent L-61-18F-COOH after a rapid screening of a tyrosine isomer library; but also allows the simple and high-yielding synthesis of the widely used PET agent L-18FFDOPA. Taken together, photoredox-mediated halide/18F interconversion strategies represent an innovative chemical tool to prepare new and clinically significant PET agents that are synthetically inaccessible or cumbersome to achieve by traditional methods.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Yes there is potential Competing Interest. The authors have filed a provisional US patent on the basis of the research in this manuscript.
This is a list of supplementary files associated with this preprint. Click to download.
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