Direct arene C–H fluorination with 18F− via organic photoredox catalysis
A metal-free route to PET probes
Positron emission tomography (PET) is a widely used imaging technique for medical diagnostics and pharmaceutical development. As the name implies, it requires tracers that emit positrons, typically through labeling with fluorine or carbon radioisotopes. W. Chen et al. devised a versatile technique to incorporate radioactive fluoride into aromatic rings. The metal-free photochemical method directly substitutes aryl carbon-hydrogen bonds with [18F]fluoride and so is particularly well suited to late-stage transformation of complex molecules into tracers.
Science, this issue p. 1170
Abstract
Positron emission tomography (PET) plays key roles in drug discovery and development, as well as medical imaging. However, there is a dearth of efficient and simple radiolabeling methods for aromatic C–H bonds, which limits advancements in PET radiotracer development. Here, we disclose a mild method for the fluorine-18 (18F)–fluorination of aromatic C–H bonds by an [18F]F− salt via organic photoredox catalysis under blue light illumination. This strategy was applied to the synthesis of a wide range of 18F-labeled arenes and heteroaromatics, including pharmaceutical compounds. These products can serve as diagnostic agents or provide key information about the in vivo fate of the labeled substrates, as showcased in preliminary tracer studies in mice.
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Supplementary Material
Summary
Materials and Methods
Figs. S1 to S101
Tables S1 to S58
Spectral Data
Radio-HPLC Traces
Movies S1 to S3
Resources
References and Notes
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Science
Volume 364 | Issue 6446
21 June 2019
21 June 2019
Copyright
Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
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Submission history
Received: 11 October 2018
Accepted: 29 May 2019
Published in print: 21 June 2019
Acknowledgments
Funding: Financial support was provided in part by the National Institutes of Health (NIGMS) awards R01GM120186 (D.A.N.) and 5R01EB014354 (Z.L.) and by the UNC Department of Radiology, Biomedical Research Imaging Center, and UNC Lineberger Comprehensive Cancer Center (start-up fund to Z.L.). N.E.S.T. is grateful for an NSF Graduate Research Fellowship. PET instrumentation was supported via an NIH High-End Instrumentation Grant (1S10OD023611-01). Author contributions: W.C. established the final labeling conditions and conducted the majority of the aromatic labeling experiments. Z.H. established the initial labeling conditions and ran a portion of the aromatic labeling scope. N.E.S.T. identified the 19F-fluorination conditions and the catalyst system, synthesized 19F-aromatic standards, and co-wrote the manuscript. B.G. contributed to the initial labeling design and discussion. M.W. performed initial labeling and PET imaging experiments. H.W. established the inflammation and tumor models and performed PET imaging analysis. Z.W. contributed to the initial labeling design and discussion. D.A.N. and Z.L. conceived and supervised the project and experiments and also co-wrote the manuscript. Competing interests: N.E.S.T. and D.A.N. are inventors on a patent filed by UNC currently pending (U.S. Patent Application No. 15/826,092). Data and materials availability: Experimental procedures, additional data, and analysis are included in the supplementary materials. Data for PET and PET/CT images in Fig. 3 and figs. S94 and S95 have been submitted to Zenodo (43–47).
Authors
Funding Information
National Science Foundation: NSF Graduate Research Fellowship
National Institutes of Health: R01 GM120186
National Institutes of Health: 5R01EB014354
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