Copper-mediated late-stage radiofluorination: five years of impact on preclinical and clinical PET imaging

Abstract

Purpose

Copper-mediated radiofluorination (CMRF) is emerging as the method of choice for the formation of aromatic C–18F bonds. This minireview examines proof-of-concept, preclinical, and in-human imaging studies of new and established imaging agents containing aromatic C–18F bonds synthesized with CMRF. An exhaustive discussion of CMRF methods is not provided, although key developments that have enabled or improved upon the syntheses of fluorine-18 imaging agents are discussed.

Methods

A comprehensive literature search from April 2014 onwards of the Web of Science and PubMed library databases was performed to find reports that utilize CMRF for the synthesis of fluorine-18 radiopharmaceuticals, and these represent the primary body of research discussed in this minireview. Select conference proceedings, previous reports describing alternative methods for the synthesis of imaging agents, and preceding fluorine-19 methodologies have also been included for discussion.

Conclusions

CMRF has significantly expanded the chemical space that is accessible to fluorine-18 radiolabeling with production methods that can meet the regulatory requirements for use in Nuclear Medicine. Furthermore, it has enabled novel and improved syntheses of radiopharmaceuticals and facilitated subsequent PET imaging studies. The rapid adoption of CMRF will undoubtedly continue to simplify the production of imaging agents and inspire the development of new radiofluorination methodologies.

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Funding

Funding from the National Institutes of Health (R01EB021155 to P.J.H.S and M.S.S; F32GM136022 to L.S.S) is gratefully acknowledged.

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All authors participated in literature search, literature review, manuscript writing, manuscript editing and content planning.

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Correspondence to Melanie S. Sanford or Peter J. H. Scott.

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All authors (Jay S. Wright, Tanpreet Kaur, Sean Preshlock, Sean S. Tanzey, Wade P. Winton, Liam S. Sharninghausen, Nicholas Wiesner, Allen F. Brooks, Melanie S. Sanford and Peter J. H. Scott) declare that there is no conflict of interest regarding the publication of this article.

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This review article does not contain any original studies with human or animal subjects performed by any of the authors.

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This article is dedicated to the memory of Dr. Giovanni Lucignani, Editor-in-Chief of Clinical and Translational Imaging, who sadly passed away recently. The energy and enthusiasm he brought to this field will be greatly missed. Ciao, amico mio.

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Wright, J.S., Kaur, T., Preshlock, S. et al. Copper-mediated late-stage radiofluorination: five years of impact on preclinical and clinical PET imaging. Clin Transl Imaging 8, 167–206 (2020). https://doi.org/10.1007/s40336-020-00368-y

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Keywords

  • Fluorine-18
  • Positron emission tomography
  • Radiotracer
  • Radioligand
  • Copper
  • Radiofluorination