Next generation fibroblast activation protein (FAP) targeting PET tracers : The tetrazine ligation allows an easy and convenient way to 18F-labeled (4-quinolinoyl)glycyl-2-cyanopyrrolidines

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Small-molecular fibroblast activation protein inhibitor (FAPI)-based tracer have been shown to be promising Positron Emission Tomography (PET) 68Ga-labeled radiopharmaceuticals to image a variety of tumors including pancreatic, breast, and colorectal cancers, among others. In this study, we developed a novel 18F-labeled FAPI derivative. [18F]6 was labeled using a synthon approach based on the tetrazine ligation. It showed subnanomolar affinity for the FAP protein and a good selectivity profile against known off-target proteases. Small animal PET studies revealed high tumor uptake and good target-to-background ratios. [18F]6 was excreted via the liver. Overall, [18F]6 showed promising characteristics to be used as a PET tracer and could serve as a lead for further development of halogen-based theranostic FAPI radiopharmaceuticals.

Original languageEnglish
Article number115862
JournalEuropean Journal of Medicinal Chemistry
Volume262
Number of pages10
ISSN0223-5234
DOIs
Publication statusPublished - 2023

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© 2023 The Authors

    Research areas

  • FAPI, Fluorine-18, PET, Tetrazine ligation, Theranostics

ID: 373617240