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Title
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Druglike, ¹⁸F-labeled PET tracers targeting fibroblast activation protein (FAP)
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Author
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Abstract
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| Fibroblast activation protein (FAP) is a very reliable biomarker for tissue remodeling. FAP has so far mainly been studied in oncology, but there is growing interest for the enzyme in other diseases like fibrosis. Recently FAP-targeting diagnostics and therapeutics have emerged, of which the so-called FAPIs are among the most promising representatives. FAPIs typically have a relatively high molecular weight and contain very polar, multi-charged chelator moieties. While this is not limiting the application of FAPIs in oncology, more druglike FAPIs could be required to optimally study diseases characterized by denser, less permeable tissue. In response, we designed the first druglike 18F-labeled FAPIs. We report target potencies, biodistribution and pharmacokinetics and demonstrate FAP-dependent uptake in murine tumor xenografts. Finally, this paper puts forward compound 10 as a highly promising, druglike FAPI for 18F-PET imaging. This molecule is fit for additional studies in fibrosis and its preclinical profile warrants clinical investigation. |
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Language
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English
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Source (journal)
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Journal of medicinal chemistry. - Washington, D.C., 1963, currens
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Publication
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Washington, D.C.
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2024
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ISSN
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0022-2623
[print]
1520-4804
[online]
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DOI
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10.1021/ACS.JMEDCHEM.3C02402
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Volume/pages
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67
:9
(2024)
, p. 7068-7087
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ISI
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001226332800001
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Pubmed ID
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38656144
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Full text (Publisher's DOI)
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Full text (open access)
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The author-created version that incorporates referee comments and is the accepted for publication version Available from 24.10.2024
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Full text (publisher's version - intranet only)
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