2. Academic Validation
  3. Druglike, 18F-labeled PET Tracers Targeting Fibroblast Activation Protein

Druglike, 18F-labeled PET Tracers Targeting Fibroblast Activation Protein

  • J Med Chem. 2024 May 9;67(9):7068-7087. doi: 10.1021/acs.jmedchem.3c02402.
Muhammet Tanc 1,  Nicolò Filippi 1,  Yentl Van Rymenant 2,  Sergei Grintsevich 1,  Isabel Pintelon 3,  Marlies Verschuuren 3,  Joni De Loose 2,  Emile Verhulst 2,  Euy Sung Moon 4,  Lorenzo Cianni 1,  Sigrid Stroobants 5,  Koen Augustyns 1,  Frank Roesch 4,  Ingrid De Meester 2,  Filipe Elvas 5,  Pieter Van der Veken 1
Affiliations

Affiliations

  • 1 Laboratory of Medicinal Chemistry, Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.
  • 2 Laboratory of Medical Biochemistry, Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.
  • 3 Laboratory of Cell Biology and Histology, Department of Veterinary Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.
  • 4 Institut für Kernchemie, Johannes Gutenberg University of Mainz, Fritz-Strassman-Weg 2, D-55128 Mainz, Germany.
  • 5 Molecular Imaging and Radiology, Faculty of Medicine and Health Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.
PMID: 38656144 DOI: 10.1021/acs.jmedchem.3c02402
Abstract

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 in 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, multicharged 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.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-158326
    FAP Inhibitor
    FAP