TY  - JOUR
AU  - Hoffmann, Chris
AU  - Gröner, Benedikt
AU  - Bahutski, Victor
AU  - Endepols, Heike
AU  - Lindemeyer, Johannes
AU  - Saniternik, Sven
AU  - Drewes, Birte
AU  - Timmer, Marco
AU  - Gokhadze, Otari
AU  - Brugger, Melanie
AU  - Neumaier, Felix
AU  - Neumaier, Bernd
AU  - Zlatopolskiy, Boris D.
TI  - Comparative evaluation of three 18F-fluorinated FAP ligands in rodent tumor models
JO  - European journal of medicinal chemistry
VL  - 299
SN  - 0009-4374
CY  - Amsterdam [u.a.]
PB  - Elsevier Science
M1  - FZJ-2025-03941
SP  - 118103
PY  - 2025
N1  - This work was supported by Deutsche Forschungsgemeinschaft (DFG; grant number ZL 65/4-1), the Shota Rustaveli National Science Foundation of Georgia (SRNSFG; grant number JFZ–II–22-074), and the Excellent Research Support Program, University of Cologne (UoC) Forum 2023 (Multimodal Preclinical Imaging Platform University Cologne [MUPIC]).
AB  - Fibroblast activation protein (FAP) is almost exclusively expressed on cancer-associated stromal cells, making it apromising target for tumor imaging by positron emission tomography (PET). While 68Ga- or Al[18F]F-labeled FAPinhibitors (FAPIs) have been characterized in detail, the potential advantages of FAPIs containing a covalentlybound 18F-label remain largely unknown. The aim of the present work was to address this gap by comparing twoFAPIs with a covalently bound 18F-label and the chelator-based radioligand Al[18F]F-FAPI-42.The 18F-labeled FAPIs were prepared by direct (6-[18F]F-FAPI) or indirect ([18F]AFA-FAPI) radiofluorination,or by the Al[18F]F chelation method (Al[18F]F-FAPI-42), which afforded the tracers in activity yields of 11–57 %and with molar activities of 5–170 GBq/μmol. Cellular uptake studies revealed significantly higher accumulationof all three candidates in HT1080-FAP compared to HT1080-WT cells. 6-[18F]F-FAPI and Al[18F]F-FAPI-42showed comparable FAP-selectivity and tumor uptake in mice inoculated with the two cell lines and rats bearingsubcutaneous DSL-6A/C1 tumors, while no in vivo FAP-selectivity was observed for [18F]AFA-FAPI. Al[18F]FFAPI-42 exhibited lower hepatobiliary excretion and faster clearance from FAP-negative tissues in the subcutaneoustumor models. In contrast, 6-[18F]F-FAPI showed higher tumor uptake and better tumor retention in anintracerebral U87 glioma tumor model. When compared to the established glioma tracer [18F]FET, both FAPtargetingtracers visualized intracerebral tumors with more than two-fold higher tumor-to-background ratios.In conclusion, while the chelator-based radioligand Al[18F]F-FAPI-42 is well-suited for visualization of peripheraltumors, 6-[18F]F-FAPI with a covalently bound 18F-label shows more favorable properties for braintumor imaging.
LB  - PUB:(DE-HGF)16
DO  - DOI:10.1016/j.ejmech.2025.118103
UR  - https://juser.fz-juelich.de/record/1046742
ER  -