Journal Article

FZJ-2025-03941

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Comparative evaluation of three 18F-fluorinated FAP ligands in rodent tumor models

Hoffmann, C.FZJ* ; Gröner, B. ; Bahutski, V. ; Endepols, H.FZJ* ; Lindemeyer, J. ; Saniternik, S. ; Drewes, B.FZJ* ; Timmer, M. ; Gokhadze, O.FZJ* ; Brugger, M.FZJ* ; Neumaier, F.FZJ* ; Neumaier, B. (Corresponding author)FZJ* ; Zlatopolskiy, B. D.FZJ*

2025
Elsevier Science Amsterdam [u.a.]

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Please use a persistent id in citations: doi:10.1016/j.ejmech.2025.118103  doi:10.34734/FZJ-2025-03941

Abstract: 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.

Note: 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]).

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Contributing Institute(s):

1. Nuklearchemie (INM-5)

Research Program(s):

1. 5253 - Neuroimaging (POF4-525) (POF4-525)

Appears in the scientific report 2025

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