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Comparative evaluation of three 18F-fluorinated FAP ligands in rodent tumor models

  • 0Forschungszentrum Jülich GmbH, Institute of Neuroscience and Medicine, Nuclear Chemistry (INM-5), Wilhelm-Johnen-Straße, Jülich, 52428, Germany; University of Cologne, Faculty of Medicine and University Hospital Cologne, Institute of Radiochemistry and Experimental Molecular Imaging, Kerpener Straße 62, 50937, Cologne, Germany.
European Journal of Medicinal Chemistry +

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August 31, 2025

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August 31, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

This study compares two novel <sup>18</sup>F-labeled fibroblast activation protein inhibitors (FAPIs) with a chelator-based FAPI for tumor imaging. 6-[<sup>18</sup>F]F-FAPI is superior for brain tumor imaging, while Al[<sup>18</sup>F]F-FAPI-42 excels in visualizing peripheral tumors.

Area Of Science

  • Radiochemistry
  • Oncology
  • Molecular Imaging

Background

  • Fibroblast activation protein (FAP) is a key target for cancer imaging.
  • <sup>68</sup>Ga- or Al[<sup>18</sup>F]F-labeled FAP inhibitors (FAPIs) are established PET tracers.
  • The advantages of FAPIs with covalently bound <sup>18</sup>F-labels are not well understood.

Purpose Of The Study

  • To compare the performance of two FAPIs with covalently bound <sup>18</sup>F-labels against a chelator-based <sup>18</sup>F-FAPI.
  • To evaluate their potential for tumor imaging via positron emission tomography (PET).

Main Methods

  • Synthesis of <sup>18</sup>F-labeled FAPIs via direct, indirect radiofluorination, and Al[<sup>18</sup>F]F chelation.
  • In vitro cellular uptake studies using HT1080-FAP and HT1080-WT cells.
  • In vivo imaging studies in mice and rats with subcutaneous and intracerebral tumor models.

Main Results

  • All three tracers showed higher uptake in FAP-expressing cells.
  • 6-[<sup>18</sup>F]F-FAPI and Al[<sup>18</sup>F]F-FAPI-42 demonstrated FAP-selectivity and tumor uptake in peripheral models.
  • [<sup>18</sup>F]AFA-FAPI lacked in vivo FAP-selectivity.
  • Al[<sup>18</sup>F]F-FAPI-42 had lower excretion and faster clearance from normal tissues.
  • 6-[<sup>18</sup>F]F-FAPI exhibited superior tumor uptake and retention in a glioma model, outperforming [<sup>18</sup>F]FET.

Conclusions

  • Al[<sup>18</sup>F]F-FAPI-42 is suitable for peripheral tumor visualization.
  • 6-[<sup>18</sup>F]F-FAPI offers improved properties for brain tumor imaging.
  • Covalently bound <sup>18</sup>F-labeled FAPIs present distinct advantages for specific tumor types.

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