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Noninvasive imaging of FAP expression using positron emission tomography: A comparative evaluation of a [18F]-labeled glycopeptide-containing FAPI with [18F]FAPI-42

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

Research on fibroblast activating protein (FAP)-targeting inhibitor (FAPI) has become an important focus for cancer imaging and radiotherapy. Quinoline-based tracers [68 Ga]FAPI-04 and [18F]FAPI-42 have been widely used for positron emission tomography (PET) imaging of most tumors. However, there exist some limitations of these tracers with high uptake in biliary duct system and unstable uptake in pancreas, unsuitable for abdominal tumors PET imaging. Here we developed a [18F]-labeled glycopeptide-containing FAPI tracer (named [18F]FAPT) for PET imaging of FAP in cancers.

Methods

[18F]FAPT was synthesized manually and automatically. The competitive binding to FAP, cellular internalization, and efflux characteristics were examined in vitro using A549-FAP cells. Dynamic MicroPET and biodistribution studies of [18F]FAPT were then conducted in A549-FAP and U87MG xenograft tumor mouse models compared with [18F]FAPI-42. Five healthy volunteers and three patients with cancer underwent [18F]FAPT PET/CT.

Results

Preclinical and clinical studies showed specific binding of [18F]FAPT to FAP and favorable pharmacokinetic properties with better hydrophilicity, lower uptake in biliary duct system, higher tumor uptake and longer tumor retention compared with [18F]FAPI-42. The biodistribution of [18F]FAPT in healthy volunteers and patients with cancer displayed low uptake in most normal tissues except for pancreas, thyroid and salivary gland, which could contribute to high tumor-to-background ratios in most cancers.

Conclusion

[18F]FAPT is better PET tracer than [18F]FAPI-42 for imaging of biliary duct system cancer, potentially providing a tool to examine FAP expression in most cancers with high tumor-to-background ratios.

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Data availability

The data sets generated and analyzed during this study, if reasonably required, can be obtained from the correspondence author.

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Acknowledgements

We thank our colleagues in the Nanfang PET center who manufactured the radiopharmaceuticals and performed the microPET and PET/CT examination. We sincerely thank the Guangzhou Atom High Tech Radiopharmaceutical Co., Ltd for giving us help in radionuclide drugs.

Funding

This work is supported by the Guangdong Basic and Applied Basic Research Foundation (2022A1515010072, 2022A1515110051, 2020A1515011399), Guangzhou Science and Technology Plan (2023B03J0529), Medical Products Administration of Guangdong Province (2021ZDB02, Drug Supervision and Administration Division 1 (2022)), Nanfang Hospital Talent Introduction Fundation of Southern Medical University (123456), and the National Natural Science Foundation of China (91949121).

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Author notes

  1. Jiawen Huang, LiLan Fu and XiaoJun Zhang contributed equally to this work.

Authors and Affiliations

  1. GDMPA Key Laboratory for Quality Control and Evaluation of Radiopharmaceuticals, PET Center and Department of Nuclear Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China

    Jiawen Huang, LiLan Fu, XiaoJun Zhang, Shun Huang, Ye Dong, Kongzhen Hu, YanJiang Han, Kemin Zhou, Cao Min, YanChao Huang & Ganghua Tang

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  1. Jiawen Huang
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Contributions

Study conception and design, GT. Acquiring data, JH, LF, XZ, DY, KH, SH, RL, and YJH. Analysis of data, JH, LF, KH, and SH. Drafting the manuscript, JH and LF. Revising the manuscript, GT. All authors contributed to the article and approved the submitted version.

Corresponding author

Correspondence to Ganghua Tang.

Ethics declarations

Ethics approval

The study was approved by the Chinese Ethics Committee of Registering Clinical Trials (ChiECRCT20210617) and registered on the Chinese Clinical Trial Registry (ChiCTR2200059004).

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Informed consents were obtained from all individual participants included in the study.

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All the authors approved the publication of this article.

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The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Huang, J., Fu, L., Zhang, X. et al. Noninvasive imaging of FAP expression using positron emission tomography: A comparative evaluation of a [18F]-labeled glycopeptide-containing FAPI with [18F]FAPI-42. Eur J Nucl Med Mol Imaging 50, 3363–3374 (2023). https://doi.org/10.1007/s00259-023-06282-5

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