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Preclinical study and first-in-human imaging of [18F]FAP-2286, and comparison with 2-[18F]FDG PET/CT in various cancer patients

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

Abstract

Purpose

Fibroblast-activated protein (FAP) is highly expressed in cancer-associated fibroblasts (CAFs) of many solid cancers, but low or absent in normal tissues. Our study aimed to develop a novel FAP-specific tracer, namely [18F]FAP-2286, and evaluated its performance in comparison with well-established agents such as [18F]FAPI-42 and [68Ga]Ga-FAP-2286 in preclinical research, as well as 2-[18F]FDG in pilot clinical study.

Methods

[18F]FAP-2286 was manually synthesized in accordance with Good Manufacturing Practice (GMP). Subsequent investigations encompassed cell uptake, competitive binding affinity, internalization and efflux assays using HT-1080hFAP cell lines. PET imaging and biodistribution studies were conducted in HEK-293ThFAP, A549hFAP, HT-1080hFAP tumor-bearing mice as well as HEK-293T, A549 and HT-1080 control groups. Furthermore, clinical evaluation of [18F]FAP-2286 was performed in fifteen patients with various cancers compared to 2-[18F]FDG PET.

Results

The radiolabeling yield of [18F]FAP-2286 was 30.53 ± 5.20%, with a radiochemical purity exceeding 97%. In cell assays, [18F]FAP-2286 showed specific uptake, high internalization fraction and low cellular efflux. Rapid tumor uptake and satisfactory tumor retention was observed on micro-PET imaging and cancer patients. Meanwhile, the clinical research demonstrated that [18F]FAP-2286 may represent an alternative for low glucose-metabolism malignant tumors PET imaging such as gastric cancers.

Conclusion

[18F]FAP-2286 showed superior imaging quality including rapid and high target uptake and satisfactory retention in both tumor-bearing mice and cancer patients. It may emerge as a promising candidate for early or delayed phase imaging and 2-[18F]FDG non-avid cancers PET scan.

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Data availability

All data are included in this published article and its supplementary information file.

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Acknowledgements

We gratefully appreciate all of the staff from the Department of Nuclear Medicine, the Sixth Affiliated Hospital and the First Affiliated Hospital of Guangzhou Medical University, for their contributions to this study. Finally, we thank to Prof. Kongzhen Hu for HEK-293ThFAP and A549hFAP cell lines.

Funding

This research was supported in part by the National Natural Science Foundation of China (No.81901772 and No.82001879), the Natural Science Foundation of Guangdong Province (No.2019A1515011893 and 2023A1515011300), the Basic and Applied Basic Research Foundation of Guangdong Province (No. 2020A1515110159), the Science and Technology Project of Guangzhou City (No. 202102010354), the State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia & The First People’s Hospital of Kashi Fund (No.SKL-HIDCA-2020-KS2) and the Zhong Nanshan Medical Foundation of Guangdong Province (ZNSA-2020003).

Author information

Author notes

  1. Zhanwen Zhang, Shaoyu Liu and **nlu Wang are corresponding authors who contributed equally to this work.

  2. Lifang Liu is the first author.

Authors and Affiliations

  1. Nuclear Medicine Department, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510120, China

    Lifang Liu, **aoting Ye & Zhanwen Zhang

  2. Department of Nuclear Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China

    Jiawei Zhong, Ziqi Zhang, **nlu Wang & Shaoyu Liu

  3. Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510120, China

    Lifang Liu, **aoting Ye & Zhanwen Zhang

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  1. Lifang Liu
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Contributions

Conceptualization, design and methodology: Shaoyu Liu, Zhanwen Zhang and **nlu Wang; experiments, data collection and analysis and writing the manuscript: Lifang Liu; part of the biodistribution and radiopharmaceutical preparation: Jiawei Zhong, Ziqi Zhang, **aoting Ye; funding acquisition: Zhanwen Zhang and Shaoyu Liu; revision of the article: all of the authors.

Corresponding authors

Correspondence to **nlu Wang, Shaoyu Liu or Zhanwen Zhang.

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Ethics approval

All animal studies were performed according to Guangzhou Medical University Institutional Animal Care and Use Committee (No. 20230330). The clinical translational study was approved by the ethics committee of The Sixth Affiliated Hospital of Sun Yat-sen University (2023ZSLYEC-597). All procedures were conducted according to the Declaration of Helsinki.

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Liu, L., Zhong, J., Zhang, Z. et al. Preclinical study and first-in-human imaging of [18F]FAP-2286, and comparison with 2-[18F]FDG PET/CT in various cancer patients. Eur J Nucl Med Mol Imaging 51, 2012–2022 (2024). https://doi.org/10.1007/s00259-024-06626-9

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