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Research ArticleFEATURED ARTICLE OF THE MONTH

PET Imaging of Fibroblast Activation Protein in Various Types of Cancer Using 68Ga-FAP-2286: Comparison with 18F-FDG and 68Ga-FAPI-46 in a Single-Center, Prospective Study

Yizhen Pang, Liang Zhao, Tinghua Meng, Weizhi Xu, Qin Lin, Hua Wu, Jingjing Zhang, Xiaoyuan Chen, Long Sun and Haojun Chen
Journal of Nuclear Medicine March 2023, 64 (3) 386-394; DOI: https://doi.org/10.2967/jnumed.122.264544
Yizhen Pang
1Department of Nuclear Medicine and Minnan PET Center, First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China;
2Department of Radiation Oncology, First Affiliated Hospital of Xiamen University, Xiamen, China;
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Liang Zhao
1Department of Nuclear Medicine and Minnan PET Center, First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China;
2Department of Radiation Oncology, First Affiliated Hospital of Xiamen University, Xiamen, China;
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Tinghua Meng
1Department of Nuclear Medicine and Minnan PET Center, First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China;
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Weizhi Xu
1Department of Nuclear Medicine and Minnan PET Center, First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China;
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Qin Lin
2Department of Radiation Oncology, First Affiliated Hospital of Xiamen University, Xiamen, China;
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Hua Wu
1Department of Nuclear Medicine and Minnan PET Center, First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China;
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Jingjing Zhang
3Department of Diagnostic Radiology, National University of Singapore, Singapore;
4Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore;
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Xiaoyuan Chen
4Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore;
5Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine and Faculty of Engineering, National University of Singapore, Singapore; and
6Nanomedicine Translational Research Program, NUS Center for Nanomedicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
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Long Sun
1Department of Nuclear Medicine and Minnan PET Center, First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China;
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Haojun Chen
1Department of Nuclear Medicine and Minnan PET Center, First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China;
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Abstract

PET imaging that targets fibroblast activation protein (FAP) on the surface of cancer-associated fibroblasts has yielded promising tumor diagnostic results. FAP-2286 contains cyclic peptides as FAP-binding motifs to optimize tumor retention compared with the small-molecule FAP inhibitor (FAPI) series (FAPI-04/46). The aim of this study was to evaluate the diagnostic accuracy of 68Ga-FAP-2286 to detect primary and metastatic lesions in patients with various types of cancer, compared with 18F-FDG and 68Ga-FAP-2286. Methods: Sixty-four patients with 15 types of cancer underwent 68Ga-FAP-2286 PET/CT for initial assessment or detection of recurrence. For comparison, 63 patients underwent paired 68Ga-FAP-2286 and 18F-FDG PET/CT and 19 patients underwent paired 68Ga-FAP-2286 and 68Ga-FAPI-46 PET/CT. Lesion uptake was quantified as SUVmax and tumor-to-background ratio. The Wilcoxon matched-pairs signed-rank test was used to compare SUVmax between PET modalities, and the McNemar test was used to compare lesion detectability. Results: Uptake of 68Ga-FAP-2286 was significantly higher than that of 18F-FDG in primary tumors (median SUVmax, 11.1 vs. 6.9; P < 0.001), lymph node metastases (median SUVmax, 10.6 vs. 6.2; P < 0.001), and distant metastases, resulting in improved image contrast and lesion detectability. All primary tumors (46/46) were clearly visualized by 68Ga-FAP-2286 PET/CT, whereas 9 of the 46 lesions could not be visualized by 18F-FDG PET/CT. The lesion detection rate of 68Ga-FAP-2286 PET/CT was superior to that of 18F-FDG PET/CT for involved lymph nodes (98% [105/107] vs. 85% [91/107], P = 0.001) and bone and visceral metastases (95% [162/171] vs. 67% [114/171], P < 0.001). 68Ga-FAP-2286 yielded tumor uptake and lesion detection rates similar to those of 68Ga-FAPI-46 in a subcohort of 19 patients. Conclusion: 68Ga-FAP-2286 is a promising FAP-inhibitor derivative for safe cancer diagnosis, staging, and restaging. It may be a better alternative to 18F-FDG for the cancer types that exhibit low-to-moderate uptake of 18F-FDG, which include gastric, pancreatic, and hepatic cancers. In addition, 68Ga-FAP-2286 and 68Ga-FAPI-46 yielded comparable clinical results.

  • fibroblast activation protein
  • FAP-2286
  • FAPI-46
  • PET/CT

Footnotes

  • Published online Sep. 2, 2022.

  • © 2023 by the Society of Nuclear Medicine and Molecular Imaging.
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Journal of Nuclear Medicine: 64 (3)
Journal of Nuclear Medicine
Vol. 64, Issue 3
March 1, 2023
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PET Imaging of Fibroblast Activation Protein in Various Types of Cancer Using 68Ga-FAP-2286: Comparison with 18F-FDG and 68Ga-FAPI-46 in a Single-Center, Prospective Study
Yizhen Pang, Liang Zhao, Tinghua Meng, Weizhi Xu, Qin Lin, Hua Wu, Jingjing Zhang, Xiaoyuan Chen, Long Sun, Haojun Chen
Journal of Nuclear Medicine Mar 2023, 64 (3) 386-394; DOI: 10.2967/jnumed.122.264544

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PET Imaging of Fibroblast Activation Protein in Various Types of Cancer Using 68Ga-FAP-2286: Comparison with 18F-FDG and 68Ga-FAPI-46 in a Single-Center, Prospective Study
Yizhen Pang, Liang Zhao, Tinghua Meng, Weizhi Xu, Qin Lin, Hua Wu, Jingjing Zhang, Xiaoyuan Chen, Long Sun, Haojun Chen
Journal of Nuclear Medicine Mar 2023, 64 (3) 386-394; DOI: 10.2967/jnumed.122.264544
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Keywords

  • fibroblast activation protein
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  • FAPI-46
  • PET/CT
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