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

  • J Nucl Med. 2023 Mar;64(3):386-394. doi: 10.2967/jnumed.122.264544.
Yizhen Pang  1  2 ,  Liang Zhao  1  2 ,  Tinghua Meng  1 ,  Weizhi Xu  1 ,  Qin Lin  2 ,  Hua Wu  1 ,  Jingjing Zhang  3  4 ,  Xiaoyuan Chen  5  6  7 ,  Long Sun  8 ,  Haojun Chen  8
Affiliations
  • 1. Department of Nuclear Medicine and Minnan PET Center, First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
  • 2. Department of Radiation Oncology, First Affiliated Hospital of Xiamen University, Xiamen, China.
  • 3. Department of Diagnostic Radiology, National University of Singapore, Singapore.
  • 4. Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
  • 5. Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; [email protected] [email protected] [email protected].
  • 6. Departments 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.
  • 7. Nanomedicine Translational Research Program, NUS Center for Nanomedicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
  • 8. Department of Nuclear Medicine and Minnan PET Center, First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China; [email protected] [email protected] [email protected].
PMID: 36215571 DOI: 10.2967/jnumed.122.264544
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.

Keywords
FAP-2286; FAPI-46; PET/CT; fibroblast activation protein.
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