Clinical translational evaluation of Al18F-NOTA-FAPI for fibroblast activation protein-targeted tumour imaging

  • Eur J Nucl Med Mol Imaging. 2021 Dec;48(13):4259-4271. doi: 10.1007/s00259-021-05470-5.
Shuailiang Wang  1  2 ,  Xin Zhou  2 ,  Xiaoxia Xu  2 ,  Jin Ding  2 ,  Song Liu  2 ,  Xingguo Hou  2 ,  Nan Li  2 ,  Hua Zhu  3 ,  Zhi Yang  4  5
Affiliations
  • 1. Institute of Medical Technology, Peking University Health Science Center, Beijing, 100191, China.
  • 2. Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education/Beijing, NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals, Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, No. 52 Fu-Cheng Rd., 100142, Beijing, China.
  • 3. Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education/Beijing, NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals, Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, No. 52 Fu-Cheng Rd., 100142, Beijing, China. [email protected].
  • 4. Institute of Medical Technology, Peking University Health Science Center, Beijing, 100191, China. [email protected].
  • 5. Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education/Beijing, NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals, Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, No. 52 Fu-Cheng Rd., 100142, Beijing, China. [email protected].
PMID: 34165601 DOI: 10.1007/s00259-021-05470-5
Abstract

Purpose: In this study, a novel aluminium-[18F]fluoride (Al18F)-labelled 1,4,7‑triazacyclononane-N,N',N″-triacetic acid (NOTA)-conjugated fibroblast activation protein inhibitor (FAPI) probe, named Al18F-NOTA-FAPI, was developed for fibroblast activation protein (FAP)-targeted tumour imaging; it could deliver hundreds of millicuries of radioactivity using automated synthesis. The tumour detection efficacy of Al18F-NOTA-FAPI was further validated in both preclinical and clinical translational studies.

Methods: The radiolabelling procedure of Al18F-NOTA-FAPI was optimized. Cell uptake and competitive binding assays were completed with the U87MG and A549 cell lines to evaluate the affinity and specificity of the Al18F-NOTA-FAPI probe. The biodistribution, pharmacokinetics, radiation dosimetry and tumour imaging efficacy of the Al18F-NOTA-FAPI probe were researched in healthy Kunming (KM) and/or U87MG model mice. After the approval of the ethical committee, the Al18F-NOTA-FAPI probe was translated into the clinic for PET/CT imaging of the first 10 Cancer patients.

Results: The radiolabelling yield of Al18F-NOTA-FAPI was 33.8 ± 3.2% using manual synthesis (n = 10), with a radiochemical purity over 99% and the specific activity of 9.3-55.5 MBq/nmol. The whole body effective dose of Al18F-NOTA-FAPI was estimated to be 1.24E - 02 mSv/MBq, which was lower than several Other FAPI probes (68Ga-FAPI-04, 68Ga-FAPI-46 and 68Ga-FAPI-74). In U87MG tumour-bearing mice, Al18F-NOTA-FAPI showed good tumour detection efficacy based on the results of micro PET/CT imaging and biodistribution studies. In an organ biodistribution study of patients, Al18F-NOTA-FAPI showed a lower SUVmean than 2-[18F]-fluoro-2-deoxy-D-glucose (2-[18F]FDG) in most organs, especially in the liver (1.1 ± 0.2 vs. 2.0 ± 0.9), brain (0.1 ± 0.0 vs. 5.9 ± 1.3), and bone marrow (0.9 ± 0.1 vs. 1.7 ± 0.4). Meanwhile, Al18F-NOTA-FAPI did not show extensive bone uptake, and was able to detect more lesions than 2-[18F]FDG in the PET/CT imaging of several patients.

Conclusion: The Al18F-NOTA-FAPI probe was successfully fabricated and applied in fibroblast activation protein-targeted tumour PET/CT imaging, which showed excellent imaging quality and tumour detection efficacy in U87MG tumour-bearing mice as well as in Cancer patients.

Trial registration: Chinese Clinical Trial Registry ChiCTR2000038080. Registered 09 September 2020. http://www.chictr.org.cn/showproj.aspx?proj=61192.

Keywords
Al18F; Clinical translational evaluation; Fibroblast activation protein; PET/CT; Tumour imaging.
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