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Purpose: This study aimed to explore the clinical staging performance of [68 Ga]Ga-DOTA-FAPI-04 PET/CT compared with that of 2-[18F]FDG PET/CT in non-small cell lung cancer (NSCLC) patients lesion by lesion. Methods: A total of 134 diagnosed or suspected NSCLC patients were enrolled in the prospective study (ChiCTR2000038080); they received paired 2-[18F]FDG PET/CT and [68 Ga]Ga-DOTA-FAPI-04 PET/CT. Of these patients, the retrospective analysis of 74 NSCLC patients with pathological results was conducted from primary tumor (T) diagnosis, lymph node (N), and metastatic lesion (M) staging. The imaging characteristics of the lung nodules and suspected metastases were obtained and analyzed, and the staging performance of 2-[18F]FDG PET/CT and [68 Ga]Ga-DOTA-FAPI-04 PET/CT was compared. Results: For T diagnosis, [68 Ga]Ga-DOTA-FAPI-04 showed better diagnostic performance than 2-[18F]FDG in 79 lung nodules of 72 patients, especially for nonsolid and small-dimension adenocarcinoma nodules. For N staging, 98 lymph nodes (LNs) with pathological results in 37 patients were analyzed. The SUVmax of [68 Ga]Ga-DOTA-FAPI-04 in the nonmetastatic LNs was significantly lower than that in the metastatic LNs. Regarding metastatic LN identification, the calculated optimum cut-off value of [68 Ga]Ga-DOTA-FAPI-04 SUVmax was 5.5, and the diagnostic accuracy using [68 Ga]Ga-DOTA-FAPI-04 and 2-[18F]FDG criteria was 94% and 30%, respectively (P < 0.001). For M staging, [68 Ga]Ga-DOTA-FAPI-04 identified more lesions than 2-[18F]FDG (257 vs. 139 lesions) in 14 patients with multiple metastases. Overall, the staging accuracy of [68 Ga]Ga-DOTA-FAPI-04 was better than that of 2-[18F]FDG in 52 patients with different pathological stages [43/52 (82.7%) vs. 27/52 (51.9%), P = 0.001]. Conclusion: Compared with 2-[18F]FDG PET/CT, [68 Ga]Ga-DOTA-FAPI-04 PET/CT demonstrated better staging performance in NSCLC patients with different pathological stages, especially those with localized disease. [ABSTRACT FROM AUTHOR]

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 [ABSTRACT FROM AUTHOR]