Background The radiotracer fluorine 18 (¹⁸F)-labeled fibroblast activation protein inhibitor (FAPI) has shown promise for visualizing several types of cancer, but the accuracy of ¹⁸F-FAPI compared with ¹⁸F-fluorodeoxyglucose (FDG) for the detection of lung cancer remains uncertain. Purpose To evaluate the effectiveness of ¹⁸F-FAPI-based PET/CT imaging for the diagnosis of primary and metastatic lung cancer lesions as compared with ¹⁸F-FDG PET/CT. Materials and Methods In this secondary analysis of a prospective trial, consecutively recruited patients from a single center with pathologically confirmed lung cancer were prospectively enrolled from December 2020 to April 2022 and underwent paired ¹⁸F-FAPI and ¹⁸F-FDG PET/CT examinations at intervals of more than 20 hours and within 7 days of each other. Histopathologic and clinical follow-up results were used as reference standards for final diagnoses. ¹⁸F-FAPI and ¹⁸F-FDG uptake were compared using the McNemar test or paired Student t test. Diagnostic accuracy was compared between the two techniques by using the McNemar χ² test. Results Sixty-eight participants (median age, 63 years [IQR, 58-68 years; range, 42-79 years]; 46 male [68%]) were evaluated. Compared with the mean tumor-to-background ratio (TBR) for FDG uptake, TBR for FAPI uptake was lower in primary lung tumors (25.3 ± 14.0 [SD] vs 32.1 ± 21.1; P < .001) but higher in metastatic lymph nodes (7.5 ± 6.6 vs 5.9 ± 8.6; P < .001) and bone metastases (8.6 ± 5.4 vs 4.3 ± 2.3; P < .001). For diagnostic accuracy in a total of 548 lesions in 68 participants, compared with ¹⁸F-FDG PET/CT, ¹⁸F-FAPI PET/CT demonstrated a higher sensitivity (99% [392 of 397 lesions] vs 87% [346 of 397]; P < .001), specificity (93% [141 of 151 lesions] vs 79% [120 of 151]; P = .004), accuracy (97% [533 of 548 lesions] vs 85% [466 of 548]; P < .001), and negative predictive value (97% [141 of 146 lesions] vs 70% [120 of 171 lesions]; P < .001), but there was no evidence of a difference for positive predictive value (98% [392 of 402 lesions] vs 92% [346 of 377 lesions]; P = .57). Conclusion ¹⁸F-FAPI PET/CT may be superior to ¹⁸F-FDG PET/CT for detecting lung cancer. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Zukotynski and Gerbaudo in this issue.

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