Evaluation of the Diagnostic Accuracy of FAPI PET/CT in Oncologic Studies: Systematic Review and Metaanalysis.

Fibroblast-activation protein is a promising target for oncologic molecular imaging. Studies show that fibroblast activation protein inhibitor (FAPI) radiotracers are accurate diagnostics with favorable tumor-to-background ratios across various cancers. Therefore, we performed a systematic review and metaanalysis to assess the diagnostic performance of FAPI PET/CT in comparison with [¹⁸F]FDG PET/CT, the most widely used radiotracer in oncology. Methods: We conducted a systematic search in MEDLINE, Embase, Scopus, PubMed, Cochrane Central Register of Controlled Trials, relevant trial registries, and bibliographies. The search consisted of combinations of terms for 3 topics: neoplasia, PET/CT, and FAPI. Two authors independently screened retrieved articles using predefined inclusion and exclusion criteria and extracted the data. Study quality was assessed using the criteria of QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2). For each study, the sensitivity, specificity, and 95% CIs were calculated to determine diagnostic accuracy for primary, nodal, and metastatic lesions. A random-effects metaanalysis was used for pooling the data, and heterogeneity was assessed (I² index). Results: Thirty-nine studies (1,259 patients) investigating the use of FAPI PET/CT were included. On a patient-based analysis, pooled sensitivity was 0.99 (95% CI, 0.97-1.0) for the detection of primary lesions. Pooled sensitivity for nodal and distant metastases was 0.91 (95% CI, 0.81-0.96) and 0.99 (95% CI, 0.96-1.0), respectively. On a paired analysis between FAPI and [¹⁸F]FDG PET/CT, FAPI had a higher sensitivity in the detection of primary, nodal, and metastatic lesions (all P < 0.001). The differences in sensitivities between FAPI and [¹⁸F]FDG were statistically significant. In terms of heterogeneity, analyses on primary lesions were moderately affected, distant metastatic lesions were highly affected, and the nodal metastatic analyses had negligible heterogeneity. Conclusion: The diagnostic performance of FAPI PET/CT is superior to that of [¹⁸F]FDG in the detection of primary, nodal, and distant metastases. However, further studies are needed to better evaluate its utility and indication in specific cancer types and clinical settings.