Abstract
BACKGROUND: Advancements in novel peptides significantly affect cancer diagnosis by targeting cancer-specific markers, thereby improving imaging modalities, such as positron emission tomography combined with computed tomography (PET/CT) for more accurate tumor detection. This systematic review and meta-analysis aimed to assess the diagnostic accuracy of [18F] Fluorodeoxyglucose (FDG) and (68)Ga-fibroblast activation protein inhibitor (FAPI- 46) PET/CT for early cancer detection. METHODS: A comprehensive search was conducted in Scopus, MEDLINE, Web of Science, and Embase databases up to March 28, 2024, using MeSH keywords. Titles and abstracts were screened to identify studies on hybrid [68Ga] FAPI- 46 and [18F] FDG, followed by a detailed full-text evaluation. Only cohort or cross-sectional studies published in English, focusing on the clinical diagnosis of cancer patients, were included, while reviews, case reports, conference proceedings, and abstracts were excluded. Random-effects meta-analysis was used for the estimation of pooled specificity and sensitivity with 95% confidence intervals (CIs). In addition, the heterogeneity was assessed across studies and subgroup meta-analyses for the detection rate via Stata. RESULTS: Among the 615 retrieved studies, nine articles were incorporated in the present systematic review, with five (n = 144 patients) eligible for meta-analysis. For [68Ga] FAPI- 46, the pooled sensitivity and specificity compared with immunohistopathology were 0.96 (95% CI 0.84, 0.99) and 0.92 (95% CI 0.53, 0.99), respectively, with a positive likelihood ratio (LR +) of 4.41 (95% CI 1.64, 11.79) and a negative likelihood ratio (LR -) of 3.07 (95% CI 1.01, 9.37). For [18F] FDG, pooled sensitivity and specificity compared with immunohistopathology were 0.73 (95% CI 0.34, 0.93) and 0.83 (95% CI 0.57, 0.95), with an LR + of 12.73 (95% CI 1.43, 113.45) and an LR - of 0.32 (95% CI 0.11, 0.17). The pooled odds ratio for the detection rate on a per-lesion basis was 1.73 (95% CI 0.99, 3.02) for [68Ga] FAPI- 46 compared with [18F] FDG. The pooled weighted mean differences in the standardized uptake value (SUV(max)) for primary tumor uptake and the tumor-to-background ratio (TBR) in [68Ga] FAPI- 46 vs. 18F-FDG were 4.40 (95% CI - 0.7, 9.5) and 6.18 (95% CI 1.74, 10.61), respectively. Moderate to high heterogeneity was noted because of the variations in patient selection, interpretation criteria, and scanning procedures. CONCLUSIONS: This study revealed that [68Ga] FAPI- 46 outperforms [18F] FDG in cancer diagnosis, with higher sensitivity (0.96 vs. 0.73) and specificity (0.92 vs. 0.83). [Ga] FAPI- 46 improved tumor detection with higher SUVmax and TBR. While FDG had a higher LR +, its lower LR - highlighted more false negatives. Accordingly, [68Ga] FAPI- 46 exhibited superior accuracy and reliability than FDG in cancer diagnosis. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD 42023472270.