Abbasi Samaneh, Dehghani Mohsen, Khademi Sara, Irajirad Rasoul, Parizi Zahra Pakdin, Sahebi Mahdieh, Sadeghi Masoumeh, Montazerabadi Alireza, Tavakoli Meysam
Department of Medical Physics, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Department of Epidemiology, School of Health, Mashhad University of Medical Sciences, Mashhad, Iran.
Syst Rev. 2025 May 10;14(1):109. doi: 10.1186/s13643-025-02835-x.
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 Ga-fibroblast activation protein inhibitor (FAPI- 46) PET/CT for early cancer detection.
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.
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) 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.
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.
PROSPERO CRD 42023472270.
新型肽的进展通过靶向癌症特异性标志物显著影响癌症诊断，从而改善成像方式，如正电子发射断层扫描与计算机断层扫描相结合（PET/CT）以更准确地检测肿瘤。本系统评价和荟萃分析旨在评估[18F]氟脱氧葡萄糖（FDG）和镓纤维母细胞激活蛋白抑制剂（FAPI-46）PET/CT用于早期癌症检测的诊断准确性。
截至2024年3月28日，使用医学主题词（MeSH）关键词在Scopus、MEDLINE、Web of Science和Embase数据库中进行全面检索。筛选标题和摘要以识别关于[68Ga]FAPI-46和[18F]FDG混合的研究，随后进行详细的全文评估。仅纳入以英文发表的队列或横断面研究，重点关注癌症患者的临床诊断，而综述、病例报告、会议论文集和摘要被排除。采用随机效应荟萃分析估计合并特异性和敏感性以及95%置信区间（CI）。此外，通过Stata评估各研究间的异质性以及检测率的亚组荟萃分析。
在检索到的615项研究中，9篇文章纳入了本系统评价，其中5篇（n = 144例患者）符合荟萃分析条件。对于[68Ga]FAPI-46，与免疫组织病理学相比，合并敏感性和特异性分别为0.96（95%CI 0.84，0.99）和0.92（95%CI 0.53，0.99），阳性似然比（LR +）为4.41（95%CI 1.64，11.79），阴性似然比（LR -）为3.07（95%CI 1.01，9.37）。对于[18F]FDG，与免疫组织病理学相比，合并敏感性和特异性分别为0.73（95%CI 0.34，0.93）和0.83（95%CI 0.57，0.95），LR +为12.73（95%CI 1.43，113.45），LR -为0.32（95%CI 0.11，0.17）。基于每个病灶的检测率，[68Ga]FAPI-46与[18F]FDG相比的合并优势比为1.73（95%CI 0.99，3.02）。[68Ga]FAPI-46与18F-FDG相比，原发肿瘤摄取的标准化摄取值（SUV）和肿瘤与背景比值（TBR）的合并加权平均差分别为4.40（95%CI -0.7，9.5）和6.18（95%CI 1.74，10.61）。由于患者选择、解读标准和扫描程序的差异，观察到中度至高度异质性。
本研究表明，[68Ga]FAPI-46在癌症诊断方面优于[18F]FDG，具有更高的敏感性（0.96对0.73）和特异性（0.92对0.83）。[Ga]FAPI-46通过更高的SUVmax和TBR改善了肿瘤检测。虽然FDG的LR +较高，但其较低的LR -突出了更多假阴性。因此，[68Ga]FAPI-46在癌症诊断中表现出比FDG更高的准确性和可靠性。
PROSPERO CRD 42023472270。
