A comprehensive meta-analysis has revealed that fibroblast activation protein inhibitor (FAPI)-based positron emission tomography demonstrates markedly superior diagnostic performance compared to fluorodeoxyglucose (FDG) PET for detecting gastrointestinal tumors and metastases. The findings, published in Academic Radiology, analyzed data from 16 studies encompassing 597 patients and represent a significant advancement in molecular imaging for gastrointestinal cancers.
Superior Diagnostic Performance in Gastric Cancer
The meta-analysis demonstrated that (68Ga)Ga-FAPI-04 PET achieved exceptional diagnostic accuracy for primary gastric cancer tumors, with 98% sensitivity and 93% specificity compared to (18F)FDG PET's substantially lower performance of 74% sensitivity and 48% specificity. This represents a 24 percentage point improvement in sensitivity and a 45 percentage point improvement in specificity.
"In gastric cancer, (68Ga)Ga-FAPI-04 exhibits superior sensitivity, specificity and semiquantitative metrics compared to (18F)FDG in both primary gastric tumor and metastases, particularly in specific pathological types, such as SRCC (signet-ring-cell carcinoma)," noted lead author Yuxuan Zhao, M.D., from the Department of Nuclear Medicine at the First Hospital of China Medical University in Liaoning, China.
Enhanced Detection of Metastatic Disease
For lymph node metastases in gastric cancer patients, (68Ga)Ga-FAPI-04 PET demonstrated double the sensitivity of (18F)FDG PET, achieving 90% versus 45% sensitivity respectively, while also providing superior specificity at 93% compared to 83% for FDG-PET. This substantial improvement in metastatic disease detection has significant implications for staging accuracy and treatment planning.
Across all gastrointestinal cancers analyzed, (68Ga)Ga-FAPI-04 PET offered 17% higher pooled sensitivity for primary tumors (99% versus 82%) and 39% higher pooled sensitivity for metastatic lymph nodes (95% versus 56%) compared to FDG-PET.
Exceptional Performance in Signet-Ring-Cell Carcinoma
The most striking advantage of FAPI-based imaging was observed in gastric signet-ring-cell carcinoma (GSRCC), where (68Ga)Ga-FAPI-04 PET achieved 99% sensitivity compared to just 46% for (18F)FDG PET—a 53% improvement. The researchers attributed this superior performance to the unique tumor biology of GSRCC.
"This could be explained by the low density of tumor cells, the high quantity of inert mucus components, and the comparatively low expression of the glucose transporter 1 (GLUT-1). The abundant tumor mesenchyme in advanced SRCC occupies the majority of the tumor mass, and many CAFs (cancer-associated fibroblasts) within the tumor stroma overexpress FAP, resulting in increased uptake of (68Ga)Ga-FAPI-04 in SRCC," explained Zhao and colleagues.
Comparative Analysis of FAPI Tracers in Colorectal Cancer
A separate meta-analysis of 12 studies involving 678 patients compared [18F]FAPI-74 and [68Ga]Ga-FAPI-04 PET/CT for metastatic colorectal cancer detection. Both tracers demonstrated excellent diagnostic accuracy, with [18F]FAPI-74 showing slightly superior sensitivity at 94% (95% CI: 91-97%) compared to [68Ga]Ga-FAPI-04 at 93% (95% CI: 89-96%). Specificities were comparable at 92% and 91% respectively.
[18F]FAPI-74 exhibited significantly higher SUVmax values with a mean difference of 2.3 (p<0.01), indicating superior tumor uptake and making it particularly effective for detecting small or low-uptake lesions. The tracer's reduced background activity in the liver and bowel improved image contrast, facilitating detection of lesions near high-background areas and proving especially effective for identifying challenging peritoneal metastases.
Clinical Implications and Future Directions
The superior diagnostic performance of FAPI-based PET imaging addresses critical limitations of conventional FDG-PET, particularly in detecting certain tumor types and metastatic disease. The technology's ability to target cancer-associated fibroblasts through FAP expression provides a complementary imaging approach that may improve staging accuracy and treatment planning.
Both FAPI tracers demonstrated favorable safety profiles with no significant adverse events reported. Patient preferences favored [18F]FAPI-74 for its longer half-life, which allowed greater flexibility in imaging schedules, while [68Ga]Ga-FAPI-04 offered logistical advantages with faster scan times, making it ideal for high-volume imaging centers.
The meta-analysis authors acknowledged limitations including the retrospective nature of eight reviewed studies and emphasized the need for larger multicenter prospective studies to further validate these findings and assess their impact on patient management outcomes.
