Qualitative and quantitative differentiation efficiency of dual-tracer PET/CT with 18F-fluorodeoxyglucose and 11C-acetate for primary hepatocellular carcinoma: a systematic review and meta-analysis

Purpose Primary hepatocellular carcinoma (HCC) represents a substantial global health challenge. Early diagnosis of HCC is crucial for improved patient outcomes. The aim of this study was to assess qualitative and quantitative diagnostic performance of PET/CT using C-11-acetate and [18F]-fluorodeoxyglucose (FDG) in detection of primary HCC and to determine if C-11-acetate added to [18F]-FDG alleviates the low sensitivity rate mentioned in guidelines. Methods Protocol was pre-registered at https://osf.io/2vcb9. We searched PubMed, Web of Science, Embase, and the Cochrane Library for included studies. Quality Assessment of Diagnostic Accuracy Studies 2 was used to assess the risk of bias. Possible sources of statistical heterogeneity were explored. Additionally, mentioned three PET/CT tests were evaluated for their diagnostic performance in differentiating HCC from its differential diagnoses. Grades of Recommendation, Assessment, Development, and Evaluation was used to assess quality of generated evidence. Results Twenty-four studies were analyzed. Qualitative dual-tracer PET/CT demonstrated 92.0% per-lesion sensitivity, and a significantly higher direct sensitivity difference of 30% to conventional CT, 44.7% to [18F]-FDG, and 12.0% to C-11-acetate. Regarding differentiation rate, [18F]-FDG was superior to C-11-acetate in poorly differentiated lesions while C-11-acetate was superior in well-differentiated lesions. Regarding size, dual tracer combination solved the high missing rate of HCC lesions in 1-2 cm and 2-5 cm groups but could not help in size < 1 cm. Conclusion Dual-tracer PET/CT utilizing C-11-acetate and [18F]-FDG represents a sensitive method for detecting primary HCC. By concurrently quantifying or qualifying the uptake of C-11-acetate and [18F]-FDG, this multimodal approach enables precise localization of intrahepatic lesions.