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

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 ¹¹C-acetate and [18F]-fluorodeoxyglucose (FDG) in detection of primary HCC and to determine if ¹¹C-acetate added to [18F]-FDG alleviates the low sensitivity rate mentioned in guidelines.

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.

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 ¹¹C-acetate. Regarding differentiation rate, [18F]-FDG was superior to ¹¹C-acetate in poorly differentiated lesions while ¹¹C-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.

Dual-tracer PET/CT utilizing ¹¹C-acetate and [18F]-FDG represents a sensitive method for detecting primary HCC. By concurrently quantifying or qualifying the uptake of ¹¹C-acetate and [18F]-FDG, this multimodal approach enables precise localization of intrahepatic lesions.