AUTHOR=Ghidaglia Jérôme , Golse Nicolas , Pascale Alina , Sebagh Mylène , Besson Florent L. 

TITLE=18F-FDG /18F-Choline Dual-Tracer PET Behavior and Tumor Differentiation in HepatoCellular Carcinoma. A Systematic Review

JOURNAL=Frontiers in Medicine

VOLUME=Volume 9 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2022.924824

DOI=10.3389/fmed.2022.924824

ISSN=2296-858X

ABSTRACT=Post-operative recurrence remains the strongest prognostic factor of resected hepatocellular carcinoma (HCC), making the accurate selection of patients with curable HCC a crucial issue. PET imaging combining both FDG and fatty acid synthase (FAS) radiotracers have shown its interest for the initial staging and therapeutic management of patients with HCC, but its use is not consensual. Importantly, first dual-tracer PET studies suggested FDG/FAS PET behavior to be linked to the degree of differentiation of HCC, a major predictive factor of post-operative recurrence. Although this molecular imaging concept may impact how dual-tracer PET will be used in early-stage HCC, its level of evidence remains unexplored. In this study, we conducted a systematic review of the available evidence-based data to clarify the relevance of dual FDG/Choline PET in characterizing the degree of differentiation of HCC tumours. 
A systematic search of the PubMed/Medline database was performed. A systematic review of the dual-tracer FDG/Choline PET behaviour of histology-proven HCC according to their degree of differentiation was conducted. The overall quality of the included studies was critically assessed based on the STROBE guidelines. Information on study date, design, patient cohort characteristics, grade of differentiation of HCC tumours, and the dual-tracer PET behaviour per HCC were independently extracted.
From 440 records initially available, 6 full-text articles (99 histology-proven HCC) provided dual-tracer FDG/Choline PET behaviour per HCC tumour grade were included in the systematic review. Based on our analysis, 43/99 HCCs were reported to be well-differentiated, and 56/99 HCCs were reported to be less-differentiated tumours. In the well-differentiated subgroup, more than half were exclusively positive for Choline (51%), whereas 39% were positive for both FDG and Choline. In the less-differentiated subgroup, 37% of HCC patients were positive exclusively for FDG, 36% were positive for both FDG and Choline, and 25% were positive exclusively for Choline.
The FDG/Choline dual-tracer PET behaviour of uptake shows high overlap between well- and less differentiated HCC, making the characterization of tumours challenging based on such PET combination alone. Given our growing knowledge of the molecular complexity of HCC, further studies are necessary to refine our understanding of radiotracers behaviour in this field.