The application of 18F-FDG PET/CT imaging for human hepatocellular carcinoma: a narrative review

Abstract

Background and objective: Primary hepatocellular carcinoma (HCC) poses a significant threat to human health. The mean overall survival (OS) of HCC is approximately 15.8 months whereas the 6-month and 1-year OS rates are only 71.6% and 49.7%, respectively. ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) has been widely used for the management of several solid cancers; however, HCC frequently displays low ¹⁸F-FDG uptake; approximately 50% of HCC cases do not take up ¹⁸F-FDG. Therefore, ¹⁸F-FDG PET is not considered very useful for the visualization of HCC and is not currently a recommended standard imaging modality for HCC. Conversely, ¹⁸F-FDG PET/CT has been reported to be clinically important in the management, staging, and prognosis of HCC patients. Currently, reports relating to ¹⁸F-FDG uptake in HCC are unclear and controversial. There is an urgent need to clarify the efficacy of ¹⁸F-FDG PET for the management of HCC.

Methods: The PubMed database was searched for all articles on the application of ¹⁸F-FDG PET/CT imaging for human HCC up to December 2021. The following search terms were used: 'Hepatocellular carcinoma', '[18F]FDG PET/CT', 'Hypoxia', '[¹¹C]Choline'.

Key content and findings: In this review, we re-evaluate the potential hypoxia-dependent uptake mechanism of ¹⁸F-FDG in HCC and review the usefulness of ¹⁸F-FDG PET/CT for identifying, managing, and investigating the biological properties of HCC.

Conclusions: ¹⁸F-FDG PET/CT is very useful for HCC visualization, management, and the evaluation of biological properties. A negative test for ¹⁸F-FDG uptake is not meaningless and may reflect a relatively better outcome. ¹⁸F-FDG-positive lesions indicate a significantly less favorable prognosis.

Keywords: 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT); Hepatocellular carcinoma (HCC); hypoxia; management; prognosis.

Figure 1

The relationship between ¹⁸F-FDG uptake and tumor hypoxia (arrow). (A) A549 ascites tumors have high ¹⁸F-FDG uptake and high pimonidazole binding and GLUT-1 expression. (B) ¹⁸F-FDG uptake was coincident with high pimonidazole binding in A549 serosa tumors. Scale bar, 2 mm. (C) High ¹⁸F-FDG uptake is coincident with high pimonidazole in HT29 subcutaneous xenograft (hypoxia, as indicated by arrows). (D) ¹⁸F-FDG uptake was significantly higher in hypoxia regions than normoxic tumor tissue. Pimonidazole is a hypoxia marker, and pimonidazole-stained positive regions suggest hypoxia. Hypoxia is defined as PO₂ less than 10 mmHg or 1.3% O₂. ¹⁸F-FDG, 18F-fluorodeoxyglucose. GLUT, glucose transporter. [This figure was originally published in Transl Oncol, Li et al., reused with permission from (16)].

Figure 2

A 52-year-old man with pathologically confirmed right lung adenocarcinoma underwent ¹⁸F-FDG PET early perfusion imaging and 60 min metabolic imaging (right lung lesion, as indicated by a circle and arrow). (A) CT image shows a mass in the upper lobe of the right lung (circle); (B) early perfusion imaging; (C) metabolic imaging. There was a significant mismatch between perfusion and metabolism. ¹⁸F-FDG PET, ¹⁸F-fluorodeoxyglucose positron emission tomography; CT, computed tomography. [This figure was originally published in Oncotarget, Shen et al., reused with permission from (20)].