Chronic Liver Disease and the Detection of Hepatocellular Carcinoma by [18F]fluorocholine PET/CT

Abstract

Positron emission tomography (PET) using the radiopharmaceutical tracer fluorine-18 fluorocholine (FCh) can elucidate tumors based on differences in choline phospholipid metabolism between tumor and surrounding tissue. The feasibility of detecting hepatocellular carcinoma (HCC) using FCh PET has been shown despite constitutively high parenchymal choline metabolism in the liver. Since HCC frequently develops in the setting of chronic liver disease, we comparatively evaluated FCh PET/CT between cirrhotic and non-cirrhotic patients with HCC to investigate the effects of hepatic dysfunction on tumor detection and the tumor-to-background ratio (TBR) of FCh uptake. FCh PET/CT was performed prospectively in 22 consecutive patients with HCC (7 newly diagnosed, 15 previously treated). Of these 22 patients, 14 were cirrhotic and 8 non-cirrhotic. Standardized uptake value (SUV) measurements were obtained by region of interest analysis of the PET images. Tumor FCh uptake and the TBR were compared between cirrhotic and non-cirrhotic patients. Liver lesions were confirmed to be HCC by biopsy in 10 patients and by Barcelona criteria in 4 patients. There was correspondingly increased liver tumor FCh uptake in 13/14 of those patients, and iso-intense tumor FCh uptake (TBR 0.94) in one non-cirrhotic patient with newly diagnosed HCC. FCh PET/CT also showed metastatic disease without local tumor recurrence in 2 previously treated patients, and was negative in 6 treated patients without tumor recurrence by radiographic and clinical follow-up. Tumor maximum SUV ranged from 6.4 to 15.3 (mean 12.1) and liver TBR ranged from 0.94 to 2.1 (mean 1.6), with no significant differences between cirrhotic and non-cirrhotic patients (SUVmax 11.9 vs. 12.2, p = 0.83; TBR 1.71 vs. 1.51, p = 0.29). Liver parenchyma mean SUV was significantly lower in cirrhotic patients (6.4 vs. 8.7, p < 0.05). This pilot study supports the general feasibility of HCC detection by FCh PET/CT. However, a broad range of tumor FCh uptake was observed, and lower liver parenchymal uptake of FCh was noted in cirrhotic patients as compared to non-cirrhotic patients. Incorporating tissue profiling into future liver imaging trials of FCh PET may help determine the molecular basis of the observed variations in tumor and hepatic FCh uptake.

Phospholipids are A Potentially Important Source of Tissue Biomarkers for Hepatocellular Carcinoma: Results of a Pilot Study Involving Targeted Metabolomics

“…The phospholipid signatures that best discriminated HCC from non-tumor liver tissue in our study included several different species of phosphatidylcholines. PET imaging using 18 F-fluorocholine is an imaging biomarker of phosphotidylcholine synthesis that is currently used for clinical detection of HCC in some regions [43,44] It has been shown to be superior to PET imaging of glucose metabolism with 18 F-fluoro-deoxy-D-glucose (FDG) for the detection of HCC, implying that lipogenesis is more salient than glycolysis as a metabolic feature of HCC [43,45,46]. Other studies have identified lipogenic networks characterized by specific lipid metabolites as being associated with HCC progression and survival [20].…”

Impact of Organic Cation Transporters (OCT-SLC22A) on Differential Diagnosis of Intrahepatic Lesions

“…Accumulation of [ 18 F]fluorodeoxyglucose in tumors correlates with higher glucose metabolism and cell proliferation (Minn et al, 1988;Bos et al, 2002). The substantial difference in the timeframe of image acquisition between [ 18 F]fluorodeoxyglucose (60-90 minutes) and FCH (10-15 minutes) PET scan suggests that, in addition to blood flow, membrane uptake rather than metabolism can determine FCH accumulation (Talbot et al, 2010;van den Esschert et al, 2011;Kwee et al, 2015). In fact, a number of studies failed to correlate intracellular accumulation of choline or FCH with choline metabolism (Utriainen et al, 2003;Yamaguchi et al, 2005;Rommel et al, 2010).…”

“…Likewise, unique accumulation of the positron emission tomography (PET) tracer [ 18 F]fluoromethylcholine (FCH) enhances the sensitivity for the detection and differentiation of focal liver lesions (Talbot et al, 2006(Talbot et al, ,2010van den Esschert et al, 2011;Kwee et al, 2015). The molecular features of the varying FCH accumulation in hepatic lesions are unknown.…”

“…at PET analysis (Talbot et al, 2006(Talbot et al, ,2010Wang et al, 2008;Kwee et al, 2015). The varying accumulation of FCH between different types of hypervascularized liver lesions might be the result of heterogeneous expression levels of relevant membrane transporters.…”

[18F]-choline PET/CT as an imaging biomarker for primary liver cancers

“…This study is different from most previous published clinical studies on the same topic (9–11). Many of the previous studies are comparative in nature, between choline or fluorocholine and the commonly used FDG for PET imaging of HCC with histological correlation in some of these studies (12). What is missing in all these previous clinical investigations are cellular characterization and validation.…”