18F]FDG accumulation in an experimental model of multistage progression of cholangiocarcinoma

Abstract

The diagnosis of cholangiocarcinoma (CCA) is difficult, and due to the insidious course of the disease, most cases present at a relatively late stage. Positron emission tomography (PET), using [(18)F]fluoro-2-deoxyglucose ([(18)F]FDG) as a tracer is one the most powerful molecular imaging techniques available. We hypothesized that [(18)F]FDG accumulates at sites of early CCA development and that FDG-PET may be of value for the early diagnosis of CCA. We added 300 mg/L thioacetamide to the drinking water of rats who went on to develop CCA within 20 weeks. From eight weeks onwards, groups of three rats were injected with [(18)F]FDG, subsequently the liver was perfused, dissected and subjected to quantitative autoradiography using a phosphor imaging system. The liver sections were stained for histology, and glutathione S-transferase (GST) enzyme activity was determined. We correlated [(18)F]FDG uptake with pathological liver changes. The experiments demonstrate that thioacetamide causes atypical bile ducts and invasive CCA. Rat livers harvested early after the start of administration of thioacetamide contained only cirrhosis and/or atypical bile ducts, but CCA and FDG accumulation were absent. At 20 weeks, all rats had developed CCA and all, except two animals with a very small carcinoma, had strongly elevated focal FDG uptake. Quantitative autoradiography revealed tumor-to-normal-liver ratios as high as 5:4. In all rats with a carcinoma, there was a backdrop of cirrhosis, and interestingly cirrhotic areas did not show elevated FDG accumulation. [(18)F]FDG accumulates in CCA, is able to distinguish CCA from liver cirrhosis, but is probably unsuitable to detect very early CCA lesions.