Type 2 diabetes enhances arterial uptake of choline in atherosclerotic mice: an imaging study with positron emission tomography tracer F-18-fluoromethylcholine

Abstract

<p><b>Background: </b>Diabetes is a risk factor for atherosclerosis associated with oxidative stress, inflammation and cell proliferation. The purpose of this study was to evaluate arterial choline uptake and its relationship to atherosclerotic inflammation in diabetic and non-diabetic hypercholesterolemic mice.<b><br /></b><b>Methods: </b>Low-density lipoprotein-receptor deficient mice expressing only apolipoprotein B100, with or without type 2 diabetes caused by pancreatic overexpression of insulin-like growth factor II (IGF-II/LDLR^−/−ApoB^100/100 and LDLR^−/−ApoB^100/100) were studied. Distribution kinetics of choline analogue ¹⁸F-fluoromethylcholine (¹⁸F-FMCH) was assessed in vivo by positron emission tomography (PET) imaging. Then, aortic uptakes of ¹⁸F-FMCH and glucose analogue ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG), were assessed ex vivo by gamma counting and autoradiography of tissue sections. The ¹⁸F-FMCH uptake in atherosclerotic plaques was further compared with macrophage infiltration and the plasma levels of cytokines and metabolic markers. <br /><b>Results: </b>The aortas of all hypercholesterolemic mice showed large, macrophage-rich atherosclerotic plaques. The plaque burden and densities of macrophage subtypes were similar in diabetic and non-diabetic animals. The blood clearance of ¹⁸F-FMCH was rapid. Both the absolute ¹⁸F-FMCH uptake in the aorta and the aorta-to-blood uptake ratio were higher in diabetic than in non-diabetic mice. In autoradiography, the highest ¹⁸F-FMCH uptake co-localized with macrophage-rich atherosclerotic plaques. ¹⁸F-FMCH uptake in plaques correlated with levels of total cholesterol, insulin, C-peptide and leptin. In comparison with ¹⁸F-FDG, ¹⁸F-FMCH provided similar or higher plaque-to-background ratios in diabetic mice. <br /><b>Conclusions: </b>Type 2 diabetes enhances the uptake of choline that reflects inflammation in atherosclerotic plaques in mice. PET tracer ¹⁸F-FMCH is a potential tool to study vascular inflammation associated with diabetes.</p>