A longitudinal 18F-fluorodeoxyglucose (18F-FDG) and 18F-sodium fluoride (18F-NaF) positron emission tomography/computed tomography (PET/CT) study in apolipoprotein E (ApoE) knockout rats fed with a Western diet

A longitudinal 18F-fluorodeoxyglucose (18F-FDG) and 18F-sodium fluoride (18F-NaF) positron emission tomography/computed tomography (PET/CT) study in apolipoprotein E (ApoE) knockout rats fed with a Western diet

Abstract

Background: Inflammation and vascular calcification are risk factors for cardiovascular disease, but their relationship is still under investigation. This longitudinal in vivo study aimed to monitor inflammation and calcification during the formation of atherosclerotic plaques in apolipoprotein E knockout (ApoE-/-) rats by 18F-fluorodeoxyglucose (18F-FDG) and 18F-sodium fluoride (18F-NaF) positron emission tomography/computed tomography (PET/CT).

Methods: In the ApoE group, male ApoE-/- rats were fed a high-fat Western diet from 13 weeks of age, and in the normal group, male SD rats of the same age were fed a normal diet. A longitudinal PET/CT study using 18F-FDG and 18F-NaF was performed at 12, 27, and 46 weeks of age. T1-weighted magnetic resonance imaging (MRI) was used as an atlas template, and the uptake of the tracers in the cardiovascular system was analyzed based on atlas 3D geometry volumes-of-interest (VOIs). After the PET/CT study, pathological and immunohistochemical examinations were performed on the corresponding lesions.

Results: The body weight and plasma cholesterol levels of the ApoE-/- rats increased with time, and at each time point, significantly higher body weight and plasma cholesterol levels were observed in the ApoE-/- rats than in the normal rats. PET/CT showed that in ApoE-/- rats, the uptake of 18F-FDG was found in the aortic arch, while the uptake of 18F-NaF was found in pulmonary arteries. The uptake of the two tracers in the ApoE group increased with time. Extensive early stage of atherosclerotic plaques, with high expression of CD68 and alizarin red, were observed in pulmonary arteries. However, only a thickened intima with very high expression of hypoxia-inducible factor-1 alpha (HIF-1α) was seen in the aortic arch.

Conclusions: In ApoE-/- rats fed a high-fat Western diet, early atherosclerotic lesions developed in the pulmonary arteries; however, 18F-FDG failed to accumulate in these lesions but to accumulate in the aortic arch with only neointimal hyperplasia and significantly high expression of hypoxia.

Keywords: 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT); 18F-sodium fluoride positron emission tomography/computed tomography (18F-NaF PET/CT); ApoE−/− rat; atherosclerosis; hypoxia.

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