Noninvasive Assessment of Hypoxia in Rabbit Advanced Atherosclerosis Using 18 F-fluoromisonidazole Positron Emission Tomographic Imaging

• DOI: 10.1161/circimaging.113.001084
• Publication Date: 2014-02-08T07:08:27Z
• Authors: Jesus Mateo; David Izquierdo-G...; Juan J. Badimon; Zahi A. Fayad; Valentin Fuster
• Keywords: Hypoxia; Fluorodeoxyglucose; Standardized uptake value; CD31

Hypoxia is an important microenvironmental factor influencing atherosclerosis progression by inducing foam-cell formation, metabolic adaptation of infiltrated macrophages, and plaque neovascularization. Therefore, imaging hypoxia could serve as a marker lesions at risk.Advanced aortic was induced in 18 rabbits atherogenic diet double balloon endothelial denudation. Animals underwent (18)F-fluoromisonidazole positron emission tomographic (18)F-fluorodeoxyglucose after 6 to 8 months (atherosclerosis induction) 12 16 (progression) initiation. Four fed standard chow served controls. Radiotracer uptake the abdominal aorta measured using standardized values. After imaging, (pimonidazole), macrophages (RAM-11), neovessels (CD31), hypoxia-inducible factor-1α were assessed immunohistochemistry.(18)F-fluoromisonidazole increased with time on (standardized value mean, 0.10±0.01 nonatherosclerotic animals versus 0.20±0.03 [P=0.002] induction 0.25±0.03 [P<0.001] progression). Ex vivo corroborated atherosclerotic rabbits. also augmented animals, mean 0.43±0.02 0.35±0.02 (P=0.031) no further increase progression. By immunohistochemistry, mainly located macrophage-rich areas within atheromatous core, whereas close lumen hypoxia-negative. Intraplaque found predominantly hypoxic regions (pimonidazole(+)/hypoxia-inducible factor-1α(+)/RAM-11(+)).Plaque increases disease present associated emerges new tool for detection lesions.