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Noninvasive assessment of hypoxia in rabbit advanced atherosclerosis using ¹⁸F-fluoromisonidazole positron emission tomographic imaging.
- Source :
-
Circulation. Cardiovascular imaging [Circ Cardiovasc Imaging] 2014 Mar; Vol. 7 (2), pp. 312-20. Date of Electronic Publication: 2014 Feb 07. - Publication Year :
- 2014
-
Abstract
- Background: Hypoxia is an important microenvironmental factor influencing atherosclerosis progression by inducing foam-cell formation, metabolic adaptation of infiltrated macrophages, and plaque neovascularization. Therefore, imaging plaque hypoxia could serve as a marker of lesions at risk.<br />Methods and Results: Advanced aortic atherosclerosis was induced in 18 rabbits by atherogenic diet and double balloon endothelial denudation. Animals underwent (18)F-fluoromisonidazole positron emission tomographic and (18)F-fluorodeoxyglucose positron emission tomographic imaging after 6 to 8 months (atherosclerosis induction) and 12 to 16 months (progression) of diet initiation. Four rabbits fed standard chow served as controls. Radiotracer uptake of the abdominal aorta was measured using standardized uptake values. After imaging, plaque hypoxia (pimonidazole), macrophages (RAM-11), neovessels (CD31), and hypoxia-inducible factor-1α were assessed by immunohistochemistry.(18)F-fluoromisonidazole uptake increased with time on diet (standardized uptake value mean, 0.10±0.01 in nonatherosclerotic animals versus 0.20±0.03 [P=0.002] at induction and 0.25±0.03 [P<0.001] at progression). Ex vivo positron emission tomographic imaging corroborated the (18)F-fluoromisonidazole uptake by the aorta of atherosclerotic rabbits. (18)F-fluorodeoxyglucose uptake also augmented in atherosclerotic animals, with an standardized uptake value mean of 0.43±0.02 at induction versus 0.35±0.02 in nonatherosclerotic animals (P=0.031) and no further increase at progression. By immunohistochemistry, hypoxia was mainly located in the macrophage-rich areas within the atheromatous core, whereas the macrophages close to the lumen were hypoxia-negative. Intraplaque neovessels were found predominantly in macrophage-rich hypoxic regions (pimonidazole(+)/hypoxia-inducible factor-1α(+)/RAM-11(+)).<br />Conclusions: Plaque hypoxia increases with disease progression and is present in macrophage-rich areas associated with neovascularization. (18)F-fluoromisonidazole positron emission tomographic imaging emerges as a new tool for the detection of atherosclerotic lesions.
- Subjects :
- Animals
Atherosclerosis complications
Disease Models, Animal
Disease Progression
Fluorine Radioisotopes
Hypoxia etiology
Male
Rabbits
Radiation-Sensitizing Agents
Reproducibility of Results
Severity of Illness Index
Aorta, Abdominal diagnostic imaging
Aortic Diseases diagnostic imaging
Atherosclerosis diagnostic imaging
Hypoxia diagnostic imaging
Misonidazole analogs & derivatives
Positron-Emission Tomography methods
Subjects
Details
- Language :
- English
- ISSN :
- 1942-0080
- Volume :
- 7
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Circulation. Cardiovascular imaging
- Publication Type :
- Academic Journal
- Accession number :
- 24508668
- Full Text :
- https://doi.org/10.1161/CIRCIMAGING.113.001084