18F-FDG imaging of human atherosclerotic carotid plaques reflects gene expression of the key hypoxia marker HIF-1α

American Journal of Nuclear Medicine and Molecular Imaging

Henrik Sillesen¹  Sune Folke Pedersen¹  Martin Græbe¹  Anne Mette F Hag¹  Liselotte Højgaard¹  Andreas Kjær¹ 

关键词: Hypoxia;    18F-FDG PET/CT imaging;    carotid atherosclerosis;    gene expression;    HIF-1α;   

DOI  :  

学科分类：过敏症与临床免疫学

来源: e-Century Publishing Corporation

【 摘 要 】

To investigate the association between gene expression of key molecular markers of hypoxia and inflammation in atherosclerotic carotid lesions with 2-deoxy-2-[¹⁸F]fluoro-D-glucose (¹⁸F-FDG) uptake as determined clinically by positron emission tomography (PET). Studies using PET have demonstrated ¹⁸F-FDG-uptake in patients with confirmed plaques of the carotid artery. Inflammatory active or “vulnerable” plaques progressively increase in bulk, develop necrotic cores, poor vessel-wall vascularization and become prone to hypoxia. We used quantitative polymerase-chain reaction (qPCR) to determine gene expression of hypoxia-inducible factor 1α (HIF-1α) and cluster of differentiation 68 (CD68) on plaques recovered by carotid endarterectomy (CEA) in 18 patients. Gene expression was compared with ¹⁸F-FDG-uptake quantified as the maximum standardized uptake value (SUV_max) on co-registered PET/computed tomography (CT) scans performed the day before CEA. Immunohistochemistry was used to validate target-gene protein expression. In univariate linear regression analysis HIF-1α was significantly correlated with ¹⁸F-FDG-uptake (SUV_max) as was CD68. A two-tailed Pearson regression model demonstrated that HIF-1α and CD68 gene expression co-variated and accordingly when entering the variables into multivariate linear regression models with SUV-values as dependent variables, HIF-1α was eliminated in the final models. ¹⁸F-FDG-uptake (SUV_max) is correlated with HIF-1α gene expression indicating an association between hypoxia and glucose metabolism in vivo. The marker of inflammation CD68 is also associated with ¹⁸F-FDG-uptake (SUV_max). As CD68 and HIF-1α gene expression co-variate their information is overlapping.

【 授权许可】

Unknown