title: (18)F-FDG imaging of human atherosclerotic carotid plaques reflects gene expression of the key hypoxia marker HIF-1α.
abstract: To investigate the association between gene expression of key molecular markers of hypoxia and inflammation in atherosclerotic carotid lesions with 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F-FDG) uptake as determined clinically by positron emission tomography (PET). Studies using PET have demonstrated (18)F-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 (18)F-FDG-uptake quantified as the maximum standardized uptake value (SUVmax) 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 (18)F-FDG-uptake (SUVmax) 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. (18)F-FDG-uptake (SUVmax) 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 (18)F-FDG-uptake (SUVmax). As CD68 and HIF-1α gene expression co-variate their information is overlapping.
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet, University of Copenhagen Blegdamsvej 9, 2100 Copenhagen, Denmark.
authors.forename: Sune Folke
authors.initials: SF
authors.lastname: Pedersen
authors.forename: Martin
authors.initials: M
authors.lastname: Græbe
authors.forename: Anne Mette F
authors.initials: AM
authors.lastname: Hag
authors.forename: Liselotte
authors.initials: L
authors.lastname: Højgaard
authors.forename: Henrik
authors.initials: H
authors.lastname: Sillesen
authors.forename: Andreas
authors.initials: A
authors.lastname: Kjær
keywords: 18F-FDG PET/CT imaging; HIF-1α; Hypoxia; carotid atherosclerosis; gene expression