Pedersen Sune Folke, Graebe Martin, Fisker Hag Anne Mette, Højgaard Liselotte, Sillesen Henrik, Kjaer Andreas
Cluster for Molecular Imaging, Nuclear Medicine and PET, University of Copenhagen, Copenhagen, Denmark.
Nucl Med Commun. 2010 May;31(5):423-9. doi: 10.1097/MNM.0b013e32833767e0.
Metabolic assessment of vascular inflammation by 2-[F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG)-PET is a promising new approach for the evaluation of the vulnerability of atherosclerotic plaques. Quantitative real-time PCR allows measurement of gene expression of markers of atherosclerotic plaque vulnerability. These techniques were applied in advanced atherosclerotic disease to relate metabolism and inflammatory activity to the gene expression profile of the vulnerable atherosclerotic plaque.
Seventeen patients with clinical symptoms of cerebral vascular events (<3 months) and an additional ipsilateral internal carotid artery stenosis of greater than 60% were recruited. FDG uptake in the carotids was determined by PET/computed tomography and expressed as mean and maximal standardized uptake values (SUVmean and SUVmax). The atherosclerotic plaques were subsequently recovered by carotid endarterectomy. The gene expression of markers of vulnerability - CD68, IL-18, matrix metalloproteinase 9, cathepsin K, GLUT-1, and hexokinase type II (HK2) - were measured in plaques by quantitative PCR.
In a multivariate linear regression model, GLUT-1, CD68, cathepsin K, and HK2 gene expression remained in the final model as predictive variables of FDG accumulation calculated as SUVmean (R=0.26, P<0.0001). In addition, a multivariate linear regression model found GLUT-1, CD68, cathepsin K, and HK2 gene expression as independent predictive variables of FDG accumulation calculated as SUVmax (R=0.30, P<0.0001).
GLUT-1, HK2, CD68, and cathepsin K remained in both multivariate models and thus provided independent information regarding FDG uptake. We suggest that FDG uptake is a composite indicator of macrophage load, overall inflammatory activity and collagenolytic plaque destabilization. Accordingly, FDG-PET could prove to be an important predictor of cerebrovascular events in patients with carotid plaques.
通过2-[F]氟-2-脱氧-D-葡萄糖正电子发射断层扫描（FDG）-PET对血管炎症进行代谢评估是一种评估动脉粥样硬化斑块易损性的有前景的新方法。定量实时聚合酶链反应可测量动脉粥样硬化斑块易损性标志物的基因表达。这些技术被应用于晚期动脉粥样硬化疾病，以将代谢和炎症活性与易损动脉粥样硬化斑块的基因表达谱联系起来。
招募了17例有脑血管事件临床症状（<3个月）且同侧颈内动脉额外狭窄大于60%的患者。通过PET/计算机断层扫描测定颈动脉的FDG摄取，并表示为平均和最大标准化摄取值（SUVmean和SUVmax）。随后通过颈动脉内膜切除术回收动脉粥样硬化斑块。通过定量聚合酶链反应测量斑块中易损性标志物——CD68、白细胞介素-18、基质金属蛋白酶9、组织蛋白酶K、葡萄糖转运蛋白-1（GLUT-1）和己糖激酶II型（HK2）——的基因表达。
在多变量线性回归模型中，GLUT-1、CD68、组织蛋白酶K和HK2基因表达作为以SUVmean计算的FDG积聚的预测变量保留在最终模型中（R=0.26，P<0.0001）。此外，多变量线性回归模型发现GLUT-1、CD68、组织蛋白酶K和HK2基因表达是以SUVmax计算的FDG积聚的独立预测变量（R=0.30，P<0.0001）。
GLUT-1、HK2、CD68和组织蛋白酶K保留在两个多变量模型中，因此提供了关于FDG摄取的独立信息。我们认为FDG摄取是巨噬细胞负荷、总体炎症活性和胶原分解性斑块不稳定的综合指标。因此，FDG-PET可能被证明是颈动脉斑块患者脑血管事件的重要预测指标。
