Centre for Pharmacology and Therapeutics, Experimental Medicine, Imperial College London, Hammersmith Hospital, London, UK (L.Z., A.A., L.W., O.D., J.C., E.C., H.J., G.B., M.R.W.); Department of Nuclear Medicine, Cardiovascular Institute and Fu Wai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (W.F.); Max-Planck Institute for Heart and Lung Research and University of Giessen and Marburg Lung Center, German Center for Lung Research, Bad Nauheim, Germany (S.D., S.S.P.); Comprehensive Cancer Imaging Centre, Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, UK (G.T., Q.N., E.O.A.); Department of Histopathology, Imperial College London, UK (M.A.E.-B.); National Heart and Lung Institute, Imperial College London, and National Pulmonary Hypertension Service, Department of Cardiology, Hammersmith Hospital, London, UK (L.S.H., J.S.R.G.); Biological Imaging Centre, Medical Research Council Clinical Sciences Centre, Imperial College London, Hammersmith Hospital, London, UK (W.G.); and Center for Diagnosis and Management of Pulmonary Vascular Diseases, Department of Cardiology, Cardiovascular Institute and Fu Wai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (J.H.).
Circulation. 2013 Sep 10;128(11):1214-24. doi: 10.1161/CIRCULATIONAHA.113.004136. Epub 2013 Jul 30.
Pulmonary arterial hypertension (PAH) is a disease of progressive vascular remodeling, characterized by dysregulated growth of pulmonary vascular cells and inflammation. A prevailing view is that abnormal cellular metabolism, notably aerobic glycolysis that increases glucose demand, underlies the pathogenesis of PAH. Increased lung glucose uptake has been reported in animal models. Few data exist from patients with PAH.
Dynamic positron emission tomography imaging with fluorine-18-labeled 2-fluoro-2-deoxyglucose ((18)FDG) ligand with kinetic analysis demonstrated increased mean lung parenchymal uptake in 20 patients with PAH, 18 with idiopathic PAH (IPAH) (FDG score: 3.27±1.22), and 2 patients with connective tissue disease (5.07 and 7.11) compared with controls (2.02±0.71; P<0.05). Further compartment analysis confirmed increased lung glucose metabolism in IPAH. Lung (18)FDG uptake and metabolism varied within the IPAH population and within the lungs of individual patients, consistent with the recognized heterogeneity of vascular pathology in this disease. The monocrotaline rat PAH model also showed increased lung (18)FDG uptake, which was reduced along with improvements in vascular pathology after treatment with dicholoroacetate and 2 tyrosine kinase inhibitors, imatinib and sunitinib. Hyperproliferative pulmonary vascular fibroblasts isolated from IPAH patients exhibited upregulated glycolytic gene expression, along with increased cellular (18)FDG uptake; both were reduced by dicholoroacetate and imatinib.
Some patients with IPAH exhibit increased lung (18)FDG uptake. (18)FDG positron emission tomography imaging is a tool to investigate the molecular pathology of PAH and its response to treatment.
肺动脉高压（PAH）是一种进行性血管重构疾病，其特征是肺血管细胞的失调生长和炎症。目前的观点认为，异常的细胞代谢，特别是增加葡萄糖需求的有氧糖酵解，是 PAH 发病机制的基础。已经在动物模型中报道了增加的肺葡萄糖摄取。PAH 患者的数据很少。
使用氟-18 标记的 2-氟-2-脱氧葡萄糖（（18）FDG）配体进行动态正电子发射断层扫描成像，并进行动力学分析，结果显示 20 例 PAH 患者（18 例特发性 PAH（IPAH）（FDG 评分：3.27±1.22）和 2 例结缔组织疾病患者的肺实质摄取增加（5.07 和 7.11）与对照组（2.02±0.71）相比（P<0.05）。进一步的房室分析证实了 IPAH 中肺葡萄糖代谢增加。在 IPAH 人群中以及在个体患者的肺部中，肺（18）FDG 摄取和代谢存在差异，这与该疾病中血管病理学的公认异质性一致。在野百合碱诱导的大鼠 PAH 模型中，也观察到肺（18）FDG 摄取增加，在用二氯乙酸和 2 种酪氨酸激酶抑制剂伊马替尼和舒尼替尼治疗后，血管病理改善，肺（18）FDG 摄取减少。从 IPAH 患者中分离出的过度增殖性肺血管成纤维细胞表现出上调的糖酵解基因表达，同时伴有细胞（18）FDG 摄取增加；这两者均被二氯乙酸和伊马替尼降低。
一些 IPAH 患者表现出增加的肺（18）FDG 摄取。（18）FDG 正电子发射断层扫描成像是一种研究 PAH 分子病理学及其对治疗反应的工具。
