Molecular imaging of lung glucose uptake after endotoxin in mice
Molecular imaging of lung glucose uptake after endotoxin in mice
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DOI：
10.1152/ajplung.00146.2005
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发表时间：
2005-11-01
影响因子：
4.9
通讯作者：
Schuster, DP
中科院分区：
文献类型：
--
作者：
Zhou, ZH;Kozlowski, J;Schuster, DP
给予葡萄糖类似物氟-18氟脱氧葡萄糖（[F-18] FDG）后的正电子发射断层成像可能有助于研究肺部的嗜酸性炎症。在这项研究中，我们试图确定增加肺[18 F] FDG摄取腹膜内毒素（Etx）后，中性粒细胞流入小鼠肺的特异性，并确定调节葡萄糖摄取Etx后Toll样受体（TLR）和TNF-α。根据γ孔计数器中的计数验证通过成像进行的肺组织放射性测量。葡萄糖摄取被量化为[F-18] FDG组织-血液放射性比（TBR），在验证该测量相对于葡萄糖摄取的“金标准”测量，“净流入速率常数”。“TBR测量是在对照组（无干预），一组给予Etx，一组给予Etx加一种额外的药物（e.例如，在一个实施例中，长春碱）或Etx。将葡萄糖摄取测量值与髓过氧化物酶测量值进行比较。使用长春碱去除中性粒细胞后，Etx后TBR的增加显著但未完全消除。Etx后TBR的增加与TLR- 4或TLR- 2（后者可能继发于Etx制剂中的肽聚糖污染物）的信号传导一致，并且通过TLR- 4的药物抑制而不是TNF-α的抑制而降低。因此，分子成像可用于非侵入性地监测Etx对小鼠肺的生物学效应，并且肺葡萄糖摄取的变化可用于监测抗炎剂的作用。这种成像能力为转化的“小鼠到人类”肺部研究提供了一个强大的新范例。
Positron emission tomographic imaging after administration of the glucose analog fluorine-18 fluorodeoxyglucose ([F-18] FDG) may be useful to study neutrophilic inflammation of the lungs. In this study, we sought to determine the specificity of the increase in lung [ 18F] FDG uptake after intraperitoneal endotoxin ( Etx) for neutrophil influx into mouse lungs and to determine the regulation of glucose uptake after Etx by Toll-like receptors ( TLRs) and TNF-alpha. Lung tissue radioactivity measurements by imaging were validated against counts in a gamma well counter. Glucose uptake was quantified as the [F-18] FDG tissue-to-blood radioactivity ratio ( TBR) after validating this measure against the "gold standard" measure of glucose uptake, the "net influx rate constant." TBR measurements were made in a control group ( no intervention), a group administered Etx, and a group administered Etx plus an additional agent ( e. g., vinblastine) or Etx administered to a mutant mouse strain. The glucose uptake measurements were compared with measurements of myeloperoxidase. Increases in TBR after Etx were significantly but not completely eliminated by neutrophil depletion with vinblastine. Increases in TBR after Etx were consistent with signaling via either TLR- 4 or TLR- 2 ( the latter probably secondary to peptidoglycan contaminants in Etx preparation) and were decreased by drug inhibition of TLR- 4 but not by inhibition of TNF-alpha. Thus molecular imaging can be used to noninvasively monitor biological effects of Etx on lungs in mice, and changes in lung glucose uptake can be used to monitor effects of anti-inflammatory agents. Such imaging capacity provides a powerful new paradigm for translational "mouse-to-human" pulmonary research.