[18F]Fluorodeoxyglucose Positron Emission Tomography for Lung Antiinflammatory Response Evaluation
[18F]Fluorodeoxyglucose Positron Emission Tomography for Lung Antiinflammatory Response Evaluation
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DOI：
10.1164/rccm.200904-0501oc
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发表时间：
2009-09-15
影响因子：
24.7
通讯作者：
Walter, Michael J.
中科院分区：
文献类型：
--
作者：
Chen, Delphine L.;Bedient, Timothy J.;Walter, Michael J.
基本原理目前很少有肺部炎症的非侵入性生物标志物可用于评估肺部对顺铂治疗的特异性反应。正电子发射断层扫描与[F-18]氟脱氧葡萄糖（FDG-PET）是一种很有前途的新方法，可用于定量肺嗜酸性inflammation.Objectives：评估FDG-PET的能力，以衡量肺的羟甲基戊二酰辅酶A还原酶抑制剂（他汀类药物）和重组人活化蛋白C（rhAPC）在实验诱导的肺部炎症的人类模型的影响。18名健康志愿者在支气管内节段性内毒素激发前随机接受安慰剂、洛伐他汀或rhAPC。内毒素滴注前后进行FDG-PET显像。[F-18]FDG摄取速率通过Patlak图解分析计算为内流常数Ki。进行支气管肺泡灌洗（BAL），以确定白细胞浓度的相关性与PET imaging results.Measurements和主要结果：有一个统计学显着减少，在K-i的洛伐他汀治疗组，没有看到在安慰剂治疗组，这表明衰减炎症的洛伐他汀治疗，尽管一个小的减少BAL总白细胞和中性粒细胞计数，没有统计学意义。在rhAPC治疗组中没有观察到显着降低K-1，与BAL参数的变化缺乏相关，并表明没有显着的hapc.Conclusions：FDG-PET成像是一种敏感的方法，用于定量肺特异性反应的hapctin治疗，并可能作为一个有吸引力的平台，在药物开发过程中的早期阶段评估新的hapctin治疗的疗效。
Rationale Few noninvasive biomarkers for pulmonary inflammation are currently available that can assess the lung-specific response to antiinflammatory treatments. Positron emission tomography with [F-18]fluorodeoxyglucose (FDG-PET) is a promising new method that can be used to quantify pulmonary neutrophilic inflammation.Objectives: To evaluate the ability of FDG-PET to measure the pulmonary antiinflammatory effects of hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) and recombinant human activated protein C (rhAPC) in a human model of experimentally-induced lung inflammation.Methods: Eighteen healthy volunteers were randomized to receive placebo, lovastatin, or rhAPC before intrabronchial segmental endotoxin challenge. FDG-PET imaging was performed before and after endotoxin instillation. The rate of [F-18]FDG uptake was calculated as the influx constant K-i by Patlak graphical analysis. Bronchoalveolar lavage (BAL) was performed to determine leukocyte concentrations for correlation with the PET imaging results.Measurements and Main Results: There was a statistically significant decrease in K-i in the lovastatin-treated group that was not seen in the placebo-treated group, suggesting attenuation of inflammation by lovastatin treatment despite a small decrease in BAL total leukocyte and neutrophil counts that was not statistically significant. No significant decrease in K-i was observed in the rhAPC-treated group, correlating with a lack of change in BAL parameters and indicating no significant antiinflammatory effect with rhAPC.Conclusions: FDG-PET imaging is a sensitive method for quantifying the lung-specific response to antiinflammatory therapies and may serve as an attractive platform for assessing the efficacy of novel antiinflammatory therapies at early phases in the drug development process.