Biomarkers for Radiation Pneumonitis Using Noninvasive Molecular Imaging.
Biomarkers for Radiation Pneumonitis Using Noninvasive Molecular Imaging.
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DOI：
10.2967/jnumed.115.160291
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发表时间：
2016-08
期刊：
影响因子：
--
通讯作者：
Clough AV
中科院分区：
文献类型：
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作者：
Medhora M;Haworth S;Liu Y;Narayanan J;Gao F;Zhao M;Audi S;Jacobs ER;Fish BL;Clough AV
我们的目标是开发微创生物标志物，在症状出现之前预测辐射引起的肺损伤。目前还没有能够预测放射性肺炎的生物标志物。在核事故或放射性恐怖主义情况下，全肺的辐射损伤是一种严重的风险。我们之前的研究表明，单次剂量的15 Gy x射线照射胸部会导致大鼠在6-8周内患上严重的肺炎。我们还开发了一种缓解放射性肺炎和纤维化的药物，可以在放射后5周开始治疗。我们使用两个功能单光子发射计算机断层扫描（SPECT）探针在体内辐照大鼠肺。注射锝标记大聚集白蛋白（99mTc-MAA）测定局部肺灌注。将99mTc-MAA的分布体积与显微ct解剖肺体积进行比较，确定灌注体积。第二种探针，锝标记的duramycin与凋亡细胞结合，用于测量同一大鼠模型中的肺细胞死亡。15 Gy后1、2、3周时肺灌注容量减少25%，2、3周时99mTc-duramycin摄取增加一倍以上。在这些时间里，受辐射和未受辐射的大鼠的体重、呼吸频率或肺组织没有变化。15 Gy后2周，离体肺的肺血管阻力和血管通透性升高。我们的研究结果表明SPECT生物标志物在观察到实质性功能或组织学损伤之前预测肺部辐射损伤的潜力。放射性肺炎的早期预测将有利于那些在治疗、事故或恐怖主义背景下接受辐射的人及时启动缓解措施。
Our goal is to develop minimally-invasive biomarkers for predicting radiation-induced lung injury before symptoms develop. Currently there are no biomarkers that can predict radiation pneumonitis. Radiation damage to the whole lung is a serious risk in nuclear accidents or in case of radiological terrorism. Our previous studies have shown a single dose of 15 Gy X-rays to the thorax causes severe pneumonitis in rats by 6–8 weeks. We have also developed a mitigator for radiation pneumonitis and fibrosis that can be started as late as 5 weeks after radiation. We used two functional single photon emission computed tomography (SPECT) probes in vivo in irradiated rat lungs. Regional pulmonary perfusion was measured by injection of technetium labeled macroaggregated albumin (99mTc-MAA). Perfused volume was determined by comparing the volume of distribution of 99mTc-MAA to the anatomical lung volume obtained by micro-CT. A second probe, technetium labeled duramycin that binds to apoptotic cells, was used to measure pulmonary cell death in the same rat model. Perfused volume of lung was decreased by ~25% at 1, 2 and 3 weeks after 15 Gy and 99mTc-duramycin uptake was more than doubled at 2 and 3 weeks. There was no change in body weight, breathing rate or lung histology between irradiated and non-irradiated rats at these times. Pulmonary vascular resistance and vascular permeability measured in isolated perfused lungs ex vivo increased at 2 weeks after 15 Gy. Our results suggest the potential for SPECT biomarkers for predicting radiation injury to the lungs before substantial functional or histological damage is observed. Early prediction of radiation pneumonitis will benefit those receiving radiation in the context of therapy, accidents or terrorism in time to initiate mitigation.