Goldklang Monica P, Tekabe Yared, Zelonina Tina, Trischler Jordis, Xiao Rui, Stearns Kyle, Romanov Alexander, Muzio Valeria, Shiomi Takayuki, Johnson Lynne L, D'Armiento Jeanine M
1 Department of Anesthesiology.
2 Department of Medicine.
Am J Respir Cell Mol Biol. 2016 Dec;55(6):848-857. doi: 10.1165/rcmb.2015-0407OC.
Evaluation of lung disease is limited by the inability to visualize ongoing pathological processes. Molecular imaging that targets cellular processes related to disease pathogenesis has the potential to assess disease activity over time to allow intervention before lung destruction. Because apoptosis is a critical component of lung damage in emphysema, a functional imaging approach was taken to determine if targeting apoptosis in a smoke exposure model would allow the quantification of early lung damage in vivo. Rabbits were exposed to cigarette smoke for 4 or 16 weeks and underwent single-photon emission computed tomography/computed tomography scanning using technetium-99m-rhAnnexin V-128. Imaging results were correlated with ex vivo tissue analysis to validate the presence of lung destruction and apoptosis. Lung computed tomography scans of long-term smoke-exposed rabbits exhibit anatomical similarities to human emphysema, with increased lung volumes compared with controls. Morphometry on lung tissue confirmed increased mean linear intercept and destructive index at 16 weeks of smoke exposure and compliance measurements documented physiological changes of emphysema. Tissue and lavage analysis displayed the hallmarks of smoke exposure, including increased tissue cellularity and protease activity. Technetium-99m-rhAnnexin V-128 single-photon emission computed tomography signal was increased after smoke exposure at 4 and 16 weeks, with confirmation of increased apoptosis through terminal deoxynucleotidyl transferase dUTP nick end labeling staining and increased tissue neutral sphingomyelinase activity in the tissue. These studies not only describe a novel emphysema model for use with future therapeutic applications, but, most importantly, also characterize a promising imaging modality that identifies ongoing destructive cellular processes within the lung.
肺部疾病的评估受到无法可视化正在进行的病理过程的限制。针对与疾病发病机制相关的细胞过程的分子成像有潜力随时间评估疾病活动，以便在肺部破坏之前进行干预。由于细胞凋亡是肺气肿中肺损伤的关键组成部分，因此采用了一种功能成像方法来确定在烟雾暴露模型中靶向细胞凋亡是否能在体内对早期肺损伤进行量化。将兔子暴露于香烟烟雾中4周或16周，并使用锝-99m-rhAnnexin V-128进行单光子发射计算机断层扫描/计算机断层扫描。成像结果与离体组织分析相关联，以验证肺破坏和细胞凋亡的存在。长期烟雾暴露兔子的肺部计算机断层扫描显示出与人类肺气肿相似的解剖结构，与对照组相比肺体积增加。肺组织形态学测量证实，烟雾暴露16周时平均线性截距和破坏指数增加，顺应性测量记录了肺气肿的生理变化。组织和灌洗分析显示了烟雾暴露的特征，包括组织细胞增多和蛋白酶活性增加。烟雾暴露4周和16周后，锝-99m-rhAnnexin V-128单光子发射计算机断层扫描信号增加，通过末端脱氧核苷酸转移酶dUTP缺口末端标记染色证实细胞凋亡增加，并且组织中中性鞘磷脂酶活性增加。这些研究不仅描述了一种用于未来治疗应用的新型肺气肿模型，而且最重要的是，还表征了一种有前景的成像方式，可识别肺内正在进行的破坏性细胞过程。
