Matrix Metalloproteinase-Targeted Imaging of Lung Inflammation and Remodeling.
Matrix Metalloproteinase-Targeted Imaging of Lung Inflammation and Remodeling.
复制标题
DOI：
10.2967/jnumed.116.176198
复制
发表时间：
2017-01
期刊：
影响因子：
--
通讯作者：
Sadeghi MM
中科院分区：
文献类型：
--
作者：
Golestani R;Razavian M;Ye Y;Zhang J;Jung JJ;Toczek J;Gona K;Kim HY;Elias JA;Lee CG;Homer RJ;Sadeghi MM
需要成像技术来检测在肺部疾病之前或伴随肺部疾病的分子和细胞过程。基质金属蛋白酶（MMPs）在肺病理的发展中起着关键作用。探讨体内MMP靶向分子成像检测肺部炎症和重塑的可行性。本研究中使用肺特异性IL-13转基因[Club细胞10-kDa蛋白（CC 10）-IL-13 Tg）]小鼠和野生型（WT）同窝仔。肺结构，基因表达和MMP活性进行了评估，通过组织学，实时逆转录聚合酶链反应，蛋白质印迹和酶谱。MMP活化通过体内微单光子发射计算机断层扫描（SPECT）/CT成像，然后通过离体平面成像。使用对照示踪剂解决信号特异性。探讨了体内MMP信号与基因表达之间的相关性。CC 10-IL-13 Tg小鼠发生了相当大的肺组织重塑和炎症。CD 68、MMP-12和MMP-13在CC 10-IL-13 Tg肺中显著升高。在体内microSPECT/CT和离体平面图像上，CC 10-IL-13 Tg小鼠的肺中MMP信号显著高于WT动物。此外，非结合类似物示踪剂显示相对于特异性示踪剂在CC 10-IL-13 Tg肺中显著更低的积累。microSPECT/CT的MMP信号与肺组织中CD 68的表达有显著相关性（r = 0.70，P < 0.01）。基于MicroSPECT/CT的MMP靶向肺部成像是可行的，并反映了肺部炎症。如果在人类中得到验证，炎症和重塑的分子成像可能有助于早期诊断和监测肺部疾病治疗干预的效果。
Imaging techniques for detection of molecular and cellular processes that precede or accompany lung diseases are needed. Matrix metalloproteinases (MMPs) play key roles in the development of pulmonary pathology. Investigate the feasibility of in vivo MMP-targeted molecular imaging for detection of lung inflammation and remodeling. Lung-specific IL-13 transgenic [Club cell 10-kDa protein (CC10)-IL-13Tg)] mice, and wild type (WT) littermates were used in this study. Lung structure, gene expression, and MMP activity were assessed by histology, real-time reverse transcription polymerase chain reaction, Western blot and zymography. MMP activation was imaged by in vivo micro single-photon emission computed tomography (SPECT)/CT followed by ex vivo planar imaging. Signal specificity was addressed using a control tracer. The correlation between in vivo MMP signal and gene expression was addressed. CC10-IL-13Tg mice developed considerable pulmonary tissue remodeling and inflammation. CD68, MMP-12 and MMP-13 were significantly higher in CC10-IL-13Tg lungs. On in vivo microSPECT/CT and ex vivo planar images, the MMP signal was significantly higher in the lungs of CC10-IL-13Tg mice than WT animals. Furthermore, a non-binding analog tracer showed significantly lower accumulation in CC10-IL-13Tg lungs relative to the specific tracer. There was a significant correlation between microSPECT/CT-derived MMP signal and CD68 expression in the lungs (r = 0.70, P < 0.01). MicroSPECT/CT-based MMP-targeted imaging of the lungs is feasible and reflects pulmonary inflammation. If validated in humans, molecular imaging of inflammation and remodeling can potentially help early diagnosis and monitoring of the effects of therapeutic interventions in pulmonary diseases.
登录
查看更多内容
DOI：
10.2967/jnumed.114.152355
发表时间：
2015-06
期刊：
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
影响因子：
--
作者：
Jung JJ;Razavian M;Challa AA;Nie L;Golestani R;Zhang J;Ye Y;Russell KS;Robinson SP;Heistad DD;Sadeghi MM
通讯作者：
Sadeghi MM
影响因子：
5.8
作者：
Hersh CP;Washko GR;Estépar RS;Lutz S;Friedman PJ;Han MK;Hokanson JE;Judy PF;Lynch DA;Make BJ;Marchetti N;Newell JD Jr;Sciurba FC;Crapo JD;Silverman EK;COPDGene Investigators
通讯作者：
COPDGene Investigators
影响因子：
4.8
作者：
Devel, L;Rogakos, V;Dive, V
通讯作者：
Dive, V
影响因子：
15.9
作者：
Lanone, S;Zheng, T;Elias, JA
通讯作者：
Elias, JA
DOI：
10.1084/jem.194.6.809
发表时间：
2001-09-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Lee CG;Homer RJ;Zhu Z;Lanone S;Wang X;Koteliansky V;Shipley JM;Gotwals P;Noble P;Chen Q;Senior RM;Elias JA
通讯作者：
Elias JA