Evaluation of tumor microenvironment in an animal model using a nanoparticle contrast agent in computed tomography imaging.
Evaluation of tumor microenvironment in an animal model using a nanoparticle contrast agent in computed tomography imaging.
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DOI：
10.1016/j.acra.2010.09.003
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发表时间：
2011-01
影响因子：
4.8
通讯作者：
Annapragada, Ananth
中科院分区：
文献类型：
--
作者：
Ghaghada, Ketan B.;Badea, Cristian T.;Karumbaiah, Lohitash;Fettig, Nicole;Bellamkonda, Ravi V.;Johnson, G. A.;Annapragada, Ananth
肿瘤血管系统的非侵入性纵向成像可以为实体瘤的发展提供新的见解，促进治疗药物的有效输送。在这项研究中，我们报告了使用纳米粒子造影剂和高分辨率计算机断层扫描（CT）成像的肿瘤血管结构的三维成像和表征。将植入4 T1/Luc同基因乳腺肿瘤细胞的5只Balb/c小鼠用于研究。全身给予纳米颗粒造影剂，并在造影前和造影后的连续时间点进行纵向CT成像，长达7天，以研究肿瘤相关血管的特征。使用定量实时聚合酶链反应（qRT-PCR）测量肿瘤血管生成生物标志物的基因表达。早期成像显示存在增选和新发展的肿瘤血管。增选的血管表现出壁渗透性和“泄漏”特征，这通过血管外基于纳米颗粒的信号增强的增加而明显，该信号增强远远超出肿瘤的边缘。肿瘤相关血管直径大于对侧正常血管直径。延迟相位成像也显示了肿瘤内和肿瘤周围区域的纳米颗粒造影剂的显著积聚。在单个肿瘤内和肿瘤间均观察到不均匀的信号增强模式。基因表达谱分析表明，在几个血管生成生物标志物内和个体肿瘤之间的显着差异。纳米颗粒造影剂和高分辨率CT成像促进了增选和新发展的肿瘤血管的可视化以及肿瘤内纳米颗粒积聚的成像。这种药物的使用可以为肿瘤血管生物学提供新的见解，并可能对肿瘤状态的监测产生影响。
Non-invasive longitudinal imaging of tumor vasculature could provide new insights into the development of solid tumors, facilitating efficient delivery of therapeutics. In this study, we report three-dimensional imaging and characterization of tumor vascular architecture using a nanoparticle contrast agent and high-resolution computed tomography (CT) imaging. Five Balb/c mice implanted with 4T1/Luc syngeneic breast tumors cells were used for the study. The nanoparticle contrast agent was systemically administered and longitudinal CT imaging was performed pre-contrast and at serial time-points post-contrast, for up to 7 days for studying the characteristics of tumor-associated blood vessels. Gene-expression of tumor angiogenic biomarkers was measured using quantitative real-time polymerase chain reaction (qRT-PCR). Early-phase imaging demonstrated the presence of co-opted and newly developed tumor vessels. The co-opted vessels demonstrated wall-permeability and ‘leakiness’ characteristics evident by an increase in extra-vascular nanoparticle-based signal enhancement visible well beyond the margins of tumor. Diameters of tumor-associated vessels were larger than the contra-lateral normal vessels. Delayed-phase imaging also demonstrated significant accumulation of nanoparticle contrast agent both within and in areas surrounding the tumor. A heterogeneous pattern of signal enhancement was observed both within and among individual tumors. Gene-expression profiling demonstrated significant variability in several angiogenic biomarkers both within and among individual tumors. The nanoparticle contrast agent and high-resolution CT imaging facilitated visualization of co-opted and newly developed tumors vessels as well as imaging of nanoparticle accumulation within tumors. The use of this agent could provide novel insights into tumor vascular biology and could have implications on the monitoring of tumor status.
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影响因子：
3.7
作者：
Karathanasis E;Chan L;Karumbaiah L;McNeeley K;D'Orsi CJ;Annapragada AV;Sechopoulos I;Bellamkonda RV
通讯作者：
Bellamkonda RV
DOI：
10.1055/s-0028-1109817
发表时间：
2010-04-01
影响因子：
1.8
作者：
Schwarz, M.;Engelhorn, T.;Doerfler, A.
通讯作者：
Doerfler, A.
影响因子：
56.9
作者：
Maisonpierre, PC;Suri, C;Yancopoulos, GD
通讯作者：
Yancopoulos, GD
影响因子：
5.7
作者：
Bullitt, Elizabeth;Reardon, David A.;Smith, J. Keith
通讯作者：
Smith, J. Keith
影响因子：
4.8
作者：
Savai, Rajkumar;Langheinrich, Alexander Claus;Banat, Andre
通讯作者：
Banat, Andre