体内
癌症
肽
临床前影像学
癌症研究
流式细胞术
正电子发射断层摄影术
化学
显像剂
离体
病理
体外
分子成像
整合素
医学
免疫学
核医学
细胞
生物
内科学
生物化学
生物技术
作者
Sven H. Hausner,Danielle DiCara,Jan Marik,John F. Marshall,Julie L. Sutcliffe
出处
期刊:Cancer Research
[American Association for Cancer Research]
日期:2007-08-15
卷期号:67 (16): 7833-7840
被引量:113
标识
DOI:10.1158/0008-5472.can-07-1026
摘要
Abstract Expression of the epithelial-specific integrin αvβ6 is low or undetectable in most adult tissues but may be increased during wound healing and inflammation and is up-regulated dramatically by many different carcinomas, making αvβ6 a promising target for the in vivo detection of cancer using noninvasive imaging. In addition, αvβ6 is recognized as promoting invasion and correlates with aggressive behavior of human cancers and thus agents that recognize αvβ6 specifically in vivo will be an essential tool for the future management of αvβ6-positive cancers. Recently, we identified the peptide NAVPNLRGDLQVLAQKVART (A20FMDV2), derived from foot-and-mouth disease virus, as a potent inhibitor of αvβ6. Using flow cytometry and ELISA, we show that this peptide is highly selective, inhibiting αvβ6-ligand binding with a IC50 of 3 nmol/L, an activity 1,000-fold more selective for αvβ6 than for other RGD-directed integrins (αvβ3, αvβ5, and α5β1). A20FMDV2 was radiolabeled on solid-phase using 4-[18F]fluorobenzoic acid, injected into mice bearing both αvβ6-negative and αvβ6-positive (DX3puro/DX3puroβ6 cell lines) xenografts and imaged using a small animal positron emission tomography (PET) scanner. Rapid uptake (<30 min) and selective retention (>5 h) of radioactivity in the αvβ6-positive versus the αvβ6-negative tumor, together with fast renal elimination of nonspecifically bound activity, resulted in specific imaging of the αvβ6-positive neoplasm. These data suggest that PET imaging of αvβ6-positive tumors is feasible and will provide an important new tool for early detection and improved management of many types of cancers. [Cancer Res 2007;67(16):7833–40]
科研通智能强力驱动
Strongly Powered by AbleSci AI