Dual In Vivo Quantification of Integrin-targeted and Protease-activated Agents in Cancer Using Fluorescence Molecular Tomography (FMT)

被引：69

作者：

Kossodo, Sylvie ^{[1
]}

Pickarski, Maureen ^{[2
]}

Lin, Shu-An ^{[2
]}

Gleason, Alexa ^{[2
]}

Gaspar, Renee ^{[2
]}

Buono, Chiara ^{[1
]}

Ho, Guojie ^{[1
]}

Blusztajn, Agnieszka ^{[1
]}

Cuneo, Garry ^{[1
]}

Zhang, Jun ^{[1
]}

Jensen, Jayme ^{[1
]}

Hargreaves, Richard ^{[2
]}

Coleman, Paul ^{[2
]}

Hartman, George ^{[2
]}

Rajopadhye, Milind ^{[1
]}

Duong, Le Thi ^{[2
]}

Sur, Cyrille ^{[2
]}

Yared, Wael ^{[1
]}

Peterson, Jeffrey ^{[1
]}

Bednar, Bohumil ^{[2
]}

机构：

[1] VisEn Med, Bedford, MA USA

[2] Merck Res Labs, West Point, PA USA

来源：

MOLECULAR IMAGING AND BIOLOGY | 2010年 / 12卷 / 05期

关键词：

Near-infrared fluorescence imaging; Cancer; Quantification; Optical tomography; Integrin alpha(v)beta(3); ALPHA(V)BETA(3) INTEGRIN; MONOCLONAL-ANTIBODY; TUMOR ANGIOGENESIS; RGD PEPTIDES; EXPRESSION; THERAPY; ALPHA-V-BETA-3; CILENGITIDE; ULTRASOUND; LIGANDS;

D O I：

10.1007/s11307-009-0279-z

中图分类号：

R8 [特种医学]; R445 [影像诊断学];

学科分类号：

1002 ; 100207 ; 1009 ;

摘要：

Integrins, especially alpha(v)beta(3) and alpha(v)beta(5), are upregulated in tumor cells and activated endothelial cells and as such, serve as cancer biomarkers. We developed a novel near-infrared-labeled optical agent for the in vivo detection and quantification of alpha(v)beta(3)/alpha(v)beta(5). A small peptidomimetic alpha(v)beta(3) antagonist was synthesized, coupled to a near-infrared fluorescent (NIRF) dye, and tested for binding specificity using integrin-overexpressing cells, inhibition of vitronectin-mediated cell attachment, binding to tumor and endothelial cells in vitro, and competition studies. Pharmacokinetics, biodistribution, specificity of tumor targeting, and the effect of an antiangiogenic treatment were assessed in vivo. The integrin NIRF agent showed strong selectivity towards alpha(v)beta(3/)alpha(v)beta(5) in vitro and predominant tumor distribution in vivo, allowing noninvasive and real-time quantification of integrin signal in tumors. Antiangiogenic treatment significantly inhibited integrin signal in vivo but had no effect on a cathepsin-cleavable NIR agent. Simultaneous imaging revealed different patterns of distribution reflecting the underlying differences in integrin and cathepsin biology during tumor progression. NIRF-labeled integrin antagonists allow noninvasive molecular fluorescent imaging and quantification of tumors in vivo, improving and providing more refined approaches for cancer detection and treatment monitoring.

引用

页码：488 / 499

页数：12

共 58 条

[1] Synergistic effects of light-emitting probes and peptides for targeting and monitoring integrin expression [J].