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Molecular Imaging and Biology
Published in: Molecular Imaging and Biology 5/2010

01-10-2010 | Research Article

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

Authors: Sylvie Kossodo, Maureen Pickarski, Shu-An Lin, Alexa Gleason, Renee Gaspar, Chiara Buono, Guojie Ho, Agnieszka Blusztajn, Garry Cuneo, Jun Zhang, Jayme Jensen, Richard Hargreaves, Paul Coleman, George Hartman, Milind Rajopadhye, Le Thi Duong, Cyrille Sur, Wael Yared, Jeffrey Peterson, Bohumil Bednar

Published in: Molecular Imaging and Biology | Issue 5/2010

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Abstract

Purpose

Integrins, especially αvβ3 and αvβ5, 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 αvβ3/αvβ5.

Procedures

A small peptidomimetic αvβ3 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.

Results

The integrin NIRF agent showed strong selectivity towards αvβ3/αvβ5 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.

Conclusions

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.
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Metadata
Title
Dual In Vivo Quantification of Integrin-targeted and Protease-activated Agents in Cancer Using Fluorescence Molecular Tomography (FMT)
Authors
Sylvie Kossodo
Maureen Pickarski
Shu-An Lin
Alexa Gleason
Renee Gaspar
Chiara Buono
Guojie Ho
Agnieszka Blusztajn
Garry Cuneo
Jun Zhang
Jayme Jensen
Richard Hargreaves
Paul Coleman
George Hartman
Milind Rajopadhye
Le Thi Duong
Cyrille Sur
Wael Yared
Jeffrey Peterson
Bohumil Bednar
Publication date
01-10-2010
Publisher
Springer-Verlag
Published in
Molecular Imaging and Biology / Issue 5/2010
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI
https://doi.org/10.1007/s11307-009-0279-z

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