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Near-Infrared Fluorescence Imaging of Tumor Integrin αvβ3 Expression with Cy7-Labeled RGD Multimers

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Abstract

Purpose

Cell adhesion molecule integrin αvβ3 is an excellent target for tumor interventions because of its unique expression on the surface of several types of solid tumor cells and on almost all sprouting tumor vasculatures. Here, we describe the development of near-infrared (NIR) fluorochrome Cy7-labeled RGD peptides for tumor integrin targeting.

Procedures

Mono-, di-, and tetrameric RGD peptides were synthesized and conjugated with Cy7. The integrin specificity of these fluorescent probes was tested in vitro for receptor binding assay and fluorescence microscopy and in vivo for subcutaneous U87MG tumor targeting.

Results

The tetrameric RGD peptide probe with the highest integrin affinity showed the highest tumor activity accumulation and strongest tumor-to-normal tissue contrast. This uptake is integrin-specific as the signal accumulated in the tumor can be effectively blocked by unconjugated RGD peptide antagonist of integrin αvβ3.

Conclusions

Noninvasive NIR fluorescence imaging is able to detect and semiquantify tumor integrin expression based upon the highly potent tetrameric RGD peptide probe.

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Acknowledgments

This work was supported, in part, by National Cancer Institute (NCI) Grant R21 CA102123, National Institute of Biomedical Imaging and Bioengineering (NIBIB) Grant R21 EB001785, Department of Defense (DOD) Breast Cancer Research Program (BCRP) IDEA Award W81XWH-04-1-0697, DOD Ovarian Cancer Research Program (OCRP) Award OC050120, DOD Prostate Cancer Research Program (PCRP) New Investigator Award (NIA) DAMD1717-03-1-0143, American Lung Association California (ALAC), the Society of Nuclear Medicine Education and Research Foundation, National Cancer Institute (NCI) Small Animal Imaging Resource Program (SAIRP) grant R24 CA93862, NCI In vivo Cellular Molecular Imaging Center (ICMIC) grant P50 CA114747, and NCI Centers of Cancer Nanotechnology Excellence (CCNE) U54 grant.

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Authors and Affiliations

  1. Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X Program, Stanford University School of Medicine, 1201 Welch Rd, P095, Stanford, CA, 94305-5484, USA

    Yun Wu, Weibo Cai & Xiaoyuan Chen

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  1. Yun Wu
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  2. Weibo Cai
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  3. Xiaoyuan Chen
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Correspondence to Xiaoyuan Chen.

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Wu, Y., Cai, W. & Chen, X. Near-Infrared Fluorescence Imaging of Tumor Integrin αvβ3 Expression with Cy7-Labeled RGD Multimers. Mol Imaging Biol 8, 226–236 (2006). https://doi.org/10.1007/s11307-006-0041-8

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