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Use of a Peptide Derived from Foot-and-Mouth Disease Virus for the Noninvasive Imaging of Human Cancer: Generation and Evaluation of 4-[¹⁸F]Fluorobenzoyl A20FMDV2 for In vivo Imaging of Integrin _vß₆ Expression with Positron Emission Tomography

¹ Department of Biomedical Engineering, University of California Davis, Davis, California and ² Centre for Tumour Biology, Barts and the London, Queen Mary's School of Medicine and Dentistry, London, United Kingdom

Requests for reprints: Julie L. Sutcliffe, Department of Biomedical Engineering, Genomics and Biomedical Sciences Facility, University of California Davis, 451 East Health Sciences Drive, Davis, CA 95616. Phone: 530-754-7107; Fax: 530-754-5739; E-mail: jlsutcliffe{at}ucdavis.edu and John F. Marshall, Centre for Tumour Biology, Institute of Cancer, Barts and the London, Queen Mary's School of Medicine and Dentistry, Charterhouse Square, London EC1M 6BQ, United Kingdom. E-mail: john.marshall{at}cancer.org.uk.

Expression of the epithelial-specific integrin _vß₆ 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 _vß₆ a promising target for the in vivo detection of cancer using noninvasive imaging. In addition, _vß₆ is recognized as promoting invasion and correlates with aggressive behavior of human cancers and thus agents that recognize _vß₆ specifically in vivo will be an essential tool for the future management of _vß₆-positive cancers. Recently, we identified the peptide NAVPNLRGDLQVLAQKVART (A20FMDV2), derived from foot-and-mouth disease virus, as a potent inhibitor of _vß₆. Using flow cytometry and ELISA, we show that this peptide is highly selective, inhibiting _vß₆-ligand binding with a IC₅₀ of 3 nmol/L, an activity 1,000-fold more selective for _vß₆ than for other RGD-directed integrins (_vß₃, _vß₅, and ₅ß₁). A20FMDV2 was radiolabeled on solid-phase using 4-[¹⁸F]fluorobenzoic acid, injected into mice bearing both _vß₆-negative and _vß₆-positive (DX3puro/DX3puroß6 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 _vß₆-positive versus the _vß₆-negative tumor, together with fast renal elimination of nonspecifically bound activity, resulted in specific imaging of the _vß₆-positive neoplasm. These data suggest that PET imaging of _vß₆-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]

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