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Tumor Paint: A Chlorotoxin:Cy5.5 Bioconjugate for Intraoperative Visualization of Cancer Foci

¹ Clinical Research Division, Fred Hutchinson Cancer Research Center; Departments of ² Neurosurgery, ³ Material Science, ⁴ Pathology, ⁵ Radiology, ⁶ Medicine, and ⁷ Pediatrics, and ⁸ Program in Neurobiology and Behavior, University of Washington; ⁹ Children's Hospital and Regional Medical Center; and ¹⁰ Puget Sound Health Care System, Seattle, Washington; and ¹¹ Cancer Biology Department, Vanderbilt University Medical School, Nashville, Tennessee

Requests for reprints: James M. Olson, Fred Hutchinson Cancer Research Center, Mailstop D4-100, 1100 Fairview Avenue N., Seattle, WA 98109. Phone: 206-667-7955; Fax: 206-667-2917; E-mail: jolson{at}fhcrc.org.

Toward the goal of developing an optical imaging contrast agent that will enable surgeons to intraoperatively distinguish cancer foci from adjacent normal tissue, we developed a chlorotoxin:Cy5.5 (CTX:Cy5.5) bioconjugate that emits near-IR fluorescent signal. The probe delineates malignant glioma, medulloblastoma, prostate cancer, intestinal cancer, and sarcoma from adjacent non-neoplastic tissue in mouse models. Metastatic cancer foci as small as a few hundred cells were detected in lymph channels. Specific binding to cancer cells is facilitated by matrix metalloproteinase-2 (MMP-2) as evidenced by reduction of CTX:Cy5.5 binding in vitro and in vivo by a pharmacologic blocker of MMP-2 and induction of CTX:Cy5.5 binding in MCF-7 cells following transfection with a plasmid encoding MMP-2. Mouse studies revealed that CTX:Cy5.5 has favorable biodistribution and toxicity profiles. These studies show that CTX:Cy5.5 has the potential to fundamentally improve intraoperative detection and resection of malignancies. [Cancer Res 2007;67(14):6882–8]

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