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

TLDR

The study aims to develop an optical imaging contrast agent that enables surgeons to distinguish cancer foci from adjacent normal tissue during surgery. The authors engineered a chlorotoxin:Cy5.5 bioconjugate that emits near‑IR fluorescence. In mouse models, CTX:Cy5.5 delineated malignant glioma, medulloblastoma, prostate, intestinal cancers, and sarcoma, detected metastatic foci as small as a few hundred cells in lymph channels, and exhibited favorable biodistribution and toxicity, indicating its potential to improve intraoperative detection and resection. Cancer Research 2007;67(14):6882–8.

Abstract

Abstract 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]