Journal
CANCER RESEARCH
Volume 67, Issue 14, Pages 6882-6888Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-06-3948
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Funding
- NCI NIH HHS [P30 CA 15704-31] Funding Source: Medline
- PHS HHS [CQ 84296, N01 C0 37007-16] Funding Source: Medline
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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 intritoperative detection and resection of malignancies.
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