Tumor paint:: A Chlorotoxin:Cy5.5 bioconjugate for intraoperative visualization of cancer foci
Tumor paint:: A Chlorotoxin:Cy5.5 bioconjugate for intraoperative visualization of cancer foci
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DOI：
10.1158/0008-5472.can-06-3948
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发表时间：
2007-07-15
期刊：
影响因子：
11.2
通讯作者：
Olson, James M.
中科院分区：
文献类型：
--
作者：
Veiseh, Mandana;Gabikian, Patrik;Olson, James M.
为了开发一种光学成像造影剂，使外科医生能够在术中区分癌灶与邻近正常组织，我们开发了一种可发出近红外荧光信号的氯毒素:Cy5.5 (CTX:Cy5.5) 生物结合物。该探针在小鼠模型中描绘出邻近非肿瘤组织的恶性神经胶质瘤、髓母细胞瘤、前列腺癌、肠癌和肉瘤。在淋巴管中检测到小至几百个细胞的转移性癌灶。基质金属蛋白酶-2 (MMP-2) 促进了与癌细胞的特异性结合，MMP-2 药理学阻断剂在体外和体内减少 CTX:Cy5.5 结合以及在用编码 MMP-2 的质粒转染后在 MCF-7 细胞中诱导 CTX:Cy5.5 结合即可证明这一点。小鼠研究表明，CTX.Cy5.5 具有良好的生物分布和毒性特征。这些研究表明，CTX:Cy5.5 有可能从根本上改善恶性肿瘤的术中检测和切除。
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.