Evaluation of a Carbonic Anhydrase IX-Targeted Near-Infrared Dye for Fluorescence-Guided Surgery of Hypoxic Tumors.
Evaluation of a Carbonic Anhydrase IX-Targeted Near-Infrared Dye for Fluorescence-Guided Surgery of Hypoxic Tumors.
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DOI：
10.1021/acs.molpharmaceut.6b00065
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发表时间：
2016-05-02
影响因子：
4.9
通讯作者：
Low PS
中科院分区：
文献类型：
--
作者：
Lv PC;Roy J;Putt KS;Low PS
在卵巢癌、肺癌和脑癌患者中进行的原理验证研究表明，荧光引导手术可以切除否则无法检测到的恶性病变，减少癌症阳性边缘的数量，并允许识别通常逃避切除的含疾病淋巴结。不幸的是，目前的肿瘤靶向荧光染料库不允许识别所有癌症，从而需要设计新的肿瘤特异性荧光染料来照亮目前无法检测的癌症。为了设计一种更通用的荧光癌症显像剂，我们已经着手合成一种荧光团，可以标记肿瘤的所有缺氧区域。我们在这里报告的合成，在体外结合和在体内成像的近红外（NIR）的荧光染料，是针对碳酸酐酶IX（CA IX），即一个广泛接受的缺氧组织的标志物。低分子量NIR探针，命名为Hypoxyfluor，显示出以高亲和力结合CA IX，并在CA IX阳性肿瘤中快速和选择性地积累。因为几乎所有的人类癌症都含有大量表达CA IX的缺氧区域，所以这种NIR探针应该有助于各种实体瘤的手术切除。
Proof-of-principle studies in ovarian, lung and brain cancer patients have shown that fluorescence-guided surgery can enable removal of otherwise undetectable malignant lesions, decrease the number of cancer-positive margins, and permit identification of disease-containing lymph nodes that would have normally evaded resection. Unfortunately, the current arsenal of tumor-targeted fluorescent dyes does not permit identification of all cancers, raising the need to design new tumor-specific fluorescent dyes to illuminate the currently undetectable cancers. In an effort to design a more universal fluorescent cancer imaging agent, we have undertaken to synthesize a fluorophore that could label all hypoxic regions of tumors. We report here the synthesis, in vitro binding and in vivo imaging of a near infrared (NIR) fluorescent dye that is targeted to carbonic anhydrase IX (CA IX), i.e. a widely accepted marker of hypoxic tissues. The low molecular weight NIR probe, named Hypoxyfluor, is shown to bind CA IX with high affinity and accumulate rapidly and selectively in CA IX positive tumors. Because nearly all human cancers contain hypoxic regions that express CA IX abundantly, this NIR probe should facilitate surgical resection of a wide variety of solid tumors.