Targeted Near-infrared Fluorescent Probes for Detection of Ovarian Cancer Lesions

描述(申请人提供)：卵巢癌(OC)是最致命的妇科癌症之一。目前检测卵巢癌的筛查方法依赖于测量血液中卵巢癌特异性抗原CA125的水平，CA125是唯一获准临床使用的卵巢癌标志物。OC的治疗策略包括手术治疗与化疗方案相结合。原发和继发性OC病变的发现对早期诊断和有效的手术治疗具有重要意义。我们建议开发一种新型的靶向荧光探针，它将特异性识别OC细胞表面的肿瘤标记物。我们将使用近红外(NIR)吲哚青氨酸荧光团Cy5.5结合到识别CA125的靶向部分。这一目标预计将显著突出正常组织和癌组织之间的差异。我们的方法的优点是，所提出的靶向部分比抗体更小，无毒和非免疫原性，并且可以比传统抗体更快地选择和产生。小尺寸将提供更好和更快的组织渗透，并将缩短荧光剂给药和检测之间的时间。应用所提出的方法将有助于在高危人群中及早发现OC，并将在不影响手术切除肿瘤效率的情况下增加手术操作的选择性。卵巢癌患者的生存和生活质量在很大程度上取决于疾病的早期发现和有效的手术治疗。光学方法检测卵巢肿瘤及其转移是发现卵巢肿瘤、手术根治和监测治疗进展的重要临床手段。我们将开发一种新型的靶向荧光探针，这将极大地提高光学方法的灵敏度和特异性。

DESCRIPTION (provided by applicant): Ovarian Cancer (OC) is one of the deadliest gynecological cancers. The current screening approach for OC detection relies on measuring the blood level of ovarian cancer-specific antigen CA125, the only OC marker that is approved for clinical use. The strategy for OC management includes a combination of surgical treatment with chemotherapy regimens. Detection of primary and secondary OC lesions is very important for early diagnosis and effective surgical treatment. We propose to develop a novel class of targeted fluorescent probes that will specifically recognize tumor markers on the surface of OC cells. We will use near infrared (NIR) indocyanine fluorophore Cy5.5 conjugated to targeting moieties that recognize CA125. This targeting is expected to accentuate differences between normal and cancerous tissues significantly. The advantage of our approach is that the proposed targeting moieties are smaller in size than antibodies, non-toxic and non-immunogenic and could be selected and produced faster than traditional antibodies. Small size will provide better and faster tissue penetration and would shorten the time between administration of the fluorescent agent and its detection. Application of the proposed approach will facilitate early detection of OC in the high risk group of patients and will increase selectivity of surgical procedures without compromising tumor removal efficiency of the surgery. Survival and quality of life of ovarian cancer patients mostly depends on early detection and effective surgical treatment of the disease. Optical methods for detection of ovarian tumors and their metastasis are essential clinical tools for detection of the disease, surgical eradication and monitoring treatment progress. We will develop a novel class of targeted fluorescent probes that will dramatically increase sensitivity and specificity of optical methods.