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。目前卵巢癌检测的筛查方法依赖于测量卵巢癌特异性抗原CA125的血液水平，CA125是唯一被批准用于临床的卵巢癌标志物。卵巢癌的治疗策略包括手术治疗与化疗方案的结合。原发性和继发性癌灶的检测对于早期诊断和有效的手术治疗非常重要。我们建议开发一类新的靶向荧光探针，将特异性识别肿瘤细胞表面的肿瘤标志物。我们将使用近红外（NIR）吲哚菁荧光团Cy5.5偶联到识别CA125的靶向部分。这种靶向预期会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片段比抗体小，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，并缩短荧光剂给药和检测之间的时间。该方法的应用将有助于在高危人群中早期发现肿瘤，并在不影响手术切除效率的情况下增加手术程序的选择性。卵巢癌患者的生存和生活质量主要取决于疾病的早期发现和有效的手术治疗。卵巢肿瘤及其转移的光学检测方法是发现疾病、手术根除和监测治疗进展的重要临床工具。我们将开发一种新型的靶向荧光探针，这将大大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.