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

用于检测卵巢癌病变的靶向近红外荧光探针

• 批准号: 7326240
• 负责人: ANTON CHESTUKHIN
• 金额: $ 19.38万
• 依托单位: PHYSICAL SCIENCES, INC
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-26 至 2009-08-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7326240
• 关键词: Affinity; Amino Acids; Animals; Antibiotic Resistance; Antibodies; Antigens; Binding; Biological Assay; Biopsy; Blood; CA-125 Antigen; Cancer Center; Cancer Patient; Cancer cell line; Cancerous; Cell Line; Cell surface; Cells; Characteristics; Chemicals; Chemotherapy-Oncologic Procedure; Class; Clinic; Clinical; Community Clinical Oncology Program; Contracts; Cultured Cells; DNA; Detection; Disease; Doctor of Philosophy; Dyes; Early Diagnosis; Evaluation; Excision; Extracellular Domain; Flow Cytometry; Fluorescent Dyes; Fluorescent Probes; Future; Generations; Goals; Gynecologic Oncology; Human; Indocyanine Green; Invasive; Laparotomy; Lesion; Letters; Libraries; Malignant Neoplasms; Malignant neoplasm of ovary; Mammalian Cell; Measures; Mediating; Microscopy; Molecular Conformation; Monitor; Monoclonal Antibodies; N-terminal; Neoplasm Metastasis; Noise; Oligonucleotides; Operative Surgical Procedures; Optical Methods; Optics; Patients; Penetration; Peritoneal; Peritoneum; Phase; Play; Positioning Attribute; Procedures; Process; Property; Protein Overexpression; Proteins; Quality of life; Reporting; Research; Risk; Role; Schedule; Screening for Ovarian Cancer; Screening procedure; Sensitivity and Specificity; Series; Signal Transduction; Single-Stranded DNA; Site; Specificity; Staging; Surface; Surface Antigens; System; TEV protease; Technology; Testing; Time; Tissues; Transmembrane Domain; Tumor Markers; United States Food and Drug Administration; Visual; Work; antibody conjugate; aptamer; base; blind; cancer cell; combinatorial; design; diagnostic accuracy; extracellular; fluorophore; immunogenic; in vivo; intraperitoneal; mouse model; neoplastic cell; novel; osteosarcoma; outcome forecast; ovarian neoplasm; size; small molecule; stable cell line; tool; tumor

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.

描述（由申请人提供）：卵巢癌（OC）是最致命的妇科癌症之一。目前OC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OC标志物。OC管理策略包括手术治疗与化疗方案相结合。发现原发和继发OC病变对早期诊断和有效的手术治疗非常重要。我们建议开发一种新型的靶向荧光探针，将特异性地识别OC细胞表面上的肿瘤标志物。我们将使用近红外（NIR）吲哚菁荧光团Cy5.5与识别CA125的靶向部分缀合。这种靶向预期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的尺寸比抗体小，无毒且无免疫原性，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穿透，并且将缩短荧光剂的施用与其检测之间的时间。所提出的方法的应用将有助于早期发现OC的高风险组的患者，并将增加选择性的外科手术，而不影响肿瘤切除效率的手术。卵巢癌患者的生存和生活质量主要取决于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检测疾病、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。