Instantaneous Tumor Spray for Real-Time Surgical Guidance

早期卵巢癌通常是无症状的。直到疾病到达一个 晚期，该病表现为广泛的腹膜内转移。 标准的护理治疗包括手术细胞减少术以切除肿瘤体积，然后以铂为基础 化疗或初次新辅助化疗，肿瘤缩小后间歇细胞减灭术。 尽管最初的治疗取得了成功，但80%-90%的晚期癌症女性经历了肿瘤复发。 手术结果可能有很大差异，因为一些癌症病变是肉眼看不见的 监测或触诊，这是外科医生实时可用的唯一工具。有重要证据表明 无病期延长，甚至治愈，与切除多少癌组织有因果关系。 一种敏感、具体、易于可视化的染料，精确地突出小(&lt；5 mm)和隐藏的其他方面 病变将更好地区分健康组织和癌症组织，使更知情的手术决定和 为卵巢癌患者带来更好的结果。 在分子靶向技术公司和威尔·康奈尔医学院之间的合作中，我们 开发一种新型的肿瘤特异性近红外荧光成像试剂来指导卵巢手术 实时的癌症手术。在初步的可行性研究中，我们已经确定了一种优化的pH敏感 近红外荧光染料(CypH-11)，在正常组织中不发光，但立即发光 当喷洒在微环境微酸性的癌症组织上时。我们假设癌症 CypH-11的选择性染色将通过定位使手术去粗过程精确和有效 通常看不见的小而隐蔽的病变，取得了较好的手术结果。这种方法可能预示着一种 外科肿瘤学的范式转变。 在第二阶段的SBIR研究中，我们将放大合成和制造CypH-11和最终的 符合cGMP的配方药瓶；进行CypH-11的临床前优化和验证 建立小鼠皮下模型，并在原位动物模型中验证其敏感性和特异性 模拟临床环境；并获得药代动力学、生物分布和毒性数据以支持 探索性Ind归档。该申请将提交给FDA，预计将进行0期首例人体试验。

Early stage ovarian cancer is typically asymptomatic. Undiagnosed until the disease has reached an advanced stage, the disease presents extensive intra-abdominal peritoneal metastases. Standard of care treatment includes either a surgical cytoreduction to remove tumor bulk, then platinum-based chemotherapy or primary neoadjuvant chemotherapy followed by interval cytoreduction after tumor shrinkage. Despite successful initial treatments, 80–90% of women with advanced cancer experience tumor recurrence. Surgical outcomes can vary considerably since some cancerous lesions are not visible to naked-eye surveillance or palpation, the only tools available to the surgeon in real-time. There is significant evidence that an extended disease-free period or even a cure are causally related to how much cancerous tissue is excised. A sensitive, specific, easy to visualize dye which precisely highlights small (< 5mm) and otherwise hidden lesions would better differentiate healthy from cancerous tissue, enable better informed surgical decisions and lead to better outcomes for ovarian cancer patients. In this collaboration between Molecular Targeting Technologies, Inc. and Weill Cornell Medical School we are developing a novel, tumor-specific agent for intraoperative near-infrared fluorescence imaging to guide ovarian cancer surgeries in real-time. In preliminary feasibility studies we have identified an optimized pH-sensitive near-infrared fluorogenic dye (CypH-11) which is non-fluorescent in normal tissues, but fluoresces immediately when sprayed onto cancer tissue, whose microenvironment is slightly acidic. We hypothesize that the cancer selective staining by CypH-11 will make the surgical debulking procedure precise and effective by locating normally unseen small and occult lesions, achieving a better surgical outcome. This approach could herald a paradigm shift in surgical oncology. In direct to Phase II SBIR studies we will scale-up synthesis and manufacture of CypH-11 and the final formulated vial in compliance with cGMP; perform preclinical optimization and validation of the CypH-11 formulation in a subcutaneous murine model and validate its sensitivity and specificity in an orthotopic model that simulates the clinical setting; and obtain pharmacokinetic, biodistribution and toxicity data to support an exploratory IND filing. The application will be submitted to the FDA anticipating a Phase 0 first-in-human study.