Instantaneous Tumor Spray for Real-Time Surgical Guidance

用于实时手术指导的瞬时肿瘤喷雾

• 批准号: 10681383
• 负责人: Brian David Gray
• 金额: $ 99.94万
• 依托单位: MOLECULAR TARGETING TECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10681383
• 关键词: Adjuvant Chemotherapy; Advanced Malignant Neoplasm; Biodistribution; Biological Products; Biopsy; Bulky Disease; Cancer Patient; Cancer cell line; Cancerous; Chemistry; Clinical; Clinical Research; Collaborations; Cyclic GMP; Data; Detection; Development; Diagnostic Neoplasm Staging; Disease; Dose; Drug Kinetics; Dyes; Early Diagnosis; Endoscopy; Evaluation; Excision; Eye; Feasibility Studies; Female; Fluorescence; Fluorescent Dyes; Formulation; Freeze Drying; Human; Image; In Vitro; Intra-abdominal; Investigational Drugs; Lesion; Letters; Light; Malignant Female Reproductive System Neoplasm; Malignant Neoplasms; Malignant neoplasm of ovary; Meta-Analysis; Methods; Modeling; Molecular Target; Mus; Near-infrared optical imaging; Neoadjuvant Therapy; Neoplasm Metastasis; Normal tissue morphology; Operative Surgical Procedures; Outcome; Palpation; Patient-Focused Outcomes; Patients; Peritoneal; Pharmaceutical Preparations; Phase; Platinum; Prior Chemotherapy; Procedures; Rattus; Recurrence; Recurrent disease; Recurrent tumor; Resected; Residual Neoplasm; Second Look Surgery; Sensitivity and Specificity; Serous; Small Business Innovation Research Grant; Solid; Stains; Surgeon; Surgical Oncology; Techniques; Technology; Time; Tissues; Toxic effect; Toxicology; Translating; Tumor Debulking; Validation; Vial device; Visual; Visualization; Woman; cancer surgery; chemotherapeutic agent; chemotherapy; experience; first-in-human; human study; image guided; imaging modality; improved; improved outcome; in vivo Model; intraperitoneal; manufacture; medical schools; mouse model; novel; personalized medicine; pre-clinical; prognostic indicator; real-time images; scale up; standard of care; subcutaneous; surgery outcome; targeted treatment; tool; tumor

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.

早期卵巢癌通常是无症状的。直到疾病发展到晚期才被诊断出来