Along the continuum for an IND: An In-Vivo large animal study for opticalimage guided surgery of spontaneous breast cancer.

沿着 IND 的连续体：光学图像引导自发性乳腺癌手术的体内大型动物研究。

• 批准号: 10701065
• 负责人: Brian Straight
• 金额: $ 80.12万
• 依托单位: AKROTOME IMAGING, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-08 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10701065
• 关键词: Abbreviations; Address; Adjuvant Therapy; Allergic Reaction; Animals; Breast-Conserving Surgery; Canis familiaris; Cessation of life; Clinical; Clinical Trials; Collaborations; Cosmetics; Cytology; Data; Detection; Development; Disadvantaged; Disease; Distant; Documentation; Dose; Drug Kinetics; Ensure; Excision; FDA approved; Frozen Sections; Goals; Health Care Costs; High Pressure Liquid Chromatography; Home; Hospitals; Hour; Human; Image; In Situ; Infiltration; Infusion procedures; Light; Malignant Neoplasms; Mammaplasty; Market Research; Maryland; Mastectomy; Methods; Molecular Probes; Morbidity - disease rate; Operating Rooms; Operative Surgical Procedures; Pathologic; Pathology; Pathway interactions; Patients; Peptide Hydrolases; Performance; Phase; Postoperative Period; Procedures; Process; Quality of life; Rattus; Recurrence; Recurrent disease; Repeat Surgery; Research; Research Design; Residual Cancers; Risk; Sampling; Savings; Sensitivity and Specificity; Signal Transduction; Specimen; Structure; Surface; Surgical Pathology; Survival Rate; Techniques; Technology; Testing; Time; Tissues; Topical application; Toxicology; Translations; Tumor Tissue; Validation; Visit; Wait Time; Woman; Work; Xenograft procedure; breast lumpectomy; cancer cell; cancer surgery; clinical translation; design; experience; fluorescence imaging; imaging agent; imaging probe; imaging study; imaging system; in vivo; malignant breast neoplasm; manufacturing scale-up; meetings; molecular imaging; mortality; mortality risk; mouse model; novel; optical imaging; phase 2 study; pre-Investigational New Drug meeting; pre-clinical; preclinical imaging; screening; standard of care; success; tumor; Abbreviations; Address; Adjuvant Therapy; Allergic Reaction; Animals; Breast-Conserving Surgery; Canis familiaris; Cessation of life; Clinical; Clinical Trials; Collaborations; Cosmetics; Cytology; Data; Detection; Development; Disadvantaged; Disease; Distant; Documentation; Dose; Drug Kinetics; Ensure; Excision; FDA approved; Frozen Sections; Goals; Health Care Costs; High Pressure Liquid Chromatography; Home; Hospitals; Hour; Human; Image; In Situ; Infiltration; Infusion procedures; Light; Malignant Neoplasms; Mammaplasty; Market Research; Maryland; Mastectomy; Methods; Molecular Probes; Morbidity - disease rate; Operating Rooms; Operative Surgical Procedures; Pathologic; Pathology; Pathway interactions; Patients; Peptide Hydrolases; Performance; Phase; Postoperative Period; Procedures; Process; Quality of life; Rattus; Recurrence; Recurrent disease; Repeat Surgery; Research; Research Design; Residual Cancers; Risk; Sampling; Savings; Sensitivity and Specificity; Signal Transduction; Specimen; Structure; Surface; Surgical Pathology; Survival Rate; Techniques; Technology; Testing; Time; Tissues; Topical application; Toxicology; Translations; Tumor Tissue; Validation; Visit; Wait Time; Woman; Work; Xenograft procedure; breast lumpectomy; cancer cell; cancer surgery; clinical translation; design; experience; fluorescence imaging; imaging agent; imaging probe; imaging study; imaging system; in vivo; malignant breast neoplasm; manufacturing scale-up; meetings; molecular imaging; mortality; mortality risk; mouse model; novel; optical imaging; phase 2 study; pre-Investigational New Drug meeting; pre-clinical; preclinical imaging; screening; standard of care; success; tumor

Project Summary/Abstract: Breast cancer is the most common cancer in women. For 2021, breastcancer.org projects 281,550 new cases of invasive breast cancer and 49,290 new cases of non-invasive (in situ) breast cancer. 43,600 deaths are also projected. Due to better screening techniques cancers are caught earlier and 75% of patients are candidates for breast conserving surgery (BCS) to remove the cancer. BCS is cosmetically preferable to the alternative (mastectomy) and long-term survival rates are equivalent. Postoperative pathology, the current “gold standard” has significant drawbacks, including the requirement for the patient to return for additional surgery if pathology finds an incomplete resection (i.e., cancer remains in the patient). In addition, current pathology methods only assess about 1/10 of 1% of the entire volume of the removed specimen. A consequence of margin undersampling is that local recurrence occurs in 5-16% of patients with pathologically clean margins, suggesting that one or more regions of tumor had not been sampled during pathological analysis resulting in tumor remaining in the patient. New methods to enhance the quality of BCS resection intraoperatively are being developed. One of the most promising is the use of fluorescent molecular probes to “light up” cancer and guide resection. All current probes, however, require large doses of imaging agent to be administered hours or days before surgery, and require extra labwork, complicating a relatively simple surgical procedure. Moreover, infiltrating cancer cells in tissues surrounding the main mass may not have developed a vasculature, and our work and that of others indicates that it is possible such tumors may not be identified using injected agents, which use such vasculature to reach the diseased tissue. Exploiting increased protease expression at the edge of breast cancers we introduce the novel concept of intraoperative in vivo topical administration of an activatable, microdose, quenched, fluorescent molecular imaging probe to identify cancer that may remain in the surgical cavity after standard- of-care resection. Building on years of preclinical ex-vivo studies, this Phase I project is anchored by a large-animal surgical study to refine and optimize the surgical workflow and technique prior to beginning formal FDA clinical trials. We will synthesize research grade probe, test its performance in PDX rats, complete a surgical optimization project in canines, and submit an IND to FDA. This technology has the potential for an abbreviated regulatory path, offering the potential to reduce re-excisions as well as the false negative rate from pathology undersampling, with a consequent savings in healthcare costs and, enhancement in patient life quality.

项目摘要/摘要：乳腺癌是女性最常见的癌症。 2021年，breastcancer.org 项目281,550例新的侵入性乳腺癌病例和49,290例非侵入性（原位）乳腺癌病例。 预计还会有43,600人死亡。由于筛查技术更好 患者是乳房保存手术（BC）的候选者，以消除癌症。 BCS在化妆上 优于替代性（乳房切除术）和长期生存率优先。术后 病理学，当前的“黄金标准”具有重要的缺点，包括对患者的要求 如果病理发现不完整的切除（即，癌症仍在 病人）。此外，当前的病理方法仅评估整个体积的1％的1/10 卸下标本。边缘不足采样的结果是，局部复发发生在5-16％ 病理清洁边缘的患者，表明一个或多个肿瘤区域尚未 在患者分析过程中取样，导致患者肿瘤保留。增强的新方法 术中BCS切除的质量正在开发。最有前途的之一是使用 荧光分子探针“点亮”癌症和指导切除。但是，所有当前探针都需要 大剂量的成像剂要在手术前几小时或几天内给药，并且需要额外的实验室工作， 使相对简单的手术程序复杂化。此外，在周围组织中浸润癌细胞 主要质量可能没有发展出脉管系统，我们的工作和其他工作表明这是 可能不会使用注射剂来鉴定这种肿瘤，这些肿瘤使用这种脉管系统到达 患病的组织。利用乳腺癌边缘的蛋白酶表达增加，我们引入了 术中术中术中的新概念，可激活，微剂，淬火， 在标准 - 护理切除。在多年的临床前研究研究的基础上，该阶段I项目由 大型手术研究，以优化和优化手术工作流程和技术 正式的FDA临床试验。我们将合成研究级探测，测试其在PDX大鼠中的性能， 在犬类中完成一个手术优化项目，并向FDA提交IND。这项技术具有 缩写的监管路径的潜力，提供减少重新陈述的潜力 病理学的负率不足采样，从而节省了医疗保健成本，并且 提高患者生活质量。