Pancreas Cancer Specific Probe for Image Guided Resection

用于图像引导切除的胰腺癌特异性探针

• 批准号: 10752431
• 负责人: ROBERT S. MANNEL
• 金额: $ 13.22万
• 依托单位: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-05-01 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10752431
• 关键词: Area; Benign; Binding; Biodistribution; Blood; Cell Line; Cells; Clinical; Contrast Media; Cytoskeleton; Data; Derivation procedure; Detection; Development; Disease; Drug Kinetics; Elements; Eligibility Determination; Excision; Fibrosis; Fluorescence; Fluorescent Dyes; Goals; Hemorrhage; Human; Image; Image-Guided Surgery; Imaging Techniques; Incidence; Indocyanine Green; Knock-out; Local Therapy; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of pancreas; Measures; Mesentery; Microscopic; Modality; Modernization; Molecular; Mus; Neoadjuvant Therapy; Operating Rooms; Operative Surgical Procedures; Pancreas; Pancreatectomy; Pancreatic Ductal Adenocarcinoma; Pancreatic duct; Pancreatitis; Patients; Peptides; Performance; Perfusion; Perioperative Care; Predisposition; Procedures; Reporter; Reporting; Resectable; Resected; Resolution; Scientist; Signal Transduction; Specificity; Surface; Surgeon; Systemic Therapy; Techniques; Testing; Time; Tissue imaging; Tissues; Toxic effect; Toxicity Tests; Translating; Visualization; base; extracellular; fluorescence imaging; image guided; imaging modality; imaging probe; improved; in vivo; interest; minimally invasive; novel; optoacoustic tomography; pancreatic ductal adenocarcinoma cell; plectin; prototype; response; skill acquisition; targeted agent; tumor; tumor specificity; ultrasound

Pancreas Cancer Specific Probe for Image Guided Resection This application is being submitted in response to the Notice of Special Interest (NOSI) identified as NOT-CA-21-100. The incidence of pancreatic ductal adenocarcinoma (PDAC) continues to rise as does the number of patients eligible for surgical resection due to improvements in neoadjuvant therapy. Surgical resection with negative resection margins remains the only opportunity for cure for patients with this disease. However, microscopically positive resection margins have been reported in up to 75% of patients undergoing resection for curative intent. Clinically available imaging techniques lack the ability to detect microscopic tumor involvement of mesenteric vessels or differentiate between fibrosis and live tumor, representing an unmet clinical need. Development of a PDAC specific near infrared (NIR) contrast agent that can be detected by multispectral optoacoustic tomography (MSOT) would improve intraoperative detection of resection margin. This proposal will synthesize a NIR reporter agent that targets plectin-1 peptide, which is aberrantly located on the surface of PDAC cells. Our synthesized probe will be optimized for binding with human PDAC. Specificity of the probe will be tested on human PDAC cell lines and tissue collected from resected PDAC. The most efficiently performing probe will then be tested for toxicity and performance in vivo in mice. Successful completion of this proposal will generate a PDAC-specific contrast probe to improve detection of viable PDAC and adjacent fibrosis in vivo using MSOT and NIR fluorescence.

用于图像引导切除的胰腺癌特异性探针 本申请是为了响应所确定的特殊利益通知 (NOSI) 而提交的 作为 NOT-CA-21-100。胰腺导管腺癌（PDAC）的发病率持续上升 由于条件的改善，有资格接受手术切除的患者数量也在增加 新辅助治疗。切除边缘为负的手术切除仍然是唯一的方法 为患有这种疾病的患者提供治愈的机会。然而，显微镜下积极切除 据报道，高达 75% 的出于治疗目的而接受切除术的患者出现切缘。 临床可用的成像技术缺乏检测微观肿瘤参与的能力 肠系膜血管或区分纤维化和活肿瘤，代表着未满足的临床 需要。开发可检测的 PDAC 特异性近红外 (NIR) 造影剂 通过多光谱光声断层扫描（MSOT）将改善术中检测 切除边缘。该提案将合成一种针对 plectin-1 肽的 NIR 报告剂， 它异常地位于 PDAC 细胞的表面。我们合成的探针将被优化 用于与人 PDAC 结合。探针的特异性将在人类 PDAC 细胞系上进行测试 以及从切除的 PDAC 中收集的组织。最有效执行的探针将是 在小鼠体内测试了毒性和性能。本提案的顺利完成将 生成 PDAC 特定的对比探针，以改进对可行 PDAC 和相邻 PDAC 的检测 使用 MSOT 和 NIR 荧光观察体内纤维化。