Highly Sensitive Detection of Occult Pancreatic Cancer Using Intraoperative Molecular Imaging

使用术中分子成像高灵敏度检测隐匿性胰腺癌

• 批准号: 10660471
• 负责人: George Poultsides
• 金额: $ 47.65万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10660471
• 关键词: Antibodies; Beds; Cancer Detection; Cetuximab; Clinical; Clinical Research; Data; Decision Making; Deposition; Detection; Development; Diagnosis; Disease; Disease-Free Survival; Disseminated Malignant Neoplasm; Distant; Early Diagnosis; Eligibility Determination; Epidermal Growth Factor Receptor; Excision; Eye Surgeon; Failure; Fc Receptor; Fluorescence; Foundations; Goals; Human; Image-Guided Surgery; Imaging technology; Infiltration; Infusion procedures; Label; Malignant Neoplasms; Malignant neoplasm of pancreas; Mission; Modality; Neoplasm Metastasis; Oncologist; Operative Surgical Procedures; Optics; Outcome; Palpation; Pancreatic Adenocarcinoma; Pathologist; Patient-Focused Outcomes; Patients; Peritoneal; Peritoneum; Primary Neoplasm; Public Health; Radiology Specialty; Recurrent disease; Refractory; Research; Resected; Residual Neoplasm; Residual state; Sensitivity and Specificity; Site; Specificity; Specimen; Staging; Surgeon; Surgical margins; Technology; Therapeutic; Time; United States National Institutes of Health; Validation; Visualization; clinical efficacy; clinical translation; cost effective; curative treatments; diagnostic accuracy; disability; efficacy evaluation; first-in-human; fluorescence imaging; imaging agent; imaging modality; imaging scientist; improved; in vivo; innovation; lymph nodes; molecular imaging; novel strategies; overexpression; pancreatic neoplasm; panitumumab; prospective; radiological imaging; radiologist; response; safety and feasibility; tool; tumor

PROJECT SUMMARY/ABSTRACT The failure of surgery to provide a long-disease free survival interval to patients with resected pancreatic cancer is related to the inability to recognize occult tumor foci at metastatic or locoregional sites. For surgery to be effective, there is a critical need for real-time detection of small, sub-clinical metastases (if present) and for visualization of the tumor’s invisible infiltration along the boundaries of the planned resection. The overall objective of this application is to clinically validate the use of a fluorescently labeled anti-EGFR antibody, panitumumab-IRDye800CW (pan800), for the intraoperative detection of low-volume (1-3 mm3) pancreatic cancer tumor foci in vivo. The central hypothesis is that Near InfraRed (NIR) intraoperative imaging with pan800 will enable ultrasensitive detection of tumor deposits that would otherwise escape detection using current imaging technology and surgical inspection/palpation. In the proposed study, patients with pancreatic adenocarcinoma eligible for surgery will undergo infusion of pan800 2-5 days prior to surgery and NIR cameras will be used intraoperatively to detect 1-3 mm³ tumor foci. The following two specific aims will be pursued: 1) Determine the diagnostic accuracy of pan800 intraoperative fluorescent imaging to detect radiographically occult (i.e., unseen by the radiologist) pancreatic adenocarcinoma metastases; and 2) Determine the efficacy of pan800 fluorescent imaging to identify visibly occult (i.e., unseen by the surgeon) residual tumor foci at the post-surgical resection bed in vivo or at the margin of the resected specimen ex vivo. Under the first aim, the sensitivity and specificity of this intraoperative imaging modality to identify small, sub-radiologic peritoneal metastases will be documented. For the second aim, the incremental yield of this modality over conventional bright-field inspection in identifying otherwise invisible tumor foci at the resection bed or specimen margin will be demonstrated. The repurposing of readily available therapeutic EGFR antibodies to surgical imaging agents is not only safe and cost effective, but also highly innovative, in the applicant’s opinion, as it can challenge the status quo related to intraoperative pancreatic cancer detection, which has not fundamentally changed over several decades. The proposed research is significant because it will build upon the previously demonstrated efficacy of pan800 to detect pancreatic cancer in vivo, providing new opportunities for its continued development as a tool to enhance intraoperative staging, support decision making, increase the likelihood of complete tumor resection, and eventually improve clinical outcomes for patients with this highly lethal malignancy.

项目概要/摘要 手术未能为胰腺切除患者提供较长的无病生存期 癌症与无法识别转移或局部区域的隐匿肿瘤灶有关。为了 为了使手术有效，迫切需要实时检测小的亚临床转移瘤（如果 存在）以及肿瘤沿计划边界的不可见浸润的可视化 切除。该应用的总体目标是临床验证荧光标记的使用 抗 EGFR 抗体帕尼单抗-IRDye800CW (pan800)，用于术中检测低容量 (1-3 mm3) 体内胰腺癌肿瘤灶。中心假设是近红外 (NIR) 使用 pan800 进行术中成像将能够超灵敏地检测肿瘤沉积物 否则可以逃避使用当前成像技术和手术检查/触诊的检测。在 拟议的研究中，符合手术条件的胰腺腺癌患者将接受输注 手术前 2-5 天使用 pan800，术中使用近红外相机检测 1-3 mm³ 肿瘤 焦点。将追求以下两个具体目标： 1）确定 pan800 的诊断准确性 术中荧光成像以检测放射学隐匿性（即放射科医生看不见的） 胰腺癌转移； 2) 确定 pan800 荧光成像的功效 识别术后切除床上明显隐匿的（即外科医生看不见的）残留肿瘤灶 体内或离体切除标本的边缘。在第一个目标下，敏感性和特异性 这种术中成像方式可以识别小的、亚放射学腹膜转移瘤 记录在案。对于第二个目标，这种模式相对于传统明场的增量产量 进行检查以识别切除床或标本边缘处不可见的肿瘤病灶 证明了。将现成的治疗性 EGFR 抗体重新用于手术显像剂 申请人认为，不仅安全且具有成本效益，而且具有高度创新性，因为它可以挑战 术中胰腺癌检测相关现状尚未根本改变 几十年来。拟议的研究意义重大，因为它将建立在先前的研究基础上 pan800在体内检测胰腺癌的功效得到证实，为其提供新的机遇 持续开发作为加强术中分期、支持决策、增加 完全切除肿瘤的可能性，并最终改善这种高度患者的临床结果 致命的恶性肿瘤。