Molecular Imaging of Fibrosis for Improved Treatment Planning of Pancreatic Ductal Adenocarcinoma

纤维化的分子成像改善胰腺导管腺癌的治疗计划

• 批准号: 10370616
• 负责人: Shadi Abdar Esfahani
• 金额: $ 26.76万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10370616
• 关键词: Abdomen; Accounting; Address; Animal Model; Appearance; Award; Biopsy; Cancer Etiology; Cancer Model; Caring; Cessation of life; Clinical; Clinical Management; Clinical Trials; Collagen; Collagen Type I; Data; Detection; Development; Diagnostic Procedure; Discipline of Nuclear Medicine; Disease; Evaluation; Excision; Fibrosis; Foundations; Future; General Hospitals; Goals; Gold; Grant; Histopathology; Human; Image; Imaging Device; Kinetics; Knowledge; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of pancreas; Massachusetts; Measurement; Measures; Mentors; Mentorship; Metabolism; Methods; Monitor; Neoadjuvant Therapy; Operative Surgical Procedures; Outcome; Pancreas; Pancreatic Ductal Adenocarcinoma; Patients; Physicians; Plasma; Positron-Emission Tomography; Procedures; Process; Prognostic Factor; Pulmonary Fibrosis; Radiation; Radiation therapy; Reproducibility; Research; Resectable; Resected; Sampling; Scientist; Signal Transduction; Solid; Specificity; Staging; Surgeon; Testing; Therapeutic; Time; Tissues; Training; Tumor Tissue; Tumor Volume; X-Ray Computed Tomography; anatomic imaging; biomarker validation; cancer biomarkers; cancer type; care costs; care outcomes; chemoradiation; clinical biomarkers; clinical care; curative treatments; experience; fluorodeoxyglucose; healthy volunteer; human subject; image guided; imaging biomarker; imaging modality; imaging probe; improved; improved outcome; kinetic model; molecular imaging; non-invasive imaging; novel; pancreas imaging; pancreatic ductal adenocarcinoma model; pre-clinical research; prognostication; programs; radiologist; response; side effect; standard of care; treatment optimization; treatment planning; treatment response; treatment strategy; tumor; uptake

Pancreatic ductal adenocarcinoma (PDAC) is an invasive and rapidly progressive malignancy with a five-year overall survival of less than 9% despite long treatment course and recent therapeutic advances. Unfortunately, currently available imaging methods do not reliably evaluate the tumor response to neoadjuvant treatment. This further requires surgical exploration and repeated biopsies for post-chemoradiotherapy (CRT) staging. Additionally, the conventional anatomical imaging tools underrepresent the local extent of the tumor, which leads to suboptimal tumor volume measurement for definition of the field of radiotherapy. Therefore, a non-invasive imaging tool for precise evaluation of treatment response and tumor size measurement is of utmost need. High degree of fibrosis, mainly collagen type I, has been recognized as the hallmark of PDAC. Tumor-associated fibrosis further increases in response to neoadjuvant CRT and is correlated with improved outcome in patients with PDAC. Building on this knowledge, the current proposal aims to develop an image-guided paradigm for improving tumor delineation and monitoring treatment response in PDAC using a novel collagen I specific PET imaging probe, 68Ga-CBP8. This project, if successful, paves the way to provide a non-invasive and more accurate imaging tool to guide clinicians with optimized treatment planning, reduced cost of care and side effects of repeated invasive procedures, and ultimately improved outcome. We hypothesize that 68Ga-CBP8 PET imaging is a reliable and repeatable method that specifically targets and quantifies PDAC-associated fibrosis. Using the dynamic 68Ga-CBP8 PET imaging and kinetic modeling, we hypothesize that imaging PDAC can be optimized for static imaging with much shorter acquisition time. In our second aim of the grant, we hypothesize that 68Ga-CBP8 PET imaging precisely quantifies the increased PDAC fibrosis following neoadjuvant CRT and thereby could be used as a surrogate of treatment response. Lastly, we will explore whether 68Ga-CBP8 PET imaging results in more precise tumor delineation by providing more accurate gross tumor volume measurement compared to the conventional CT or MRI when correlated to the tumor size on histopathology gold standard. This research will be performed by Dr. Shadi Abdar Esfahani, a nuclear medicine and abdominal radiologist at Massachusetts General Hospital. She will be exceptionally mentored by Dr. Peter Caravan, a pioneer in PET/MR molecular imaging of fibrosis, and co-mentored by Dr. Kenneth Tanabe, a pancreas surgeon and leading expert in clinical trials and biomarker validation for pancreatic cancer. Building upon the strong clinical experience and solid pre-clinical research on molecular imaging of cancer models, Dr. Esfahani’s goal is to become an independent physician-scientist by developing a program for translational, quantitative PET/MR imaging of novel cancer biomarkers with the ultimate goal of improving clinical care and outcome. This K08 award will provide her with the training and mentorship needed to achieve independence and apply for her first R01.

胰腺导管腺癌（PDAC）是一种侵袭性和快速进展的恶性肿瘤， 尽管疗程较长且最近的治疗取得了进展，但总生存率仍低于9%。不幸的是， 目前可用的成像方法不能可靠地评价肿瘤对新辅助治疗的反应。这 进一步需要手术探查和重复活检以进行化放疗后（CRT）分期。 此外，传统的解剖成像工具不能充分反映肿瘤的局部范围，这导致 用于定义放射治疗场的次优肿瘤体积测量。因此，非侵入性 用于精确评估治疗反应和肿瘤尺寸测量的成像工具是最迫切需要的。高 纤维化程度，主要是I型胶原，已被认为是PDAC的标志。肿瘤相关 新辅助CRT后纤维化进一步增加，并与患者结局改善相关 关于PDAC在此基础上，目前的建议旨在制定一个图像引导的范例， 使用新型I型胶原特异性PET改善PDAC中的肿瘤描绘和监测治疗反应 成像探头，68 Ga-CBP 8。这个项目，如果成功，铺平了道路，提供一个非侵入性和更多的 精确的成像工具，可指导临床医生优化治疗计划，降低护理成本和副作用 反复的侵入性手术，并最终改善结果。我们假设68 Ga-CBP 8 PET 成像是一种可靠且可重复的方法，其特异性靶向并定量PDAC相关的纤维化。 使用动态68 Ga-CBP 8 PET成像和动力学建模，我们假设成像PDAC可以是 针对静态成像进行了优化，采集时间更短。在我们的第二个目标中，我们假设 68 Ga-CBP 8 PET成像精确定量了新辅助CRT后PDAC纤维化的增加， 因此可以用作治疗反应的替代物。最后，我们将探讨68 Ga-CBP 8 PET是否 通过提供更精确的大体肿瘤体积测量，成像导致更精确的肿瘤描绘 与常规CT或MRI相比，当与组织病理学金标准上的肿瘤大小相关时。 这项研究将由Shadi Abdar Esfahani博士进行，他是一名核医学和腹部放射科医生， 马萨诸塞州综合医院。她将得到PET/MR先驱Peter Caravan博士的特别指导 纤维化的分子成像，并由胰腺外科医生和首席专家Kenneth田边博士共同指导 用于胰腺癌的临床试验和生物标志物验证。基于丰富的临床经验， Esfahani博士致力于癌症模型分子成像的临床前研究，他的目标是成为 独立的医生-科学家通过开发一个程序，用于翻译，定量PET/MR成像的新的 癌症生物标志物，最终目标是改善临床护理和结果。这个K 08奖将为她提供 获得实现独立所需的培训和指导，并申请她的第一个R 01。