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: 10656169
• 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/10656169
• 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; Dryness; Evaluation; Excision; Fibrosis; Foundations; Future; General Hospitals; Goals; Grant; Histopathology; Human; Image; Imaging Device; Kinetics; Knowledge; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of pancreas; Managed Care; 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; 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、快速进展的恶性肿瘤，五年内发病率 尽管治疗过程较长且近期治疗取得进展，但总生存率仍低于 9%。很遗憾， 目前可用的成像方法不能可靠地评估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放化疗（CRT）分期。 此外，传统的解剖成像工具未能充分体现肿瘤的局部范围，这导致 用于定义放射治疗领域的次优肿瘤体积测量。因此，一种非侵入式 迫切需要用于精确评估治疗反应和肿瘤大小测量的成像工具。高的 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，并与患者预后的改善相关 与 PDAC。基于这些知识，当前的提案旨在开发一种图像引导范例 使用新型胶原蛋白 I 特异性 PET 改善 PDAC 中的肿瘤描绘并监测治疗反应 成像探头，68Ga-CBP8。该项目如果成功，将为提供非侵入性和更多 准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 重复侵入性操作，并最终改善结果。我们假设 68Ga-CBP8 PET 成像是一种可靠且可重复的方法，专门针对和量化 PDAC 相关纤维化。 使用动态 68Ga-CBP8 PET 成像和动力学模型，我们假设成像 PDAC 可以 针对静态成像进行了优化，采集时间更短。在我们的第二个拨款目标中，我们假设 68Ga-CBP8 PET 成像可精确量化新辅助 CRT 后增加的 PDAC 纤维化， 因此可以用作治疗反应的替代指标。最后，我们将探讨68Ga-CBP8 PET是否 成像通过提供更准确的肿瘤总体积测量来实现更精确的肿瘤轮廓 当与组织病理学金标准上的肿瘤大小相关时，与传统 CT 或 MRI 相比。 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。 马萨诸塞州总医院。她将得到 PET/MR 领域先驱 Peter Caravan 博士的特别指导 纤维化的分子成像，由胰腺外科医生和领先专家 Kenneth Tanabe 博士共同指导 胰腺癌的临床试验和生物标志物验证。凭借丰富的临床经验和 Esfahani 博士对癌症模型分子成像进行了扎实的临床前研究，他的目标是成为一名 独立医师科学家，开发新的转化、定量 PET/MR 成像程序 癌症生物标志物的最终目标是改善临床护理和结果。这个K08奖将为她提供 获得实现独立并申请第一个 R01 所需的培训和指导。

项目成果

DNA Damage by Radiopharmaceuticals and Mechanisms of Cellular Repair.

• DOI: 10.3390/pharmaceutics15122761
• 发表时间: 2023-12-12
• 期刊: Pharmaceutics
• 影响因子: 5.4
• 作者: Khazaei Monfared Y;Heidari P;Klempner SJ;Mahmood U;Parikh AR;Hong TS;Strickland MR;Esfahani SA
• 通讯作者: Esfahani SA

Noninvasive Quantification of Radiation-Induced Lung Injury using a Targeted Molecular Imaging Probe.

使用靶向分子成像探针对辐射引起的肺损伤进行无创定量。

• DOI: 10.1101/2023.09.25.23295897
• 发表时间: 2023
• 期刊: medRxiv : the preprint server for health sciences
• 作者: Abston,Eric;Zhou,IrisY;Saenger,JonathanA;Shuvaev,Sergey;Akam,Eman;Esfahani,ShadiA;Hariri,LidaP;Rotile,NicholasJ;Crowley,Elizabeth;Montesi,SydneyB;Humblet,Valerie;Arabasz,Grae;Catana,Ciprian;Fintelmann,FlorianJ;Caravan,P
• 通讯作者: Caravan,P