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）是一种侵入性且快速进行的恶性肿瘤，五年 目的地长期治疗课程和最近的治疗进展的总生存率不到9％。很遗憾， 当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 进一步需要手术探索和重复的活检，以进行化学后疗法（CRT）分期。 此外，常规的解剖成像工具不足以给出肿瘤的局部范围 为了定义放射疗法的定义，肿瘤体积的次级肿瘤体积测量值。因此，无创 用于精确评估治疗反应和肿瘤大小测量的成像工具是最需要的。高的 纤维化程度，主要是I型胶原蛋白，已被认为是PDAC的标志。肿瘤相关 纤维化进一步增加了对新辅助CRT的响应，并且与患者的预后改善相关 与PDAC。基于这些知识，当前的提案旨在为图像引导的范式开发 使用新型胶原蛋白I特异性PET改善PDAC中肿瘤描述和监测治疗反应 成像探针，68GA-CBP8。如果成功的话，该项目为提供非侵入性和更多更多的方式铺平了道路 准确的成像工具，可以指导临床医生进行优化的治疗计划，降低护理成本和副作用 我们假设有68GA-CBP8的重复入侵程序，并最终改善了预后。 成像是一种可靠且可重复的方法，它专门针对和量化了与PDAC相关的纤维化。 使用动态68GA-CBP8 PET成像和动力学建模，我们假设Imaging PDAC可以是 以较短的获取时间为静态成像进行了优化。在我们的第二个目标中，我们假设 68GA-CBP8 PET成像精确地量化了新辅助CRT和 因此可以用作治疗反应的替代物。最后，我们将探索是否68GA-CBP8宠物 成像通过提供更准确的总肿瘤体积测量来产生更精确的肿瘤描述 与常规CT或MRI相比，与组织病理学金标准的肿瘤大小相关时。 这项研究将由Shadi Abdar Esfahani博士进行，核医学和腹部放射科医生 马萨诸塞州综合医院。她将由宠物/先生的先驱彼得·卡拉万（Peter Caravan）博士特殊修补。 纤维化的分子成像，并由胰腺外科医生兼领先的专家Kenneth Tanabe博士合作 在临床试验和胰腺癌的生物标志物验证中。基于强大的临床经验和 关于癌症模型分子成像的固定前研究，Esfahani博士的目标是成为一种 独立的物理科学家通过开发用于转化，定量PET/MR成像的程序 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 培训和心态需要实现独立并申请她的第一个R01。

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