Improved Radiation Therapy of Hypoxic Tumor Regions by Integrated PET, EPR, and MR Imaging - Resubmission 01

通过集成 PET、EPR 和 MR 成像改进缺氧肿瘤区域的放射治疗 - 重新提交 01

基本信息

批准号：
10314063
负责人：
Chin-Tu Chen
金额：
$ 62.27万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-01-01 至 2024-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10314063
关键词：
3-Dimensional 3D Print Affect Animals Behavior Biochemical Biological Blood Vessels Breast Carcinoma Cervix Uteri Chemicals Clinical Data Data Correlations Defect Dependence Dose Effectiveness Electrodes Electron Spin Resonance Spectroscopy France Gold Head and neck structure Human Hypoxia Image Inbred C3H Mice Kinetics Magnetic Resonance Magnetic Resonance Imaging Malignant Neoplasms Maps Measurement Measures Methodology Methods Misonidazole Multimodal Imaging Mus Organ Outcome Oxygen Paper Partial Pressure Patients Perfusion Peripheral Phase II Clinical Trials Physiological Positron-Emission Tomography Precision therapeutics Predictive Value Protocols documentation Publications Radiation Radiation Dose Unit Radiation therapy Randomized Reporting Research Project Grants Resistance Source Standardization Statistical Methods Structure Time Tissues Translations Treatment outcome Tumor Volume Validation Work base clinical practice clinically relevant contrast enhanced experimental study fibrosarcoma human imaging image guided image guided radiation therapy imaging approach imaging modality imaging system improved interest mouse model multimodality novel parametric imaging physiologic model pre-clinical preclinical study predictive modeling quantitative imaging radiation delivery radiation effect radiotracer sarcoma therapy outcome tool tumor tumor hypoxia tumor microenvironment uptake

项目摘要

Hypoxic resistance to radiation therapy has been known for over a century. However, effective image-guided approaches to target resistant hypoxic tumor regions have been lacking. A recent publication of the results from a Phase II clinical trial in France indicates that positron emission tomography (PET) using 18F-fluoro- misonidazole (FMISO) to define region-of-interest (ROI) for hypoxic tumor targeting was shown to fail in improving tumor control and treatment outcome. The long-term objective of this proposed research project is to develop novel integrated multi-modality imaging approaches to effectively guide radiation delivery for significantly improving therapy precision and treatment outcome of resistant hypoxic tumor regions. Our recent work in animal studies using electron paramagnetic resonance (EPR) images (EPRI) of absolute pO2 has demonstrated that targeting the hypoxic regions of tumors with extra radiation dose (i.e., boost in dose painting) increases tumor cure. This involved novel 3D rapidly printed radiation blocks and conformal animal radiation. We showed improved tumor cure by comparing uniform radiation delivery of the dose to all tumors sufficient to cure 15% of tumors (determined in separate experiments) and then randomized to receive extra doses of radiation to either (1) all hypoxic tumor volumes determined by the EPR pO2 image (pO2 < 10 torr) or (2) equal volume dose boosts to better-oxygenated tumor. The results showed that treatment (1) offered a significantly better outcome, including sparing critical organs from damage caused by high dose radiation. This demonstrates that EPR pO2 images have the potential to guide improved radiation therapy of hypoxic tumors. Unfortunately, EPR images are currently not available for routine uses in clinical practice. We hypothesize that using EPRI pO2 images as the gold standard, novel quantitative hypoxia parametric imaging methodologies based on PET-FMISO data can be established, incorporating consideration and correlation of data from other clinically available hypoxia-related imaging methods such as dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) and Iodopamidol diamagnetic chemical exchange saturation transfer (Idia-CEST or ICEST) pH MRI. These clinically available MRI studies will sharpen the hypoxic tumor region definition for more effective radiation boost delivery in improving treatment outcomes. We will initially pursue the following specific aims in animal studies: (1) Implementing and validating novel quantitative multi-modality PET/MR/EPR imaging methodologies; (2) Developing statistical methodologies for deriving modified parametric images by integrating multi-modality PET and MRI data in order to emulate EPR images; (3) Employing the established methods developed in Aim (2) for validation in delivering improved precision radiotherapy of hypoxic tumors to achieve better treatment outcomes using multi-modality parametric imaging.

对放射治疗的缺氧性抗性已有一个多世纪以来。但是，有效的图像引导缺乏靶向性低氧肿瘤区域的方法。结果的最新出版物从法国的II期临床试验中表明，正电子发射断层扫描（PET）使用18F-氟-y Misonidazole（FMISO）定义了缺氧肿瘤靶向的利益区域（ROI）改善肿瘤控制和治疗结果。这个拟议的研究项目的长期目标是开发新颖的集成多模式成像方法，以有效指导辐射输送显着改善了耐药性低氧肿瘤区域的治疗精度和治疗结果。我们最近使用电子顺磁共振（EPR）图像（EPRI）的动物研究工作证明靶向具有额外辐射剂量的肿瘤的低氧区域（即，剂量提升绘画）增加肿瘤治疗。这涉及小说3D快速印刷的辐射块和共形动物辐射。我们通过比较剂量的均匀辐射递送到所有肿瘤，显示出改善的肿瘤治疗足以治愈15％的肿瘤（在单独的实验中确定），然后随机接受额外辐射剂量（1）所有由EPR PO2图像（PO2 <10 torr）或（2）相等的体积剂量促进了更好的氧气肿瘤。结果表明，治疗（1）提供了明显更好的结果，包括避免高剂量辐射造成的损害的关键器官。这证明EPR PO2图像有可能指导改善缺氧肿瘤的放射治疗。不幸的是，EPR图像目前尚未用于临床实践中的常规用途。我们假设这一点使用EPRI PO2图像作为黄金标准，新型定量低氧参数成像方法基于PET-FMISO数据，可以建立，并结合其他数据的考虑和相关性临床上可用的与缺氧相关的成像方法，例如动态对比增强的磁共振成像（DCE-MRI）和碘氨基二醇二磁化学交换饱和饱和转移（IDIA-CEST或 ICEST）PH MRI。这些临床上可用的MRI研究将使低氧肿瘤区域的定义提高在改善治疗结果中，更有效的辐射增强输送。我们最初将追求以下动物研究中的具体目的：（1）实施和验证新的定量多模式宠物/MR/EPR 成像方法；（2）开发用于通过整合多模式的PET和MRI数据以模拟EPR图像；（3）雇用已建立的 AIM（2）中开发的方法用于验证可改善缺氧肿瘤的精确放射疗法的方法使用多模式参数成像获得更好的治疗结果。