A preclinical integrated PET/EPR imaging system

临床前集成 PET/EPR 成像系统

基本信息

批准号：
10625275
负责人：
Boris Epel
金额：
$ 35.91万
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：
2020-06-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10625275
关键词：
18F-fluorothymidine Adopted Advanced Malignant Neoplasm Affect Aftercare Algorithms Animal Model Area Attention Biological Process Blood flow Cancer Biology Cancer Diagnostics Cancer Model Cell Proliferation Cell membrane Clinic Clinical Complex Correlation Studies Data Development Diagnosis Diameter Disease Dose Electron Spin Resonance Spectroscopy Electronics Electrons Event Extracellular Matrix Failure Future Genes Glucose Hybrids Hypoxia Image Knowledge Length Magnetic Resonance Imaging Malignant Neoplasms Maps Measurement Measures Metabolic Metabolism Methods Misonidazole Modeling Mus Noise Oxygen Paint Performance Perfusion Physiologic pulse Physiological Physiological Processes Pilot Projects Population Positron-Emission Tomography Property Radiation Radiation Dose Unit Radiation therapy Research Research Project Grants Resistance Resolution Rodent Role Small Animal Imaging Systems Specific qualifier value Speed System Systems Integration Techniques Technology Therapeutic Agents Tissues Tracer Treatment outcome Variant Visualization Water X-Ray Computed Tomography angiogenesis animal imaging attenuation cancer cell cancer imaging cancer therapy cohort contrast imaging data acquisition data streams design detector effective therapy expectation fluorodeoxyglucose fluorodeoxyglucose positron emission tomography image reconstruction imager imaging capabilities imaging modality imaging system improved in vivo in vivo imaging innovation inorganic phosphate interest interstitial method development neoplastic cell non-invasive imaging novel parametric imaging pre-clinical pressure reconstruction response software development success therapy resistant tool treatment risk treatment strategy tumor tumor hypoxia tumor microenvironment uptake

项目摘要

Abstract We propose to develop an integrated system for positron emission tomography (PET) and electron paramagnetic resonance (EPR) simultaneous imaging of rodents for use in studying cancer and cancer treatment. Cancer is a complex and heterogeneous functional disease. Therefore, effective treatment of cancer shall account for the specific cellular-type populations and their states, as well as the tumor microenvironment. In vivo imaging has an important role in providing such information. PET, already widely used in the clinic, can measure many metabolic and physiological states of tumor, including glucose utilization with 18F-fluorodeoxyglucose (FDG) and cell proliferation with 18F-fluorothymidine (FLT). PET tracers for imaging tumor specific cell-membrane or intracellular molecules or genes, and for imaging tumor microenvironment including angiogenesis and extracellular matrix, are also available or under active development. The partial oxygen pressure, pH and interstitial inorganic phosphate in the space surrounding the cancer cells also shall be considered as they will affect metabolic and physiological processes, and hence the treatment outcome. Particularly, knowing the tissue oxygen level is of importance for cancer treatment. It has been well known that hypoxic tumor cells are resistant to various therapeutic agents. Therefore, many believe that dose painting in which the radiation dose to the tumor is adjusted according to the local tissue oxygen level can improve cancer cure. Our recent data in mice shows that performing dose painting based on EPR oxygen maps can reduce the radiation dose to well-oxygenated areas of the tumor by 30%, resulting in not only improved treatment outcome but also reduced post treatment risks and complications. To date, EPR imaging is the only proven method for absolute in vivo measurement of the tissue oxygen level. While PET hypoxia imaging with 18F-Misonidazole (FMISO) has been investigated, FMISO uptake depends on many factors other than tissue oxygen concentration in nontrivial ways. This can explain why similar positive results with dose painting have not been observed in the clinic when performed based on PET-FMISO images. The proposed integrated system will be a powerful research tool for studying many heterogenous functional abnormalities in tumor and for developing and improving cancer treatment. In this project, we also will employ the developed system to conduct a small pilot study for purpose of validating the system for real animal imaging and demonstrating its potential usefulness for studying the correlation between PET-FMISO images and EPR oxygen maps. Such correlation, when identified, can lead to the development of methods for correcting the PET-FMISO images such that they can be successfully employed for dose painting to yield improved cancer cure. If successful, the clinical impact will be significant and immediate as FMISO-PET imaging can be readily employed in the clinic.

抽象的我们建议开发一个用于正电子发射断层扫描（PET）和电子的集成系统顺磁共振（EPR）同时在研究癌症和癌症中使用的啮齿动物成像治疗。癌症是一种复杂而异质的功能疾病。因此，有效的治疗癌症应解释特定的细胞型种群及其状态以及肿瘤微环境。体内成像在提供此类信息方面具有重要作用。宠物，已经在诊所中广泛使用，可以测量许多肿瘤的代谢和生理状态，包括葡萄糖利用18F-氟脱氧葡萄糖（FDG）和与18F-氟噻甲别凡的细胞增殖（flt）。用于成像肿瘤特异性细胞膜或细胞内分子或基因的宠物示踪剂，以及用于成像肿瘤微环境，包括血管生成和细胞外基质，也可用或正在积极发展。部分氧气压力，pH和间质性无机磷酸盐还应考虑癌细胞周围的空间，因为它们会影响代谢和生理过程，因此治疗结果。特别是知道组织氧气水平对于癌症治疗很重要。众所周知，低氧肿瘤细胞具有抗性到各种治疗剂。因此，许多人认为辐射剂量的剂量绘画根据局部组织氧气调节肿瘤可以改善癌症治疗。我们最近小鼠的数据表明，基于EPR氧图进行剂量绘画可以减少辐射剂量为肿瘤的氧化良好区域降低30％，不仅改善了治疗结果而且还降低了治疗后风险和并发症。迄今为止，EPR成像是唯一经过证明的绝对体内测量组织氧水平的方法。而宠物缺氧成像已经研究了18F-米诺唑唑（FMISO），FMISO摄取取决于许多因素组织氧浓度以非平凡的方式。这可以解释为什么类似剂量的类似阳性结果根据PET-FMISO图像进行绘画，在诊所中尚未观察到绘画。拟议的集成系统将是研究许多异源的强大研究工具肿瘤的功能异常以及发展和改善癌症治疗。在这个项目中，我们还将采用开发系统进行小型试点研究，以验证真实动物成像的系统，并证明其研究相关性的潜在有用性在PET-FMISO图像和EPR氧图之间。当确定时，这种相关性可能导致开发纠正PET-FMISO图像的方法，使它们可以成功用于剂量绘画以改善癌症治疗。如果成功，临床影响将是可以在诊所中很容易使用大量和直接作为FMISO-PET成像。