A preclinical integrated PET/EPR imaging system

临床前集成 PET/EPR 成像系统

• 批准号: 10032946
• 负责人: Boris Epel
• 金额: $ 34.9万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10032946
• 关键词: Adopted; Advanced Malignant Neoplasm; Affect; Aftercare; Algorithms; Animal Model; Area; Attention; Biological Process; Blood flow; Caliber; Cancer Biology; Cancer Diagnostics; Cancer Model; Cell Proliferation; Cell membrane; Clinic; Clinical; Complex; Correlation Studies; Data; Development; Diagnosis; Disease; Dose; Electron Spin Resonance Spectroscopy; Electronics; Electrons; Event; Extracellular Matrix; Failure; Future; Genes; Glucose; Gold; Hybrids; Hypoxia; Image; Imaging Techniques; Imaging technology; Knowledge; Lead; Length; Magnetic Resonance Imaging; Malignant Neoplasms; Maps; Measurement; Measures; Metabolic; Metabolism; Methods; Misonidazole; Modeling; Mus; Noise; Oxygen; Performance; Perfusion Weighted MRI; Physical Performance; 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; Speed; System; Therapeutic Agents; Tissues; Tracer; Treatment outcome; Variant; Water; X-Ray Computed Tomography; angiogenesis; animal imaging; attenuation; base; 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; image visualization; 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

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.

摘要 我们建议开发一个集成的系统，正电子发射断层扫描（PET）和电子 用于研究癌症的啮齿动物的顺磁共振（EPR）同步成像和癌症 治疗癌症是一种复杂的异质性功能性疾病。因此，有效的治疗 癌症的诊断应考虑特定的细胞类型群体及其状态，以及肿瘤的类型。 微环境体内成像在提供这种信息方面具有重要作用。PET，已经 广泛应用于临床，可以测量肿瘤的多种代谢和生理状态，包括 18 F-氟脱氧葡萄糖（FDG）的葡萄糖利用和18 F-氟胸苷的细胞增殖 （FLT）.用于对肿瘤特异性细胞膜或细胞内分子或基因成像的PET示踪剂，和 用于成像肿瘤微环境，包括血管生成和细胞外基质， 或正在积极发展中。研究了不同pH值、氧分压和间隙无机磷含量对土壤pH值的影响。 还应考虑癌细胞周围的空间，因为它们将影响代谢和 生理过程，因此治疗结果。特别是知道了组织氧含量 水平对癌症治疗至关重要。众所周知，缺氧肿瘤细胞对 各种治疗剂。因此，许多人认为，剂量绘画中的辐射剂量 根据肿瘤局部组织的氧含量进行调整，可以提高癌症的治愈率。我们最近 在小鼠中的数据显示，基于EPR氧图进行剂量绘制可以减少辐射， 将肿瘤氧合良好区域的剂量降低30%，不仅改善了治疗效果， 而且降低了治疗后的风险和并发症。到目前为止，EPR成像是唯一被证明 组织氧水平的绝对体内测量方法。而PET缺氧成像， 已研究了18F-米索咪唑（FMISO），FMISO摄取取决于许多因素， 组织氧浓度的变化。这可以解释为什么剂量与剂量的相似阳性结果 当基于PET-FMISO图像进行时，在临床中未观察到绘画。 该集成系统将成为研究许多异构系统的有力工具。 肿瘤的功能异常以及开发和改善癌症治疗。在本项目中， 我们亦会利用已发展的系统进行小型试验研究，以验证 系统的真实的动物成像和展示其潜在的有用性，研究相关性 PET-FMISO图像和EPR氧气图之间的差异。这种相关性，一旦确定，可能导致 开发用于校正PET-FMISO图像的方法，以便可以成功地 用于剂量涂敷以产生改进的癌症治疗。如果成功，临床影响将是 这是显著和直接的，因为FMISO-PET成像可以容易地在临床中使用。