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.

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 啮齿类动物的顺磁共振 (EPR) 同步成像用于研究癌症和癌症 治疗。癌症是一种复杂且异质的功能性疾病。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 微环境。体内成像在提供此类信息方面具有重要作用。 PET，已经 临床广泛应用，可以测量肿瘤的多种代谢和生理状态，包括 18F-氟脱氧葡萄糖 (FDG) 的葡萄糖利用和 18F-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进行成像的 PET 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，也可提供 或正在积极开发中。氧分压、pH 值和间隙无机磷酸盐 还应考虑癌细胞周围的空间，因为它们会影响新陈代谢和 生理过程，从而产生治疗结果。特别是了解组织氧 水平对于癌症治疗具有重要意义。众所周知，缺氧的肿瘤细胞具有抵抗力 至各种治疗剂。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含氧水平来调整可以提高癌症的治愈率。我们最近的 小鼠数据表明，根据 EPR 氧图进行剂量绘制可以减少辐射 肿瘤氧合良好区域的剂量减少了 30%，不仅改善了治疗效果 而且还减少了治疗后的风险和并发症。迄今为止，EPR 成像是唯一经过验证的 体内绝对测量组织氧水平的方法。而 PET 缺氧成像 18F-米索硝唑 (FMISO) 已被研究，FMISO 的吸收取决于许多因素，除了 以非平凡的方式测量组织氧浓度。这可以解释为什么剂量相似的阳性结果 当基于 PET-FMISO 图像进行操作时，尚未在临床中观察到绘画。 所提出的集成系统将成为研究许多异质性的强大研究工具 肿瘤的功能异常以及开发和改善癌症治疗。在这个项目中， 我们还将利用开发的系统进行小型试点研究，以验证 用于真实动物成像的系统并展示其在研究相关性方面的潜在用途 PET-FMISO 图像和 EPR 氧图之间的比较。这种相关性一旦被识别，可能会导致 开发用于校正 PET-FMISO 图像的方法，以便它们能够成功地 用于剂量涂敷以改善癌症治疗。如果成功的话，临床影响将是 FMISO-PET 成像可以很容易地应用于临床，因此意义重大且直接。