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 我们建议开发一种用于正电子发射断层扫描(PET)和电子的集成系统 用于研究癌症和癌症的啮齿动物的顺磁共振(EPR)同步成像 治疗。癌症是一种复杂的、异质性的功能性疾病。因此，有效的治疗 应考虑特定的细胞类型人群及其状态，以及肿瘤 微环境。活体成像在提供此类信息方面发挥着重要作用。宠物，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 18F-脱氧葡萄糖(FDG)对葡萄糖的利用及18F-氟代胸苷对细胞增殖的影响 (外语)。用于肿瘤特异性细胞膜或细胞内分子或基因成像的PET示踪剂，以及 也可用于肿瘤微环境的成像，包括血管生成和细胞外基质 或正在积极开发中。氧分压、pH和间隙无机磷 癌细胞周围的空间也应被考虑，因为它们将影响代谢和 生理过程，因此治疗结果。特别是，了解组织中的氧气 水平对癌症的治疗具有重要意义。众所周知，缺氧的肿瘤细胞具有抗药性。 不同的治疗剂。因此，许多人认为剂量画中的辐射剂量 对肿瘤根据局部组织氧水平进行调整，可提高肿瘤治愈率。我们最近 小鼠的数据显示，根据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减少30%，不仅改善了治疗结果 而且还减少了治疗后的风险和并发症。到目前为止，EPR成像是唯一得到证实的 体内绝对测量组织含氧量的方法。在进行PET乏氧显像时 18F-咪唑(FMISO)已被研究，FMISO的摄取取决于许多其他因素 组织氧浓度以不平凡的方式。这可以解释为什么剂量的阳性结果相似 基于PET-FMISO图像的涂装尚未在临床上观察到。 提出的集成系统将为研究多种异构性提供有力的研究工具 肿瘤中的功能异常以及开发和改进癌症治疗。在这个项目中， 我们亦会利用所开发的系统进行一项小型试验研究，以验证 真实动物成像系统及其在研究相关性方面的潜在用处 在PET-FMISO图像和EPR血氧地图之间。这种关联一旦确定，可能会导致 PET-FMISO图像校正方法的研究进展 用于剂量涂装，以提高癌症治疗效果。如果成功，临床影响将是 由于FMISO-PET成像具有重要和即时的意义，因此可以很容易地在临床上使用。