Multimodal Marker for imaging oximetry in radiotherapy

项目摘要 尽管组织氧水平在诊断、预后和预后中具有临床意义和重要性， 尽管本发明涉及多种病理的治疗，但目前显然存在对量化组织的方法的未满足的需求， 氧气水平，具有临床使用所需的合理准确度、可靠性和稳健性 设置.这项建议的总体目标是使电子顺磁的独特能力， 共振（EPR）血氧仪应用于临床领域，特别是用于增强癌症治疗。我们有 发现了独特的固态传感器，称为氧芯片和程序，使无与伦比的可靠性， 在一段时间内-可能是无限期地-重复询问特定组织部位的组织氧水平。 然而，这些传感器主要限于涉及小动物的实验室研究。我们有 在一小群癌症患者中证实， 需要创新的传感器来提供增强的检测能力、安全性、稳定性和鲁棒性， 一种常规的临床工具我们建议开发一种新型的氧芯片传感器与增强检测 灵敏度、临床成像过程中易于识别以及长期安全性和稳定性--所有这些都特别 专为更深的肿瘤测量而设计和优化。拟议的发展，加上 EPR血氧测定技术的独特能力，将是一种有价值的临床工具，能够提供真实的- 及时了解肿瘤氧水平，以增强癌症治疗和临床结果。以下 提出了具体的目标：（1）氧芯片的表征，以建立其适用于时间和 常规临床成像中的空间定位。嵌入GNP的OxyChips将受到仔细的检查， 在临床相关成像条件下进行评价，以确定其在时间和空间上的适用性 在常规临床成像期间定位。评估将包括区域显著性（即，OxyChip的可见性 相对于其局部肿瘤环境），可检测性的定量测量，（即，信噪比和 对比度噪声比），以及用于视觉和定量增强 氧芯片(2)在临床前兔肿瘤模型中评价包埋有GNP的新型OxyChip， 确定其在临床环境中用于成像和氧气测量的安全性、稳健性和实用性。我们 将使用兔乳腺肿瘤模型确定新传感器的临床适用性。的 评价标准将包括使用临床成像模式对肿瘤中的传感器进行可视化， 如CT、CB-CT、平面X射线和超声。该研究将进一步提高EPR的性能 氧芯片用于癌症治疗。

PROJECT SUMMARY Despite the clinical significance and importance of tissue oxygen levels in the diagnosis, prognosis, and treatment of several pathologies, currently there is clearly an unmet need for methods to quantify tissue oxygen levels with a reasonable degree of accuracy, reliability, and robustness required for use in the clinical settings. The overall objective of this proposal is to bring the unique capability of electron paramagnetic resonance (EPR) oximetry to the clinical realm, particularly for enhancement of cancer treatment. We have discovered unique solid-state sensors, called OxyChips and procedures that enable unsurpassed reliability and repeated interrogation of tissue oxygen levels at specific tissue sites over a period—possibly indefinitely. However, these sensors are limited primarily to laboratory research involving small animals. We have observed—in a small cohort of cancer patients—that translation of this novel technology to clinical applications would require innovative sensors to provide enhanced detection capability, safety, stability, and robustness as a routine clinical tool. We propose to develop a novel class of the OxyChip sensor with enhanced detection sensitivity, easy identification during clinical imaging, and long-term safety and stability—all specifically designed and optimized for measurement in deeper tumors. The proposed developments, combined with the unique capabilities of the EPR oximetry technology, will be a valuable clinical tool capable of providing real- time knowledge of tumor oxygen levels for enhanced cancer treatments and clinical outcomes. The following specific aims are proposed: (1) Characterization of OxyChips to establish their suitability for temporal and spatial localization in routine clinical imaging. The OxyChips embedded with GNP will be subjected to careful evaluation under clinically relevant imaging conditions to determine its suitability for temporal and spatial localization during routine clinical imaging. Evaluation will include regional conspicuity (i.e., visibility of OxyChip with respect to its local tumor environment), quantitative measure of detectability, (i.e., signal-to-noise ratio and contrast-to-noise ratio), and image processing methods for visual and quantitative enhancement of the OxyChips. (2) Evaluation of the new OxyChips embedded with GNP in a pre-clinical rabbit tumor model to establish their safety, robustness, and utility for imaging and oxygen measurements in the clinical settings. We will determine the capability of the new sensors for clinical applicability using rabbit breast tumor model. The evaluation criteria will include visualization of the sensors in the tumor using clinical imaging modalities, such as CT, CB-CT, planar X-ray, and ultrasound. The proposed research will further advance the capability of EPR oximetry with OxyChip for cancer treatment.