PROTON REPORTERS FOR PO2 IN TUMORS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 众所周知，实体瘤中的缺氧区甚至缺氧区可能会限制非手术治疗的疗效，包括放射治疗、光动力治疗、化疗。在肿瘤生长的不同阶段和对干预/治疗的反应中，对肿瘤氧合的准确评估可能会更好地了解肿瘤的发展，并可能作为治疗结果的预后指标，潜在地允许个体化的癌症治疗。我们最近发现了一种pO2：六甲基二硅氧烷(HMDSO)的1H磁共振探针。PI开发了一种新的、基于HMDSO的定量磁共振血氧仪技术PISTOL(硅烷质子成像以映射组织氧合水平)，用于绘制组织间质pO2的图谱。这项技术已被应用于研究肿瘤微环境对治疗的反应。第一个子项目的目标是优化基于HMDSO的纳米乳液的合成和表征，作为1H MRI基羟胺类药物的pO2纳米探针(资金来源1)，并将其用于研究肿瘤对联合化疗的反应。第二个子项目(资金来源2)的目标是研究高压氧与二氧化硅敏感的光动力疗法结合起来的反应，以及二氧化硅纳米探针对癌症的影响。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. It is well-known that hypoxic or even anoxic regions in solid-growing tumors may limit the efficacy of non-surgical therapy, including radiotherapy, photodynamic therapy, chemotherapy. Accurate assessment of tumor oxygenation at various stages of tumor growth and in response to interventions/therapy may provide a better understanding of tumor development and may serve as a prognostic indicator for treatment outcome, potentially allowing individualized cancer therapy. We have recently identified a 1H MRI probe of pO2: hexamethyldisiloxane (HMDSO). The PI has developed a new, HMDSO-based quantitative MR oximetry technique PISTOL (Proton Imaging of Silanes to Map Tissue Oxygenation Levels) for mapping of tissue interstitial pO2. This technique has been applied to study the tumor microenvironmenental response to therapy in this project. The goal of the first subproject is to optimize synthesis and characterization of HMDSO based nanoemulsions as pO2 nanoprobes (funding source 1) for 1H MRI based oximentry and uses them to study tumor response to combination chemotherapy. The goal of the second subproject (funding source 2) is to study the response of combining hyperbaric oxygen with pO2-sensitive photodynamic therapy of cancer with pO2 nanoprobes.