PROTON REPORTERS FOR PO2 IN TUMORS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者的研究机构。 众所周知，实体瘤中的缺氧甚至缺氧区域可能限制非手术治疗的疗效，包括放射治疗、光动力治疗、化学治疗。在肿瘤生长的各个阶段和对干预/治疗的响应中对肿瘤氧合的准确评估可以提供对肿瘤发展的更好理解，并且可以作为治疗结果的预后指标，可能允许个体化癌症治疗。我们最近确定了一个1H MRI探针pO 2：六甲基二硅氧烷（HMDSO）。PI开发了一种新的基于HMDSO的定量MR血氧测定技术PISTOL（用于绘制组织氧合水平的硅烷质子成像），用于绘制组织间质pO 2。本项目已将该技术应用于肿瘤微血管反应的研究。第一个子项目的目标是优化基于HMDSO的纳米乳剂的合成和表征，作为基于1H MRI的oximentry的pO 2纳米探针（资金来源1），并使用它们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pO 2纳米探针癌症pO 2敏感光动力疗法相结合的反应。

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.