RARE EARTH NANOPROBES FOR OPTICAL IMAGING AND DISEASE TRACKING

描述(申请人提供)：用于光学成像和疾病跟踪PI的稀土纳米探针：Prabas V.Moghe，PhD；Richard E.Riman，PhD；Charles M.Roth，PhD。合作者：马克·皮尔斯博士、Shridar Ganesan博士、医学博士该项目旨在开发一个新的纳米级成像探针库，以识别和动态跟踪触发转移性癌症和动脉粥样硬化等难以治疗的疾病的快速扩散的微小病变。通过造成死亡和发病以及增加医疗费用，这些疾病目前给社会造成了惊人的损失。治疗这些疾病的技术正在显示改进，但如果与早期诊断和药物治疗效果的快速反馈相结合，显然会有更好的结果。在这份R01提案中，我们寻求利用短波红外(SWIR)成像这一迄今尚未开发的光谱区域的转化潜力，通过推进发射稀土纳米探测器的可调SWIR来实现。我们的团队已经展示了一系列新的稀土纳米探测器的潜力，与其他光学荧光成像方式相比，它可以在组织内更深的位置成像，并且几乎没有自发荧光，散射减少。该项目的具体目标是开发新的SWIR成像探针和技术，以检测和跟踪体内的微损伤并确定其分子表型。合成了一种新型的高发光强度的多光谱稀土掺杂荧光粉纳米探针板，并对其光子性能进行了测试。这些探针能够有效地标记和解决工程设计的亚表面病变细胞团的SWIR发射，这一能力将在体外进行基准测试(目标1)。在AIM 2中，一套三种融合的SWIR探针体内成像工具将得到优化，包括针对乳腺癌细胞转移病变的生物功能化探针的设计、淋巴结病变的SWIR宏观成像以及病变的SWIR原位共聚焦显微镜。在目标3中，我们将研究病变靶向探针在药物治疗后检测和跟踪体内转移病变的发展和消退的能力。这项研究的结果将包括更灵敏地识别和阐明体内疾病损害的分子决定因素的新工具。潜在的应用包括用于早期发现癌症转移的淋巴结跟踪的组织节约成像，以及心血管疾病和动脉粥样硬化血栓形成等血管病变的成像。R01的预期影响将是一流的成像探头/硬件框架，相当于“活体光学活检”，以可视化疾病微病变的发生、生长和治疗，超出目前可能的空间分辨率(“分子表型”)和亚表面病变组织检测(“深度穿透”)的限制。

DESCRIPTION (provided by applicant): Rare Earth Nanoprobes for Optical Imaging and Disease Tracking PIs: Prabhas V. Moghe, PhD,; Richard E. Riman,PhD; Charles M. Roth, PhD. Collaborators: Mark Pierce, PhD., Shridar Ganesan, MD, PhD. This project aims to develop a library of new nanoscale imaging probes to identify and dynamically track microlesions that trigger the rapid spread of difficult to treat diseases like metastatic cancers and atherothrombosis. By causing mortality and morbidity as well as increasing health care costs, these diseases currently take a staggering toll on society. Technologies to treat these diseases are showing improvements, but clearly would have better outcomes when integrated with early diagnoses and rapid feedback on the effectiveness of pharmacotherapy. In this R01 proposal, we seek to harness the transformative potential of a hitherto undeveloped region of the optical spectrum, short wave infrared (SWIR)-based imaging, by advancing tunable SWIR emitting rare earth nanoprobes. Our team has demonstrated the potential of a new family of rare earth nanoprobes to image deeper within tissues than other modalities of optical fluorescence imaging, and with little autofluorescence and reduced scattering. The specific goals of this project are to develop new SWIR imaging probes and technology to detect and track microlesions in vivo and to identify their molecular phenotype. A novel panel of multispectral rare earth doped phosphor nanoprobes with high luminescence intensity will be synthesized and tested for their photonic properties. The ability of these probes to effectively label and resolve the SWIR-emission from engineered, sub-surface diseased cell clusters will be benchmarked in vitro (Aim 1). A suite of three convergent in vivo imaging tools for the SWIR probes will be optimized in Aim 2, including the design of biofunctionalized probes for targeting to metastatic lesions of breast cancer cells, SWIR macroscopic imaging of the lesions in the lymph nodes, and SWIR in situ confocal microscopy of lesions. In Aim 3, we will investigate the ability of the lesion-targeted probes to detect and track the development and regression of metastatic lesions in vivo following pharmacotherapy. Outcomes from this study will include new tools for more sensitively identifying and elucidating the molecular determinants of disease lesions in vivo. Potential applications include tissue- sparing imaging of lymph node tracking for early detection of cancer metastasis, as well as imaging of vascular lesions such as those in cardiovascular disease and atherothrombosis. The envisioned impacts of the R01 would be a first-in-class imaging probe/hardware framework, equivalent to an "optical biopsy in vivo", to visualize the incidence, growth, and treatment of disease microlesions, stretching beyond the currently possible limits of spatial resolution ("molecular phenotyping") and detection of sub-surface diseased tissues ("depth penetration").