Contrast Agents for Far Red and Near Infrared Imaging

描述(申请人提供)：监测免疫细胞相互作用的工具 而它们的后果将加速成功的发展 癌症、艾滋病毒疾病和自身免疫性疾病的免疫疗法。高水平 自发荧光和光谱重叠限制了稳定的荧光标记的使用 用于细胞蛋白质或细胞膜与其他可见探针。高水平的组织 吸收和散射排除了完整动物的实时光学成像。 PTIR合成了五种新的细胞跟踪染料，在667-837 nm处有荧光 范围(远红外线-近红外线)。标记细胞的S/N高达15倍 对于PKH26；光谱重叠特性适用于许多其他 荧光探针；以及化学稳定性的可行性标准， 光稳定性好，对细胞活力和生长无影响。 标记细胞在肺表面微血管中也很容易被成像。 完整的器官显微镜和裸鼠皮下注射部位， 证明了非侵入性全身成像的潜力。 在第二阶段，PTIR将开发两种用于临床前使用和筛查的试剂盒和 启动支持临床细胞跟踪染料的研究。第一个工具包将是 适用于标准的3-4色仪器，第二适用于高端仪器。 我们的合作者将通过监控病毒的扩散来评估这两个套件 淋巴细胞亚群，决定了肿瘤细胞可被追踪的深度 在大鼠完整的肺标本中，并确定最小数量 在完好无损的动物体内，可以在深层和浅部成像的细胞。 建议的商业应用： 在远红或近红外发射的膜标记染料在三个市场具有巨大的商业潜力：1)为基础和临床研究人员服务的研究市场 使用流式细胞仪；2)类似且快速增长的光学成像市场，特别是 完整的器官或全身成像；以及具有适当光化学作用的分子 性质，3)光诊断和/或光疗。

DESCRIPTION (Provided by Applicant): Tools to monitor immune cell interactions and their consequences will accelerate development of successful immunotherapies for cancer, HIV disease, and autoimmune disorders. High levels of autofluorescence and spectral overlap limit use of stable fluorescent labels for cell proteins or membranes with other visible probes. High levels of tissue absorption and scattering preclude real time optical imaging in intact animals. PTIR has synthesized five new cell tracking dyes fluorescing in the 667-837 nm range (far red - near infrared). S/N for labeled cells were up to 15x of those for PKH26; spectral overlap properties were suitable for use with many other fluorescent probes; and feasibility criteria for chemical stability, photostability, and lack of effect on cell viability and growth were met. Labeled cells were also readily imaged in superficial lung microvessels using intact organ microscopy and at subcutaneous injections sites in nude mice, attesting to the potential for noninvasive, whole body imaging. In Phase II PTIR will develop two kits f or preclinical use and screening and initiate studies to support a clinical cell tracking dye. The first kit will be for standard 3-4 color instruments, the second for high-end instrumentation. Our collaborators will evaluate both kits by monitoring proliferation of lymphocyte subsets, determining the depth to which tumor cells can be tracked in intact lung preparations from rats, and determining the minimum number of cells which can be imaged at deep vs. superficial sites in intact animals. PROPOSED COMMERCIAL APPLICATION: Membrane labeling dyes emitting in the far red or near infrared have significant commercial potential in three markets; 1) a research market serving both basic and clinical investigators using flow cytometers; 2) a similar and rapidly growing market in optical imaging, especially intact organ or whole body imaging; and for molecules with suitable photochemical properties, 3) photodiagnosis and/or phototherapy.