19F MRI probes and autoimmune disease

本方案包括技术开发部分和基本免疫生物学部分。它包括三个特定目标：(1)开发新的细胞内MRI试剂和相关的细胞标记方案，以及测量细胞标记效率和寿命；(2)通过标记免疫细胞（如树突状细胞（dc）和巨噬细胞）的定量细胞毒性、增殖和免疫学分析来进行生物学表征；(3)体内研究，将标记的免疫细胞注射到NOD小鼠体内，并使用极高场（11.7 T） MRI成像。我们将可视化标记细胞在静脉注射后的生物分布，以及局灶注射到特定组织部位后的延时细胞迁移。我们将检验这一假设，即不同的dc亚群在体内根据其成熟状态有不同的迁移模式。使用NOD小鼠，我们将检验成熟dc预防糖尿病的能力部分取决于其迁移能力的假设。这项技术的一个长期应用是监测体内细胞治疗药物的贩运。拟议的研究项目是高度跨学科的，我们

This proposal has a technology development component and a basic immunobiological component. It consists of three Specific Aims: (1) development of novel intracellular MRI agents and associated cell labeling protocols, and measurement of the cell labeling efficiency and lifetime; (2) biological characterizations via quantitative cytotoxicity, proliferation, and immunological assays of labeled immune cells, such as dendritic cells (DCs) and macrophages; and (3) in vivo studies where labeled immune cells will be injected into NOD mice and imaged using extremely-high field (11.7 T) MRI. We will visualize the biodistribution of the labeled cells following intravenous inoculation and the time-lapse cell migration following focal injection into specific tissue sites. We will test the hypothesis that different subsets of DCs have different migratory patterns in vivo based on their maturation state. Using the NOD mouse we will test the hypothesis that the ability of mature DCs to prevent diabetes is dependent, in part, on their migratory capacity. A long-term application of this technology is monitoring the trafficking of cellular therapeutics in vivo. The proposed research project is highly interdisciplinary, and we have assembled a diverse team of investigators in the Pittsburgh area with expertise in in vivo magnetic resonance microscopy (Ahrens), immunology (Morel) and biological reagent design (Ernst/Waggoner).