FUNCTIONAL IMAGING & MASS ANALYSIS OF PANCREATIC B CELLS

功能成像

• 批准号: 6222048
• 负责人: KENNETH A. KROHN
• 金额: $ 34.82万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-30 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6222048
• 关键词: 5 hydroxytryptophan; Primates; artificial endocrine pancreas; bioimaging /biomedical imaging; dihydroxyphenylalanine; functional magnetic resonance imaging; insulin; insulin dependent diabetes mellitus; laboratory rat; nicotinamide; nuclear magnetic resonance spectroscopy; oxygen consumption; pancreatic islet function; pancreatic islets; phosphorus; positron emission tomography; radionuclides; radiopharmacology; streptozotocin

DESCRIPTION (adapted from the application) We propose a collaboration of imaging scientists and experts in B-cell biology to develop new imaging technology and agents to assess B-cell mass and function. Advances in in vivo imaging methods have not yet made an impact on study of the endocrine pancreas. Our premise is that this inherently chemical organ needs to be imaged with chemical resolution as well as structural resolution in order to advance research in B-cell biology and the pathophysiology of diabetes. Complementary nuclear medicine (PET) and magnetic resonance (MRS) methods will be applied to an in vitro artificial organ system and to small animal in vivo imaging studies of healthy and diabetic animals. New imaging tools will be developed and validated to answer some fundamental questions about the biology of normal and injured B-cells. In SA1 we will use principally MRS to determine the amount of viable cell mass in our in vitro organ and compare this measure with oxygen metabolism and insulin release. We anticipate that the 31P peak ratios will be a robust indicator of B-cell viable mass that is more sensitive than the insulin release assay and will permit direct comparisons between imaging agents for B cells and islets. In SA2 we will also use the artificial organ model to evaluate a series of compounds for their potential as imaging agents to quantitative B-cell mass in vivo. Because only a small fraction of the pancreas is B-cells, a successful imaging agent will require a high level of selectivity over acinar cells as well as cells of neighboring organs. Selectivity could derive from chemical specificity of a radiotracer and/or from a unique time course of the tracer in B-cells, as analyzed by mathematical models. Because there is no existing literature on radiopharmaceuticals with the desired specificity for the endocrine pancreas, we have searched broadly to find good candidate imaging agents for radiolabeling. We have identified selective B-cell toxins, dyes for in vitro staining of islets, unique B-cell surface receptors, and molecules that play a role in the cell's specific biochemical function related to insulin production and release. Good candidate molecules will be labeled with PET nuclides and used in SA3 to image the natural history of B-cell mass in animal models of both spontaneous and toxin-induced diabetes. Imaging using the small animal PET will be compared with functional measures, including insulin release and other assays developed in SA1. The application of non-invasive islet imaging will allow investigators to answer questions about the etiology and natural history of type I diabetes, to improve ways to predict who will develop clinical disease, and to various drugs in preventing progressive beta cell destruction.

描述（改编自应用程序） 我们建议成像科学家和B细胞生物学专家合作 开发新的成像技术和试剂来评估B细胞质量， 功能体内成像方法的进步尚未对 胰腺内分泌的研究我们的前提是这种固有的化学物质 器官需要用化学分辨率和结构分辨率成像， 决议，以推进研究在B细胞生物学和 糖尿病的病理生理学补充核医学（PET）和磁 磁共振（MRS）方法将应用于体外人工器官系统 以及健康和糖尿病动物的小动物体内成像研究。 新的成像工具将被开发和验证，以回答一些基本的问题。 关于正常和受损B细胞的生物学问题。在SA 1中，我们将使用 MRS主要用于确定我们体外培养中活细胞质量的量， 并将该测量与氧代谢和胰岛素释放进行比较。我们 预计31 P峰比率将是B细胞存活的可靠指标， 质量比胰岛素释放测定更敏感， 直接比较B细胞和胰岛的显像剂。在SA 2中， 还将使用人工器官模型来评估一系列化合物， 它们作为体内定量B细胞质量的显像剂的潜力。因为 只有一小部分胰腺是B细胞，一种成功的显像剂， 将需要高水平的选择性超过腺泡细胞以及 邻近器官选择性可能来源于一种 放射性示踪剂和/或来自B细胞中示踪剂的独特时间过程，如 通过数学模型分析。因为没有现有的文献 对内分泌胰腺具有所需特异性的放射性药物， 我们已经广泛地寻找了良好的候选显像剂， 放射性标记。我们已经确定了选择性B细胞毒素，染料， 胰岛的染色，独特的B细胞表面受体，以及发挥作用的分子。 在与胰岛素产生相关的细胞特定生化功能中的作用 然后释放良好的候选分子将用PET核素标记， 在SA 3中用于成像动物模型中B细胞质量的自然史， 自发性和毒素诱发的糖尿病。使用小动物PET成像 将与功能测量进行比较，包括胰岛素释放和其他 在SA 1中开发的测定。无创性胰岛成像的应用将 允许研究人员回答有关病因学和自然史的问题 I型糖尿病，以改善方法来预测谁将发展临床 疾病，以及用于预防进行性β细胞破坏的各种药物。