TARGETED RESPONSIVE MR AND PET AGENTS FOR BETA-CELL IMAGING

用于 β 细胞成像的靶向响应 MR 和 PET 试剂

• 批准号: 7357906
• 负责人: XIAOFENG SUN
• 金额: $ 1.17万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7357906
• 关键词: peptides

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. This is Project #2 in a pending PPG grant renewal led by Chris Newgard of Duke University. The goal is to merge the beta - cell metabolic strategies described in Project #1 and islet targeting core with state-of-the-art imaging agent technologies to create novel PET and MR agents for molecular imaging of the beta-cell in vivo. Our goal is to develop imaging agents that not only target the pancreatic beta-cell in vivo but also respond to beta-cell metabolism by functional activation. Before moving to animal experiments, we will initially develop a platform for both high resolution MR and PET imaging of cultured rat beta-cells and isolated rat islets and use this technology to screen for entrapment of redox sensitive PET agents and redox sensitive PARACEST agents in beta-cells. Proof of concept studies on agents that specifically target beta -cells will be performed using multimeric peptides identified by phage display panning of insulinoma INS 832/1 cells and isolated rat islets. Given these peptides or others identified in Core B, we will develop an efficient labeling approach to attach either 18F or cyclen-based ligands to all targeting peptides to create MR (pH sensitive Gd3+-based agents, PARACEST-based Zn2+ and glucose sensors) and PET agents (both 18F and 64Cu) to measure a) beta-cell mass and b) beta-cell function. A final aim is to combine the technologies of aims 1 & 2 to create targeted & responsive MR and PET agents that not only report beta-cell mass but also provide an imaging index of beta-cell function.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中得到体现。列出的机构是中心的机构，不一定是研究者的机构。这是由杜克大学 Chris Newgard 领导的待定 PPG 资助续签项目#2。目标是将项目 #1 中描述的 β 细胞代谢策略和胰岛靶向核心与最先进的成像剂技术相结合，以创建用于体内 β 细胞分子成像的新型 PET 和 MR 试剂。我们的目标是开发不仅能靶向体内胰腺β细胞，还能通过功能激活对β细胞代谢做出反应的显像剂。在进行动物实验之前，我们将首先开发一个平台，用于对培养的大鼠 β 细胞和分离的大鼠胰岛进行高分辨率 MR 和 PET 成像，并使用该技术筛选氧化还原敏感 PET 试剂和氧化还原敏感 PARACEST 试剂在 β 细胞中的包埋情况。将使用通过噬菌体展示淘选胰岛素瘤 INS 832/1 细胞和分离的大鼠胰岛鉴定的多聚肽，对特异性靶向 β 细胞的药物进行概念验证研究。鉴于核心 B 中确定的这些肽或其他肽，我们将开发一种有效的标记方法，将 18F 或基于 Cyclen 的配体附着到所有靶向肽上，以创建 MR（基于 pH 敏感的 Gd3+ 试剂、基于 PARACEST 的 Zn2+ 和葡萄糖传感器）和 PET 试剂（18F 和 64Cu），以测量 a) β 细胞质量和 b) β 细胞功能。最终目标是将目标 1 和 2 的技术结合起来，创建有针对性的响应性 MR 和 PET 试剂，不仅可以报告 β 细胞质量，还可以提供 β 细胞功能的成像指数。