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.

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。这是由杜克大学的克里斯·纽加德领导的PPG拨款更新计划中的第二个项目。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显像剂技术相结合，以创建用于体内β细胞分子成像的新型PET和MR显像剂。我们的目标是开发成像剂，不仅针对体内胰腺β细胞，而且通过功能激活对β细胞代谢作出反应。在进行动物实验之前，我们将首先开发一个平台，用于培养的大鼠β细胞和分离的大鼠胰岛的高分辨率MR和PET成像，并使用该技术筛选β细胞中氧化还原敏感PET剂和氧化还原敏感PARACEST剂的包裹。利用胰岛素瘤INS 832/1细胞和分离的大鼠胰岛的噬菌体展示计划鉴定的多聚肽，将对特异性靶向β细胞的药物进行概念验证研究。鉴于这些肽或其他在核心B中鉴定的肽，我们将开发一种有效的标记方法，将18F或基于环素的配体连接到所有靶向肽上，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。最终目标是结合目标1和目标2的技术来创建靶向和响应的MR和PET试剂，不仅报告β细胞质量，还提供β细胞功能的成像指数。