TARGETED RESPONSIVE MR AND PET AGENTS FOR B-CELL IMAGING

用于 B 细胞成像的靶向响应 MR 和 PET 试剂

基本信息

批准号：
8147683
负责人：
Dean Sherry
金额：
$ 36.82万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-01 至 2012-05-09
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8147683
关键词：
Acetates Acetyl Coenzyme A Animal Experiments Animal Model Animals Arts B-Lymphocytes Binding Biological Carbon Cell Line Cell physiology Cell surface Cells Citrate (si)-Synthase Citric Acid Cycle Collaborations Complex Contrast Media Detection Dose Environment Funding Glucose Goals Human Image Insulin Islet Cell Label Ligands Lipids Magnetic Resonance Imaging Measures Metabolic Metabolic Pathway Metabolism Molecular Weight Oxidation-Reduction Pancreas Peptides Perfusion Phage Display Positron-Emission Tomography Propionates Proteins Pyruvate Pyruvates RIPK2 gene Rattus Relative (related person)Reporting Resolution Specificity Surface System Techniques Technology Testing Translating Water Work base cellular imaging cyclen design glucose sensor imaging modality in vivo indexing insulin secretion insulinoma islet molecular imaging novel research clinical testing research study response tool uptake

项目摘要

The goal of Project 2 is to merge the metabolic strategies of Project 1 and islet targeting core (Core B) and with state-of-the-art imaging agent technologies to create novel PET and MR agents for molecular imaging of the b-cell in vivo. Our goal is to develop imaging agents that not only target the pancreatic b-cell in vivo but also respond to b-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 b-cells and isolated rat islets and use this technology to screen for entrapment of redox sensitive PET agents (64Cu-ATSM) and redox sensitive PARACEST agents (cyclen-based tetraamide complexes of Eu3+ or Tm3+) in b-cells. Proof 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) b-cell mass and b) b 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 b-cell mass but also provide an imaging index of b-cell function.

项目2的目的是合并项目1的代谢策略和目标核心（核心B）以及最先进的成像剂技术，以创建新颖的PET和MR代理，以用于体内B细胞的分子成像。我们的目标是开发成像剂，不仅针对体内胰腺B细胞，而且还通过功能激活对B细胞代谢做出反应。在进行动物实验之前，我们最初将开发一个平台，用于培养的大鼠B细胞和孤立的高分辨率MR和PET成像大鼠胰岛并使用这项技术筛选了B细胞中氧化还原敏感的PET剂（64CU-ATSM）和氧化还原敏感的偏执药物（基于Cyclen的EU3+或TM3+）的氧化还原敏感剂。使用多聚肽进行的证明通过噬菌体显示胰岛素瘤INS 832/1细胞和分离的大鼠胰岛的平移鉴定。鉴于这些在核心B中鉴定出的肽或其他肽，我们将开发一种有效的标签方法，将18F或基于Cyclen的配体连接到所有靶向肽中以创建MR（pH敏感的GD3+基于GD3+的代理，基于Paracest的Zn2+和葡萄糖传感器）和PET Ensorts）和PET Entert（18F和64CU）（18F和64CU），以测量A）b-Cell Mass and b-Cell Mass and B）Bind and b）b）b）B）B）最终目的是结合目标1和2的技术，以创建有针对性和响应的MR 以及不仅报告B细胞质量而且还提供B细胞功能的成像索引的宠物代理。