TARGETED RESPONSIVE MR AND PET AGENTS FOR BETA-CELL IMAGING

点击翻译按钮获取中文摘要

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.