METABOLIC IMAGING AGENTS

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. The specific aims are to: 1) Optimize our existing glucose-responsive PARACEST agent for mapping the tissue distribution of glucose in vivo. We have demonstrated that changes in extracellular glucose concentration can be mapped by MRI in isolated mouse liver by CEST imaging using a glucose-responsive PARACEST agent. This assumes that the boronate agent is equally distributed throughout all extracellular space of liver. Further experiments are envisioned to test this hypothesis. 2) Develop a single injection method for mapping tissue pH by MRI. We were first to demonstrate that tissue pH can be mapped by MRI in kidney, heart & tumors in vivo by monitoring dynamic contrast enhancement (DCE) after injection of two agents, a pH insensitive agent (GdDOTp5-) and a pH sensitive agent (GdDOTA-4Amp5-). In an effort to make pH imaging of tissue more feasible clinically, we propose to develop a single injection protocol using a mixture T1 and T2 agents. 3) Develop high sensitivity LlPOCEST particles for imaging low pH regions of tissues. It has been demonstrated that the sensitivity of CEST can be magnified many fold by using liposomes containing high concentrations of lanthanide shift reagent trapped in the inner core. All water trapped in the inner core along with a complex is shifted to a different frequency than extra-liposomal water and this new resonance can be used as an antenna to initiate CEST. Since exchange of water in this case is determined by the diffusion characteristics of the lipid bilayer, one should be able to prepare liposomes with surface functionalities that respond to changes in extraliposomal pH.