PARACEST AGENTS: OPTIMIZATION FOR HUMAN MR IMAGING

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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 a bioengineering research partnership (BRP) application involving scientists in Boston (Beth Israel Deaconess Medical Center), Dallas (University of Texas at Dallas) and Albany, NY (GE Center Research Center) to optimize the chemistry, biodistribution, and toxicology of PARACEST agents, optimize pulse sequences and data collection for imaging with PARACEST agents on clinical scanners, and demonstrate their efficacy in large animal imaging at 3T. In principle, PARACEST agents can be tailored to any number of biological application because the CEST effect depends upon water exchange rates and these rates can be modified using rational chemical principles. This feature also makes them an attractive platform for the development of responsive agents. To realize the full potential of these compounds as contrast agents in vivo, a number of basic, theoretical and practical questions must be systematically addressed. These include establishing the relationships among the magnitude of the effect measured in an imaging experiment and the water exchange lifetime, the magnitude of the chemical shift difference between the bound and bulk water, the strength of the saturating RF field, SAR, concentration, and local environment in vivo. This proposal will address all of these issues.