About the Seminar:
Magnetic resonance imaging (MRI) is often considered too insensitive for molecular imaging of biological processes. Although many Gd3+-based contrast agents have been reported in the chemistry literature over the past 30 years, only a few have been demonstrated to provide important biological information in vivo. A key parameter in the design of more sensitive Gd3+-based MRI contrast agents is the rate of water exchange. Our approach to optimize this rate will be illustrated in the design of sensors for in vivo imaging of free Zn2+ ions released from the pancreas and prostate in response to glucose. Insulin produced by pancreatic -cells is stored in granules as a zinc complex which is released in response to high glucose. As a result, the local concentration of Zn2+ ions in the extracellular space of -cells during insulin secretion increases to ~400 M and as we have demonstrated, this change is readily detected by MRI using a zinc-responsive agent. The normal human prostate has been reported to have the highest levels of free Zn2+ while malignant prostate cells undergo a metabolic transformation that results in less accumulation of Zn2+. This loss of tissue Zn2+ in prostate cancer offers a potential opportunity to distinguish malignancy from benign prostatic hyperplasia (BPH), and inflammation. The ability to fine-tune water exchange rates is also key in maximizing the sensitivity of paramagnetic chemical exchange saturation transfer (paraCEST) agents. The chemistry of these novel reporters and their limitations for use in vivo to image tissue pH and tissue redox will be discussed. Other MR techniques, including CEST imaging and hyperpolarized nuclei also offer considerable potential for providing new insights into the tumor microenvironment and tumor metabolism.
About the Speaker:
A. Dean Sherry is currently a Professor of Chemistry at the University of Texas at Dallas. He is the Director of the Advanced Imaging Research Center, at UT-Southwestern. He is also a Professor of Radiology at the University of Texas Southern Medical Center in Dallas. As well as a Distinguished Chair in Systems Biology, at UT-Dallas. Dr. Sherry is also the associate editor of Contrast Media & Molecular Imaging, for John Wiley. Among his many awards, in 2015 he won the Gold Medal Award for the International Society for Magnetic Resonance in Medicine (ISMRM). He currently has 455 publications.