Zoltan Kovacs, Ph.D.
Zoltan Kovacs, Ph.D., specializes in the design and synthesis of novel agents for magnetic resonance imaging and radiopharmaceutical applications.
One major current emphasis of Dr. Kovacs’ work is generating hyperpolarized compounds for magnetic resonance spectroscopy (MRS) and imaging (MRI). Conventional MRI is not well suited for imaging the distribution of molecules in living tissue and for tracing metabolic pathways because of its inherently low sensitivity. The technology of supercharging the nuclear spin of molecules, called dynamic nuclear polarization (DNP) can dramatically increase the sensitivity of MRS and MRI analysis.
Dr. Kovacs is designing hyperpolarized 13C-labeled compounds that can be used as tracers to analyze the flux of molecules through metabolic pathways in healthy and diseased tissues. While 13C labeled substrates can directly enter the metabolic processes, their application is limited by rapid loss of spin polarization, called T1 relaxation, ranging from few seconds to a couple of minutes. Dr. Kovacs is developing tracer molecules based on the nonradioactive isotope yttrium-89, which can have a relaxation time of up to ten minutes. Dr. Kovacs is developing various hyperpolarized 89Y-containing complexes that could be used to measure physiological parameters such as pH, temperature, and the oxidation/reduction state of molecules. For example, Dr. Kovacs and his colleagues are exploring an 89Yttrium-complex of the ligand dioctyl terephthalate (DOTP) that can measure pH in the range relevant for living tissues.
Dr. Kovacs and his colleagues are also synthesizing new molecules that can attach to isotopes of metals in the lanthanide family for use in MRI, nuclear, and optical imaging. These isotope-containing molecules can also used as radiopharmaceuticals, which target cancers with radioactive isotopes.
He is also collaborating with biochemist Paul Blount, Ph.D., to develop responsive or “smart” MRI probes that can selectively target tissues to render them visible in MRI scans. These probes consist of liposomes, loaded with MRI contrast-enhancing lanthanide compounds. Liposomes are self assembled lipid bilayer vesicles with an aqueous core. They are excellent drug carriers because they are intrinsically biocompatible, and various drug molecules can easily be loaded in the core. The researchers use a modified mechanosensitive bacterial channel (MscL) as a nanovalve to control the water exchange through the lipid bilayer. Designed to open and close in response to a stimulus, the nanovalve will regulate the water exchange rate through the lipid bilayer and thereby alter the MRI image contrast. Since many cancerous tumors have an acidic microenvironment, Dr. Blount and Dr. Kovacs concentrate on generating a nanosystem in which this process will eventually be modulated by pH. The potential biomedical applications of such nanomachines could range from smart imaging agents to multifunctional devices that combine diagnostics and therapeutics.
For publication information please view Dr. Kovacs' faculty profile.