Vanderbilt-Ingram Cancer Center

The VICC.ORG Investigator Directory

Eduard Y Chekmenev, Ph.D.

Assistant Professor of Radiology and Radiological Sciences
VICC Member

Contact Information:

1161 21st Ave South
AA-1105
Nashville, TN 37232
(615) 322-1329
Fax: (615) 322-0734

Profile

Dr. Chekmenev was recruited to the department of Radiology and the Vanderbilt University Institute of Imaging Science as an Assistant Professor of Radiology and Radiological Sciences at Vanderbilt University in July 2009. He is an expert in the field of hyperpolarized MR tracers and heteronuclear NMR and MRI. He has co-authored more than 30 publications in peer-reviewed scientific journals, several book chapters and patents. Conventional (1H) and heteronuclear (13C, 23Na, 31P, etc.) in vivo MR imaging and spectroscopy provide the scientific and medical communities with a number of biomarkers for various diseases such as cancer, Alzheimer's disease and migraine. This is possible, because MR imaging and spectroscopy of metabolites directly and non-invasively report on metabolic concentrations and fluxes.

His primary research interest is the development of MR conventional and hyperpolarized (i.e. significantly more sensitive) 13C and 15N tracers/biomarkers for real time metabolic molecular imaging on sub-second and second time scale. The National Cancer Institute funds his research efforts for development of hyperpolarized MR tracers to image tumor metabolism in real time. In 2012, he became a recipient of a 5-year Era of Hope Scholar Award from Department of Defense (DOD) Congressionally Directed Breast Cancer Research Program.

Research Description:

The long term goal of our research is to answer the questions about cancer metabolic disorders at molecular, cellular and tissue level and its correlation with genetic disorders and pathology. We focus on development of the predictors (often termed biomarkers) about the patient outcome and response to therapy as early as several minutes after drug administration using real time metabolic imaging. Funded projects (by NIH/NCI and Prevent Cancer Foundation) in our laboratory are conducted in cellular and rodent models of human cancer utilizing Magnetic Resonance Imaging (MRI) and its variant Magnetic Resonance Spectroscopic Imaing (MRSI) modalities. We use MR hyperpolared 13C and 15N labeled metabolic contrast agents to achieve unprecedented spatial resolution and high contrast. The advantage of the hyperpolarization techniques is the increase in MR sensitivity by 10,000-1,000,000 fold, which overcomes previous sensitivity limitations of MRI. Our laboratory at VUIIS currently utilizes parahydrogen gas and commercially availabe hyperpolarized 129Xe gas to hyperpolarize 13C and 15N contrast agents. These contrast agents are non-radioactive and use no ionizing radiation during imaging and enable a new generation of ultrasensitive, ultrafast MR imaging techniques that will be optimized for use in oncology. The persistence of polarization through chemical reactions of biochemical pathways allows sub-second MRI and MRSI examinations in real time whereas current standard of care in oncology PET-CT exam requires long examiation time and expose patients to ionizing radiation. We also hope to address the central issues, necessary for successful introduction of Clinical Trials of non-invasive and non-radioactive hyperpolarized MRSI using injectacble hyperpolarized choline, glutamate, glutamine and succinate and others as in vivo contrast imaging reagents. These biomarkers potentially allow direct imaging of real time metabolic activity of choline kinase (ChoK), succinate dehydrogenase (SDH), etc. as well as indirect imaging of hypoxia inducing factor HIF-1α and other oncogenes. We also work on receptor imaging using hyperpolarized MR, which can be useful for in vivo cancer research as well as for in vitro structural and functional studies of proteins and especially membrane associated proteins. We would like to demonstrate efficacy of hyperpolarized biomarkers for early detection of cancer and response to treatment using sub-second MRI and ultrafast MRSI and demonstrate the advantages of hyperpolarized metabolic tracers in defining tumor growth, heterogeneity and prediction of a positive response to therapy, when compared to conventional MRI and PET-CT.

Ultrafast hyperpolarized MRSI will have far-reaching impact on all areas of oncology in which current imaging technologies are insufficiently precise or insensitive to early diagnosis. We hope not only investigate underlying metabolic events of cancer with real-time metabolic imaging in laboratory setting, but also provide US population with fast, safe low-cost metabolic MR exams in the future that will be useful for population screening and treatment follow-up and would replace or augment ionizing mammography screening and expensive radioactive PET-CT.

Publications:

• Kurhanewicz, J, Vigneron, DB, Brindle, K, Chekmenev, EY, Comment, A, Cunningham, CH, Deberardinis, RJ, Green, GG, Leach, MO, Rajan, SS, Rizi, RR, Ross, BD, Warren, WS, Malloy, CR Analysis of cancer metabolism by imaging hyperpolarized nuclei: prospects for translation to clinical research. Neoplasia, 13(2), 81-97, 2011.
• Waddell, KW, Coffey, AM, Chekmenev, EY In situ detection of PHIP at 48 mT: demonstration using a centrally controlled polarizer. J Am Chem Soc, 133(1), 97-101, 2011.
• Chekmenev, EY, Vollmar, BS, Cotten, M Can antimicrobial peptides scavenge around a cell in less than a second. Biochim Biophys Acta, 1798(2), 228-34, 2010.
• Chekmenev, EY, Norton, VA, Weitekamp, DP, Bhattacharya, P Hyperpolarized (1)H NMR Employing Low gamma Nucleus for Spin Polarization Storage. J Am Chem Soc, 131(9), 3164-5, 2009.
• Hoevener, JB, Chekmenev, EY, Harris, KC, Perman, WH, Robertson, LW, Ross, BD, Bhattacharya, P PASADENA hyperpolarization of 13C biomolecules: equipment design and installation. MAGMA, 22(2), 111-21, 2009.
• Hoevener, JB, Chekmenev, EY, Harris, KC, Perman, WH, Tran, TT, Ross, BD, Bhattacharya, P Quality assurance of PASADENA hyperpolarization for 13C biomolecules. MAGMA, 22(2), 123-34, 2009.
• Lisitza, N, Muradian, I, Frederick, E, Patz, S, Hatabu, H, Chekmenev, EY Toward 13C hyperpolarized biomarkers produced by thermal mixing with hyperpolarized 129Xe. J Chem Phys, 131(4), 044508, 2009.
• Chekmenev, EY, Bhattacharya, P, Ross, BD Development of Hyperpolarized Metabolic Contrast Agents using PASADENA. Cambridge Isotope Laboratories, Application Note#21, 2008.
• Chekmenev, EY, Chow, SK, Tofan, D, Weitekamp, DP, Ross, BD, Bhattacharya, P Fluorine-19 NMR chemical shift probes molecular binding to lipid membranes. J Phys Chem B, 112(20), 6285-7, 2008.
• Chekmenev, EY, Hoevener, J, Norton, VA, Harris, K, Batchelder, LS, Bhattacharya, P, Ross, BD, Weitekamp, DP PASADENA hyperpolarization of succinic acid for MRI and NMR spectroscopy. J Am Chem Soc, 130(13), 4212-3, 2008.
• Gor''kov, PL, Witter, R, Chekmenev, EY, Nozirov, F, Fu, R, Brey, WW Low-E probe for (19)F-(1)H NMR of dilute biological solids. J Magn Reson, 189(2), 182-9, 2007.
• Bhattacharya, P, Chekmenev, EY, Perman, WH, Harris, KC, Lin, AP, Norton, VA, Tan, CT, Ross, BD, Weitekamp, DP Towards hyperpolarized (13)C-succinate imaging of brain cancer. J Magn Reson, 186(1), 150-5, 2007.
• Gor''kov, PL, Chekmenev, EY, Li, C, Cotten, M, Buffy, JJ, Traaseth, NJ, Veglia, G, Brey, WW Using low-E resonators to reduce RF heating in biological samples for static solid-state NMR up to 900 MHz. J Magn Reson, 185(1), 77-93, 2007.
• Gor''kov, PL, Chekmenev, EY, Fu, R, Hu, J, Cross, TA, Cotten, M, Brey, WW A large volume flat coil probe for oriented membrane proteins. J Magn Reson, 181(1), 9-20, 2006.
• Li, C, Mo, Y, Hu, J, Chekmenev, E, Tian, C, Gao, FP, Fu, R, Gor''kov, P, Brey, W, Cross, TA Analysis of RF heating and sample stability in aligned static solid-state NMR spectroscopy. J Magn Reson, 180(1), 51-7, 2006.
• Hu, J, Chekmenev, EY, Cross, TA Anisotropic Chemical Shift Perturbation Induced by Ions in Conducting Channels. Modern Magnetic Resonance, 3279-283, 2006.
• Chekmenev, EY, Gor''kov, PL, Cross, TA, Alaouie, AM, Smirnov, AI Flow-through lipid nanotube arrays for structure-function studies of membrane proteins by solid-state NMR spectroscopy. Biophys J, 91(8), 3076-84, 2006.
• Chekmenev, EY, Jones, SM, Nikolayeva, YN, Vollmar, BS, Wagner, TJ, Gor''kov, PL, Brey, WW, Manion, MN, Daugherty, KC, Cotten, M High-field NMR studies of molecular recognition and structure-function relationships in antimicrobial piscidins at the water-lipid bilayer interface. J Am Chem Soc, 128(16), 5308-9, 2006.
• Chekmenev, EY, Vollmar, BS, Forseth, KT, Manion, MN, Jones, SM, Wagner, TJ, Endicott, RM, Kyriss, BP, Homem, LM, Pate, M, He, J, Raines, J, Gor''kov, PL, Brey, WW, Mitchell, DJ, Auman, AJ, Ellard-Ivey, MJ, Blazyk, J, Cotten, M Investigating molecular recognition and biological function at interfaces using piscidins, antimicrobial peptides from fish. Biochim Biophys Acta, 1758(9), 1359-72, 2006.
• Chekmenev, EY, Waddell, KW, Hu, J, Gan, Z, Wittebort, RJ, Cross, TA Ion-binding study by 17O solid-state NMR spectroscopy in the model peptide Gly-Gly-Gly at 19.6 T. J Am Chem Soc, 128(30), 9849-55, 2006.
• Waddell, KW, Chekmenev, EY, Wittebort, RJ Peptide 17O chemical shielding and electric field gradient tensors. J Phys Chem B, 110(45), 22935-41, 2006.
• Buffy, JJ, Traaseth, NJ, Mascioni, A, Gor''kov, PL, Chekmenev, EY, Brey, WW, Veglia, G Two-dimensional solid-state NMR reveals two topologies of sarcolipin in oriented lipid bilayers. Biochemistry, 45(36), 10939-46, 2006.
• Chekmenev, EY, Hu, J, Gor''kov, PL, Brey, WW, Cross, TA, Ruuge, A, Smirnov, AI 15N and 31P solid-state NMR study of transmembrane domain alignment of M2 protein of influenza A virus in hydrated cylindrical lipid bilayers confined to anodic aluminum oxide nanopores. J Magn Reson, 173(2), 322-7, 2005.
• Hu, J, Chekmenev, EY, Gan, Z, Gor''kov, PL, Saha, S, Brey, WW, Cross, TA Ion solvation by channel carbonyls characterized by 17O solid-state NMR at 21 T. J Am Chem Soc, 127(34), 11922-3, 2005.
• Waddell, KW, Chekmenev, EY, Wittebort, RJ Single-crystal studies of peptide prolyl and glycyl 15N shielding tensors. J Am Chem Soc, 127(25), 9030-5, 2005.
• Fu, R, Brey, WW, Shetty, K, Gor''kov, P, Saha, S, Long, JR, Grant, SC, Chekmenev, EY, Hu, J, Gan, Z, Sharma, M, Zhang, F, Logan, TM, Brüschweller, R, Edison, A, Blue, A, Dixon, IR, Markiewicz, WD, Cross, TA Ultra-wide bore 900 MHz high-resolution NMR at the National High Magnetic Field Laboratory. J Magn Reson, 177(1), 1-8, 2005.
• Chekmenev, EY, Zhang, Q, Waddell, KW, Mashuta, MS, Wittebort, RJ 15N Chemical shielding in glycyl tripeptides: measurement by solid-state NMR and correlation with X-ray structure. J Am Chem Soc, 126(1), 379-84, 2004.
• Pometun, MS, Chekmenev, EY, Wittebort, RJ Quantitative observation of backbone disorder in native elastin. J Biol Chem, 279(9), 7982-7, 2004.
• Fan, T. W. M. ; Lane, A. N. ; Chekmenev, E. ; Wittebort, R. J. ; Higashi, R. M. Synthesis and physico-chemical properties of peptides in soil humic substances. J. Peptide Res., 63(3), 253-264, 2004.
• Zhang, Q, Chekmenev, EY, Wittebort, RJ 17O quadrupole coupling and chemical shielding tensors in an H-bonded carboxyl group: alpha-oxalic acid. J Am Chem Soc, 125(30), 9140-6, 2003.
• Chekmenev, EY, Xu, RZ, Mashuta, MS, Wittebort, RJ Glycyl C(alpha) chemical shielding in tripeptides: measurement by solid-state NMR and correlation with X-ray structure and theory. J Am Chem Soc, 124(40), 11894-9, 2002.

Education

• Perm State University, Perm, Russia, BS, 1998 (Chemistry)
• University of Louisville, Louisville, KY, MS, 2002 (Chemistry)
• University of Louisville, Louisville, KY, PhD, 2003 (Chemistry)
• National High Magnetic Field lab, Tallahassee, FL Postdoc, 2003-2005 (NMR in biophysics)
• Huntington Med. Res. Institutes, Pasadena, CA, Postdoc (2006), (Hyperpolarized MRI)
• California Institute of Technology, Pasadena, CA, Postdoc, 2007-2009 (Hyperpolarized MRI)
• Huntington Med. Res. Institutes, Pasadena, CA, Postdoc, 2008-2009 (Hyperpolarized MRI)