Profile

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

The following timeline graph is generated from all co-authored publications.

Featured publications are shown below:

1. Propane- Heterogeneously Hyperpolarized by Parahydrogen. Kovtunov KV, Truong ML, Barskiy DA, Salnikov OG, Bukhtiyarov VI, Coffey AM, Waddell KW, Koptyug IV, Chekmenev EY (2014) J Phys Chem C Nanomater Interfaces 118(48): 28234-28243
   › Primary publication · 25506406 (PubMed) · PMC4259496 (PubMed Central)
2. NMR hyperpolarization techniques for biomedicine. Nikolaou P, Goodson BM, Chekmenev EY (2015) Chemistry 21(8): 3156-66
   › Primary publication · 25470566 (PubMed) · PMC4418426 (PubMed Central)
3. Irreversible catalyst activation enables hyperpolarization and water solubility for NMR signal amplification by reversible exchange. Truong ML, Shi F, He P, Yuan B, Plunkett KN, Coffey AM, Shchepin RV, Barskiy DA, Kovtunov KV, Koptyug IV, Waddell KW, Goodson BM, Chekmenev EY (2014) J Phys Chem B 118(48): 13882-9
   › Primary publication · 25372972 (PubMed) · PMC4259498 (PubMed Central)
4. LIGHT-SABRE enables efficient in-magnet catalytic hyperpolarization. Theis T, Truong M, Coffey AM, Chekmenev EY, Warren WS (2014) J Magn Reson : 23-6
   › Primary publication · 25299767 (PubMed) · PMC6097635 (PubMed Central)
5. Sodium 3D COncentration MApping (COMA 3D) using (23)Na and proton MRI. Truong ML, Harrington MG, Schepkin VD, Chekmenev EY (2014) J Magn Reson : 88-95
   › Primary publication · 25261742 (PubMed) · PMC4198170 (PubMed Central)
6. Inhalable curcumin: offering the potential for translation to imaging and treatment of Alzheimer's disease. McClure R, Yanagisawa D, Stec D, Abdollahian D, Koktysh D, Xhillari D, Jaeger R, Stanwood G, Chekmenev E, Tooyama I, Gore JC, Pham W (2015) J Alzheimers Dis 44(1): 283-95
   › Primary publication · 25227316 (PubMed) · PMC4297252 (PubMed Central)
7. Synthetic approach for unsaturated precursors for parahydrogen induced polarization of choline and its analogs. Shchepin RV, Chekmenev EY (2013) J Labelled Comp Radiopharm 56(13): 655-62
   › Primary publication · 25196027 (PubMed) · PMC4159776 (PubMed Central)
8. High-resolution low-field molecular magnetic resonance imaging of hyperpolarized liquids. Coffey AM, Kovtunov KV, Barskiy DA, Koptyug IV, Shchepin RV, Waddell KW, He P, Groome KA, Best QA, Shi F, Goodson BM, Chekmenev EY (2014) Anal Chem 86(18): 9042-9
   › Primary publication · 25162371 (PubMed) · PMC4165454 (PubMed Central)
9. Toward hyperpolarized molecular imaging of HIV: synthesis and longitudinal relaxation properties of (15) N-Azidothymidine. Shchepin RV, Chekmenev EY (2014) J Labelled Comp Radiopharm 57(10): 621-4
   › Primary publication · 25156931 (PubMed) · PMC4287256 (PubMed Central)
10. Temperature-ramped (129)Xe spin-exchange optical pumping. Nikolaou P, Coffey AM, Barlow MJ, Rosen MS, Goodson BM, Chekmenev EY (2014) Anal Chem 86(16): 8206-12
    › Primary publication · 25008290 (PubMed) · PMC4139178 (PubMed Central)
11. Dephosphorylation and biodistribution of 1-¹³C-phospholactate in vivo. Shchepin RV, Pham W, Chekmenev EY (2014) J Labelled Comp Radiopharm 57(8): 517-24
    › Primary publication · 24995802 (PubMed) · PMC4287379 (PubMed Central)
12. Heterogeneous solution NMR signal amplification by reversible exchange. Shi F, Coffey AM, Waddell KW, Chekmenev EY, Goodson BM (2014) Angew Chem Int Ed Engl 53(29): 7495-8
    › Primary publication · 24889730 (PubMed) · PMC6284233 (PubMed Central)
13. Sub-second proton imaging of 13C hyperpolarized contrast agents in water. Truong ML, Coffey AM, Shchepin RV, Waddell KW, Chekmenev EY (2014) Contrast Media Mol Imaging 9(5): 333-41
    › Primary publication · 24753438 (PubMed) · PMC4198480 (PubMed Central)
14. Parahydrogen induced polarization of 1-(13)C-phospholactate-d(2) for biomedical imaging with >30,000,000-fold NMR signal enhancement in water. Shchepin RV, Coffey AM, Waddell KW, Chekmenev EY (2014) Anal Chem 86(12): 5601-5
    › Primary publication · 24738968 (PubMed) · PMC4063326 (PubMed Central)
15. Multidimensional mapping of spin-exchange optical pumping in clinical-scale batch-mode 129Xe hyperpolarizers. Nikolaou P, Coffey AM, Ranta K, Walkup LL, Gust BM, Barlow MJ, Rosen MS, Goodson BM, Chekmenev EY (2014) J Phys Chem B 118(18): 4809-16
    › Primary publication · 24731261 (PubMed) · PMC4055050 (PubMed Central)
16. XeNA: an automated 'open-source' (129)Xe hyperpolarizer for clinical use. Nikolaou P, Coffey AM, Walkup LL, Gust BM, Whiting N, Newton H, Muradyan I, Dabaghyan M, Ranta K, Moroz GD, Rosen MS, Patz S, Barlow MJ, Chekmenev EY, Goodson BM (2014) Magn Reson Imaging 32(5): 541-50
    › Primary publication · 24631715 (PubMed) · PMC4011489 (PubMed Central)
17. The feasibility of formation and kinetics of NMR signal amplification by reversible exchange (SABRE) at high magnetic field (9.4 T). Barskiy DA, Kovtunov KV, Koptyug IV, He P, Groome KA, Best QA, Shi F, Goodson BM, Shchepin RV, Coffey AM, Waddell KW, Chekmenev EY (2014) J Am Chem Soc 136(9): 3322-5
    › Primary publication · 24528143 (PubMed) · PMC3985893 (PubMed Central)

Keywords & MeSH Terms

MeSH terms are retrieved from PubMed records. Learn more.

Key: MeSH Term Keyword

Alzheimer Disease Anti-Infective Agents Calcium-Transporting ATPases Calibration Cations, Monovalent chemistry and spin physics of hyperpolarized metabolic MRI tracers in biomedical research. Real time metabolic imaging of breast cancer using hyperpolarized MRI tracers. Computer-Aided Design Crystallization Curcumin Equipment Design Feasibility Studies Female Hydrophobic and Hydrophilic Interactions Influenza A virus Instrumentation Membrane Proteins Mice, Transgenic Molecular Dynamics Simulation Muscle Proteins Niacinamide Nitrogen Isotopes Nuclear Magnetic Resonance, Biomolecular Phosphatidylcholines Phosphatidylglycerols Proline Putrescine Quality Assurance, Health Care Rats, Sprague-Dawley Sodium Chloride Spectrum Analysis Spin Labels Zidovudine