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  • Detection of Metabolic Changes using Hyperpolarized C-13 MRI in a Negative F-18-FDG PET Rat Brain Cancer Model Lauritzen, M., Datta, K., Merchant, M., Jang, T., Hurd, R., Liu, S., Recht, L., Spielman, D. SOC NUCLEAR MEDICINE INC. 2019
  • Reversed metabolic reprogramming as a measure of cancer treatment efficacy in rat C6 glioma model. PloS one Datta, K., Lauritzen, M. H., Merchant, M., Jang, T., Liu, S. C., Hurd, R., Recht, L., Spielman, D. M. 2019; 14 (12): e0225313

    Abstract

    Metabolism in tumor shifts from oxidative phosphorylation to inefficient glycolysis resulting in overproduction of lactate (Warburg effect), and cancers may be effectively treated if this imbalance were corrected. The aim of this longitudinal study of glioblastoma in a rat model was to determine whether the ratio of lactate (surrogate marker for glycolysis) to bicarbonate (for oxidative phosphorylation), as measured via in vivo magnetic resonance imaging of hyperpolarized 13C-labeled pyruvate accurately predicts survival.C6 Glioma implanted male Wistar rats (N = 26) were treated with an anti-vascular endothelial growth factor antibody B20.4.1.1 in a preliminary study to assess the efficacy of the drug. In a subsequent longitudinal survival study, magnetic resonance spectroscopic imaging (MRSI) was used to estimate [1-13C]Lactate and [1-13C]Bicarbonate in tumor and contralateral normal appearing brain of glioma implanted rats (N = 13) after injection of hyperpolarized [1-13C]Pyruvate at baseline and 48 hours post-treatment with B20.4.1.1.A survival of ~25% of B20.4.1.1 treated rats was noted in the preliminary study. In the longitudinal imaging experiment, changes in 13C Lactate, 13C Bicarbonate and tumor size measured at baseline and 48 hours post-treatment did not correlate with survival. 13C Lactate to 13C Bicarbonate ratio increased in all the 6 animals that succumbed to the tumor whereas the ratio decreased in 6 of the 7 animals that survived past the 70-day observation period.13C Lactate to 13C Bicarbonate ratio (Lac/Bic) at 48 hours post-treatment is highly predictive of survival (p = 0.003). These results suggest a potential role for the 13C Lac/Bic ratio serving as a valuable measure of tumor metabolism and predicting therapeutic response.

    View details for DOI 10.1371/journal.pone.0225313

    View details for PubMedID 31830049

  • Hyperpolarized Sodium [1-C-13]-Glycerate as a Probe for Assessing Glycolysis In Vivo JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Park, J., Wu, M., Datta, K., Liu, S., Castillo, A., Lough, H., Spielman, D. M., Billingsley, K. L. 2017; 139 (19): 6629?34

    Abstract

    Hyperpolarized 13C magnetic resonance spectroscopy (MRS) provides unprecedented opportunities to obtain clinical diagnostic information through in vivo monitoring of metabolic pathways. The continuing advancement of this field relies on the identification of molecular probes that can effectively interrogate pathways critical to disease. In this report, we describe the synthesis, development, and in vivo application of sodium [1-13C]-glycerate ([13C]-Glyc) as a novel probe for evaluating glycolysis using hyperpolarized 13C MRS. This agent was prepared by a concise synthetic route and formulated for dynamic nuclear polarization. [13C]-Glyc displayed a high level of polarization and long spin-lattice relaxation time-both of which are necessary for future clinical investigations. In vivo spectroscopic studies with hyperpolarized [13C]-Glyc in rat liver furnished metabolic products, [13C]-labeled pyruvate and lactate, originating from glycolysis. The levels of production and relative intensities of these metabolites were directly correlated with the induced glycolytic state (fasted versus fed groups). This work establishes hyperpolarized [13C]-Glyc as a novel agent for clinically relevant 13C MRS studies of energy metabolism and further provides opportunities for evaluating intracellular redox states in biochemical investigations.

    View details for PubMedID 28467066

  • Doublet asymmetry for estimating polarization in hyperpolarized C-13-pyruvate studies NMR IN BIOMEDICINE Datta, K., Spielman, D. M. 2017; 30 (2)

    Abstract

    Hyperpolarized (13) C MRS allows in vivo interrogation of key metabolic pathways, with pyruvate (Pyr) the substrate of choice for current clinical studies. Knowledge of the liquid-state polarization is needed for full quantitation, and asymmetry of the C2 doublet, arising from 1% naturally abundant [1,2-(13) C]Pyr in any hyperpolarized [1-(13) C]Pyr sample, has been suggested as a direct measure of in vivo C1 polarization via the use of an in vitro calibration curve. Here we show that different polarization levels can yield the same C2 -doublet asymmetry, thus limiting the utility of this metric for quantitation. Furthermore, although the time evolution of doublet asymmetry is poorly modeled using the expected dominant relaxation mechanisms of carbon-proton dipolar coupling and chemical shift anisotropy, the inclusion of a C-C dipolar coupling term can explain the observed initial evolution of the C2 doublet asymmetry beyond its expected thermal equilibrium value.

    View details for DOI 10.1002/nbm.3670

    View details for Web of Science ID 000397274200003

    View details for PubMedCentralID PMC5330392

  • C-pyruvate studies. NMR in biomedicine Datta, K., Spielman, D. M. 2017; 30 (2)

    Abstract

    Hyperpolarized (13) C MRS allows in vivo interrogation of key metabolic pathways, with pyruvate (Pyr) the substrate of choice for current clinical studies. Knowledge of the liquid-state polarization is needed for full quantitation, and asymmetry of the C2 doublet, arising from 1% naturally abundant [1,2-(13) C]Pyr in any hyperpolarized [1-(13) C]Pyr sample, has been suggested as a direct measure of in vivo C1 polarization via the use of an in vitro calibration curve. Here we show that different polarization levels can yield the same C2 -doublet asymmetry, thus limiting the utility of this metric for quantitation. Furthermore, although the time evolution of doublet asymmetry is poorly modeled using the expected dominant relaxation mechanisms of carbon-proton dipolar coupling and chemical shift anisotropy, the inclusion of a C-C dipolar coupling term can explain the observed initial evolution of the C2 doublet asymmetry beyond its expected thermal equilibrium value.

    View details for DOI 10.1002/nbm.3670

    View details for PubMedID 28004867

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