Dataset Information

First hyperpolarized [2-¹³C]pyruvate MR studies of human brain metabolism.

ABSTRACT: We developed methods for the preparation of hyperpolarized (HP) sterile [2-¹³C]pyruvate to test its feasibility in first-ever human NMR studies following FDA-IND & IRB approval. Spectral results using this MR stable-isotope imaging approach demonstrated the feasibility of investigating human cerebral energy metabolism by measuring the dynamic conversion of HP [2-¹³C]pyruvate to [2-¹³C]lactate and [5-¹³C]glutamate in the brain of four healthy volunteers. Metabolite kinetics, signal-to-noise (SNR) and area-under-curve (AUC) ratios, and calculated [2-¹³C]pyruvate to [2-¹³C]lactate conversion rates (k_PL) were measured and showed similar but not identical inter-subject values. The k_PL measurements were equivalent with prior human HP [1-¹³C]pyruvate measurements.

SUBMITTER: Chung BT

PROVIDER: S-EPMC6880930 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

First hyperpolarized [2-13C]pyruvate MR studies of human brain metabolism.

Chung Brian T BT Chen Hsin-Yu HY Gordon Jeremy J Mammoli Daniele D Sriram Renuka R Autry Adam W AW Le Page Lydia M LM Chaumeil Myriam M MM Shin Peter P Slater James J Tan Chou T CT Suszczynski Chris C Chang Susan S Li Yan Y Bok Robert A RA Ronen Sabrina M SM Larson Peder E Z PEZ Kurhanewicz John J Vigneron Daniel B DB

Journal of magnetic resonance (San Diego, Calif. : 1997) 20191008

We developed methods for the preparation of hyperpolarized (HP) sterile [2-13C]pyruvate to test its feasibility in first-ever human NMR studies following FDA-IND & IRB approval. Spectral results using this MR stable-isotope imaging approach demonstrated the feasibility of investigating human cerebral energy metabolism by measuring the dynamic conversion of HP [2-13C]pyruvate to [2-13C]lactate and [5-13C]glutamate in the brain of four healthy volunteers ...[more]

PMID: 31648132

Similar Datasets

Project description:The detection and treatment monitoring of inflammatory states remain challenging in part due to the multifactorial mechanisms of immune activation and spectrum of clinical manifestations. Currently, diagnostic strategies tend to be subjective and limited quantitative tools exist to monitor optimal treatment strategies. Pro-inflammatory M1 polarized macrophages exhibit a distinct metabolic glycolytic phenotype compared to the continuum of M2 polarization states. In the present study, the distinct metabolic phenotypes of resting and activated macrophages were successfully characterized and quantified using hyperpolarized carbon-13 (13C) labeled pyruvate and its metabolic products, i.e. lactate, as a biomarker of resting, disease and treated states. Methods: Mouse macrophage J774A.1 cells were used as a model system in an NMR compatible bioreactor to facilitate dynamic hyperpolarized 13C measurements. The glycolytic metabolism of the cells in the quiescent or resting state were compared with macrophages stimulated by lipopolysaccharide, a classical M1 activator using hyperpolarized 13C labeled pyruvate. Additionally, the activated macrophages were also treated with a non-steroidal anti-inflammatory drug to assess the changes in hyperpolarized lactate signal. The hyperpolarized lactate signals were then correlated using biochemical and molecular assays. Results: We first validated our model system of inflammatory cells by the hallmarks of M1 polarization using steady state metabolic profiling with high resolution NMR in conjunction with nitric oxide Greiss assay, enzyme activity, and mRNA expression. Subsequently, we clearly showed that the cutting edge technology of hyperpolarized 13C NMR can be used to detect elevated lactate levels in M1 polarized macrophages in comparison to control and non-steroidal anti-inflammatory drug treated M2 states. Conclusion: Hyperpolarized 13C lactate has the potential to serve as a biomarker to non-invasively detect and quantify pro-inflammatory state of immune regulatory cells and its response to therapy.

Dataset Information

First hyperpolarized [2-¹³C]pyruvate MR studies of human brain metabolism.

Publications

First hyperpolarized [2-<sup>13</sup>C]pyruvate MR studies of human brain metabolism.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure