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Hyperpolarized micro-nmr system and methods

A nuclear magnetic resonance, hyperpolarization technique used in the analysis of biological and non-biological samples

Inactive Publication Date: 2019-03-15
MEMORIAL SLOAN KETTERING CANCER CENT
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  • Abstract
  • Description
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  • Application Information

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Problems solved by technology

However, due to its limited sensitivity, this method requires many cells of interest (10 7 orders of magnitude), and the analytical application of DNP-NMR is challenging for a limited number of samples, including primary cancer cells, stem cells, or organoids

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Embodiment Construction

[0142] hyperpolarized micro-magnetic resonance spectrometer

[0143] Figure 1A Fundamental differences in glycolytic metabolism between cancer cells and normal cells are illustrated. Pyruvate, a 3-carbon intermediate of glycolysis, is primarily converted to lactate by lactate dehydrogenase (LDH, EC 1.1.2.4) in the cytoplasm, or by pyruvate dehydrogenase (PDH, EC 1.2.4.1 ) into acetyl-CoA. LDH is often overexpressed in cancer cells, driving the conversion of pyruvate to lactate. In normal cells, pyruvate is oxidized to a greater extent and used for ATP generation in the mitochondria. When [1- 13 C] When pyruvate enters cells directly through monocarboxylate transporters (MCTs), it enters the intracellular pyruvate pool and is metabolized, resulting in higher [1- 13 C] Lactic acid ( Figure 1A with 7 ). Then [1- 13 C] Hyperpolarization of pyruvate provides a means to non-invasively probe the final step of glycolysis through dramatic MR signal enhancement.

[0144] ...

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Abstract

Described herein are micro-coil hyperpolarized NMR systems and methods for measuring metabolic flux in living and non-living samples. Such systems can perform high throughput measurements (with multiple coils) of metabolic flux without destroying the material, making it useful to analyze tumor biopsies, cancer stem cells, and the like. In certain embodiments, a hyperpolarized micromagnetic resonance spectrometer (HMRS), described herein, is used to achieve real-time, significantly more sensitive (e.g., 103-fold more sensitive) metabolic analyses of live cells or non-living samples. In this platform, a suspension mixed with hyperpolarized metabolites is loaded into a miniaturized detection coil (e.g., about 2 [mu]L), where the flux analysis can be completed within a minute without significant changes in viability. The sensitive and rapid analytical capability of the provided systems enables rapid assessment of metabolic changes by a given drug, which may direct therapeutic choices in patients.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to US Application Serial No. 62 / 306,538, filed March 10, 2016, the disclosure of which is incorporated herein by reference in its entirety. technical field [0003] The present invention generally relates to systems and methods for analyzing biological and non-biological samples. In certain embodiments, the invention relates to the detection of metabolic data by a microcoil hyperpolarized nuclear magnetic resonance (NMR) system. [0004] Government funding [0005] This invention was made with government support under grant numbers EB014328 and CA008748 awarded by the National Institutes of Health. The government has certain rights in this invention. Background technique [0006] Metabolic reprogramming is widely recognized as a hallmark of cancer, and understanding the metabolic dynamics described by metabolite turnover rates or "fluxes" can shed light on the biology of tumorigen...

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01R33/30G01R33/465G01N24/08G01R33/28G01R33/36
CPCG01N24/08G01R33/282G01R33/302G01R33/3635G01R33/465G01N24/088G01R33/34092
Inventor 凯文·R·克沙里郑尚武
Owner MEMORIAL SLOAN KETTERING CANCER CENT
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