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Imaging agents and methods of use thereof

Inactive Publication Date: 2010-04-15
HUNTINGTON MEDICAL RES INST
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

The in vivo study of metabolism with 1H, 13C or 15N NMR by previous methods has been possible only with little or no spatial localization and prolonged signal averaging that largely precludes the study of dynamics and is severely limited by cost.
However, in biology, NMR spectroscopy has yet to reach its full potential for the simple reason of time limitation associated with high number of transients required to obtain sufficient SNR under the biological constraints of low concentration, physiological temperature, and high dielectric losses.

Method used

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  • Imaging agents and methods of use thereof
  • Imaging agents and methods of use thereof
  • Imaging agents and methods of use thereof

Examples

Experimental program
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Effect test

example 1

In Vivo 13C PASADENA Imaging

[0046]Utilizing a PASADENA polarizer, the inventors injected hyperpolarized 13C-molecules in rats. Transmitting at the 13C-frequency, images were acquired using TrueFISP pulse sequences, 3D FIESTA (acronyms for transient versions of so-called steady state free procession image sequences) and fast CSI (chemical shift imaging) sequences. Examples of 13C images acquired utilizing PASADENA hyperpolarization (FIGS. 3-4) were produced using 13C-labeled hydroxyethyl acrylate which on hydrogenation forms hydroxyethyl propionate.

[0047]Sub-second carbon imaging is greatly simplified when the signal of interest exceeds the background signal from natural abundance resonances. This is possible when a 13C hyperpolarized agent is injected. Substantially enhanced images can be acquired during an interval several times the T1 of 13C polarization. Long T1 (in excess of ten seconds) is obtained for 13C in small molecules at sites where there is no directly attached proton. ...

example 2

In Vivo Spectroscopy

[0051]The inventors have used 13C labeled isotopes of intrinsic biological molecules, such as glucose, which are metabolized in the body via the TCA cycle that can be tracked with MR spectroscopy. This allows the elucidation of biochemical processes such as glutamate neurotransmission and metabolite synthesis rates in vivo. However, based on the Boltzmann distribution, 13C NMR suffers from inherently low SNR, requiring the use of lengthy pulse sequences which limits its use due to heat deposition and the instability of the subjects over literally hours of scan time. This is where hyperpolarization demonstrates strong potential. The low SNR issues are overcome by polarizations up to 26,000 times greater SNR as demonstrated above. One of the challenges of hyperpolarized imaging is the need for fast spectroscopy sequences due to the fast relaxation of the hyperpolarized signal. Therefore the inventors developed fast chemical shift imaging techniques that allow for t...

example 3

Identifying Hyperpolarization Precursors

[0053]PASADENA: Directed synthesis of PASADENA precursor molecules, suitably enriched with 13C, provides nontoxic tracking reagents with known desired biological properties, including in some cases intracellular transport and metabolism. New reagents may be necessary for the versatile implementation of PASADENA imaging and spectroscopy. Identifying molecules to introduce parahydrogen in biological systems is a feature of the invention.

[0054]The PASADENA precursors may have at least one of the following features: (1) an unsaturated bond suitable for hydrogenation by molecular addition; (2) a hydrogenation reaction with a time scale that is shorter than the low-field singlet state relaxation times (typically tens of seconds) of the nascent protons on intermediates and products; (3) an isotopically-enriched 13C site with scalar coupling to the added protons; (4) water solubility and low toxicity; (5) an ability to be introduced into a specific bi...

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Abstract

Compositions and methods useful in connection with magnetic resonance imaging are provided. Metabolites hyperpolarized by dynamic nuclear polarization are used as reporter molecules in nuclear magnetic resonance (“NMR”) spectroscopy to study metabolic pathways and diagnose disease states. The reporter molecules include hyperpolarized glutamine and hyperpolarized acetate. The invention includes the reporter molecules, compositions including the reporter molecules in pharmaceutically acceptable carriers, methods for studying metabolic pathways that include introducing one or more of the reporter molecules to a mammalian subject and imaging a target substance using NMR spectroscopy, and kits useful in studying metabolic pathways that incorporate one or more of the reporter molecules and instructions for their use.

Description

FIELD OF INVENTION[0001]The invention relates to compositions and methods useful in connection with magnetic resonance imaging. In particular, the invention relates to Dynamic Nuclear Polarization (“DNP”) hyperpolarization of metabolites for nuclear magnetic resonance (“NMR”) spectroscopy and magnetic resonance imaging (“MRI”).BACKGROUND OF THE INVENTION[0002]Magnetic resonance (“MR”) imaging has become a well-accepted and commonly-used technique for studying a wide range of physiologic processes. This technology is useful in connection with disease diagnosis and prognosis, and in the broader study of biological systems. Indeed, many hospitals and medical facilities have MR imaging equipment on-site, and routinely make use of it to aid in the diagnosis and monitoring of an array of diseases and physiologic conditions. Contrast agents or reporter molecules are used in connection with MR imaging, and a wide range of products is commercially available to image various systems. Along th...

Claims

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Application Information

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IPC IPC(8): A61K49/10C07C229/26C07C69/02
CPCA61K49/10G01N24/08G01R33/5601G01R33/4608G01R33/4806G01R33/282
Inventor ROSS, BRIAN D.BHATTACHARYA, PRATIP
Owner HUNTINGTON MEDICAL RES INST
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