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Dissolution Dynamic Nuclear Polarization Instrumentation for Real-time Enzymatic Reaction Rate Measurements by NMR

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Published on: February 23, 2016

Exchange-linked dissolution agents in dissolution-DNP (13)C metabolic imaging.

Ralph E Hurd¹, Daniel Spielman, Sonal Josan

¹GE Healthcare, California, USA.

Magnetic Resonance in Medicine

|November 21, 2012

Summary

Unlabeled agents in hyperpolarized metabolic imaging enhance [1-(13)C]lactate signals by increasing pool sizes. This indicates that labeling rates are limited by in vivo steady-state metabolite availability.

Keywords:

13C dissolution‐DNP hyperpolarized metabolic imaging

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Area of Science:

Metabolic imaging
Hyperpolarized contrast agents
In vivo studies

Background:

Hyperpolarized metabolic imaging offers real-time insights into cellular metabolism.
Understanding pool size limitations is crucial for optimizing imaging agent efficacy.
Nicotinamide adenine dinucleotide (NADH) availability influences metabolic pathways.

Purpose of the Study:

To investigate the impact of unlabeled exchange-linked dissolution agents on hyperpolarized metabolic imaging.
To determine pool size limits and saturation effects relative to NADH availability.
To assess the influence of unlabeled sodium lactate and pyruvate on metabolic signal enhancement.

Main Methods:

Acquisition of 3D dynamic metabolic images after injecting hyperpolarized [1-(13)C]pyruvate or [1-(13)C]lactate.
Comparison of apparent rate constants and [1-(13)C]lactate signal-to-noise ratios with and without unlabeled agents.
Evaluation of isotope exchange in both forward (pyruvate to lactate) and reverse (lactate to pyruvate) directions.

Main Results:

Addition of unlabeled sodium lactate significantly increased [1-(13)C]lactate signal in liver, kidney, and vascular regions.
Injection of hyperpolarized [1-(13)C]lactate with unlabeled sodium pyruvate yielded exchange rate constants (Klp) in kidney and vascular regions.
Observed signal enhancements suggest effective utilization of exchange-linked agents.

Conclusions:

Results support significant (13)C-exchange between pyruvate and lactate pools.
Labeling rates in hyperpolarized metabolic imaging appear to be constrained by in vivo steady-state pool sizes.
Unlabeled agents can effectively modulate metabolic signals, aiding in the assessment of metabolic dynamics.