Hyperpolarized Substrate Precipitation for Biocompatible SABRE Solutions
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Solution Overview
Problem
Current methods for producing hyperpolarized [1-13C]pyruvate using SABRE are limited by the use of toxic solvents and catalysts, making them unsuitable for direct biomedical applications, and there is a need for cost-effective and safe preparation of hyperpolarized contrast agents for clinical use.
Innovation Solution
A method involving precipitation of hyperpolarized substrates from toxic solvents using non-polar organic solvents, followed by filtration and redissolution in biocompatible solvents, utilizing Signal Amplification by Reversible Exchange (SABRE) for hyperpolarization.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If SABRE hyperpolarization is performed using traditional solvents and catalysts, then high polarization efficiency is achieved, but the solution becomes toxic and unsuitable for biomedical applications
Solution Approach 1:
The patent extracts and removes the toxic components (traditional solvents and catalysts) from the hyperpolarization system by performing the SABRE reaction in water, thereby eliminating harmful factors while preserving the hyperpolarization efficiency
Solution Approach 2:
The patent changes the fundamental parameter of the solvent system from organic solvents to water, and adjusts catalyst composition to water-compatible formulations, enabling non-toxic hyperpolarized contrast agent production while maintaining high polarization efficiency
2Object-affected harmful factors
If d-DNP technique is used for hyperpolarization, then high polarization is achieved, but the instrumentation cost and complexity increase significantly
Solution Approach 1:
The patent replaces expensive, complex d-DNP instrumentation with simpler, more affordable SABRE-based hyperpolarization equipment that can achieve comparable signal enhancement, making the technology accessible and cost-effective for clinical use
Solution Approach 2:
The patent substitutes the complex mechanical and cryogenic system of d-DNP with the chemically-based SABRE approach, eliminating the need for superconducting magnets and cryogenic operation while achieving similar or superior hyperpolarization effects
3Object-affected harmful factors
If d-DNP method is employed, then hyperpolarized contrast agents can be produced, but the hyperpolarization time becomes excessively long
Solution Approach 1:
The patent performs preliminary preparation of water-soluble substrates and catalysts before the hyperpolarization step, enabling the SABRE reaction to proceed rapidly in aqueous solution without the time-consuming steps required by d-DNP, thereby achieving fast hyperpolarization suitable for clinical throughput
Solution Approach 2:
The patent utilizes the periodic nature of the SABRE reaction cycles, where parahydrogen is periodically introduced to regenerate hyperpolarization, enabling continuous production of polarized samples at high rates compared to the single-shot d-DNP approach
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
Enables the production of biocompatible hyperpolarized solutions suitable for clinical use, allowing for rapid and efficient preparation of contrast agents like [1-13C]pyruvate, suitable for real-time biomedical applications.
Implementation Method 1
Signal Amplification by Reversible Exchange (SABRE) is based on the simultaneous, temporary binding of the to-be-polarized substrate and p-H2 to an Ir-IMes hexacoordinate complex and polarization transfer between the two reactants at the catalyst
Implementation Method 2
the precipitated hyperpolarized substrate can be separated from the first solvent, the non-polar organic solvent, or any combination thereof by filtration
Implementation Method 3
the method further includes redissolving the precipitated hyperpolarized substrate in a biocompatible solvent such as, for example, water or a physiologically-acceptable buffer
Data Source
AI summary
In one aspect, the disclosure relates to precipitated hyperpolarized substrates, methods of making the same, contrast agents comprising the same, and methods of diagnosing and/or monitoring the progress of a disease using the same. In one aspect, the method comprises contacting a solution containing a first solvent and a hyperpolarized substrate with a non-polar organic solvent. In a further aspect, the precipitated hyperpolarized substrate can be separated from the first solvent, the non-polar organic solvent, or any combination thereof by filtration. In still another aspect, the method further includes redissolving the precipitated hyperpolarized substrate in a biocompatible solvent such as, for example, water or a physiologically-acceptable buffer. In any of these aspects, hyperpolarization of the substrate can be accomplished using Signal Amplification by Reversible Exchange (SABRE).