Hyperpolarized Carboxylic Acid Preparation via Precursor Glass Formation
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Solution Overview
Problem
Magnetic Resonance Imaging (MRI) techniques face limitations due to low sensitivity, particularly for carboxylic organic acids that cannot form a glass form upon freezing, requiring additional glass-forming agents which can pose tolerability issues and result in low concentrations of the hyperpolarized molecule.
Innovation Solution
A process involving mixing carboxylic organic acids with suitable precursors, such as anhydrides or esters, to form a glass form suitable for Dynamic Nuclear Polarization (DNP) experiments, followed by transformation into a hyperpolarized form using an aqueous carrier, eliminating the need for additional glass-forming agents and allowing higher concentrations of the active acid.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a glass-forming agent (such as DMSO) is added to carboxylic organic acid to enable glass form formation for DNP, then the acid can be hyperpolarized, but the tolerability issues arise upon in-vivo injection and the concentration of the active acid becomes low
Solution Approach 1:
The patent uses an anhydride or ester as an intermediary substance that serves dual purposes: it enables glass form formation for DNP hyperpolarization and simultaneously serves as a safe, biocompatible carrier that can be injected in-vivo. The precursor molecule acts as a mediator between the requirement for glass formation and the requirement for in-vivo safety, eliminating the need for toxic glass-forming agents like DMSO.
Solution Approach 2:
The patent changes the chemical state and composition of the system by using a precursor (anhydride or ester) that can be transformed into the active carboxylic acid after hyperpolarization. This parameter change allows the system to achieve glass formation capability without using toxic additives, as the precursor itself provides the necessary physical properties for glass formation while remaining biocompatible.
2Reliability
If a glass-forming agent is added to carboxylic organic acid to enable glass form formation for DNP, then the acid can be hyperpolarized, but the concentration of the active acid in the final solution becomes low
Solution Approach 1:
The precursor (anhydride or ester) acts as an intermediary that enables glass formation without diluting the final active acid concentration. Since the precursor is chemically converted to the active acid after hyperpolarization, the amount of active acid in the final solution corresponds to the total amount of precursor plus original acid used, rather than being diluted by separate glass-forming agents.
Solution Approach 2:
The patent merges the functions of glass-forming agent and active acid source into a single substance (the precursor). The anhydride or ester serves both as the glass-forming component and as the source of the active carboxylic acid, eliminating the need for separate glass-forming agents that would dilute the final concentration.
3Measurement precision
If MRI sensitivity is improved through hyperpolarization, then diagnostic capability increases, but the complexity of the preparation process increases due to additional steps and materials
Solution Approach 1:
The precursor serves as an intermediary that simplifies the overall process by combining multiple functions: it provides glass formation capability, serves as the source of active acid, and eliminates the need for separate glass-forming agents. This reduces the number of steps and materials required compared to conventional approaches.
Solution Approach 2:
The precursor molecule performs multiple functions simultaneously: it acts as a glass-forming agent, serves as a carrier for the active acid, and becomes the source of the hyperpolarized active acid after chemical transformation. This multi-functionality reduces the overall complexity of the preparation process by eliminating the need for separate components for each function.
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
This method enables the preparation of hyperpolarized carboxylic organic acids without additional glass-forming agents, achieving higher concentrations and improving MRI sensitivity by maintaining the acid in a polarized form, suitable for in-vivo diagnostic applications.
Implementation Method 1
the sample upon freezing forms a so called 'glass' form
Implementation Method 2
subjecting the mixture of step a) to dynamic nuclear polarisation (DNP) methods
Implementation Method 3
the transformation of the mixture into the active organic acid according to the step c) is effected by hydrolysis
Data Source
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AI summary
The present invention relates to a process for the preparation of aqueous solutions of hyperpolarized carboxylic organic acids ready for use in in-vivo MR diagnostic imaging, and the use of the corresponding anhydrides or esters as glass-forming agents.