Hyperpolarized Glutamine Anhydrous DNP Mixture
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Solution Overview
Problem
Conventional methods for hyperpolarizing amino acids, such as glutamine, using dynamic nuclear polarization (DNP) result in the formation of undesirable by-products, which can affect the accuracy of metabolic imaging in MRI applications.
Innovation Solution
A method involving the preparation of a DNP mixture comprising glutamine, Rb+ or Cs+ hydroxide, a polarizing agent, and an anhydrous solvent, with a water content of less than 10%, followed by a DNP process, significantly reduces the formation of by-products like glutamate and pyro-glutamate, enhancing the reliability of MR imaging.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional DNP method using aqueous solution of alkali metal hydroxide is used to hyperpolarize glutamine, then hyperpolarization is achieved, but formation of undesirable by-products (glutamate and pyro-glutamate) occurs
Solution Approach 1:
The patent changes the water content parameter from conventional high levels to less than 10% (w/w), and changes the cation parameter from conventional alkali metals (Na+, K+) to alkali earth metals (Rb+, Cs+), thereby resolving the contradiction between achieving hyperpolarization and avoiding by-product formation
Solution Approach 2:
The patent converts the potentially harmful interaction between hydroxide and glutamine that causes by-product formation into a beneficial process by using anhydrous conditions and specific cations, where the hydroxide now serves only to facilitate hyperpolarization without causing degradation
2Ease of operation
If water content is increased to improve solubility and handling, then ease of operation improves, but by-product formation increases
Solution Approach 1:
The patent optimizes the water content parameter to a specific range (less than 10% w/w, preferably less than 5%) and changes the cation type to Rb+ or Cs+, achieving a balance where sufficient solubility and handling ease are maintained while by-product formation is substantially eliminated
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 approach results in a hyperpolarized glutamine preparation with minimal by-products, improving the accuracy of metabolic imaging by maintaining the integrity of glutamine during MRI, thereby providing reliable metabolic activity measurements.
Implementation Method 1
conventional methods forhyperpolarizing amino acids, such as glutamine, using dynamic nuclear polarization (DNP)
Implementation Method 2
submitting a subject, which has been pre-admistered with ahyperpolarized glutamine obtained according the DNP method described above and which has been positioned in said MRI system, to a radiation frequency selected to excite nuclear spin transitions in a non-zero nuclear spin nuclei of said glutamine
Data Source
Figure 1(a)~1(b)
AI summary
Method for manufacturing a hyperpolarized amino acid, in particular glutamine, which substantially limits the formation of by-products, with respect to conventional aqueous preparations of sodium hydroxide with amino acids. The amino acid is in particular admixed with the hydroxide in the substantial absence of water and the dry mixture is dissolved in an anhydrous solvent in the presence of a polarizing agent. The obtained mixture is then subjected to a DNP process and can be used in metabolic MR imaging.