Hyperpolarized 13C-Pyruvate MR Imaging Agent Production
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Solution Overview
Problem
Current MR contrast agents, such as paramagnetic metal chelates, pose risks due to potential toxic metal ion release and lack specificity, and hyperpolarized imaging agents face challenges with signal decay and distribution in MR imaging, particularly in detecting small tumors and metastases.
Innovation Solution
A method for producing a liquid composition of hyperpolarized 13C-pyruvate using dynamic nuclear polarization (DNP) with a radical of formula (I), enhancing 13C nuclear polarization, and converting 13C-pyruvic acid to 13C-pyruvate, which is then dissolved with a buffer to create a suitable MR imaging agent for enhanced tumor imaging.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If paramagnetic metal chelates are used as MR contrast agents, then contrast enhancement and tumor detection are improved, but toxic metal ion release and lack of specificity occur
Solution Approach 1:
The patent extracts and eliminates the harmful metal ion component from the contrast agent system. Instead of using paramagnetic metal chelates that can release toxic metal ions, the invention employs hyperpolarized 13C-pyruvate which contains no metal ions, thereby removing the source of toxicity while maintaining imaging capability through metabolic visualization
Solution Approach 2:
The patent introduces 13C-pyruvate as an intermediary substance that mediates the imaging process through metabolic conversion rather than direct contrast enhancement. Pyruvate enters cells and is converted to lactate through glycolysis, providing indirect visualization of metabolic activity and tumor presence without requiring potentially harmful metal ions
2Illumination intensity
If hyperpolarized imaging agents are used, then signal intensity and contrast are improved, but signal decay and distribution challenges occur
Solution Approach 1:
The patent changes the physical and chemical parameters of the imaging agent by using 13C-pyruvate with specific metabolic properties. The compound's short half-life and rapid metabolic conversion to lactate create a time-sensitive imaging window that must be exploited quickly, while the hyperpolarization state provides sufficient signal intensity during this period
Solution Approach 2:
The patent ensures continuous useful action by utilizing the metabolic conversion pathway where pyruvate is continuously converted to lactate within cells. This continuous metabolic process maintains the imaging signal throughout the circulation time of the agent, providing sustained visualization of tumor metabolism rather than a single transient contrast enhancement
3Measurement precision
If conventional contrast agents are used, then tumor detection is possible, but specificity and safety are reduced
Solution Approach 1:
The patent applies self-service by using 13C-pyruvate, which is a natural metabolic intermediate that the body processes through its own enzymatic systems. The compound utilizes existing cellular metabolism (glycolysis pathway) to provide imaging contrast, eliminating the need for foreign metal ions or complex chemical structures that could trigger immune reactions or metabolic disturbances
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
The method achieves high polarisation levels of 13C-pyruvate, allowing for improved MR imaging, particularly in detecting tumors and metabolic processes, with enhanced contrast and specificity, and is well-tolerated by the body, enabling effective in vivo MR tumour imaging and metabolic studies.
Implementation Method 1
enhancing the 13C nuclear polarisation of pyruvic acid and/or pyruvate in the mixture via DNP
Implementation Method 2
adding a buffer and a base to the frozen mixture to dissolve it and to convert the 13C-pyruvic acid into a 13C-pyruvate
Data Source
AI summary
The invention relates to a method of producing a composition comprising hyperpolarised 13C-pyruvate, the composition and its use as an imaging agent for MR imaging.