Glucosamine Contrast Agents for CEST MRI Imaging
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Solution Overview
Problem
Current imaging methods using glucose and its analogues for cancer diagnosis face challenges due to rapid conversion of glucose to lactic acid and toxicity issues with derivatives like 2-DG and FDG at high concentrations, limiting their effectiveness and safety for imaging, especially in diabetic patients.
Innovation Solution
The use of glucosamine and its derivatives as contrast agents in imaging techniques, such as CEST MRI, which do not affect blood glucose levels or insulin sensitivity, allowing for safe and effective imaging of tissue abnormalities and cancer diagnosis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If glucose is used for imaging, then imaging can be performed, but glucose is rapidly converted to lactic acid by glycolysis resulting in inferior CEST signal
Solution Approach 1:
The patent changes the chemical structure parameter of glucose by replacing the hydroxyl group at position 2 with an amino group, creating glucosamine. This structural modification prevents rapid conversion to lactic acid while maintaining uptake by cancer cells through the Warburg effect, thereby extending signal duration and improving imaging reliability.
2Measurement precision
If 2-DG or FDG analogues are used for imaging, then imaging sensitivity is improved, but toxicity occurs at high concentrations
Solution Approach 1:
The patent modifies the chemical structure by introducing an amino group at position 2 of glucose, creating glucosamine. This structural change maintains the ability to be phosphorylated by hexokinase and accumulate in cancer cells, providing high imaging sensitivity, while avoiding the toxicity issues associated with 2-DG and FDG at high concentrations.
3Reliability
If glucose derivatives are used for imaging, then imaging capability is achieved, but blood glucose levels or insulin sensitivity are affected
Solution Approach 1:
The patent changes the chemical structure of glucose by substituting the hydroxyl group at position 2 with an amino group. This modification allows the compound to be recognized and transported by glucose transporters and phosphorylated by hexokinase, maintaining imaging capability, while not affecting blood glucose levels or insulin sensitivity, thus enabling use in diabetic patients.
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
Glucosamine and its derivatives provide enhanced CEST signals, enabling effective imaging of tumors and metastases with improved safety for diabetic patients and those sensitive to glucose levels, potentially replacing PET-CT as a standard imaging modality for tumor detection and therapy response.
Implementation Method 1
The CEST-MRI method enables to image glucose and glucose derivatives with enhanced sensitivity
Data Source
AI summary
Provided are formulations including a contrast agent selected from glucosamine, a salt thereof and a glucosamine derivative, for use in imaging.