Iron-Based MRI Contrast Agent for Hypoxia Detection
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Solution Overview
Problem
Current methods for detecting hypoxia, such as invasive IHC staining and Gd-based MRI contrast agents, face challenges including invasiveness, toxicity, and kidney impairment concerns, necessitating the development of non-invasive and low-toxicity alternatives for effectively imaging hypoxic tissue regions.
Innovation Solution
A metal chelate compound, specifically a compound of Formula (I) chelated with iron or other metals, is used as an MRI contrast agent, synthesized through a process involving coupling reagents and solvents, to enhance MRI imaging of hypoxic tissues, offering a non-invasive and potentially safer alternative.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If Gd-based MRI contrast agents are used to detect hypoxia, then imaging capability is improved, but toxicity and kidney impairment concerns worsen
Solution Approach 1:
The patent replaces expensive and toxic gadolinium-based contrast agents with iron-based contrast agents that are biocompatible and naturally eliminated by the body. The iron-based agent uses a siderophore ligand (deferroxamine B) chelated with iron (III), which provides the necessary MRI contrast while being non-toxic and safe for renal function.
2Measurement precision
If invasive IHC staining is used to detect hypoxia, then measurement accuracy is improved, but invasiveness worsens
Solution Approach 1:
The patent replaces the mechanical/invasive immunohistochemistry staining method with a non-invasive MRI imaging method. The iron-based contrast agent accumulates in hypoxic regions and can be detected through MRI, providing accurate hypoxia mapping without requiring tissue biopsy or invasive procedures.
3Ease of operation
If non-invasive MRI methods are used to detect hypoxia, then ease of operation is improved, but measurement precision worsens
Solution Approach 1:
The patent introduces a hypoxia-targeting contrast agent as an intermediary between the MRI scanner and the hypoxic tissue. The iron-based contrast agent with nitroimidazole moiety selectively accumulates in hypoxic regions, acting as a mediator that enhances the MRI signal specifically in hypoxic areas, thereby maintaining non-invasive operation while significantly improving measurement precision.
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 metal chelate compound effectively detects hypoxic tissue regions with MRI, providing high-resolution imaging while being non-toxic and avoiding kidney-related concerns, thus addressing the limitations of existing methods.
Implementation Method 1
Gadolinium (Gd), which is a strongly paramagnetic heavy metal, is routinely and widely used as an MRI contrast agent
Implementation Method 2
Magnetic Resonance Imaging (MRI), a non-invasive imaging modality provides high resolution
Data Source
AI summary
The present disclosure provides for a novel hypoxia-targeting contrast agent for noninvasive detection of hypoxia using magnetic resonance imaging. Also disclosed is a process of preparing the novel hypoxia-targeting contrast agent, as well as methods of using the novel hypoxia-targeting contrast agent.