Gadolinium Complex MRI Contrast Agent with DO3A-Tranexamic Acid Ligand
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Solution Overview
Problem
Current MRI contrast agents have low water solubility and magnetic relaxation rates, and are highly cytotoxic, limiting their effectiveness and safety for medical imaging.
Innovation Solution
A gadolinium complex comprising a DO3A-tranexamic acid or its ester compound is synthesized, offering high relaxivity and enhanced thermodynamic and kinetic stability, along with bifunctionality for liver-specific and blood-pool contrasting effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional Gd(III) complexes are used as MRI contrast agents, then contrast enhancement is achieved, but water solubility is low and cytotoxicity is high
Solution Approach 1:
The patent modifies the ligand structure by introducing hydrophilic groups (carboxylic acid, hydroxyl, or ether groups) and adjusting the steric environment around the gadolinium ion. This changes the physical and chemical parameters of the complex, resulting in improved water solubility and reduced cytotoxicity while maintaining contrast enhancement effectiveness through preserved paramagnetic properties.
Solution Approach 2:
The patent creates composite ligand structures combining DO3A macrocyclic framework with tranexamic acid derivatives containing hydrophilic functional groups. This composite approach integrates the stability of macrocyclic chelates with the water solubility and reduced toxicity of hydrophilic side chains, achieving multiple desired properties simultaneously.
2Reliability
If conventional Gd(III) complexes are used, then MRI contrast is achieved, but magnetic relaxation rate is low
Solution Approach 1:
The patent optimizes the coordination geometry and electronic environment of the gadolinium ion by modifying the ligand's donor atoms and steric arrangement. This changes the magnetic relaxation parameters, specifically increasing the longitudinal relaxation rate (r1) through enhanced water proton interaction and optimized electron spin relaxation pathways.
3Reliability
If conventional Gd(III) complexes are used, then contrast enhancement is achieved, but water solubility is low
Solution Approach 1:
The patent introduces hydrophilic functional groups (carboxylic acid, hydroxyl, or ether groups) at specific positions on the ligand structure. This fundamentally changes the polarity and solvation characteristics of the complex, dramatically improving water solubility while preserving the paramagnetic gadolinium center's contrast enhancement capability.
4Productivity
If conventional Gd(III) complexes are used, then MRI imaging is performed, but thermodynamic stability is insufficient
Solution Approach 1:
The patent employs a composite ligand design where the DO3A macrocyclic framework provides rigid chelation and high thermodynamic stability through preorganized coordination geometry, while the attached tranexamic acid derivatives with hydrophilic groups contribute additional coordination sites and steric protection. This composite structure enhances the overall stability constant of the gadolinium complex.
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 gadolinium complex provides improved contrast enhancement with higher relaxivity and stability, reducing cytotoxicity and enhancing imaging quality, making it suitable for wide-ranging use as an MRI contrast agent.
Implementation Method 1
Magnetic resonance imaging (MRI) is a medical imaging technique used to obtain anatomical, physiological and biochemical information based on relaxation of proton spin in a magnetic field. The contrast agent affects the relaxation, thereby altering the relaxation times in different tissues
Data Source
AI summary
The present invention relates to a magnetic resonance imaging (MRI) contrast agent including a gadolinium complex, more particularly to a DO3A-tranexamic acid or its ester compound, which is represented by the Chemical Formula 1. A DO3A-tranexamic acid or its ester compound may be prepared according to the present invention and a gadolinium complex may be prepared using the compound. An MRI contrast agent including the gadolinium complex prepared according to the present invention as an active ingredient has higher relaxivity as compared to the currently commercially available contrast agent. In addition, the MRI contrast agent according to the present invention has bifunctionality of liver-specific and blood-pool contrasting effect. Accordingly, since the MRI contrast agent including the gadolinium complex according to the present invention satisfies the key properties required for a contrast agent for MRI, it can be widely used as an MRI contrast agent and can provide enhanced contrasting effect as compared to the existing contrast agent.