Phosphonated Macrocyclic Ligands for MRI Contrast Agents
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current MRI contrast agents, particularly those with Gd(III) chelates, face challenges in achieving high relaxivity, which limits their diagnostic efficacy and requires higher doses and longer imaging times.
Innovation Solution
Development of novel tetraaza macrocyclic ligands with phosphonated or phosphinated residues and pendant arms with hydroxyl residues, forming chelated complexes with Gd(III) ions to enhance relaxivity for improved MRI contrast.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional Gd(III) chelates with octadentate polyaminopolycarboxylic ligands are used, then high thermodynamic complex stability is achieved, but relaxivity is limited
Solution Approach 1:
The patent modifies the ligand structure by replacing carboxylic acid groups with phosphonic or phosphinic acid groups, changing the chemical parameters of the chelating agent. This substitution increases the number of coordinating oxygen atoms and alters the electronic properties, resulting in enhanced relaxivity while maintaining complex stability
Solution Approach 2:
The invention creates composite chelating ligands that combine macrocyclic structures with pendant arms containing phosphonic/phosphinic groups. This composite structure integrates the stability of macrocyclic complexes with the high relaxivity of phosphonate-containing ligands, achieving both desired properties simultaneously
2Measurement precision
If higher doses of contrast agents are administered, then diagnostic efficacy is improved, but imaging time and patient exposure increase
Solution Approach 1:
By changing the chemical composition of the contrast agent to include phosphonic or phosphinic acid groups, the relaxivity parameter is significantly increased. This allows achieving the same diagnostic efficacy at lower concentrations, thereby reducing both the dose required and the imaging time needed
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 new complexes exhibit significantly higher relaxivity, allowing for reduced dosing and shorter imaging times while providing enhanced diagnostic imaging quality.
Implementation Method 1
The intensity of the signal recorded in MRI imaging stems, essentially, from the local value of the longitudinal relaxation rate 1/T1... Gd(III) is highly paramagnetic with seven unpaired electron and a long electronic relaxation time, making it an excellent candidate as a relaxation agent
Implementation Method 2
The combination of phosphonated or phosphinated residue(s) on the macrocyclic chelating cage and suitable substituents on the pendant arm provides chelated complexes having improved relaxivity
Data Source
AI summary
The present invention relates to new class of functionalized polyazamacrocycles including at least one phosphonic or phosphinic group linked to a nitrogen atom of the macrocyclic cage, and capable of chelating paramagnetic metal ions, their chelated complexes with metal ions and the use thereof as contrast agents, particularly suitable for Magnetic Resonance Imaging (MRI) analysis.