Dimeric MRI Contrast Agents for Relaxivity and Toxicity
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current MRI contrast agents, particularly those based on Gd(III) chelates, face challenges in achieving high relaxivity, which limits their diagnostic efficacy and requires higher doses and longer imaging times, while also posing toxicity risks due to free metal ion release.
Innovation Solution
Development of novel dimeric macrocyclic chelating ligands with hydroxylated residues linked through amine groups, forming complexes with paramagnetic metal ions like Gd(III), which exhibit enhanced relaxivity and stability, reducing the need for higher doses and shortening imaging times.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional Gd(III) chelate contrast agents are used, then diagnostic imaging capability is provided, but relaxivity is insufficient requiring higher doses and longer imaging times
Solution Approach 1:
The patent combines two macrocyclic chelating units into a single dimeric molecule through a linker containing basic nitrogen atoms. This merging of two contrast agent units into one molecular structure doubles the paramagnetic effect per molecule, significantly increasing relaxivity and reducing the required dose for effective imaging.
Solution Approach 2:
The invention creates a composite molecular structure integrating two macrocyclic Gd(III) chelate units with a basic nitrogen-containing linker. This composite design leverages the synergistic effect of multiple paramagnetic centers in close proximity, enhancing the overall relaxivity beyond what single macrocyclic units can achieve.
2Measurement precision
If higher doses of contrast agent are administered to improve signal intensity, then diagnostic image quality improves, but toxicity risk increases due to free metal ion release
Solution Approach 1:
By merging two macrocyclic chelating units into one dimeric molecule, the patent achieves higher signal intensity per administered molecule. This reduces the total number of gadolinium ions needed in the body to achieve diagnostic quality images, thereby lowering the risk of toxicity from free metal ion release.
Solution Approach 2:
The invention changes the molecular parameter of relaxivity by creating a dimeric structure with enhanced paramagnetic properties. This parameter change allows achieving the same image quality with lower gadolinium concentration, reducing toxicity while maintaining diagnostic effectiveness.
3Measurement precision
If conventional contrast agents are used, then imaging is performed, but acquisition time is prolonged due to insufficient relaxivity
Solution Approach 1:
The dimeric structure combines two Gd(III) chelating units with enhanced paramagnetic effects, accelerating the relaxation rate of water protons. This increased relaxivity shortens the time required to acquire diagnostic quality images, reducing imaging time while maintaining or improving image quality.
Solution Approach 2:
The invention modifies the relaxivity parameter by introducing a dimeric macrocyclic structure with basic nitrogen atoms that enhance water proton relaxation. This parameter optimization enables faster image acquisition, reducing the time penalty associated with conventional single-unit contrast agents.
4Object-affected harmful factors
If stable chelate complexes are formed to prevent metal ion release, then toxicity is reduced, but relaxivity may be compromised
Solution Approach 1:
The patent merges two macrocyclic chelating units into a dimeric structure that provides both enhanced stability (reducing metal ion release) and enhanced relaxivity. The dual-unit structure offers redundant chelation sites that firmly bind gadolinium ions while simultaneously providing stronger paramagnetic effects for improved imaging.
Solution Approach 2:
The composite dimeric molecule combines stable macrocyclic chelating units with a basic nitrogen-containing linker, creating a structure that achieves both high stability (low toxicity) and high relaxivity. The synergistic design ensures gadolinium ions remain tightly bound while maximizing the contrast enhancement effect.
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 dimeric complexes demonstrate significantly higher relaxivity values compared to existing agents, allowing for reduced dosing and potentially faster imaging processes with improved diagnostic image quality and reduced toxicity.
Implementation Method 1
novel dimeric macrocyclic chelating ligands with hydroxylated residues linked through amine groups, forming complexes with paramagnetic metal ions like Gd(III), which exhibit enhanced relaxivity and stability
Implementation Method 2
The intensity of the signal recorded in MRI imaging stems, essentially, from the local value of the longitudinal relaxation rate 1/T1 and the transverse rate 1/T2 of water protons, and increases with increasing of the 1/T1 value
Implementation Method 3
The dimeric complexes demonstrate significantly higher relaxivity values compared to existing agents, allowing for reduced dosing and potentially faster imaging processes with improved diagnostic image quality
Data Source
AI summary
The present invention relates to new class of dimeric macrocycles 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.