Cyclic Gadolinium Chelate for Liver MRI With Lower Ion Leakage
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Solution Overview
Problem
Existing liver-specific MRI contrast agents with linear chelate structures have low in vivo stability, leading to gadolinium ion leakage and limited clinical use.
Innovation Solution
A novel compound with a cyclic structure, represented by Formula 1, specifically binds to liver tissue through organic-anion transporting peptides, enhancing liver contrast and stability, minimizing gadolinium ion leakage.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If a linear chelate structure is used for liver-specific MRI contrast agent, then liver-specific contrast enhancement is achieved, but in vivo stability deteriorates leading to gadolinium ion leakage
Solution Approach 1:
The linear chelate structure is segmented and reconfigured into a cyclic structure where the ligand forms a ring with the gadolinium ion at its center. This cyclic arrangement divides the coordination sphere into a stable macrocyclic framework, preventing gadolinium ion leakage while preserving liver-specific targeting capabilities through the organic-anion transporting peptide component
Solution Approach 2:
The contrast agent combines multiple components into a composite structure: a macrocyclic ligand framework providing stability, gadolinium ion providing magnetic contrast, and organic-anion transporting peptide providing liver-specific targeting. This composite approach integrates the beneficial properties of each component while mitigating their individual limitations
2Reliability
If gadolinium ion leakage is prevented through stable chelation, then in vivo stability is improved, but contrast enhancement capability may be reduced
Solution Approach 1:
The patent optimizes the coordination geometry and bond strength parameters of the gadolinium-chelate complex within the cyclic structure. By adjusting the ligand design and coordination mode, the complex achieves optimal balance between kinetic stability (preventing leakage) and magnetic relaxation efficiency (providing contrast enhancement), with relaxation rates of r1 = 3.8-4.2 mM⁻¹s⁻¹ and r2 = 5.5-6.5 mM⁻¹s⁻¹
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 compound achieves improved in vivo stability and enhanced liver contrast, reducing side effects and enabling effective diagnosis of liver diseases such as cancer metastasis, liver cysts, and biliary obstruction.
Implementation Method 1
The contrast agent plays the role of further sharpening the contrast between tissues through widening the difference in relaxation rates between tissues by affecting the relaxation action using a paramagnetic or superparamagnetic material
Implementation Method 2
the compound according to the present invention specifically binds to liver tissue
Data Source
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AI summary
The present invention relates to a novel compound and an MRI contrast agent containing same. The compound according to the present invention can minimize MRI contrast agent side effects caused by the release of gadolinium ions within the body, on the basis of the outstanding kinetic stability, and can be very usefully employed as an MRI contrast agent for diagnosing liver diseases, owing to the superior level of contrast enhancement for the liver in an MRI image of the body in comparison with other organs.