L-Histidine Mediator for Gadolinium Chelation in MRI Contrast Safety
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Gadolinium Based Contrast Agents (GBCAs) can cause toxicity and free gadolinium accumulation in tissues, leading to conditions like Nephrogenic Systemic Fibrosis (NSF) in patients with renal insufficiency, due to the dissociation of the complex and transmetallation reactions involving endogenous ions.
Innovation Solution
The use of L-Histidine or its salts to prevent the release of free gadolinium from GBCAs by reducing transmetallation reactions with divalent ions like Zn2+ and Cu2+, thereby decreasing gadolinium accumulation in target organs such as bones and skin.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If Gadolinium Based Contrast Agents are administered to enhance MRI signal, then diagnostic capability is improved, but Gadolinium dissociation and transmetallation reactions cause free gadolinium accumulation and toxicity
Solution Approach 1:
L-Histidine acts as an intermediary substance that binds to free gadolinium ions released from GBCA through transmetallation reactions. By introducing this mediator, the harmful free gadolinium is sequestered into a less toxic complex, reducing its ability to cause NSF and other toxic effects while allowing the original GBCA to perform its diagnostic function.
Solution Approach 2:
The invention converts the harmful transmetallation reaction (which was previously seen as purely detrimental) into a beneficial process. By controlling the transmetallation between gadolinium and L-Histidine, the harmful free gadolinium is transformed into a less toxic L-Histidine-gadolinium complex, thereby converting a harmful mechanism into a protective one.
2Object-affected harmful factors
If L-Histidine is administered to prevent free gadolinium release, then Gadolinium toxicity is reduced, but the mechanism involves transmetallation that may compete with essential divalent ions
Solution Approach 1:
The invention exploits parameter changes in metal ion binding affinity and concentration. L-Histidine is administered at high doses temporarily to create a transient state where it outcompetes essential divalent ions for gadolinium binding. This parameter change is temporary and controlled, allowing the system to return to normal ion homeostasis after the protective period.
Solution Approach 2:
L-Histidine is administered preliminarily before or with GBCA to establish protective binding capacity in advance. This preliminary action ensures that when free gadolinium is released from GBCA, L-Histidine is already present in sufficient concentrations to immediately bind it, preventing toxicity before it can occur.
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
L-Histidine significantly reduces the release and accumulation of free gadolinium, lowering the risk of toxicity and NSF in patients, particularly those with renal impairment, by administering it orally before or with GBCA administration.
Implementation Method 1
L-Histidine or salts thereof for the prevention of metal accumulation, in particular Gadolinium (Gd 3+) accumulation
Implementation Method 2
The use of L-Histidine or its salts to prevent the release of free gadolinium from GBCAs by reducing transmetallation reactions with divalent ions like Zn2+ and Cu2+
Data Source
AI summary
The present invention discloses the use of L-Histidine to reduce Gadolinium accumulation i nto target org ans, preventing its toxic effects, after administration of gadolinium based contrast agents. The invention thus, also disclose the use of L-Histidine to prevent the NSF syndrome in patients with renal functionality impairment. A kit of part is also disclosed by the use of which toxicity associated to free Gd3+, deriving from GDBCA, is prevented by oral administration of L- histidine before administration of the contrast agent. A method for the prevention of toxic metal accumulation which consists in the ad min istration, preferably by the oral route, of L-Histidine is also disclosed. L-Histidine is preferably administered a s a single oral dose comprised from 0.2-20 g.