Multivalent Dendrimer Contrast Agents for CT Imaging
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Solution Overview
Problem
Conventional X-ray-based computed tomography (CT) is ineffective in distinguishing soft tissues with similar electron densities and requires high concentrations of iodinated contrast agents, leading to adverse side effects, especially in patients with impaired renal function.
Innovation Solution
Development of multivalent CT or MR contrast agents with a moiety, such as polymers, that provide multivalent attachment of high Z-elements like iodine, confined through encapsulation or conjugation to enhance CT contrast at lower concentrations, reducing toxicity and vascular permeation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If high concentrations of iodinated contrast agents are used to enhance CT contrast, then radiographic contrast is improved, but adverse side effects increase
Solution Approach 1:
The patent segments the contrast agent into multiple iodine atoms covalently bound to a single polymer backbone, creating a multivalent contrast agent. This segmentation allows the contrast effect to be distributed across multiple binding sites, enabling enhanced contrast at lower overall concentrations and reducing adverse effects.
Solution Approach 2:
The patent creates a composite contrast agent system combining polymer backbone structures with covalently bound iodine atoms. This composite approach integrates the contrast-enhancing property of iodine with the biocompatibility and circulation properties of the polymer, achieving both improved contrast and reduced toxicity.
2Measurement precision
If high concentrations of iodinated contrast agents are used to enhance CT contrast, then radiographic contrast is improved, but vascular permeation increases
Solution Approach 1:
By segmenting the contrast function across multiple iodine atoms bound to a single polymer molecule, the patent reduces the per-molecule permeation risk while maintaining total contrast effect. The polymer backbone acts as a carrier that limits individual iodine atom leakage.
Solution Approach 2:
The polymer backbone serves as an intermediary carrier that holds multiple iodine atoms in a stable configuration. This intermediary structure prevents direct vascular permeation of iodine while still delivering the contrast effect, effectively mediating between contrast enhancement and permeation prevention.
3Measurement precision
If high concentrations of iodinated contrast agents are used to enhance CT contrast, then radiographic contrast is improved, but imaging lifetime decreases
Solution Approach 1:
The patent segments the contrast agent into a stable polymer-iodine complex that resists rapid clearance. The covalent bonding creates a more stable molecular structure that circulates longer in the bloodstream, extending imaging lifetime while maintaining contrast enhancement.
Solution Approach 2:
The composite polymer-iodine structure provides both the contrast-enhancing iodine and the circulation-stabilizing polymer properties. This composite design simultaneously achieves improved radiographic contrast and extended imaging lifetime by combining the benefits of both materials.
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 use of these agents allows for prolonged circulation and enhanced CT contrast at lower concentrations, reducing toxicity and enabling improved imaging without the adverse effects associated with high iodine doses.
Implementation Method 1
contrast agents using high atomic number elements, such as iodine, have been used in clinical applications to increase the radiographic contrast of clinical targets in CT
Data Source
AI summary
Multivalent CT or MR contrast agents and methods of making and using thereof are described herein. The agents contain a moiety, such as a polymer, that provides multivalent attachment of CT or MR contrast agents. Examples include, but are not limited to, multivalent linear polymers, branched polymers, or hyperbranched polymers, such as dendrimers, and combinations thereof. The dendrimer is functionalized with one or more high Z-elements, such as iodine. The high Z-elements can be covalently or non-covalently bound to the dendrimer. The dendrimers are confined in order to enhance CT contrast. In some embodiments, the moiety is confined by encapsulating the dendrimers in a material to form particles, such as nanoparticles. In other embodiments, the dendrimer is confined by conjugating the moiety to a material, such as a polymer, which forms a gel upon contact with bodily fluids.