Charge-Balanced Imaging Agents for Renal Function Assessment
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Solution Overview
Problem
Current near-infrared (NIR) fluorescence imaging agents face challenges due to poor in vivo properties, such as undesirable fluorescence in the gastrointestinal tract and low signal-to-background ratios, primarily because they are not efficiently cleared by the kidneys and exhibit non-specific background uptake in normal tissues.
Innovation Solution
Development of charge-balanced imaging agents with a net charge of +1, 0, or −1, achieved by incorporating ionic groups to improve solubility and biodistribution, allowing for better renal filtration and reduced non-specific binding, thereby enhancing the signal-to-background ratio during imaging.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional fluorophores are used as imaging agents, then optical imaging can be performed, but the signal-to-background ratio is low due to non-specific background uptake in normal tissues and undesirable fluorescence in the gastrointestinal tract
Solution Approach 1:
The patent applies parameter changes by modifying the charge state of the fluorophore from highly charged (e.g., +2, -2) to charge-balanced states (net charge of 0, +1, or -1). This fundamental parameter change in the molecular charge resolves the technical contradiction by eliminating non-specific background uptake in normal tissues and preventing accumulation in the gastrointestinal tract, thereby dramatically improving the signal-to-background ratio without sacrificing imaging capability
Solution Approach 2:
The patent applies local quality by introducing specific ionic groups (such as carboxylates, sulfonates, or quaternary ammonium groups) at strategic positions on the fluorophore molecule. These localized ionic modifications create charge-balanced structures that maintain solubility and biodistribution properties while eliminating harmful non-specific binding, thus resolving the contradiction between achieving good optical properties and avoiding background fluorescence
2Illumination intensity
If fluorophores with improved optical properties are used, then imaging quality increases, but in vivo properties deteriorate due to poor solubility and inefficient renal clearance
Solution Approach 1:
The patent applies parameter changes by adjusting the charge balance of the fluorophore to achieve optimal solubility and renal clearance. By transitioning from highly charged molecules to charge-balanced molecules with net charge of 0, +1, or -1, the patent simultaneously maintains good optical properties while dramatically improving in vivo reliability through enhanced solubility and efficient renal filtration
Solution Approach 2:
The patent applies composite materials by combining the fluorophore core structure with specific ionic groups (such as zwitterionic moieties, carboxylates, or quaternary ammonium groups). This composite approach creates molecules that integrate both optical functionality and improved pharmacokinetic properties, resolving the contradiction between optical performance and in vivo reliability
3Stability of the object's composition
If highly charged fluorophores are used to improve solubility, then in vivo stability increases, but renal filtration efficiency decreases
Solution Approach 1:
The patent applies parameter changes by optimizing the charge state from highly charged to charge-balanced (net charge 0, +1, or -1). This parameter optimization resolves the contradiction by maintaining sufficient in vivo stability through ionic groups while enabling efficient renal filtration, as the balanced charge prevents the molecular size and charge density that would otherwise impede glomerular filtration
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 charge-balanced imaging agents demonstrate improved in vivo properties, leading to higher resolution imaging with reduced background noise and efficient renal clearance, as evidenced by their ability to maintain a high signal-to-background ratio and rapid equilibration between intravascular and extravascular spaces.
Implementation Method 1
detecting an optical signal from the irradiated tissue or cells, wherein the signal-to-background ratio of the detected optical signal is at least about 1.1
Data Source
AI summary
The present invention relates to a method for detecting renal disease and for assessing the efficacy of dialysis treatment using imaging agents having desirable in vivo properties.