Charge-Balanced Imaging Agents for NIR Tissue Fluorescence
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Solution Overview
Problem
Current near-infrared (NIR) fluorescence imaging agents face challenges due to poor in vivo properties, such as rapid liver clearance and non-specific background uptake, leading to low signal-to-background ratios in medical imaging applications.
Innovation Solution
Development of charge-balanced imaging agents with a net charge of +1, 0, or −1, achieved by incorporating ionic groups into dye molecules or conjugates, which improves biodistribution and clearance, resulting in enhanced signal-to-background ratios during tissue or cell imaging.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional fluorophores are used as imaging agents, then optical properties are achieved, but in vivo properties deteriorate due to rapid liver clearance and non-specific background uptake
Solution Approach 1:
The patent applies parameter changes by modifying the charge state of fluorophores from highly charged or neutral to charge-balanced states (net charge of +1, 0, or -1). This parameter modification fundamentally alters in vivo behavior, enabling renal clearance while reducing non-specific uptake in liver and gastrointestinal tract, thereby improving both reliability of in vivo properties and signal-to-background ratio
Solution Approach 2:
The invention creates composite imaging agents by combining fluorophore molecules with specific charge-balancing ionic groups. These composite structures integrate the optical properties of fluorophores with the favorable pharmacokinetic properties of charge-balanced molecules, achieving both good optical characteristics and superior in vivo behavior including efficient renal clearance
2Loss of substance
If fluorophores are cleared through the liver, then elimination occurs, but fluorescence throughout the gastrointestinal tract increases causing background noise
Solution Approach 1:
The patent changes the clearance pathway parameter by modifying the charge balance of fluorophores. This parameter change shifts elimination from hepatic metabolism to renal filtration, preventing the harmful side effect of gastrointestinal fluorescence while maintaining efficient clearance from the body
3Quantity of substance
If highly charged or neutral fluorophores are used, then solubility is achieved, but biodistribution and clearance properties deteriorate
Solution Approach 1:
The invention applies parameter changes by adjusting the charge state parameter from highly charged/neutral to charge-balanced states. This modification maintains adequate solubility while dramatically improving biodistribution and clearance properties, enabling preferential renal elimination and reduced non-specific tissue uptake
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 behavior, reducing non-specific binding and enhancing imaging resolution by maintaining a high signal-to-background ratio, facilitating superior clinical imaging characteristics.
Implementation Method 1
Near infrared (NIR) fluorescence has potential importance in the medical field
Implementation Method 2
irradiating the tissue or cells at a wavelength absorbed by the dye or conjugate
Data Source
AI summary
The present invention relates to compositions for and methods of optically imaging tissues or cells using imaging agents having desirable in vivo properties that result in improved signal-to-background ratio.