NIR Fluorescent Contrast Agents for High Signal-to-Background Imaging

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Solution Overview

Problem

Current near-infrared (NIR) fluorophores for medical imaging face challenges such as low signal-to-background ratio due to inadequate accumulation at target sites and non-specific background uptake, necessitating the development of improved NIR fluorescent imaging agents with enhanced physicochemical properties for better targeting and clearance.

Innovation Solution

Development of specific NIR fluorescent contrast agents with defined chemical structures, such as those represented by Formulas (I) to (V), which exhibit peak absorbance in the 600-900 nm range, allowing for targeted imaging of various biological tissues and organs with improved sensitivity and specificity, and efficient elimination from the body.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If current NIR fluorophores are used as imaging agents, then the imaging process can be performed, but the signal-to-background ratio is low due to inadequate accumulation at target sites and non-specific background uptake

Engineering Contradiction:
Improvesignal-to-background ratioVSAvoidtargeting specificity
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent modifies the chemical structure of NIR fluorophores by changing physical and chemical parameters such as molecular weight, charge distribution, and functional group composition. These parameter changes enable the fluorophores to achieve optimal accumulation at target sites while minimizing non-specific background uptake, thereby resolving the contradiction between signal-to-background ratio and targeting specificity

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention creates composite imaging agents by combining NIR fluorophores with targeting moieties and pharmacokinetic modifiers. This composite approach allows the fluorophore to simultaneously achieve high signal intensity at targets and rapid clearance from non-target tissues, resolving the contradiction between accumulation capability and background interference

Inventive Principle:
Principle #40Composite materials

2Measurement precision

If NIR fluorophores are designed to accumulate at target sites, then imaging sensitivity improves, but clearance efficiency from the body deteriorates

Engineering Contradiction:
Improveimaging sensitivityVSAvoidclearance efficiency
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The patent introduces dynamic pharmacokinetic properties to the NIR fluorophores, enabling them to rapidly transition from the intravascular space to target tissues and then to excretion. This dynamic behavior allows the agent to achieve high imaging sensitivity at targets while maintaining efficient clearance, resolving the contradiction between accumulation and elimination

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The invention imparts different properties to different parts of the imaging agent: the fluorophore portion provides optical properties for sensitivity, while the molecular scaffold and functional groups provide pharmacokinetic properties for rapid clearance. This local differentiation of properties resolves the contradiction between accumulation capability and clearance efficiency

Inventive Principle:
Principle #3Local quality

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

These agents effectively accumulate in target tissues or organs, providing high signal-to-background ratios and enabling precise imaging, thereby enhancing diagnostic capabilities in medical applications like image-guided surgery and in vitro diagnostics.

Implementation Method 1

near-infrared fluorescent contrast agents... peak absorbance in the 600-900 nm range... providing high signal-to-background ratios and enabling precise imaging

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentEP4147724A1Near-infrared fluorescent contrast bioimaging agents and methods of use thereof
Publication Date: 2023.03.15 GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION INC
  • EP4147724A1 patent drawingFigure 1~6
  • EP4147724A1 patent drawingFigure 7~12
  • EP4147724A1 patent drawingFigure 13~18

AI summary

The instant invention provides near-infrared fluorescent biological contrast agents and methods of using them.