ICB Near-Infrared Fluorescent Contrast Agent for Sentinel Lymph Node Mapping
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Solution Overview
Problem
Current near-infrared (NIR) fluorophores for sentinel lymph node (SLN) mapping suffer from poor physicochemical properties, leading to low signal accumulation at the target, high background uptake, and rapid elimination, which results in a low signal-to-background ratio (SBR).
Innovation Solution
The development of indocyanine blue (ICB), also known as MHI85 or CUR-438, which is a near-infrared fluorescent contrast agent with improved hydrophilicity, solubility, and targeting specificity, allowing it to effectively accumulate in sentinel lymph nodes and provide clear imaging.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If ICG is used for SLN mapping, then SLN mapping can be performed, but the agent shows rapid elimination from the body and poor aqueous stability
Solution Approach 1:
The patent modifies the chemical structure of ICG by introducing sulfur atoms to create ICB, changing the physicochemical parameters including increased hydrophilicity and improved aqueous stability, which results in enhanced retention in sentinel lymph nodes while maintaining imaging effectiveness
2Reliability
If hydrophobic compounds are used for SLN mapping, then targeting can be achieved, but solubility and ease of formulation are poor
Solution Approach 1:
The patent changes the hydrophobicity parameter of the contrast agent by introducing polar sulfur atoms and modifying the chemical structure, transforming ICG from a hydrophobic compound with formulation difficulties to ICB, which is highly water-soluble and easily formulatable while retaining targeting capability
3Measurement precision
If current fluorophores are used as imaging agents, then imaging can be performed, but signal-to-background ratio is low due to poor accumulation and high background uptake
Solution Approach 1:
The patent optimizes the physicochemical parameters of the fluorophore by structural modification (adding sulfur atoms), which improves target accumulation and reduces non-specific background uptake, thereby significantly enhancing the signal-to-background ratio for more precise imaging
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
ICB achieves enhanced retention in sentinel lymph nodes, improved solubility, and efficient clearance from the body, resulting in a higher signal-to-background ratio (SBR) and effective SLN mapping.
Implementation Method 1
Near-infrared fluorescent contrast agents... peak absorbance at about 600 nm to 900 nm... irradiating the cells at a wavelength absorbed by ICB; and detecting a signal from ICB
Data Source
AI summary
The instant invention provides near-infrared fluorescent biological contrast agents having higher hydrophilicity and solubility than standard imaging agents and methods of using them for the imaging and mapping of sentinel lymph nodes.