99mTc-Labeled Alpha-Hydroxy Acid for Hydrogen Sulfide Detection

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Solution Overview

Problem

Current methods for detecting hydrogen sulfide are limited in their ability to accurately measure its concentration and distribution, particularly in vivo, and are often expensive and restricted in use.

Innovation Solution

A composition comprising a compound represented by formula 1, where 99mTc is labeled with alpha-hydroxy acid, is used for detecting and measuring hydrogen sulfide concentrations. This compound reacts with hydrogen sulfide to form an insoluble material, enabling imaging and concentration measurement.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If fluorescence method is used to detect hydrogen sulfide, then hydrogen sulfide generation site can be shown in image, but fluorescence is weak in permeability and cannot be used to detect or image hydrogen sulfide generated in humans or large animals

Engineering Contradiction:
Improvedetection accuracyVSAvoidpermeability limitation
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent uses a radioactive isotope (99mTc) as an intermediary substance that combines with hydrogen sulfide to form a detectable complex. This intermediary approach allows detection in large animals and humans by overcoming the permeability limitations of fluorescence methods, while maintaining detection accuracy through radioactive labeling and imaging techniques

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces the fluorescence-based optical detection system with a radioactive detection system. By substituting the mechanical/optical field (fluorescence) with a nuclear field (radioactive isotope emission), the method achieves deeper tissue penetration and enables imaging in large animals and humans that was previously impossible with fluorescence methods

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

2Measurement precision

If radioactive isotope method (64Cu) is used to detect hydrogen sulfide, then hydrogen sulfide generation site deep in human body can be imaged with high resolution, but the price is very expensive and there are many restrictions in use

Engineering Contradiction:
Improveimaging resolutionVSAvoidcost and accessibility
Core Design Contradiction:
Measurement precisionVSEase of manufacture

Solution Approach 1:

The patent employs 99mTc, a short-lived radioactive isotope (6-hour half-life) that can be produced more economically than 64Cu. This disposable, short-lived isotope approach reduces costs and restrictions compared to longer-lived isotopes requiring expensive cyclotrons, while still providing sufficient imaging resolution and time for diagnostic procedures

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The patent changes the radioactive isotope parameter from 64Cu to 99mTc, altering the half-life, production method, and cost characteristics. This parameter change enables more widespread use and reduces manufacturing complexity while maintaining the essential function of high-resolution imaging of hydrogen sulfide generation sites

Inventive Principle:
Principle #35Parameter changes

3Measurement precision

If conventional detection methods (methylene blue method, ion selective electrode method) are used to measure hydrogen sulfide concentration, then concentration can be measured in samples, but it is impossible to know its distribution more accurately

Engineering Contradiction:
Improveconcentration measurementVSAvoiddistribution information
Core Design Contradiction:
Measurement precisionVSLoss of information

Solution Approach 1:

The patent employs radioactive labeling that produces detectable signal changes (gamma radiation emission) when 99mTc binds to hydrogen sulfide. This signal change enables not only concentration measurement but also spatial distribution mapping through imaging techniques, thereby recovering the distribution information that was lost in conventional bulk measurement methods

Inventive Principle:
Principle #32Color changes

Solution Approach 2:

The patent replaces conventional chemical/electrical detection methods with radioactive detection and imaging technology. This substitution transforms the measurement from bulk concentration analysis to spatially-resolved distribution mapping, enabling accurate visualization of hydrogen sulfide distribution in biological systems while maintaining concentration measurement capability

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

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 composition allows for effective detection and measurement of hydrogen sulfide in both in-vitro and in-vivo settings, facilitating the diagnosis and imaging of diseases associated with hydrogen sulfide generation, such as inflammation and cancer.

Implementation Method 1

This compound reacts with hydrogen sulfide to form an insoluble material, enabling imaging and concentration measurement

Methodology Applied
Scientific EffectPrecipitation: Precipitation

Implementation Method 2

a method for detecting hydrogen sulfide using a radioactive isotope that emits radiation with strong penetrating power has been developed

Methodology Applied
Scientific EffectRadioactive decay: Radioactive Decay

Data Source

PatentUS12287322B2Composition for detecting hydrogen sulfide or measuring hydrogen sulfide concentration and composition comprising same as effective ingredient for diagnosing or imaging in vivo inflammation, tissues having hypoxic damage, or cancer
Publication Date: 2025.04.29 SEOUL NATIONAL UNIVERSITY R&DB FOUNDATION
  • US12287322B2 patent drawing
  • US12287322B2 patent drawing
  • US12287322B2 patent drawing

AI summary

The present invention relates to a composition for detecting hydrogen sulfide or measuring a concentration of hydrogen sulfide, and a composition comprising same as an effective ingredient for diagnosing or imaging in vivo inflammation, tissues having hypoxic damage, or cancer. The composition for detecting hydrogen sulfide or measuring a concentration of hydrogen sulfide according to the present invention, which comprises the compound represented by formula 1 (99mTc-alpha-hydroxy acid) having alpha-hydroxy acid labeled with 99mTc, enables the detection or concentration measurement of hydrogen sulfide in in-vitro and in-vivo levels and, as such, can be advantageously used for detecting hydrogen sulfide and measuring a concentration of hydrogen sulfide and furthermore for discovering biological roles of hydrogen sulfide in vivo, especially, for detecting, imaging, and quantitatively measuring hydrogen sulfide in a disease selected from the group consisting of angiogenesis, inflammation, cancer, Alzheimer's disease, cardiovascular ischemia, and cerebrovascular ischemia, or in hypoxic tissues.