Labeled Substrates for Bacterial Infection Imaging

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Solution Overview

Problem

Current diagnostic methods for infectious diseases, particularly those affecting deep or obscure sites, are labor-intensive, time-consuming, and often inaccurate, with limitations in differentiating between infection, inflammation, and cancer, and require invasive procedures or imaging techniques that are not always effective.

Innovation Solution

Development of small molecule metabolic tracers that target unique biochemical pathways in infectious organisms, such as prokaryotes, using labeled substrates like 18F-fluorodeoxysorbitol, which are selectively taken up by these organisms, allowing for non-invasive detection and monitoring of infections through imaging agents like PET, SPECT, and MRI.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If standard diagnostic methods (microscopy and microbiologic culture) are used, then diagnosis can be obtained, but the process is labor-intensive and time-consuming

Engineering Contradiction:
Improvediagnosis accuracyVSAvoiddiagnosis time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent replaces traditional mechanical/manual diagnostic methods (microscopy, culture techniques) with nuclear medicine imaging technology. The radiopharmaceutical agents enable non-invasive detection of infections through imaging, eliminating the need for labor-intensive sample processing and culture procedures while providing rapid results.

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

2Measurement precision

If invasive tissue sampling is performed to obtain accurate diagnosis, then diagnostic accuracy improves, but patient risk and procedure complexity increase

Engineering Contradiction:
Improvediagnosis accuracyVSAvoidpatient risk
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent substitutes invasive mechanical sampling procedures with non-invasive nuclear medicine imaging. The radiopharmaceutical agents are administered systemically and accumulate at infection sites, allowing detection through external imaging without tissue biopsy, thereby eliminating sampling risks while maintaining diagnostic accuracy.

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

Solution Approach 2:

The patent introduces radiopharmaceutical agents as intermediaries between the diagnostic system and the infection site. These agents specifically target infectious organisms and can be detected through imaging, serving as a safe mediator that provides accurate diagnostic information without requiring direct tissue sampling.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Ease of operation

If nuclear medicine imaging techniques (18F-fluorodeoxyglucose PET) are used, then non-invasive detection is achieved, but the ability to differentiate between infection, cancer, and sterile inflammation is lost

Engineering Contradiction:
Improvenon-invasive detectionVSAvoidspecificity for infection
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The patent applies the principle of local quality by designing radiopharmaceutical agents with specific biochemical properties that match unique metabolic pathways of infectious organisms. Different agents target different bacterial characteristics (cell wall synthesis, nucleic acid synthesis, carbohydrate metabolism), enabling specific identification of bacterial infections versus other conditions through pattern recognition.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent utilizes parameter changes in bacterial metabolism that differ from host and inflammatory cell metabolism. By targeting specific bacterial metabolic pathways (e.g., folate synthesis, cell wall precursors) that are absent or minimal in eukaryotic cells, the agents achieve specific labeling of bacterial infections while excluding sterile inflammation and cancer.

Inventive Principle:
Principle #35Parameter changes

4Measurement precision

If traditional imaging techniques are used, then structural abnormalities can be detected, but early infections and indolent infections are missed

Engineering Contradiction:
Improvestructural abnormality detectionVSAvoiddetection delay
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent employs preliminary action by detecting metabolic activity of infectious organisms before structural changes occur. The radiopharmaceutical agents accumulate at sites of active bacterial metabolism, allowing detection of early infections and indolent infections that have not yet produced visible structural abnormalities on traditional imaging.

Inventive Principle:
Principle #10Preliminary action

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

Enables rapid and accurate detection and monitoring of infectious organisms, differentiating between infection and inflammation, and assessing antibiotic efficacy, with improved sensitivity and specificity compared to traditional methods, particularly for gram-negative bacteria.

Implementation Method 1

wherein the substrate is a compound that is solely utilized by the metabolism of the infectious organism

Methodology Applied
Scientific EffectMetabolic uptake:

Implementation Method 2

wherein the label of the labeled substrate is a detectable moiety selected from the group consisting of radionuclides, near-infrared dyes, fluorescent dyes, PET, SPECT and MRI imaging agents

Methodology Applied
Scientific EffectRadionuclide emission: Radioactive Decay

Data Source

PatentUS11268958B2Bacteria-specific labeled substrtates as imaging biomarkers to diagnose, locate, and monitor infections
Publication Date: 2022.03.08 JOHNS HOPKINS UNIVERSITY
  • US11268958B2 patent drawing
  • US11268958B2 patent drawing
  • US11268958B2 patent drawing

AI summary

The methods of the present invention exploit unique biochemical pathways present within infectious organisms to develop small molecule metabolic tracers. Labeled substrates created using these inventive methods were created. The labeled substrates can be used to determine whether a subject is infected with an infectious organism by imaging means, and with use of two or more such labeled substrates, methods of differentiating gram negative infection from gram positive infection, and methods of localizing and quantifying infectious disease burden are provided. The methods of the present invention can assist in the clinical decision to begin empiric antibiotic therapy, determine its efficacy, as well as the choice of antibacterial agents.