Quantitative Mapping of Mitochondrial Complex I Expression via PET Imaging

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Solution Overview

Problem

Current methods lack a non-invasive means to quantify mitochondrial complex I (MC-I) expression levels in vivo, relying on invasive in vitro assays that require biopsies or surgery, which is clinically undesirable for assessing various diseases linked to MC-I deficiencies.

Innovation Solution

A non-invasive PET imaging method using a PET ligand like 18F-Flurpiridaz, which binds reversibly to MC-I, allowing for quantitative mapping of MC-I expression and myocardial blood flow, enabling in vivo assessment of MC-I levels and related disorders.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If in vitro assay is used to measure MC-I expression, then measurement precision is improved, but ease of operation deteriorates due to requiring biopsy or surgery

Engineering Contradiction:
ImproveMC-I expression measurementVSAvoidinvasive procedure requirement
Core Design Contradiction:
Measurement precisionVSEase of operation

Solution Approach 1:

The patent uses a PET ligand as an intermediary substance that binds to MC-I in living tissue, enabling indirect measurement of MC-I expression through PET imaging. This mediator allows in vivo quantification without direct tissue extraction, resolving the contradiction between measurement precision and ease of operation

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces the mechanical invasive procedure (biopsy/surgery) with a non-invasive imaging system (PET scanner). The mechanical system of tissue extraction is substituted by a detection system that measures MC-I expression through the binding of radioligand and subsequent gamma ray detection

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

2Ease of operation

If in vivo PET imaging with MC-I ligand is used, then ease of operation is improved, but measurement precision may deteriorate due to binding reaction complexity

Engineering Contradiction:
Improvenon-invasive measurementVSAvoidMC-I expression quantification
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The patent performs preliminary kinetic analysis and validation to establish the binding characteristics of the PET ligand to MC-I before clinical application. By pre-characterizing the binding reaction kinetics and validating the imaging protocol, the method ensures measurement precision is maintained despite the complexity of in vivo binding

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent uses dynamic PET imaging to capture the time-dependent binding behavior of the ligand to MC-I, providing feedback information about the binding kinetics. This feedback allows for quantitative analysis that accounts for the complex binding reaction, maintaining measurement precision through continuous monitoring and modeling

Inventive Principle:
Principle #23Feedback

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 accurate and precise non-invasive quantification of MC-I expression levels and myocardial blood flow, facilitating the diagnosis of MC-I-related diseases and providing a tool for evaluating therapeutic agents, with potential applications in cardiac and neuropsychiatric disorders.

Implementation Method 1

administering a PET ligand which binds reversibly to MC-I in the tissues of a living subject

Methodology Applied
Scientific EffectReversible binding: Adsorption

Implementation Method 2

imaging the subject with a positron emission tomography (PET) imaging system

Methodology Applied
Scientific EffectPositron emission: Radioactive Decay

Data Source

PatentEP2882863B1System and method for quantitative mapping of mitocondrial complex 1
Publication Date: 2021.07.14 THE GENERAL HOSPITAL CORP
  • EP2882863B1 patent drawingFigure 1A~1B
  • EP2882863B1 patent drawingFigure 1C
  • EP2882863B1 patent drawingFigure 2A~2B

AI summary

A system and method is provided for processing a positron emission tomography (PET) image of a subject having received a dose of a radiotracer that serves as chemical analog of an MC-I inhibitor. Specifically, the processing may includes identifying portions of the at least one PET image that represent MC-I expression levels.