Hyperpolarized 13C Esters for Tissue Differentiation in MRI

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Solution Overview

Problem

Current methods for diagnosing cancer lack specificity in distinguishing tumor tissue from healthy tissue, and there is a need for a technique that can effectively detect cancerous tissue and monitor treatment efficacy.

Innovation Solution

The use of hyperpolarized 13C esters, which are metabolized by carboxylesterase in cancer tissues to produce distinct signals different from those in healthy tissues, allowing for the detection of tumors and evaluation of treatment effectiveness through 13C-MR investigation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional MRI or contrast-enhanced MRI is used, then images can be obtained in a non-invasive way, but the ability to specifically distinguish tumor tissue from healthy tissue is insufficient

Engineering Contradiction:
Improvetissue differentiation capabilityVSAvoidimaging technique complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent changes the chemical parameter of the imaging agent by using hyperpolarized 13C-labeled esters with specific molecular structures that are substrates for carboxylesterase enzymes. This chemical parameter change enables specific metabolic tracking of tumor tissue, improving tissue differentiation capability while maintaining non-invasive MRI imaging.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent introduces hyperpolarized 13C-labeled esters as intermediary metabolic markers that mediate between the MRI imaging system and the tumor tissue metabolism. These esters serve as specific substrates for carboxylesterase enzymes in tumor cells, enabling indirect detection of tumor tissue through their metabolic activity, thereby improving differentiation capability.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If hyperpolarized 13C-labeled esters are used as metabolic markers, then tumor tissue can be specifically detected through carboxylesterase metabolism, but the complexity of the imaging technique increases

Engineering Contradiction:
Improvetumor detection specificityVSAvoidimaging technique complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent employs the endogenous carboxylesterase enzymes present in tumor tissue to automatically metabolize the administered hyperpolarized 13C-labeled ester substrates. The tumor tissue's own metabolic machinery performs the conversion, eliminating the need for external enzymatic systems or complex preparation procedures, thereby improving detection specificity while managing technical complexity.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

Instead of introducing complex external systems to detect tumor tissue, the patent inverts the approach by having the tumor tissue itself perform the detection function through its natural carboxylesterase enzyme activity. The tumor cells metabolize the substrate and produce detectable metabolites, turning the diagnostic function back to the tissue's inherent capability.

Inventive Principle:
Principle #13The other way round (Inversion)

3Measurement precision

If conventional MRI methods are used, then non-invasive imaging is achieved, but the detection of early stage tumors and metastases is limited

Engineering Contradiction:
Improveearly tumor detection capabilityVSAvoidmetabolic information
Core Design Contradiction:
Measurement precisionVSLoss of information

Solution Approach 1:

The patent introduces hyperpolarized 13C-labeled esters as intermediary metabolic markers that mediate between the MRI imaging system and the tumor tissue metabolism. These esters serve as specific substrates for carboxylesterase enzymes in tumor cells, enabling indirect detection of tumor tissue through their metabolic activity, thereby improving differentiation capability.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the chemical parameter of the imaging agent by using hyperpolarized 13C-labeled esters with specific molecular structures that are substrates for carboxylesterase enzymes. This chemical parameter change enables specific metabolic tracking of tumor tissue, improving tissue differentiation capability while maintaining non-invasive MRI imaging.

Inventive Principle:
Principle #35Parameter changes

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

This approach enables selective differentiation between tumor and non-tumor tissues, providing valuable information for cancer diagnosis and monitoring the progression or treatment of tumors, including aggressive forms.

Implementation Method 1

hyperpolarized 13C esters, which are metabolized by carboxylesterase in cancer tissues to produce distinct signals

Methodology Applied
Scientific EffectHydrolysis: Hydrolysis

Data Source

PatentEP2950826B1Hyperpolarized esters as metabolic markers in MRI
Publication Date: 2019.09.18 BRACCO IMAGING SPA
  • EP2950826B1 patent drawingFigure 1
  • EP2950826B1 patent drawingFigure 2A~2B
  • EP2950826B1 patent drawingFigure 3A~3B

AI summary

The invention relates to a method of Magnetic Resonance (MR) detection, in particular 13C-MR detection, by using a diagnostic medium comprising a hyperpolarized ester, in particular ethyl acetoacetate. The method comprises the detection of the MR signal of a hyperpolarized 13C carboxylic ester and of its respective hyperpolarized metabolite.