Fluorine-Containing Contrast Medium for MRI

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Solution Overview

Problem

Conventional contrast media for MRI diagnosis using fluorine as a detection nucleus lack high sensitivity and stability in vivo.

Innovation Solution

A fluorine-containing compound represented by specific general formulas, which includes alkyl groups and nitroxide radicals, is used as a contrast medium to enhance MRI sensitivity and stability by optimizing spin-lattice and spin-spin relaxation times and reducing susceptibility to reducing agents.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional contrast media containing metal ions are used for 19F-MRI diagnosis, then MRI imaging capability is achieved, but safety concerns arise due to metal ion toxicity

Engineering Contradiction:

ImprovesafetyVSAvoidmetal ion toxicity

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The invention extracts and removes metal ions from the contrast medium formulation. The patent describes a contrast medium comprising fluorinated compounds with nitroxide radicals that does not contain metal ions, thereby eliminating metal ion toxicity while maintaining MRI contrast enhancement capability through the paramagnetic properties of the nitroxide radicals

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The invention employs organic fluorinated compounds with nitroxide radicals as replaceable contrast agents that can be administered and eliminated without long-term retention. These compounds provide the necessary paramagnetic effect for MRI imaging without the persistent safety concerns associated with metal ion accumulation in the body

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

2Measurement precision

If nitroxide compounds are used to enhance MRI sensitivity, then detection sensitivity improves, but stability deteriorates due to easy reduction by reducing agents

Engineering Contradiction:

Improvedetection sensitivityVSAvoidchemical stability

Core Design Contradiction:

Measurement precisionVSStability of the object's composition

Solution Approach 1:

The invention creates a composite molecular structure combining fluorinated compounds with nitroxide radicals. This composite structure maintains the paramagnetic properties of nitroxide for high detection sensitivity while the fluorinated framework provides chemical stability and resistance to reduction by biological reducing agents such as ascorbic acid

Inventive Principle:

Principle #40Composite materials

Solution Approach 2:

The invention modifies the chemical parameters of the nitroxide compound by introducing fluorinated groups and specific molecular structures (as shown in the patent formulas). These parameter changes increase the redox potential and decrease the ease of reduction, thereby improving stability in vivo while maintaining the unpaired electron necessary for paramagnetic MRI contrast

Inventive Principle:

Principle #35Parameter changes

3Measurement precision

If contrast media are designed for high MRI sensitivity, then image quality improves, but in vivo stability deteriorates

Engineering Contradiction:

ImproveMRI sensitivityVSAvoidin vivo stability

Core Design Contradiction:

Measurement precisionVSDuration of action of stationary object

Solution Approach 1:

The invention changes key chemical parameters including the introduction of fluorinated alkyl groups with specific chain lengths, aromatic rings, and cyclic structures. These parameter modifications optimize the balance between paramagnetic strength (for sensitivity) and metabolic stability (for duration of action), creating compounds that maintain their structure and function throughout the diagnostic window

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention applies different structural qualities to different parts of the molecule: the nitroxide radical portion provides paramagnetic activity for sensitivity, while the fluorinated hydrocarbon portions provide metabolic stability and resistance to enzymatic degradation. This local differentiation of functional qualities achieves both high sensitivity and prolonged in vivo stability

Inventive Principle:

Principle #3Local quality

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 fluorine-containing compound provides a highly stable and high-sensitivity magnetic resonance image, avoiding the limitations of metal ion safety concerns and chemical shift artifacts, while maintaining stability and sensitivity in vivo.

Implementation Method 1

optimizing spin-lattice and spin-spin relaxation times

Methodology Applied

Scientific EffectSpin-lattice relaxation:

Implementation Method 2

optimizing spin-lattice and spin-spin relaxation times

Methodology Applied

Scientific EffectSpin-spin relaxation:

Implementation Method 3

magnetic resonance imaging (hereinafter sometimes referred to as 'MRI') diagnosis

Methodology Applied

Scientific EffectMagnetic resonance:

Implementation Method 4

A fluorine-containing compound represented by specific general formulas, which includes alkyl groups and nitroxide radicals

Methodology Applied

Scientific EffectParamagnetism:

Data Source

PatentUS20240156994A1Fluorine-containing compound and contrast medium

Publication Date: 2024.05.16 TDK CORP

AI summary

A fluorine-containing compound represented by Formula (1) or Formula (2) (R1, R2, and R3 in Formula (1) and R4 and R5 in Formula (2) each represent a C1-10 alkyl group unsubstituted or substituted with a substituent containing no fluorine atoms, and X1 in Formula (1) and X2 and X3 in Formula (2) are any of Formulae (3-1) to (3-4).)