Hyperpolarized MRI Precursors for High Solubility and Yield

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Solution Overview

Problem

Existing PHIP-SAH methods for hyperpolarizing biorelevant imaging agents face challenges in producing clinically relevant polarizations, concentrations, and purities due to poor solubility in organic solvents and low reaction yields with parahydrogen.

Innovation Solution

Development of novel precursors, such as compounds of Formulas I, II, III, and IV, which include a PHIP transfer moiety and a biorelevant imaging agent, allowing for efficient hydrogenation and polarization transfer to achieve high solubility and chemical yield, enabling the production of hyperpolarized biorelevant imaging agents with enhanced nuclear spin polarization.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If existing PHIP-SAH methods are used to hyperpolarize biorelevant imaging agents, then polarization can be achieved, but the solubility in organic solvents is poor and reaction yields with parahydrogen are low

Engineering Contradiction:

Improveconcentration of hyperpolarized imaging agentVSAvoidsolubility in organic solvents

Core Design Contradiction:

Quantity of substanceVSEase of manufacture

Solution Approach 1:

The patent modifies the chemical structure of precursors by changing parameters such as introducing specific functional groups (R1-R6 substituents), varying carbon chain lengths, and adjusting molecular weight to optimize both solubility in organic solvents and reaction yields with parahydrogen, thereby resolving the contradiction between manufacturability and product concentration

Inventive Principle:

Principle #35Parameter changes

2Quantity of substance

If existing PHIP-SAH methods are used to hyperpolarize biorelevant imaging agents, then polarization can be achieved, but the reaction yields with parahydrogen are low

Engineering Contradiction:

Improvechemical yield of hyperpolarized imaging agentVSAvoidreaction efficiency with parahydrogen

Core Design Contradiction:

Quantity of substanceVSEase of manufacture

Solution Approach 1:

The patent systematically varies chemical parameters of the precursor molecules including substituent types (R1-R6), molecular weight, and structural configuration to enhance reaction efficiency with parahydrogen gas, directly addressing the low chemical yield problem while maintaining ease of manufacture

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent employs composite precursor structures combining biorelevant imaging agent moieties with specific PHIP-active functional groups, creating molecules that simultaneously exhibit high reactivity with parahydrogen and good solubility properties, thereby resolving the yield-efficiency contradiction

Inventive Principle:

Principle #40Composite materials

3Quantity of substance

If existing PHIP-SAH methods are used to hyperpolarize biorelevant imaging agents, then polarization can be achieved, but the purity of the hyperpolarized product is insufficient for clinical applications

Engineering Contradiction:

Improvepurity of hyperpolarized imaging agentVSAvoidcomplexity of purification process

Core Design Contradiction:

Quantity of substanceVSDevice complexity

Solution Approach 1:

The patent designs precursors with built-in purification advantages, such as incorporating removable protecting groups and designing reaction pathways that produce minimal byproducts, enabling straightforward purification to clinical-grade purity without complex processing steps

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

The proposed solution increases the concentration and purity of hyperpolarized biorelevant imaging agents, improving their suitability for clinical applications by enhancing solubility and chemical yield in both water and organic solvents, thereby overcoming previous limitations in PHIP-SAH techniques.

Implementation Method 1

Parahydrogen induced polarization (PHIP) is a method for polarizing metabolites forhyperpolarized (HP) Magnetic Resonance Imaging (MRI)

Methodology Applied

Scientific EffectParahydrogen induced polarization (PHIP):

Implementation Method 2

Z comprises: (i) a carbon-carbon double bond (—C═C—) which is substituted to include 1H (proton), 2H (deuterium), or a combination thereof, or (ii) a carbon-carbon triple bond (—C≡C—)

Methodology Applied

Scientific EffectHydrogenation: Hydrogenation

Data Source

PatentUS20250091980A1Systems and methods for generation of hyperpolarized materials

Publication Date: 2025.03.20 NVISION QUANTUM TECHNOLOGIES GMBH

AI summary

The present disclosure describes hyperpolarized materials for use in nuclear magnetic resonance, magnetic resonance imaging, or similar applications. The present disclosure describes methods for producing hyperpolarized materials for use in nuclear magnetic resonance, magnetic resonance imaging, or similar applications. The present disclosure describes precursor compounds for use in producing hyperpolarized materials for use in nuclear magnetic resonance, magnetic resonance imaging, or similar applications.