[F-18]FEONM Purification via High-Pressure Diphenyl HPLC

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Solution Overview

Problem

Current methods for producing [F-18]FEONM involve toxic solvents and require multiple purification steps, making it difficult to achieve a non-toxic product suitable for direct intravenous injection in PET imaging, especially for Alzheimer disease-related protein imaging.

Innovation Solution

A high-pressure purification method using a semipreparative diphenyl column with a non-toxic ethanol solution and filter sterilization to remove unreacted precursors, reducing toxicity and shortening production time, allowing for direct intravenous injection.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Object-affected harmful factors

If traditional purification methods with toxic solvents are used, then purification can be achieved, but the product cannot be directly used for intravenous injection due to toxicity

Engineering Contradiction:

ImprovetoxicityVSAvoiddirect injection capability

Core Design Contradiction:

Object-affected harmful factorsVSEase of manufacture

Solution Approach 1:

The patent changes the solvent parameter from toxic solvents (acetonitrile, dichloromethane) to non-toxic ethanol, enabling direct intravenous injection while maintaining purification effectiveness through optimized HPLC conditions

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent uses ethanol, a non-toxic and readily available solvent, replacing expensive and toxic solvents, making the process safer and more suitable for pharmaceutical applications

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

2Object-affected harmful factors

If multiple purification steps are used to reduce solvent toxicity, then product safety improves, but production time increases

Engineering Contradiction:

Improvesolvent toxicityVSAvoidproduction time

Core Design Contradiction:

Object-affected harmful factorsVSLoss of time

Solution Approach 1:

The patent combines the purification and solvent removal steps into a single HPLC purification process using ethanol, eliminating the need for separate evaporation and re-dissolution steps required by traditional methods

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The patent implements continuous purification through HPLC with ethanol elution, maintaining product purity while avoiding intermittent toxic solvent exchanges and multiple processing cycles

Inventive Principle:

Principle #20Continuity of useful action

3Productivity

If high-pressure purification is used to improve purification efficiency, then production time decreases, but equipment complexity increases

Engineering Contradiction:

Improvepurification efficiencyVSAvoidequipment complexity

Core Design Contradiction:

ProductivityVSDevice complexity

Solution Approach 1:

The patent employs high-pressure liquid chromatography (HPLC) using ethanol as mobile phase, leveraging hydraulic principles to achieve rapid and efficient purification with a single pass through the diphenyl column

Inventive Principle:

Principle #29Pneumatics and hydraulics

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 method achieves high radiochemical purity and increased lipophilicity of [F-18]FEONM, enabling dual radiography of Alzheimer disease-related proteins with reduced solvent toxicity and extended PET application potential.

Implementation Method 1

injecting the crude product of [F-18]FEONM with an injector and a semipreparative diphenyl column via semipreparative high pressure pumping unit to isolate and purify

Methodology Applied

Scientific EffectChromatography: Chromatography

Implementation Method 2

filter sterilizing remaining crude product of [F-18]FEONM obtained after eluting said (TEONM) precursor to obtain a purified product of [F-18]FEONM

Methodology Applied

Scientific EffectFiltration: Filter (physical)

Data Source

PatentUS11247947B2Method of high-pressure purification of [f-18]FEONM

Publication Date: 2022.02.15 ATOMIC ENERGY COUNCIL INSTITUTE OF NUCLEAR ENERGY RESEARCH

AI summary

A method is provided to purify [F-18]FEONM under a high pressure. The synthesis processes of [F-18]FEONM are integrated. An isolation process of non-toxic radio-high performance liquid chromatography (radio-HPLC) is used to purify the crude product. The method integrates a convention [F-18]FDG synthesizer and a novel radio-HPLC system together in a heat chamber. After radiofluorinating the precursor, the reaction product is purified with an alumina solid-phase column in advance to obtain the crude product while fluorine-18 is removed. Then, diphenyl semipreparative HPLC column is used for a final purification. A non-toxic solvent is used for mobile-phase eluting to remove the unreacted precursor and the phase-transfer solvent. The radiofluorination has a reaction yield about 50 percent (%). The method has an uncorrected radiochemical yield of 10˜20%. Both of the radio-HPLC and the radio-thin layer chromatography (radio-TLC) have radiochemical purity higher than 95%.