Direct Elution of Reactive [18F] Fluoride Without Evaporation

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Solution Overview

Problem

Current methods for producing [18F]fluoride for radiolabelling require an evaporation step, which is difficult to implement in automated 'Lab-on-chip' devices and limits the preparation duration and radiochemical yield, and makes it challenging to label sensitive compounds at lower temperatures.

Innovation Solution

A method that prepares reactive [18F]fluoride without an evaporation step using an anion exchange resin and an organic solution containing a polar aprotic solvent and an organic base, allowing for efficient elution and radiolabelling at room temperature, suitable for 'Lab-on-chip' systems and sensitive compounds.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If an evaporation step is used to remove excess water after fluoride recovery, then the radiochemical yield is improved, but the preparation duration increases and the process becomes difficult to implement in automated Lab-on-chip devices

Engineering Contradiction:
Improveradiochemical yieldVSAvoidpreparation duration
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The patent extracts and removes the problematic evaporation step from the traditional radiolabelling process. By using an organic solvent-based elution medium that directly provides reactive fluoride ions without requiring water removal, the invention eliminates the time-consuming evaporation step while maintaining high radiochemical yields through direct nucleophilic substitution reactions in the organic medium.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent changes the physical and chemical parameters of the elution medium by using organic solvents (such as acetonitrile, dimethyl sulfoxide, or dimethylformamide) instead of aqueous solutions. This parameter change allows the fluoride ions to remain reactive without requiring evaporation, thereby reducing preparation time while maintaining reaction efficiency.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If an evaporation step is implemented to dry the fluoride solution, then the radiolabelling efficiency is improved, but the device complexity increases and automation becomes difficult

Engineering Contradiction:
Improveradiolabelling efficiencyVSAvoidequipment complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The invention removes the evaporation step and associated complex equipment from the radiolabelling process. By using organic solvent-based elution that directly yields reactive fluoride ions suitable for nucleophilic substitution, the patent simplifies the overall process and enables easier automation in Lab-on-chip devices without compromising radiolabelling efficiency.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent replaces the mechanical evaporation process with a chemical solution approach. Instead of using heat and mechanical removal of solvent, the invention uses chemically pre-prepared organic elution media that directly provide reactive fluoride ions, thereby eliminating the need for complex evaporation equipment and enabling simpler automated systems.

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

3Quantity of substance

If traditional aqueous elution methods are used, then the fluoride recovery yield is high, but the subsequent radiolabelling requires additional drying steps and cannot be performed at room temperature

Engineering Contradiction:
Improvefluoride recovery yieldVSAvoidoperational simplicity
Core Design Contradiction:
Quantity of substanceVSEase of operation

Solution Approach 1:

The patent changes the composition parameters of the elution medium by using organic solvents instead of aqueous solutions. This parameter change maintains high fluoride recovery yield through anion exchange resin while simultaneously providing reactive fluoride ions that can directly participate in nucleophilic substitution reactions without requiring additional drying steps, thereby simplifying the overall operation.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The organic elution medium serves multiple functions simultaneously: it elutes the fluoride ions from the anion exchange resin with high efficiency, provides an anhydrous environment suitable for nucleophilic substitution, and acts as the reaction medium for the radiolabelling step. This multi-functionality eliminates the need for separate drying and reaction preparation steps.

Inventive Principle:
Principle #6Universality (Multi-functionality)

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 eliminates the need for evaporation, reduces preparation time, increases radiochemical yield, simplifies automated equipment, and enables labelling of temperature-sensitive precursors, making the process more efficient and adaptable for microfluidic devices.

Implementation Method 1

fluoride recovery is based on the use of an anion-exchange resin. The recovery is carried out in two steps, extraction and elution: first the anions (not only fluoride) are separated from the enriched [18O]water and trapped on the said resin

Methodology Applied
Scientific EffectIon exchange: Ion Exchange

Implementation Method 2

a second compound (B) that is an organic base sufficiently strong to be able to tear off the acidic hydrogen of first compound (A) in an acid-base reaction, which leads to the formation of an organic salt (S)

Methodology Applied
Scientific EffectAcid-base reaction: Chemical Bonding

Data Source

PatentEP2164590B1Method for the direct elution of reactive 18f fluoride from an anion exchange resin in an organic medium suitable for radiolabelling without any evaporation step by the use of strong organic bases
Publication Date: 2013.03.06 TRASIS
  • EP2164590B1 patent drawingFigure 1(A)~1(B)

AI summary

The present invention relates to a method to extract out of an aqueous solution, concentrate and/or reformulate [18F] fluorides without any evaporation step characterised in that the eluting solution is a organic solution having a water content <3%, containing at least: an organic solvent suitable for the subsequent radiolabelling reaction; a first compound (A) which is a molecule containing at least one acidic hydrogen and a second compound (B) which is an organic base sufficiently strong to be able to tear off the acidic hydrogen of first compound (A) in an acid-base reaction leading to the formation of an organic salt (S).