Fluoride Trapping Cassette for Multi-Batch PET Production

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Solution Overview

Problem

Current automated synthesis systems for [18F]-labelled compounds, such as the GE Healthcare FASTlab cassette, are limited in producing multiple batches of [18F]FDG due to residual activity and contamination issues, requiring multiple hot cells and complicating the recycling of QMA columns, which hampers efficient production and purity of subsequent batches.

Innovation Solution

A novel system and method for trapping [18F]fluoride and recovering [18O]water using a single cassette with a configuration that allows for two consecutive batches, utilizing a first and second anion exchange column with a common pathway and valve system to manage fluid communication, enabling efficient trapping and elution of [18F]fluoride while minimizing contamination and maintaining cassette position availability for additional components.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If a single cassette is used to produce multiple batches of [18F]FDG, then productivity is improved, but contamination and residual activity increase

Engineering Contradiction:
Improvenumber of batches per cassetteVSAvoidcontamination and residual activity
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The system divides the single cassette into multiple independent trapping pathways, each with its own QMA column and valve control. This segmentation allows each pathway to be independently flushed and prepared for subsequent batches, preventing cross-contamination while maintaining high productivity through multi-batch capability within a single cassette.

Inventive Principle:
Principle #1Segmentation

2Loss of substance

If QMA column recycling is implemented, then loss of substance is reduced, but device complexity increases

Engineering Contradiction:
Improveradioactive material wasteVSAvoidcassette configuration complexity
Core Design Contradiction:
Loss of substanceVSDevice complexity

Solution Approach 1:

The QMA column is designed to serve multiple functions across different batches. The same column can trap [18F]fluoride in one batch, be flushed and cleaned, then trap [18F]fluoride again in subsequent batches. The valve system enables this column to be selectively connected to different pathways (enriched water recycling, solvent addition, product collection) making it a universal component that reduces waste while the standardized design keeps complexity manageable.

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

3Productivity

If enriched water recycling pathway is added, then productivity is improved, but device complexity increases

Engineering Contradiction:
Improvebatch production efficiencyVSAvoidcassette pathway complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The enriched water recycling pathway is pre-configured within the cassette structure, with dedicated tubing and valve connections already in place. This preliminary arrangement allows the system to immediately recycle enriched water from the product collection vial back to the trapping pathway without requiring additional external connections or complex manual reconfiguration, thereby improving productivity while keeping the added complexity integrated and manageable.

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

This configuration allows for the production of two batches of [18F]-labelled compounds with improved yields and reduced contamination, enabling flexible use of solvents like ethanol and acetonitrile, and maintains the cassette's compactness, thus overcoming the limitations of prior art systems by allowing efficient recycling and reduced Kryptofix 222 contamination in the final product.

Implementation Method 1

a first end (4a) of a first length of tubing (4) fluidly connected to a common pathway (2) in between a second anion exchange column (5) and an [18F]fluoride inlet (1)

Methodology Applied
Scientific EffectIon exchange: Ion Exchange

Implementation Method 2

a valve (3c, 4c, 5c, 6c, 7c, 8c) having three ports and means to put any two of the three associated ports in fluid communication with each other while fluidly isolating the third port

Methodology Applied
Scientific EffectValve control: Valve

Data Source

PatentEP3218333B1Fluoride trapping arrangement
Publication Date: 2023.06.07 GE HEALTHCARE LTD
  • EP3218333B1 patent drawingFigure 1
  • EP3218333B1 patent drawingFigure 2
  • EP3218333B1 patent drawingFigure 3

AI summary

The present invention provides a new chemical process, a new cassette configuration, and new software for the automated production of multiple batches of an [18F] labelled compound on a single cassette. The invention allows one synthesizer in one hot cell to produce sequentially a plurality of batches of [18F]-labelled PET tracer in the same day. In particular, the present invention provides a novel arrangement useful for the trapping of [18F]fluoride and recovery of [180]water.