Automated Solid-Phase Radiofluorination Using Polymer-Supported Phosphazenes

Abstract

O]H 2 O and subsequent radiofluorination of a broad range of substrates directly on the resin. The highest radiochemical yields were obtained with aliphatic sulfonates (69%) and bromides (42%); the total radiosynthesis time was 35-45 min. The multivariate analysis showed that the radiochemical yields and purities were controlled by the resin load, reaction temperature, and column packing effects. The resins could be reused several times with the same or different substrates. The fully automated on-column radiofluorination methodology was applied to the radiosynthesis of the important PET radiotracers [ recovery and processing, and column reusability can make solid phase radiofluorination an attractive radiochemistry platform for the emerging dose-on-demand instruments for bedside production of PET radiotracers.

Fluorine-18 Patents (2009–2015). Part 2: New Radiochemistry

“…This approach to [ 18 F]fluorination is desirable as it does not require the use of complicated synthesis module setup and is potentially more automatable. For example, a column design method patented [22] and reported [23] by inventors at the Technical University of Denmark details a reusable phosphazene-PEG appended polystyrene column design for solid-phase [ 18 F]fluorination reactions. Target water is first passed over the resin, thereby trapping the [ 18 F]HF present in target water via reaction with immobilized phosphazene.…”

18F-labelling innovations and their potential for clinical application

“…The first study of 18 Ffluorination on the resin led only to poor RCY compared to a substitution in solution, presumably due to a slower reaction of [ 18 F]fluoride with the labelling precursor [62]. However, an enormous improvement could be made by using phosphazene bases fixed on a polymer support, which allowed nearly quantitative trapping and drying of [ 18 F]fluoride with dry organic solvents and subsequent radiofluorination on the solid phase [63].…”

How Far Are We from Dose On Demand of Short-Lived Radiopharmaceuticals?

“…Although the use of microfluidic conditions is leading to radiochemical reactions being completed in less time than traditional approaches, to further decrease the overall radiochemical processing times, new methods are required to decrease or eliminate the time taken to process and activate the starting [ 18 [26]. The PS-P 2 tBu resin was able to trap >99% of [ 18 F]fluoride, with no leaching of activity was observed when the column was subsequently dried with helium gas.…”