Facile purification and click labeling with 2-[18F]fluoroethyl azide using solid phase extraction cartridges

Abstract

A facile method was developed to purify 2-[18F]fluoroethyl azide ([18F]FEA) using a C18 cartridge and an Oasis® HLB cartridge in series, in which [18F]FEA was exclusively trapped on the HLB cartridge. [18F]FEA can be eluted for reactions in solution; alternatively click labeling can be carried out on the HLB cartridge itself by loading an alkyne substrate and copper (I) catalyst dissolved in DMF onto the cartridge. This solid phase extraction methodology for purification and click labeling with [18F]FEA, either in solution or on the cartridge, is safe, simple, reproducible in high yield, and compatible with automated synthesis of 18F-labeled PET tracers.

Fluorine-18 labelled building blocks for PET tracer synthesis

“…148 Furthermore, these 'click'-reactions usually show high specificity, robustness and yields. 149 Many different functional groups are well tolerated, making additional protection and deprotection steps unnecessary. 150 Moreover, the click reaction is an excellent method to build up libraries of compounds for screening campaigns to ultimately select the best PET tracer.…”

“…161 This was also reported by other research groups. 149 Next to the flow-and-trap-distillation method, a vacuum distillation method has been developed by Zhou et al They reported radiochemical yields of over 80% (dc) within 10 minutes including formation of [ 18 F]fluoroethyl azide, distillation into a dry ice cooled trapping vial and warming up to room temperature. 162 However, due to co-distillation of the side-product vinyl azide, the precursor for the follow-up reaction was needed in large excess.…”

“…151,163 Another approach used a silica-based C18 cartridge and a Water Oasis HLB cartridge in series. 149 For some tracer syntheses, successful one-pot procedures have been described. 164,165 However, the one-pot method often promotes side-reactions, which necessitates elaborate purification of the PET tracer.…”

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

“…These solutions allow the reduction of inherent void volumes, therefore improving the atom efficiency in the purification process. Also, similar solutions may be useful for the cases in which a simple solid-phase extraction (SPE) would be sufficient to purify the relevant molecule [36,37]. Polymer chemistry advancement possibly represents the field where useful innovations can have a relevant impact on miniaturized purifications.…”

Unexpected Direct Synthesis of N‐Vinyl Amides through Vinyl Azide–Enolate [3+2] Cycloaddition

“…[13] Furthermore,t he mechanism shown for path Aw ould not account for the different reactivity observed between the three-carbon-atom iodo azide 12 and the two-carbon-atom iodo azide 14.A control experiment conducted in the absence of an aldehyde (Scheme 4, path B) showed rapid conversion of 14 into azidoethene (39)b yN MR spectroscopy upon exposure to potassium tert-butoxide. [14] These conditions are similar to those originally developed by Hassner and co-workers in as eries of seminal studies on the formation of substituted vinyl azides. [15] Azidoethene (39)c ould then undergo rapid cycloaddition with an enolate to give at riazole intermediate 40,f rom which nitrogen extrusion and a1 ,2-hydride shift would give N-vinyl amide 38 either through ac oncerted process or an asynchronous sequence involving an intermediate diazonium ion.…”