Single‐Step Radiosynthesis of “¹⁸F‐Labeled Click Synthons” from Azide‐Functionalized Diaryliodonium Salts

Abstract

Positron emission tomography (PET) is an increasingly important biomedical imaging technique that relies on the development of radiotracers labeled with positron-emitters to achieve biochemical specificity. Fluorine-18 (<i>t</i>_1/2 = 109.7 min) is an attractive positron-emitting radiolabel for organic radiotracers, primarily because of its longer half-life and greater availability relative to those for the main alternative, carbon-11 (<i>t</i>_1/2 = 20.4 min). Rapid simple methods are sought for labeling prospective PET radiotracers with fluorine-18 from cyclotron-produced aqueous [¹⁸F]fluoride ion, which must often be converted first into a suitably reactive labeling synthon for use in a subsequent labelling reaction. Use of ¹⁸F-labeled synthons in 'click chemistry' attracts increasing attention for labeling PE Tradiotracers. Here we describe rapid single-step radiosyntheses of azido- or azidomethyl-bearing [¹⁸F]fluoroarenes from the reactions of diaryliodonium salts with no-carrier-added [¹⁸F]fluoride ion within a microfluidic apparatus to provide previously poorly accessible ¹⁸F-labeled click synthons in radiochemical yields of 15% for [¹⁸F]4-fluorophenyl azide and about 40% for each of the [¹⁸F](azidomethyl)-fluorobenzenes. The radiosyntheses of the latter synthons was possible under 'wet conditions', so obviating the need to dry the cyclotron-produced [¹⁸F]fluoride ion and greatly enhancing the practicality of the method.