Radiofluorination of diaryliodonium tosylates under aqueous–organic and cryptand-free conditions

Abstract

Positron emission tomography (PET) has growing importance as a molecular imaging technique for clinical research and drug development. Methods for producing PET radiotracers utilizing cyclotron-produced [18F]fluoride ion (t1/2 = 109.7 min) without the need for complete removal of irradiated target [18O]water and addition of cryptand are keenly sought for practical convenience and efficiency. Several structurally diverse diaryliodonium tosylates, XArI+Ar′Y TsO− (X = H or p-MeO), were investigated in a microfluidic apparatus for their reactivity towards radiofluorination with high specific activity (no-carrier-added) [18F]fluoride ion in mixtures of DMF and irradiated target [18O]water in the absence of cryptand. Salts bearing a para or ortho electron-withdrawing group Y (e.g., Y = p-CN) reacted rapidly (~ 3 min) to give the expected major [18F]fluoroarene product, [18F]ArY, in useful moderate radiochemical yields even when the solvent had [18O]water content up to 28%. Salts bearing electron-withdrawing groups in meta position (e.g., Y = m-NO2), or an electron-donating substituent (Y = p-OMe), gave low radiochemical yields under the same conditions.

Evaluation of aromatic radiobromination by nucleophilic substitution using diaryliodonium salt precursors

“…Water was well tolerated in the reaction. This observation is the same as that for radiofluorination using iodonium precursors in aqueous solutions . When KBr (0.1 mg) was added as carrier, the yield remained high.…”

Development of Customized [18F]Fluoride Elution Techniques for the Enhancement of Copper-Mediated Late-Stage Radiofluorination

“…[ 18 F]Fluoride is generally considered to be strongly hydrated in polar protic solvents and thereby deactivated for nucleophilic reactions (although several recent examples suggest that this might not always be the case) 3–6 . As such, a well-established three-step process is typically used to increase the reactivity of nucleophilic [ 18 F]fluoride (Fig.…”

Facile room temperature synthesis of fluorine-18 labeled fluoronicotinic acid-2,3,5,6-tetrafluorophenyl ester without azeotropic drying of fluorine-18

“…This multistep and harsh fluorine-18 labeling procedure restricts the access to the many useful fluorine-18 labeled PET imaging agents. Various modifications have been made to improve these standard protocols such as the use of ionic liquid media [20], the effect of additives [21, 22], green fluorination [23], titania-catalyzed radiofluorination [24], minimalist approach [25] or fluorination of diaryliodonium tosylates under aqueous-organic conditions [26] but these modifications have not been widely accepted by the PET community. Therefore, there is a clear need of the development of quicker and milder nucleophilic fluorination method for the extended use of fluorine-18 PET tracers in nuclear medicine.…”