Radiosynthesis and Evaluation of [¹⁸F]Selectfluor bis(triflate)

Abstract

Selectfluor, one of the most reactive and commonly used electrophilic fluorinating N–F reagents, has been radiolabeled with 18F. The resulting new [18F]‐labeled N–F reagent is safe, nontoxic, and easy to handle. The combined use of [18F]Selectfluor bis(triflate) and AgOTf allows for the preparation of electron‐rich 18F‐aromatic compounds through a simple “shake and mix” protocol at room temperature (see scheme; SA=specific activtiy).

Radiosynthesis and Preclinical Evaluation of [18F]F-DPA, A Novel Pyrazolo[1,5a]pyrimidine Acetamide TSPO Radioligand, in Healthy Sprague Dawley Rats

“…Reported herein is the use of a mild electrophilic [ 18 F]fluorination reagent, 1-(chloromethyl)-4-[ 18 F]fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(triflate) ([ 18 F]Selectfluor bis(triflate)) [26] for the preparation of [ 18 F]F-DPA, and the evaluation of this radiotracer in healthy rats. The metabolic profile and biodistribution of [ 18 F]F-DPA were compared with that of the closely-related radiotracer [ 18 F]DPA-714.…”

Metal-free 18F-labeling of aryl-CF2H via nucleophilic radiofluorination and oxidative C–H activation

“…The purified [ 18 F] 3a was isolated in 38% radiochemical yield (non-decay corrected, based on the added activity of [ 18 F] 2a ) with specific activity of 22.2 GBq/µmol at end-of-synthesis (~25 min synthesis time from the addition of [ 18 F] 2a ). As shown in Table 3, the current method gives superior specific activity among other reported synthesis of [ 18 F]aryl-CF 2 H. 6a,7,8 Efforts were also made to further improve the specific activity by changing the counterion of the current fluorinating reagents to PF 6 − (F-TEDA-PF 6 ) and OTf − (1-chloromethyl-4-fluoro-1,4-diazoniabicyclo [2.2.2]octane bis(trifluoromethane sulfonate; F-TEDA-OTf; see SI for its preparation), though none of them gave the desired product [ 18 F] 3a . Since the tetrafluoroborate anion (BF 4 − ) had been proven to give comparably high specific activity as that of OTf − in an analogous radiosynthesis of aryl-[ 18 F]fluoride from (mesityl)(aryl)iodonium salt precursors, 15 it is reasonable to postulate there was limited exchange reactions between 19 F and 18 F during the present radiolabeling conditions.…”

“…Initial methods relied on the silver(I)-mediated fluorodecarboxylation of α-fluorarylacetic acids with [ 18 F]Selectfluor bis(triflate), an electrophilic fluorinating reagent derived from [ 18 F]F 2 . 6 An alternative 18 F-incorporation method employed a silver(I)-mediated halogen exchange strategy with readily available [ 18 F]fluoride under mild reaction conditions, but required aryl-CHFCl precursors prepared by multi-step synthesis. 7 Our recent work disclosed a more practical method, starting from easily accessed aryl (pseudo)halides, via the activation of a benzoyl auxiliary, to form the [ 18 F]Ar–CF 2 H functionality with an excellent substrate scope.…”

“…14 Obtaining high specific activity is an ongoing challenge for many 18 F-labeling of multi-fluorinated compounds. 6a,7,8 As shown in Scheme 6, we measured the specific activity of aryl-CF 2 H product [ 18 F] 3a by our protocol (see SI for details). Briefly, compound [ 18 F] 2a was synthesized and isolated using a commercial automated radiofluorination unit (GE TRACERlab™ FX FN ; Figure S1, SI), starting from 1.7 GBq of [ 18 F]fluoride, in 61% radiochemical yield (non-decay corrected) with >99% radiochemical purity and 51.8 GBq/µmol specific activity at the end-of-synthesis (~60 min synthesis time from [ 18 F]fluoride).…”

Oxime formation for fluorine-18 labeling of peptides and proteins for positron emission tomography (PET) imaging: A review

“…Fluorine-18 ( 18 F) is a radioactive isotope of fluorine and of major importance in nuclear pharmacy [2,3]. The half-life of 18 F is 109.7 min and 18 F has a very clean positron decay process (97% b + emission) [4]. 18 F is the most often used radionuclide for clinical positron emission tomography (PET) imaging and 2-[ 18 F]fluoro-2-deoxy-D-glucose ([ 18 F]FDG) is the most used PET tracer.…”