Automated synthesis of 18F‐labelled analogs of metomidate,vorozole and harmine using commercial platform

Three ¹⁸F‐labelled PET tracers, 2‐[¹⁸F]fluoroethyl 1‐[(1R)‐1‐phenylethyl]‐1H‐imidazole‐5‐carboxylate ([¹⁸F]FETO), 6‐[(S)‐(4‐chlorophenyl)‐(1H)‐1,2,4‐triazol‐1‐yl)methyl]‐1‐(2‐[¹⁸F]fluoroethyl)‐1H‐benzotriazole ([¹⁸F]FVOZ) and 7‐[2‐(2‐[¹⁸F]fluoroethoxy)ethoxy]‐1‐9H‐ β ‐carboline ([¹⁸F]FHAR) were synthesized by a one‐step nucleophilic fluorination using the automated commercial platform TRACERLab FX_FN. The labelled products were obtained with 16–20% isolated decay corrected radiochemical yields after 70–75 min synthesis time. The radiochemical and chemical purities were more than 98% in all cases. The synthesis using commercial platform may make these tracers more accessible for clinical research. Copyright © 2010 John Wiley & Sons, Ltd.     

Synthesis of 18F‐labeled cyclooxygenase‐2 (COX‐2) inhibitor as a potential PET imaging agent

A new PET tracer for COX‐2 imaging, the 6‐ethoxy‐3‐(4‐methanesulfonylphenyl)‐4‐(4‐[¹⁸F]fluorophenyl)pyran‐2‐one ([¹⁸F]EFMP), was synthesized. For F‐18 radiolabeling, a trimethylammonium precursor and a brominated precursor were synthesized from 1,1,2,3‐tetrachlorocycloprop‐2‐ene in 6 steps. The radiolabeling was achieved through nucleophilic substitution using no‐carrier‐added (n.c.a.) fluorine‐18. Solid‐phase extraction and semi‐preparative‐HPLC purification produced [¹⁸F]EFMP in 14.6±3.3% (n =4) decay corrected radiochemical yield with a specific activity of 487±85.1 (n =4) Ci/mmol and greater than 98% radiochemical purity. Copyright © 2006 John Wiley & Sons, Ltd.     

Fully automated radiosynthesis of [1‐(2‐[18F]fluoroethyl),1H[1,2,3]triazole 4‐ethylene] triphenylphosphonium bromide as a potential positron emission tomography tracer for imaging apoptosis

A novel phosphonium salt bearing a fluorine‐18 labelled triazole has been designed as a potential imaging agent for apoptosis. The radiosynthesis of [1‐(2‐[¹⁸F]fluoroethyl),1H[1,2,3]triazole 4‐ethylene] triphenylphosphonium bromide ([¹⁸F]MitoPhos_01) has been carried out on a fully automated system in a two‐step reaction. Radiolabelling an ethyl azide and then carrying out a copper‐mediated 1,3‐cycloaddition reaction has allowed for total synthesis time to be slightly more than 1 h from aqueous [¹⁸F]fluoride. After purification by HPLC, the average radiochemical yield was determined to be 9% (not decay corrected); the specific activity was on average 70 GBq/µmol at the end of synthesis, and the radiochemical purity was >99%.     

One‐step radiosynthesis of 4‐nitrophenyl 2‐[18F]fluoropropionate ([18F]NFP); improved preparation of radiolabeled peptides for PET imaging

The versatile ¹⁸F‐labeled prosthetic group, 4‐nitrophenyl 2‐[¹⁸F]fluoropropionate ([¹⁸F]NFP), was synthesized in a single step in 45 min from 4‐nitrophenyl 2‐bromopropionate, with a decay corrected radiochemical yield of 26.2% ± 2.2%. Employing this improved synthesis of [¹⁸F]NFP, [¹⁸F]GalactoRGD — the current ‘gold standard’ tracer for imaging the expression of α_Vβ₃ integrin — was prepared with high specific activity in 90 min and 20% decay corrected radiochemical yield from [¹⁸F]fluoride.     

Facile synthesis of N‐succinimidyl 4‐[18F]fluorobenzoate ([18F]SFB) for protein labeling

An efficient preparation of N‐succinimidyl 4‐[¹⁸F]fluorobenzoate ([¹⁸F]SFB) based on a convenient three‐step, one‐pot procedure is described. [¹⁸F]Fluorination of the precursor ethyl 4‐(trimethylammonium triflate)benzoate gave ethyl 4‐[¹⁸F]fluorobenzoate. Saponification of the ethyl 4‐[¹⁸F]fluorobenzoate with aqueous tetrapropylammonium hydroxide yielded the corresponding 4‐[¹⁸F]fluorobenzoate salt ([¹⁸F]FBA), which was then treated with N,N,N,N′‐tetramethyl‐O‐(N‐succinimidyl)uronium hexafluorophosphate. The purified [¹⁸F]SFB was used for the labeling of Avastin^? (Bevacizumab) through [¹⁸F]fluorobenzoylation of the Avastin's α‐amino groups. The decay‐corrected radiochemical yields of [¹⁸F]SFB were as high as 44% (based on [¹⁸F]fluoride (n=10) with a synthesis time of less than 60 min. [¹⁸F]Avastin was produced in decay‐corrected radiochemical yields of up to 42% (n=5) within 30 min (based on [¹⁸F]SFB). The radiochemical purities of [¹⁸F]SFB and [¹⁸F]Avastin were greater than 95%. Copyright © 2008 John Wiley & Sons, Ltd.     

A novel probe for imaging amyloid‐β: Synthesis of F‐18 labelled BF‐108, an Acridine Orange analog

The synthesis of 3‐(2‐[¹⁸F]fluoroethyl)ethylamino‐6‐diethylaminoacridine ([¹⁸F]BF‐108), a potential positron‐labelled probe for imaging amyloid‐β is described. The precursor tosylate derivative was fluorinated with [¹⁸F]KF/ Kryptofix 222 in acetonitrile, and the crude product was purified by semi‐preparative HPLC to give the radiolabelled BF‐108. The radiochemical purity was >95% and the maximum specific activity was 33.9 TBq/mmol at the end of the synthesis (EOS). The synthesis time was 130 min from the end of bombardment (EOB). Copyright © 2003 John Wiley & Sons, Ltd.     

Simple preparation of new [18F]F‐labeled synthetic amino acid derivatives with two click reactions in one‐pot and SPE purification

New [¹⁸F]fluorinated 1,2,3‐triazolyl amino acid derivatives were efficiently prepared from Huisgen 1,3‐dipolar cycloaddition reactions, well known as click reaction. We developed two simultaneous click reactions in one‐pot with a simple solid‐phase extraction (SPE) purification method. [¹⁸F]fluoro‐1‐propyne was obtained at a 45% non‐decay corrected radiochemical yield based on the [¹⁸F]fluoride ion. The one‐pot and simultaneous two click reactions were performed with unprotected azido‐alkyl amino acid, [¹⁸F]fluoro‐1‐propyne, and lipophilic additive alkyne to produce three synthetic amino acid derivatives, AMC‐101 ( [¹⁸F]‐6a ), AMC‐102 ( [¹⁸F]‐6b ), and AMC‐103 ( [¹⁸F]‐6c ) with 29%, 28%, and 24% of non‐decay corrected radiochemical yields, respectively. All radiotracers indicated that radiochemical purities were >95% without any residual organic solvent. Our new method involving two click reactions in one‐pot showed high radiochemical and chemical purity by easy removal of the residual precursor from the simultaneous two click reactions.     

Copper‐mediated reduction of 2‐[18F]fluoroethyl azide to 2‐[18F]fluoroethylamine

¹⁸F‐labelled fluoroalkylamines are attractive reagents for the preparation of positron emission tomography tracers containing amine, amide, and N‐heterocyclic moieties. Herein, we report that 2‐[¹⁸F]fluoroethylamine can be obtained from 2‐[¹⁸F]fluoroethyl azide by reduction with elemental copper under acidic conditions. Azide to amine reduction was achieved in near quantitative analytical yields within 30 min by heating a solution of 2‐[¹⁸F]fluoroethyl azide in the presence of copper wire and aqueous trifluoroacetic acid. Subsequent reaction of 2‐[¹⁸F]fluoroethylamine with benzoyl chloride in the presence of triethylamine provided N‐[¹⁸F]fluoroethyl benzamide in 63% decay‐corrected radiochemical yield from 2‐[¹⁸F]fluoroethyl azide. The utility of the Cu(0)/H⁺ azide reduction method was further exemplified by preparation of the potential GABA_A tracer 9H‐β‐carboline N‐2‐[¹⁸F]fluoroethylamide, which was obtained in 46% decay‐corrected radiochemical yield by reaction of 2‐[¹⁸F]fluoroethylamine with the corresponding 9H‐β‐carboline pentafluorophenyl ester. Copyright © 2012 John Wiley & Sons, Ltd.     

The synthesis of a new probe for PET imaging reporter gene HSV1‐tk: 2‐amino‐6‐[18F] fluoro‐9‐ (4‐hydroxy‐3‐hydroxymethylbutyl) purine (6‐[18F]fluoropenciclovir)

The one step radiosynthesis of 2‐amino‐6‐ [¹⁸F]fluoro‐9‐(4‐hydroxy‐3‐hydroxymethylbutyl) purine (6‐[¹⁸F]fluoropenciclovir) 6 is reported. Radiolabeled product 6‐[¹⁸F]fluoropenciclovir 6 was prepared by radiofluorination of compound 4 with [¹⁸F]KF and isolated by a silica Sep‐Pak cartridge. The radiochemical yield of compound 6 was 45–55% decay corrected (d.c.) in six runs with radiochemical purity >98% and the radiosynthesis time was 35–42 min from end of bombardment (EOB). Copyright © 2006 John Wiley & Sons, Ltd.     

[18F]FPyKYNE,a fluoropyridine‐based alkyne reagent designed for the fluorine‐18 labelling of macromolecules using click chemistry

FPyKYNE (2‐fluoro‐3‐pent‐4‐yn‐1‐yloxypyridine) is a novel fluoropyridine‐based structure, designed for the fluorine‐18 labelling of macromolecules using copper‐catalysed Huisgen 1,3‐dipolar cycloaddition (click chemistry). FPyKYNE (non‐labelled as reference), as well as the 2‐bromo, 2‐nitro and 2‐trimethylammonium analogues (as precursors for labelling with fluorine‐18), was synthesized in 44, 95, 60 and 41%, respectively, from commercially available 5‐chloropent‐1‐yne and the appropriate 2‐substituted‐3‐hydroxypyridines. [¹⁸F]FPyKYNE was synthesized in one single radiochemical step by reaction of no‐carrier‐added K[¹⁸F]F‐Kryptofix^®222 (DMSO, 165°C, 3–5 min) followed by C‐18 SepPak cartridge pre‐purification and finally semi‐preparative HPLC purification on a Hewlett Packard SiO₂ Zorbax^® Rx‐SIL. Using the 2‐nitropyridine or the pyridin‐2‐yltrimethylammonium trifluoromethanesulphonate precursor for labelling (30 and 10 µmol, respectively), incorporation yields up to 90% were observed and 7.0–8.9 GBq (190–240 mCi) of [¹⁸F]FPyKYNE ([¹⁸F]‐1) could be isolated within 60–70 min (HPLC purification included), starting from a 37.0 GBq (1.0 Ci) [¹⁸F]fluoride batch (overall decay‐corrected and isolated yields: 30–35%). Copyright © 2008 John Wiley & Sons, Ltd.     

An improved preparation of [18F]AV-45 by simplified solid-phase extraction purification

Amyvid (florbetapir f18, [¹⁸F]AV-45, [¹⁸F] 5 ) was the first FDA-approved positron emission tomography imaging agent targeting β-amyloid (Aβ) plaques for assisting the diagnosis of Alzheimer disease. This work aimed to improve the [¹⁸F]AV-45 ([¹⁸F] 5 ) preparation by using solid-phase extraction (SPE) purification. [¹⁸F]AV-45 ([¹⁸F] 5 ) was synthesized by direct nucleophilic radiofluorination of O-tosylated precursor (1 mg) at 120°C in anhydrous dimethyl sulfoxide (DMSO), followed by acid hydrolysis of the N-Boc protecting group. Purification was accomplished by loading the crude reaction mixture to a cartridge (Oasis HLB 3 cc) and eluting with different combinations of solvents. This method removed the chemical impurity while leaving [¹⁸F]AV-45 ([¹⁸F] 5 ) on the cartridge. The final dose was eluted by ethanol. [¹⁸F]AV-45 ([¹⁸F] 5 ) was produced within 51 minutes (radiochemical yield 42.7 ± 5.9%, decay corrected, n = 3), and the radiochemical purity was greater than 95%. Total chemical impurity per batch (24.1 ± 2.7 μg per batch) was below the limit described in the package insert of Amyvid, florbetapir f18 (chemical mass: less than 50 μg/dose). In summary, [¹⁸F]AV-45 ([¹⁸F] 5 ) was produced efficiently and reproducibly using a cartridge-based SPE purification. This method brings the process closer for routine preparation, similar to the commercially used [¹⁸F]FDG.     

Radiosynthesis and bioconjugation of [18F]FPy5yne,a prosthetic group for the 18F labeling of bioactive peptides

A new ¹⁸F‐based prosthetic group has been prepared for the labeling of azide‐modified peptides for use in PET imaging. 2‐[¹⁸F]fluoro‐3‐(hex‐5‐ynyloxy)pyridine ([¹⁸F]FPy5yne, [¹⁸F]‐1) was prepared via efficient nucleophilic heteroaromatic substitution of either the corresponding 2‐nitro (2) or 2‐trimethylammonium trifluoromethanesulfonate pyridine (3). Best radiochemical yield of [¹⁸F]FPy5yne from 2 was 91% by radioTLC (15 min, 110°C, DMSO). From 3, best radiochemical yield by radioTLC was 93% (15 min, 110°C, MeCN). HPLC‐purified [¹⁸F]FPy5yne was ligated to model peptide N₃–(CH₂)₄–CO–YKRI–OH by way of Cu^I‐mediated Huisgen [3+2] cycloaddition in the presence of copper‐stabilizing ligand tris(benzyltriazolylmethyl)amine (TBTA) and N,N‐diisopropylethylamine (DIEA). Bioconjugate radiochemical yields were obtained in average yields of 89%±8.6% (n=4), as judged by radioHPLC. Best non‐decay‐corrected, collected radiochemical yield of modified peptide from end‐of‐bombardment was 5.8% (18.7% decay‐corrected), with a total preparation time of 160 min from start of synthesis. Copyright © 2008 John Wiley & Sons, Ltd.     

Synthesis of 6‐acrylamido‐4‐(2‐[18F]fluoroanilino)quinazoline: a prospective irreversible EGFR binding probe

Acrylamido‐quinazolines substituted at the 6‐position bind irreversibly to the intracellular ATP binding domain of the epidermal growth factor receptor (EGFR). A general route was developed for preparing 6‐substituted‐4‐anilinoquinazolines from [¹⁸F]fluoroanilines for evaluation as EGFR targeting agents with PET. By a cyclization reaction, 2‐[¹⁸F]fluoroaniline was reacted with N′‐(2‐cyano‐4‐nitrophenyl)‐N,N‐dimethylimidoformamide to produce 6‐nitro‐4‐(2‐[¹⁸F]fluoroanilino)quinazoline in 27.5% decay‐corrected radiochemical yield. Acid mediated tin chloride reduction of the nitro group was achieved in 5 min (80% conversion) and subsequent acylation with acrylic acid gave 6‐acrylamido‐4‐(2‐[¹⁸F]fluoroanilino)quinazoline in 8.5% decay‐corrected radiochemical yield, from starting fluoride, in less than 2 h. Copyright © 2005 John Wiley & Sons, Ltd.     

Rapid synthesis of maleimide functionalized fluorine‐18 labeled prosthetic group using “radio‐fluorination on the Sep‐Pak” method

Following our recently published fluorine‐18 labeling method, “Radio‐fluorination on the Sep‐Pak”, we have successfully synthesized 6‐[¹⁸F]fluoronicotinaldehyde by passing a solution (1:4 acetonitrile: t‐butanol) of its quaternary ammonium salt precursor, 6‐(N,N,N‐trimethylamino)nicotinaldehyde trifluoromethanesulfonate ( 2 ), through a fluorine‐18 containing anion exchange cartridge (PS‐HCO₃). Over 80% radiochemical conversion was observed using 10 mg of precursor within 1 minute. The [¹⁸F]fluoronicotinaldehyde ([¹⁸F] 5 ) was then conjugated with 1‐(6‐(aminooxy)hexyl)‐1H‐pyrrole‐2,5‐dione to prepare the fluorine‐18 labeled maleimide functionalized prosthetic group, 6‐[¹⁸F]fluoronicotinaldehyde O‐(6‐(2,5‐dioxo‐2,5‐dihydro‐1H‐pyrrol‐1‐yl)hexyl) oxime, 6‐[¹⁸F]FPyMHO ([¹⁸F] 6 ). The current Sep‐Pak method not only improves the overall radiochemical yield (50 ± 9%, decay‐corrected, n = 9) but also significantly reduces the synthesis time (from 60‐90 minutes to 30 minutes) when compared with literature methods for the synthesis of similar prosthetic groups.     

Synthesis of 6‐chloro‐3‐((2‐(S)‐azetidinyl)methoxy)‐5‐(2‐[18F]fluoropyridin‐4‐yl)pyridine ([18F]NIDA 522131), a novel potential radioligand for studying extrathalamic nicotinic acetylcholine receptors by PET

6‐Chloro‐3‐((2‐(S)‐azetidinyl)methoxy)‐5‐(2‐[¹⁸F]fluoropyridin‐4‐yl)pyridine ([¹⁸F]NIDA 522131), a potential radioligand for studying extrathalamic nicotinic acetylcholine receptors by positron‐emission tomography, was synthesized via no‐carrier‐added nucleophilic [¹⁸F]fluorination of 6‐chloro‐3‐((1‐(tert‐butoxycarbonyl)‐2‐(S)‐azetidinyl)methoxy)‐5‐(2‐iodopyridin‐4‐yl)vinyl)pyridine, followed by acidic deprotection. The overall radiochemical yield of the radiosynthesis was 4–8% (non‐decay‐corrected), the specific radioactivity was in the range of 167–335 GBq/µmol (4500–9000 mCi/µmol) and the radiochemical purity was greater than 99%. Preparation of [¹⁸F]NIDA522131 via corresponding bromo‐derivative 2 is also described. Copyright © 2004 John Wiley & Sons, Ltd.     

Preparation and stability of ethanol‐free solution of [18F]florbetapir ([18F]AV‐45) for positron emission tomography amyloid imaging

We have developed an ethanol‐free formulation method of [¹⁸F]florbetapir ([¹⁸F]AV‐45) using a commercially available automated JFE multi‐purpose synthesizer. We have also evaluated the radiochemical stability in an ethanol‐free solution of [¹⁸F]AV‐45 under visible light irradiation and dark conditions by comparison with a conventional 10% ethanol solution of [¹⁸F]AV‐45. [¹⁸F]AV‐45 was obtained with a radiochemical yield of 55.1 ± 2.2% (decay‐corrected to end of bombardment), specific activity of 591.6 ± 90.3 GBq/µmol and radiochemical purity of >99% within a total synthesis time of about 73 min. The radiochemical purity of [¹⁸F]AV‐45 formulated by dissolving the ethanol‐free solution was found to decrease as a function of the period of exposure to visible light. In contrast, the visible light photolysis could be suppressed by adding 10% ethanol to the formulation or by avoiding exposure to visible light. In the radiosynthesis of [¹⁸F]AV‐45 formulated by dissolving the ethanol‐free solution, [¹⁸F]AV‐45 could be obtained with high radiochemical purity and high stability by avoiding exposure to visible light. Copyright © 2013 John Wiley & Sons, Ltd.     

Synthesis of [18F]‐labeled N‐3(substituted) thymidine analogues: N‐3([18F]fluorobutyl) thymidine ([18F]‐FBT) and N‐3([18F]fluoropentyl) thymidine ([18F]‐FPT) for PET

Syntheses of N‐3(substituted) analogues of thymidine, N‐3([¹⁸F]fluorobutyl)thymidine ([¹⁸F]‐FBT) and N‐3([¹⁸F]fluoropentyl)thymidine ([¹⁸F]‐FPT) are reported. 1,4‐Butane diol and 1,5 pentane diol were converted to their tosyl derivatives 2 and 3 followed by conversion to benzoate esters 4 and 5, respectively. Protected thymidine 1 was coupled separately with 4 and 5 to produce 6 and 7 , which were hydrolyzed to 8 and 9 , then converted to their mesylates 10 and 11 , respectively. Compounds 10 and 11 were fluorinated with n‐Bu₄N[¹⁸F] to produce 12 and 13 , which by acid hydrolysis yielded 14 and 15 , respectively. The crude products were purified by HPLC to obtain [¹⁸F]‐FBT and [¹⁸F]‐FPT. The radiochemical yields were 58–65% decay corrected (d.c.) for 14 and 46–57% (d.c.) for 15 with an average of 56% in three runs per compound. Radiochemical purity was >99% and specific activity was >74 GBq/µmol at the end of synthesis (EOS). The synthesis time was 65–75 min from the end of bombardment (EOB). Copyright © 2006 John Wiley & Sons, Ltd.     

Novel probes for imaging amyloid‐β: F‐18 and C‐11 labeling of 2‐(4‐aminostyryl)benzoxazole derivatives

2‐(4‐Methylaminostyryl)‐6‐(2‐[¹⁸F]fluoroethoxy)benzoxazole ([¹⁸F]BF‐168) was prepared and found to be a potential probe for imaging amyloid‐β. The precursor, a 6‐(2‐tosyloxyethoxy)benzoxazole derivative, was fluorinated with [¹⁸F]KF and Kryptofix 222 in acetonitrile, and the crude product purified by semi‐preparative HPLC to give [¹⁸F]BF‐168. The radiochemical purity was >95% and the maximum specific activity was 106 TBq/mmol at the end of synthesis. The synthesis time was 110 min from the end of bombardment. 2‐(4‐[N‐methyl‐¹¹C]methylaminostyryl)‐5‐fluorobenzoxazole ([¹¹C]BF‐145) was also prepared from 2‐(4‐aminostyryl)‐5‐fluorobenzoxazole, [¹¹C]MeI and 5 N NaOH in DMSO, and purified by semi‐preparative HPLC. The radiochemical purity was >95% and the specific activity was 40–70 TBq/mmol at the end of synthesis. The synthesis time was 45 min from the end of bombardment. Copyright © 2004 John Wiley & Sons, Ltd.     

Automated radiosynthesis of no‐carrier‐added 4‐[18F]fluoroiodobenzene: a versatile building block in 18F radiochemistry

4‐[¹⁸F]Fluoroiodobenzene ([¹⁸F]FIB) is a versatile building block in ¹⁸F radiochemistry used in various transition metal‐mediated C–C and C–N cross‐coupling reactions and [¹⁸F]fluoroarylation reactions. Various synthesis routes have been described for the preparation of [¹⁸F]FIB. However, to date, no automated synthesis of [¹⁸F]FIB has been reported to allow access to larger amounts of [¹⁸F]FIB in high radiochemical and chemical purity. Herein, we describe an automated synthesis of no‐carrier‐added [¹⁸F]FIB on a GE TRACERlab? FX automated synthesis unit starting from commercially available (4‐iodophenyl)diphenylsulfonium triflate as the labelling precursor. [¹⁸F]FIB was prepared in high radiochemical yields of 89 ± 10% (decay‐corrected, n = 7) within 60 min, including HPLC purification. The radiochemical purity exceeded 95%, and specific activity was greater than 40 GBq/µmol. Typically, from an experiment, 6.4 GBq of [¹⁸F]FIB could be obtained starting from 10.4 GBq of [¹⁸F]fluoride. Copyright © 2013 John Wiley & Sons, Ltd.     

A simplified protocol for the automated production of succinimidyl 4‐[18F]fluorobenzoate on an IBA Synthera module

The important peptide labelling reagent succinimidyl 4‐[¹⁸F]fluorobenzoate ([¹⁸F]SFB) has been synthesised in 75–85% decay corrected radiochemical yield using the IBA Synthera platform (IBA Cyclotron Solutions, Louvain‐la‐neuve, Belgium) with the fluorodeoxyglucose‐integrated fluidic processor nucleophilic and only four reagent vials in a single reactor. (4‐ethoxycarbonylphenyl) trimethylammonium triflate was used as the labelling precursor and 1 M aqueous tetramethylammonium hydroxide for the hydrolysis of the intermediate ethyl 4‐[¹⁸F]fluorobenzoate. N,N,N′,N′‐tetramethyl‐O‐(N‐succinimidyl)uronium tetrafluoroborate (TSTU) was then used to form [¹⁸F]SFB from 4‐[¹⁸F]fluorobenzoate. By omitting the addition of acetic acid and introducing a combined hydrolysis/water removal step, the synthesis time was shortened to 58 minutes. After SepPak purification, the radiochemical purity of [¹⁸F]SFB was 95.8–98.2%. These simplifications might be of significance to users of other automated synthesis modules.