Synthesis of N‐(3‐[18F]Fluoropropyl)‐2β‐carbomethoxy‐3β‐(4‐iodophenyl)nortropane ([18F]FP‐β‐CIT)

N‐(3‐[¹⁸F]fluoropropyl)‐2β‐carbomethoxy‐3β‐(4‐iodophenyl)nortropane ([¹⁸F]FP‐β‐CIT) was synthesized in a two‐step reaction sequence. In the first reaction, 1‐bromo‐3‐(nitrobenzene‐4‐sulfonyloxy)‐propane was fluorinated with no‐carrier‐added fluorine‐18. The resulting product, 1‐bromo‐3‐[¹⁸F]‐fluoropropane, was distilled into a cooled reaction vessel containing 2β‐carbomethoxy‐3β‐(4‐iodophenyl)‐nortropane, diisopropylethylamine and potassium iodide. After 30 min, the reaction mixture was subjected to a preparative HPLC purification. The product, [¹⁸F]FP‐β‐CIT, was isolated from the HPLC eluent with solid‐phase extraction and formulated to yield an isotonic, pyrogen‐free and sterile solution of [¹⁸F]FP‐β‐CIT. The overall decay‐corrected radiochemical yield was 25 ± 5%. Radiochemical purity was > 98% and the specific activity was 94 ± 50 GBq/µmol at the end of synthesis. Copyright © 2006 John Wiley & Sons, Ltd.     

Simplified synthesis of N‐(3‐[18F]fluoropropyl)‐2β‐carbomethoxy‐3β‐(4‐fluorophenyl)nortropane ([18F]β‐CFT‐FP) using [18F]fluoropropyl tosylate as the labelling reagent

A synthesis method has been developed for the labelling of N‐(3‐[¹⁸F]fluoropropyl)‐2β‐carbomethoxy‐3β‐(4‐fluorophenyl)nortropane ([¹⁸F]β‐CFT‐FP), a potential radioligand for visualization of the dopamine transporters by positron emission tomography. The two‐step synthesis includes preparation of [¹⁸F]fluoropropyl tosylate and its use without purification in the fluoroalkylation of 2β‐carbomethoxy‐3β‐(4‐fluorophenyl)nortropane (nor‐β‐CFT). The final product is purified by HPLC. Optimization of the two synthesis steps resulted in a greater than 30% radiochemical yield of [¹⁸F]β‐CFT‐FP (decay corrected to end of bombardment). The synthesis time including HPLC‐purification was approximately 90 min. The radiochemical purity of the final product was higher than 99% and the specific radioactivity at the end of synthesis was typically 20 GBq/µmol. In comparison to alkylation by [¹⁸F]fluoropropyl bromide, the procedure described here results in an improved overall radiochemical yield of [¹⁸F]β‐CFT‐FP in a shorter time. Copyright © 2005 John Wiley & Sons, Ltd.     

Radiosynthesis of 1‐(4‐(2‐[18F]fluoroethoxy)benzenesulfonyl)‐3‐butyl urea: a potential β‐cell imaging agent

Tolbutamide ( 1 ) is a sulfonurea agent used to stimulate insulin secretion in type 2 diabetic patients. Its analogue 1‐(4‐(2‐[¹⁸F]fluoroethoxy)benzenesulfonyl)‐3‐butyl urea ( 3 ) was synthesized in overall radiochemical yields of 45% as a potential β‐cell imaging agent. Compound 3 was synthesized by ¹⁸F‐fluoroalkylation of the corresponding hydroxy precursor ( 2 ) with 2‐[¹⁸F]fluoroethyltosylate in DMF at 120°C for 10 min followed by purification with HPLC in a synthesis time of 50 min. Insulin secretion experiments of the authentic ¹⁹F‐standard compound on rat islets showed that the compound has a similar stimulating effect on insulin secretion as that of tolbutamide ( 1 ). The partition coefficient of compound 3 between octanol/water was determined to be 1.3±0.3 (n=5). Copyright © 2002 John Wiley & Sons, Ltd.     

Preparation of 3′‐deoxy‐3′‐[18F]fluorothymidine ([18F]FLT) in ionic liquid, [bmim][OTf]

Although 3′‐deoxy‐3′‐[¹⁸F]fluorothymidine ([¹⁸F]FLT) is a prospective radiopharmaceutical for the imaging of proliferating tumor cell, it is difficult to prepare large amount of [¹⁸F]FLT. We herein describe the preparation of [¹⁸F]FLT in an ionic liquid, [bmim][OTf] (1‐butyl‐3‐methyl‐imidazolium trifluoromethanesulfonate). At optimized condition, [¹⁸F]fluorinationin ionic liquid with 5 µl of 1 M KHCO₃ and 5 mg of the precursor yielded 61.5 ± 4.3% (n=10). Total elapsed time was about 70 min including HPLC purification. The rapid synthesis of [¹⁸F]FLT can be achieved by removing all evaporation steps. Overall radiochemical yield and radiochemical purity were 30 ± 5% and >95%, respectively. This method can use a small amount of a nitrobenzenesulfonate precursor and can be adapted for automated production. Copyright © 2006 John Wiley & Sons, Ltd.     

Radiosynthesis of 3‐(3‐[18F]fluoropropoxy)‐4‐(benzyloxy)‐N‐[(1‐dimethylaminocyclopentyl)methyl]‐5‐methoxybenzamide,a potential PET radiotracer for the glycine transporter GlyT‐2

The recently described selective and potent GlyT2 antagonist, 4‐benzyloxy‐3,5‐dimethoxy‐N‐[(1‐dimethylaminocyclopentyl) methyl]benzamide (IC₅₀=16 nM) provided an important additional tool to further characterize GlyT2 pharmacology. In order to identify an effective PET radioligand for in vivo assessment of the GlyT‐2 transporter, 3‐(3‐[¹⁸F]fluoropropoxy)‐4‐(benzyloxy)‐N‐((1‐dimethylaminocyclopentyl) methyl)‐5‐methoxybenzamide ([¹⁸F] 3 ), a novel analog of 4‐benzyloxy‐3,5‐dimethoxy‐N‐[(1‐dimethylaminocyclopentyl) methyl]benzamide was synthesized using a one‐pot, two‐step method. The NCA radiofluorination of 1,3‐propanediol di‐p‐tosylate in the presence of K₂CO₃ and Kryptofix‐222 in acetonitrile gave 81% 3‐[¹⁸F]fluoropropyl tosylate, which was subsequently coupled with 4‐benzyloxy‐3‐hydroxy‐5‐methoxy‐N‐[(1‐dimethylaminocyclopentyl) methyl]benzamide in the same reaction vessel. Solvent extraction and HPLC (Eclipse XDB‐C8 column, 80/20/0.1 MeOH/H₂O/Et₃N, 3.0 ml/min) gave [¹⁸F] 3 in 98.5% radiochemical purity. The radiochemical yield was determined to be 14.0–16.2% at EOS, and the specific activity was 1462±342 GBq/µmol. The time of synthesis and purification was 128 min. The final product was prepared as a sterile saline solution suitable for in vivo use. Copyright © 2006 John Wiley & Sons, Ltd.     

Efficient O‐ and N‐(β‐fluoroethylation)s with NCA [18F]β‐fluoroethyl tosylate under microwave‐enhanced conditions

Reactions of no‐carrier‐added (NCA) [¹⁸F]β‐fluoroethyl tosylate with amine, phenol or carboxylic acid to form the corresponding [¹⁸F]N‐(β‐fluoroethyl)amine, [¹⁸F]β‐fluoroethyl ether or [¹⁸F]β‐fluoroethyl ester, were found to be rapid (2–10 min) and efficient (51–89% conversion) under microwave‐enhanced conditions. These conditions allow reactants to be heated rapidly to 150°C in a low boiling point solvent, such as acetonitrile, and avoid the need to use high boiling point solvents, such as DMSO and DMF, to promote reaction. The microwave‐enhanced reactions gave about 20% greater radiochemical yields than thermal reactions performed at similar temperatures and over similar reaction times. With a bi‐functional molecule, such as DL‐pipecolinic acid, [¹⁸F]β‐fluoroethyl tosylate reacts exclusively with the amino group. Copyright © 2004 John Wiley & Sons, Ltd.     

Expedient synthesis of [18F]‐labeled α‐trifluoromethyl ketones

Several [¹⁸F]‐labeled α‐trifluoromethyl ketones have been synthesized. Reactions of 2,2‐difluoro‐1‐aryl‐1‐trimethylsiloxyethenes ( 1a–d ) with [¹⁸F]‐F₂ at low temperature produced [¹⁸F]‐labeled α‐trifluoromethyl ketones ( 2a–d ). Radio‐labeled products were isolated by purification with column chromatography in 22–28% yields, decay corrected (d.c.) in three runs per compound. Radiochemical purity was >99% with specific activities 15–20 GBq/mmol at the end of synthesis (EOS). The synthesis time was 35–40 min from the end of bombardment (EOB). This one‐step simple method is highly useful for the radiochemical synthesis of potential biologically active [¹⁸F]‐labeled α‐trifluoromethyl ketones for PET imaging. Copyright © 2003 John Wiley & Sons, Ltd.     

Microwave‐assisted radiosynthesis of [18F]ASEM,a radiolabeled α7‐nicotinic acetylcholine receptor antagonist

An improvement of the original radiochemical synthesis of [¹⁸F]ASEM, an α7‐nicotinic acetylcholinergic receptor radioligand, is reported. The new procedure utilizes microwave‐assisted radiofluorination. In addition, a new preparative HPLC method was developed to eliminate a chemical impurity in the final product. Quality control procedures were also enhanced to improve detection of product with enhanced resolution of potential impurities. [¹⁸F]ASEM was produced in 20.1 ± 8.9% non‐decay corrected (NDC) yield with an average synthesis time of 57 min and an average specific radioactivity of 856 ± 332 GBq/µmol (23 ± 9 Ci/µmol).     

Fully automated synthesis and purification of 4‐(2′‐methoxyphenyl)‐1‐[2′‐(N‐2″‐pyridinyl)‐p‐[18F]fluorobenzamido]ethylpiperazine

We have developed an efficient synthesis method for the rapid and high‐yield automated synthesis of 4‐(2′‐methoxyphenyl)‐1‐[2′‐(N‐2″‐pyridinyl)‐p‐[¹⁸F]fluorobenzamido]ethylpiperazine (p‐[¹⁸F]MPPF). No‐carrier‐added [¹⁸F]F^? was trapped on a small QMA cartridge and eluted with 70% MeCN(aq) (0.4 mL) containing Kryptofix 222 (2.3 mg) and K₂CO₃ (0.7 mg). The nucleophilic [¹⁸F]fluorination was performed with 3 mg of the nitro‐precursor in DMSO (0.4 mL) at 190 °C for 20 min, followed by the preparative HPLC purification (column: COSMOSIL Cholester, Nacalai Tesque, Kyoto, Japan; mobile phase: MeCN/25 mm AcONH₄/AcOH = 200/300/0.15; flow rate: 6.0 mL/min) to afford p‐[¹⁸F]MPPF (retention time = 9.5 min). p‐[¹⁸F]MPPF was obtained automatically with a radiochemical yield of 38.6 ± 5.0% (decay corrected, n = 5), a specific activity of 214.3 ± 21.1 GBq/µmol, and a radiochemical purity of >99% within a total synthesis time of about 55 min. Copyright © 2012 John Wiley & Sons, Ltd.     

Radiosynthesis of the α4β2 nicotinic acetylcholine receptor ligand: 5‐((1‐[11C]‐methyl‐2‐(S)‐pyrrolidinyl)methoxy)‐2‐chloro‐3‐((E)‐2‐(2‐fluoropyridin‐4‐yl)vinyl)pyridine

5‐((1‐[¹¹C]‐methyl‐2‐(S)‐pyrrolidinyl)methoxy)‐2‐chloro‐3‐((E)‐2‐(2‐fluoropyridin‐4‐yl)‐vinyl)pyridine ([¹¹C]‐FPVC) was synthesized from [¹¹C]‐methyl iodide and the corresponding normethyl precursor. The average time of synthesis, purification, and formulation was 42 min with an average non‐decay‐corrected radiochemical yield of 19%. The average specific radioactivity was 359 GBq/µmol (9691 mCi/µmole) at end of synthesis (EOS). Copyright © 2006 John Wiley & Sons, Ltd.     

Synthesis of [18F]FETO,a novel potential 11‐β hydroxylase inhibitor

Recent publications reported high uptake of the carbon‐11 labelled 11β‐hydroxylase inhibitors (R)–[O–methyl‐¹¹C]metomidate ([¹¹C]MTO) and (R)–[O–ethyl‐¹¹C]etomidate ([¹¹C]ETO) in adrenocortical incidentalomas with excellent selectivity for positron emission tomography (PET). In our studies [¹⁸F]FETO, (the [¹⁸F]fluoroethyl ester of etomidate, (R)‐1‐(1‐phenylethyl)‐1H‐imidazole‐5‐carboxylic acid, 2′‐[¹⁸F]fluoroethyl ester), an analogue of [¹¹C]MTO and [¹¹C]ETO was chosen due to the suspected similarity of the pharmacokinetic and pharmacodynamic properties, and was prepared in the following two step procedure: First, [¹⁸F]fluoride was reacted with 2‐bromoethyl triflate using the kryptofix/acetonitrile method to yield 2–bromo‐[¹⁸F]fluoroethane ([¹⁸F]BFE). In the second step, [¹⁸F]BFE was reacted with the tetrabutylammonium salt of (R)‐1‐(1‐phenylethyl)‐1H‐imidazole‐5‐carboxylic acid to yield [¹⁸F]FETO, a novel inhibitor of the 11β‐hydroxylase. The proposed synthesis of [¹⁸F]FETO allows the production of sufficient amounts of this new PET‐tracer to serve 1–2 patients with an overall synthesis time of less than 80 min. Copyright © 2003 John Wiley & Sons, Ltd.     

Synthesis and in vitro evaluation of 18F‐β‐carboline alkaloids as PET ligands

A one‐step ¹⁸F‐labelling strategy was used to prepare four ¹⁸F‐labelled analogues of 7‐methoxy‐1‐methyl‐9H‐β‐carboline (harmine): 7‐(2‐[¹⁸F]fluoroethoxy)‐1‐methyl‐9H‐β‐carboline (5), 7‐(3‐[¹⁸F]fluoro‐propoxy)‐1‐methyl‐9H‐β‐carboline (6), 7‐[2‐(2‐[¹⁸F]fluoroethoxy)ethoxy]‐1‐methyl‐9H‐β‐carboline (7), and 7‐{2‐[2‐(2‐[¹⁸F]fluoroethoxy)ethoxy]‐ethoxy}‐1‐methyl‐9H‐β‐carboline (8). These were synthesized as potential positron emission tomography ligands for monoamine oxidase A (MAO‐A). A solution of pure labelled compound in buffer was obtained in <70 min from end of radionuclide production, with a decay‐corrected yield of up to 23%. The average specific binding to MAO‐A in rat brain, determined by autoradiography experiments, was highest for compounds 7 and 8 (89±2 and 96±1%, respectively), which was obtained at <1 nM radioligand concentration. Copyright © 2008 John Wiley & Sons, Ltd.     

Synthesis of 2‐[(4‐[18F]Fluorobenzoyloxy)methyl]‐1,4‐naphthalenedione from 2‐hydroxymethyl 1,4‐naphthoquinone and 4‐[18F]fluorobenzoic acid using dicyclohexyl carbodiimide

2‐[(4‐[¹⁸F]Fluorobenzoyloxy)methyl]‐1,4‐naphthalenedione ([¹⁸F]7 ) and 4‐[¹⁸F]fluorobenzoic acid ([¹⁸F]8 . This coupling reaction was fast and gave quantitative yields. Further investigations are warranted on the use of DCC as a coupling agent in Positron Emission Tomography. The synthesis including HPLC purification and reformulation has been fully automated on a modified FDG synthesiser with two reactor vials. [¹⁸F]1 was found to be stable in plasma and saline, but underwent rapid metabolism in a phase 1 metabolite assay using rat S9 liver fractions. An in vivo evaluation of [¹⁸F]相似文献   

Radiosynthesis of 3‐(2′‐[18F]fluoro)‐flumazenil ([18F]FFMZ)

Recently, two fluorine‐18 labelled derivatives of flumazenil were described: 5‐(2′‐[¹⁸F]fluoroethyl)‐5‐desmethylflumazenil (ethyl 8‐fluoro‐5‐[¹⁸F]fluoroethyl‐6‐oxo‐5,6‐dihydro‐4H‐benzo‐[f]imidazo[1,5‐a] [1,4]diazepine‐3‐carboxylate; [¹⁸F]FEFMZ) and 3‐(2′‐[¹⁸F]fluoro)‐flumazenil (2′‐[¹⁸F]fluoroethyl 8‐fluoro‐5‐methyl‐6‐oxo‐5,6‐dihydro‐4H‐benzo‐[f]imidazo[1,5‐a]‐[1,4]diazepine‐3‐carbo‐ xylate; [¹⁸F]FFMZ). Since the biodistribution data of the latter were superior to those of the former we developed a synthetic approach for [¹⁸F]FFMZ starting from a commercially available precursor, thereby obviating the need to prepare a precursor by ourselves. The following two‐step procedure was developed: First, [¹⁸F]fluoride was reacted with 2‐bromoethyl triflate using the kryptofix/acetonitrile method to yield 2‐bromo‐[¹⁸F]fluoroethane ([¹⁸F]BFE). In the second step, distilled [¹⁸F]BFE was reacted with the tetrabutylammonium salt of 3‐desethylflumazenil (8‐fluoro‐5‐methyl‐6‐oxo‐5,6‐dihydro‐4H‐benzo‐[f]imidazo[1,5‐a] [1,4]diazepine‐3‐carboxylic acid) to yield [¹⁸F]FFMZ. The synthesis of [¹⁸F]FFMZ allows for the production of up to 7 GBq of this PET‐tracer, enough to serve several patients. [¹⁸F]FFMZ synthesis was completed in less than 80 min and the radiochemical purity exceeded 98%. Copyright © 2003 John Wiley & Sons, Ltd.     

An improved radiosynthesis of O‐(2‐[18F]fluoroethyl)‐O‐(p‐nitrophenyl)methylphosphonate: A first‐in‐class cholinesterase PET tracer

O‐(2‐Fluoroethyl)‐O‐(p‐nitrophenyl) methylphosphonate 1 is an organophosphate cholinesterase inhibitor that creates a phosphonyl‐serine covalent adduct at the enzyme active site blocking cholinesterase activity in vivo . The corresponding radiolabeled O‐(2‐[¹⁸F]fluoroethyl)‐O‐(p‐nitrophenyl) methylphosphonate, [ ¹⁸ F]1 , has been previously prepared and found to be an excellent positron emission tomography imaging tracer for assessment of cholinesterases in live brain, peripheral tissues, and blood. However, the previously reported [ ¹⁸ F]1 tracer synthesis was slow even with microwave acceleration, required high‐performance liquid chromatography separation of the tracer from impurities, and gave less optimal radiochemical yields. In this paper, we report a new synthetic approach to circumvent these shortcomings that is reliant on the facile reactivity of bis‐(O,O‐p‐nitrophenyl) methylphosphonate, 2 , with 2‐fluoroethanol in the presence of DBU. The cold synthesis was successfully translated to provide a more robust radiosynthesis. Using this new strategy, the desired tracer, [ ¹⁸ F]1 , was obtained in a non‐decay–corrected radiochemical yield of 8 ± 2% (n = 7) in >99% radiochemical and >95% chemical purity with a specific activity of 3174 ± 345 Ci/mmol (EOS). This new facile radiosynthesis routinely affords highly pure quantities of [ ¹⁸ F]1 , which will further enable tracer development of OP cholinesterase inhibitors and their evaluation in vivo .     

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.     

Simple and high radiochemical yield synthesis of 2′‐Deoxy‐2′‐[18F]fluorouridine via a new nosylate precursor

We synthesized 2'‐deoxy‐2'‐[¹⁸F]fluorouridine ( 7 ) as a radiotracer for positron emission tomography from a new nosylate precursor ( 6 ). This new precursor was synthesized from uridine in four steps. The overall synthetic yield was 9.4% and we have high stability of >98% purity up to 6 months at 4°C. The optimal manual [¹⁸F]fluorination conditions were 30 mg of the precursor 6 in 500 µl of acetonitrile at 145°C for 15 min with 370 MBq of [¹⁸F]fluoride. The [¹⁸F]fluorination yield was 76.5±2.7% (n = 3). After hydrolysis of protecting groups with 1 N HCl and purification by HPLC, the overall radiochemical yield and purity were 26.5±1.4% and 98.2±2.5%, respectively. The preparation time was 70.0±10.5 min (n = 3 for each result). We also developed an automated method with a radiochemical yield and purity of 24.0±2.8 and 98.0±1.5% (n = 10) using a GE TracerLab MX chemistry module. This new nosylate precursor for 2'‐deoxy‐2'‐[¹⁸F]fluorouridine synthesis showed higher radiochemical yields and reproducibility than previous methods. Copyright © 2006 John Wiley & Sons, Ltd.     

18F‐labelling of a potent nonpeptide CCR1 antagonist: synthesis of 1‐(5‐chloro‐2‐{2‐[(2R)‐4‐(4‐[18F]fluorobenzyl)‐2‐methylpiperazin‐1‐yl]‐2‐oxoethoxy}phenyl)urea in an automated module

The synthesis of 1‐(5‐chloro‐2‐{2‐[(2R)‐4‐(4‐[¹⁸F]fluorobenzyl)‐2‐methylpiperazin‐1‐yl]‐2‐oxoethoxy}phenyl)urea ( [¹⁸F]4 ), a potent nonpeptide CCR1 antagonist, is described as a module‐assisted two‐step one‐pot procedure. The final product was obtained utilizing the reductive amination of the formed 4‐[¹⁸F]fluorobenzaldehyde ( 2 ) with a piperazine derivative 3 and sodium cyanoborohydride. After HPLC purification of the final product [¹⁸F]4 , its solid phase extraction, formulation and sterile filtration, the isolated (not decay‐corrected) radiochemical yields of [¹⁸F]4 were between 7 and 13% (n=28). The time of the entire manufacturing process did not exceed 95 min. The radiochemical purity of [¹⁸F]4 was higher than 95%, the chemical purity ?60% and the enantiomeric purity >99.5%. The specific radioactivity was in the range of 59–226 GBq/µmol at starting radioactivities of 23.6–65.0 GBq [¹⁸F]fluoride. Copyright © 2006 John Wiley & Sons, Ltd.     

Synthesis of 3‐[[4‐(4‐[18F] fluorophenyl)piperazin‐1‐yl]methyl]‐1H‐pyrrolo[2,3‐b]pyridine

3‐[[4hyphen;(4‐[¹⁸F]fluorophenyl)piperazin‐1‐yl] methyl] ‐1H‐pyrrolo[2,3‐b]pyridine, acandidate to image dopamine D₄ receptors, was synthesised via electrophilic fluorination of a trimethylstannyl precursor with high specific radioactivity [¹⁸F]F₂. The precursor was obtained by a facile four‐step synthetic approach; the trimethylstannyl leaving group was introduced by displacement of iodine utilising palladium catalysis and hexamethyldistannane in an inert solvent. The total radiosynthesis time was 50 min, including purification and formulation for injection. Decay corrected radiochemical yield was <1% as calculated from the amount of [¹⁸F]F^? produced. Specific radioactivity at the end of synthesis was 12.8–16.4 GBq/μmol. Radiochemical purity was 88–92%. Ex vivo studies in rats showed homogeneous distribution of radioactivity within rat brain. Copyright © 2002 John Wiley & Sons, Ltd.     

Two‐step radiosynthesis of [18F]N‐succinimidyl‐4‐fluorobenzoate ([18F]SFB)

The acylation reagent [¹⁸F]N‐succinimidyl‐4‐fluorobenzoate (¹⁸F‐SFB) has been prepared using a new two‐step approach. The starting material p‐[¹⁸F]fluorobenzaldehyde (¹⁸F‐FBA) was obtained by an improved radiosynthesis with a decay‐corrected radiochemical yield of 66±6 % (n=3). Reaction of ¹⁸F‐FBA with (diacetoxyiodine)benzene and N‐hydroxysuccinimide and preparative HPLC purification furnished ¹⁸F‐SFB in an r.c.y. of 49±6 % (n=3), based on the starting radioactivity of ¹⁸F‐FBA. The radiochemical purity of ¹⁸F‐SFB was >99%. Alternatively, purification by solid phase extraction gave ¹⁸F‐SFB with an r.c.y. of 77±9% (n=4) and a radiochemical purity of 89±5% (n=4). This radiochemical synthesis only used non‐aqueous solvents, which simplifies the method and facilitates subsequent applications of ¹⁸F‐SFB. Copyright © 2009 John Wiley & Sons, Ltd.