Efficient synthesis of 6‐chloro‐3‐((2‐(S)‐azetidinyl)methoxy)‐5‐((E)‐2‐(2‐[18F]fluoropyridin‐4‐yl)vinyl)pyridine ([18F]NIDA 52289), a very high affinity radioligand for nicotinic acetylcholine receptors

6‐Chloro‐3‐((2‐(S)‐azetidinyl)methoxy)‐5‐((E)‐2‐(2‐[¹⁸F]fluoropyridin‐4‐yl)vinyl)pyridine ([¹⁸F]NIDA 52289), a very high affinity radioligand for studying nicotinic acetylcholine receptors (nAChRs) by positron‐emission tomography, was synthesized through Kryptofix 222 assisted no‐carrier‐added nucleophilic [¹⁸F]fluorination of 6‐chloro‐3‐((1‐(tert‐butoxycarbonyl)‐2‐(S)‐azetidinyl)methoxy)‐5‐((E)‐2‐(2‐bromopyridin‐4‐yl)vinyl)pyridine, followed by acidic deprotection. The overall radiochemical yield of the radiosynthesis was 10% (non‐decay‐corrected), the specific radioactivity was in the range of 93–326 GBq/µmol (2.5–8.8 mCi/µmol) and the radiochemical purity was greater than 99%. Copyright © 2004 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 N‐(piperidin‐1‐yl)‐5‐(4‐methoxyphenyl)‐1‐(2‐chlorophenyl)‐4‐[18F]fluoro‐1H‐pyrazole‐3‐carboxamide by nucleophilic [18F] fluorination: a PET radiotracer for studying CB1 cannabinoid receptors

The feasibility of nucleophilic displacement of bromide in the 4‐bromopyrazole ring with [¹⁸F]fluoride has been demonstrated by the synthesis of two radiolabeled compounds: N‐(piperidin‐1‐yl)‐5‐(4‐methoxyphenyl)‐1‐(2‐chlorophenyl)‐4‐[¹⁸F]fluoro‐1H‐pyrazole‐3‐carboxamide, ([¹⁸F] NIDA‐42033) 1b and 1‐(2‐chlorophenyl)‐4‐[¹⁸F]fluoro‐5‐(4‐methoxyphenyl)‐1H‐pyrazole‐3‐carboxylic acid, ethyl ester 4 . The radiochemical yields were in the range of 1–6%. [¹⁸F]NIDA‐42033, a potential radiotracer for the study of CB₁ cannabinoid receptors in the animal brain by positron emission tomography, has been synthesized in sufficient quantities with specific radioactivity greater than 2500 mCi/μmol and radiochemical purity >95%. Copyright © 2002 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 2‐[18F]fluoroadenosine (2‐[18F]FAD) as potential radiotracer for studying malignancies by PET

2‐[¹⁸F]fluoroadenosine (2‐[¹⁸F]FAD), a potential radioligand for assessment of adenylate metabolism, was synthesized by carrier‐added and no‐carrier‐added procedures via nucleophilic radiofluorination of 2‐fluoroadenosine and 2‐iodoadenosine. The radiochemical yield, specific radioactivity and radiochemical purity of carrier‐added and no‐carrier‐added 2‐[¹⁸F]FAD were 5%, 22–30 mCi/µmol and 99%, and 0.5%, 1200–1700 mCi/µmol and 99%, respectively. 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.     

Radiosynthesis of 2‐exo‐(2′‐[18F]Fluoro‐3′‐(4‐fluorophenyl)‐pyridin‐5′‐yl)‐7‐azabicyclo[2.2.1]heptane ([18F]F2PhEP), a potent epibatidine‐based radioligand for nicotinic acetylcholine receptor PET imaging

2‐exo‐(2′‐Fluoro‐3′‐(4‐fluorophenyl)‐pyridin‐5′‐yl)‐7‐azabicyclo[2.2.1]heptane (F₂PhEP), a novel, epibatidine‐based, α4β2‐selective nicotinic acetylcholine receptor antagonist of low toxicity, as well as the corresponding N‐Boc‐protected chloro‐ and bromo derivatives as precursors for labelling with fluorine‐18 were synthesized from 7‐tert‐butoxycarbonyl‐7‐azabicyclo[2.2.1]hept‐2‐ene in 13, 19 and 8% overall yield, respectively. [¹⁸F]F₂PhEP was prepared in 8–9% overall yield (non‐decay‐corrected) using 1 mg of the bromo derivative in the following two‐step radiochemical process: (1) no‐carrier‐added nucleophilic heteroaromatic ortho‐radiofluorination with the activated K[¹⁸F]F‐Kryptofix^®₂₂₂ complex in DMSO using microwave activation at 250 W for 90 s, followed by (2) quantitative TFA‐induced removal of the N‐Boc protective group. Radiochemically pure (>95%) [¹⁸F]F₂PhEP (1.48–1.66 GBq, 74–148 GBq/µmol) was obtained after semi‐preparative HPLC (Symmetry^® C18, eluent aqueous 0.05 M NaH₂PO₄ CH₃CN: 78/22 (v:v)) in 75–80 min starting from an 18.5 GBq aliquot of a cyclotron‐produced [¹⁸F]fluoride production batch. 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.     

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.     

One‐step radiosynthesis of 4‐[18F]flouro‐3‐nitro‐N‐2‐propyn‐1‐yl‐benzamide ([18F]FNPB): a new stable aromatic porosthetic group for efficient labeling of peptides with fluorine‐18

4‐[¹⁸F]flouro‐3‐nitro‐N‐2‐propyn‐1‐yl‐benzamide ([¹⁸F]FNPB) was developed as a new stable aromatic prosthetic group for more efficient click labeling of peptides. A new aromatic precursor 3,4‐dinitro‐N‐2‐propyn‐1‐yl‐benzamide was radiofluorinated using [¹⁸F]KF/K2.2.2 followed by HPLC purification to obtain the desired product [¹⁸F]FNPB. [¹⁸F]FNPB was synthesized with a 58% radiochemical yield, a specific activity > 350 GBq/µmol, and radiochemical purity was exceeded 98% in 40 min. The in vitro stability studies showed no detectable radiodefluorination over 2 h in mouse plasma. The click labeling yield of three different peptides with [¹⁸F]FNPB were all above 87%. The in vitro study suggests that [¹⁸F]FNPB may be stable in vivo and could have general application in labeling peptides with high radiochemical yield for positron emission tomography applications. Copyright © 2012 John Wiley & Sons, Ltd.     

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.     

18F‐Labelled vorozole analogues as PET tracer for aromatase

One‐ and two‐step syntheses for the ¹⁸F‐labelling of 6‐[(S)‐(4‐chlorophenyl)(1H‐1,2,4‐triazol‐1‐yl)methyl]‐1‐(2‐[¹⁸F]fluoroethyl)‐1H‐benzotriazole, [¹⁸F]FVOZ, 1 and 6‐[(S)‐(4‐chlorophenyl)(1H‐1,2,4‐triazol‐1‐yl)methyl]‐1‐[2‐(2‐[¹⁸F]fluoroethoxy)ethyl]‐1H‐benzotriazole, [¹⁸F]FVOO, 2 were developed. In the two‐step synthesis, the nucleophilic fluorination step was performed by reacting (S)‐6‐[(4‐chlorophenyl)‐(1H‐1,2,4‐triazol‐1‐yl)methyl]‐1H‐benzotriazole (VOZ) with either the ¹⁸F‐labelled ethane‐1,2‐diyl bis(4‐methylbenzenesulfonate) or the oxydiethane‐2,1‐diyl bis(4‐methylbenzenesulfonate). The radiochemical yields were in the range of 9–13% after the 110–120 min total syntheses and the specific radioactivities were 175±7 GBq/µmol and 56 GBq/µmol for compounds 1 and 2, respectively. In the one‐step synthesis, the precursor 2‐{6‐[(4‐chlorophenyl)(1H‐1,2,4‐triazol‐1‐yl)methyl]‐1H‐1,2,3‐benzotriazol‐1‐yl}ethyl 4‐methylbenzenesulfonate (7) or 1‐[2‐(2‐bromoethoxy)ethyl]‐6‐[(4‐chlorophenyl)(1H‐1,2,4‐triazol‐1‐yl)methyl]‐1H‐benzotriazole (8) was directly labelled via an ¹⁸F nucleophilic substitution to give the corresponding tracer. The labelled compounds were obtained in 36–99% radiochemical yield after 75‐min syntheses. The specific radioactivities are 100 GBq/µmol for compound 1 and 80 GBq/µmol for compound 2. In vitro autoradiography using frozen rat brains illustrated specific binding in the medial amygdala, the bed nucleus of stria terminalis and the preoptic area, all of which corresponded well to the result of ¹¹C‐labelled vorozole. Copyright © 2008 John Wiley & Sons, Ltd.     

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.     

Synthesis of 18F‐labelled stilbenes from 4‐[18F]fluorobenz‐aldehyde using the Horner–Wadsworth–Emmons reaction

The first application of the Horner–Wadsworth–Emmons reaction in ¹⁸F‐chemistry is described. This carbonyl‐olefination reaction was performed via a ‘multi‐step/one‐pot’ reaction by the coupling of benzylic phosphonic acid esters (3,5‐bis‐methoxymethoxybenzyl)‐phosphonic acid diethyl ester 2e , (4‐methoxy‐methoxybenzyl)‐phosphonic acid diethyl ester 3e and (4‐dimethyl‐aminobenzyl)phosphonic acid diethyl ester 4d ) with 4‐[¹⁸F]fluorobenzaldehyde to give the corresponding ¹⁸F‐labelled stilbenes [¹⁸F]2g , [¹⁸F]3g and [¹⁸F]4e exclusively as the expected E‐isomers. The radiochemical yields ranged from 9% to 22% (based upon [¹⁸F]fluoride, including HPLC purification). The specific activity reached up to 90 GBq/µmol. Copyright © 2007 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   

Synthesis and stability of S‐(2‐[18F]fluoroethyl)‐L‐homocysteine for potential tumour imaging

The F‐18 labelled methionine derivative S‐(2‐[¹⁸F]fluoroethyl)‐L‐homocysteine ([¹⁸F]FEHCys) was prepared by a one‐pot two‐step synthesis via the protected S‐(2‐bromoethyl)‐L‐homocysteine 1 and S‐(2‐chloroethyl)‐L‐homocysteine 2 precursors. The bromoethyl derivative 1 gave higher radiochemical yields (40% at 5 min) at 100°C compared with the chloro‐analogue (22% at 100°C in 30 min). However, [¹⁸F]FEHCys was found to be unstable in aqueous systems being transformed to the corresponding hydroxyl derivative within 20 min. Copyright © 2008 John Wiley & Sons, Ltd.     

Synthesis of [18F]3‐[1‐(3‐fluoropropyl)‐(S)‐pyrrolidin‐2‐ylmethoxy]pyridine ([18F]NicFP): a potential α4β2 nicotinic acetylcholine receptor radioligand for PET

Nicotinic acetylcholine receptors are widely distributed throughout the human brain and are believed to play a role in several neurological and psychiatric disorders. In order to identify an effective PET radioligand for in vivo assessment of the α4β2 subtype of nicotinic receptor, we synthesized [¹⁸F]3‐[1‐(3‐fluoropropyl)‐(S)‐pyrrolidin‐2‐ylmethoxy]pyridine (NicFP). The in vitro K_D of NicFP was determined to be 1.1 nM, and the log P value obtained by HPLC analysis of the unlabelled standard was found to be 2.2. The radiosynthesis of [¹⁸F]NicFP was carried out by a nucleophilic substitution reaction of anhydrous [¹⁸F]fluoride and the corresponding mesylate precursor. After purification by HPLC, the radiochemical yield was determined to be 11.3±2.1% and the specific activity was 0.47±0.18 Ci/μmol (EOS, n = 3). The time of synthesis and purification was 99±2 min. The final product was prepared as a sterile saline solution suitable for in vivo use. Copyright © 2003 John Wiley & Sons, Ltd.     

Radiosynthesis of [18F]DPA‐714, a selective radioligand for imaging the translocator protein (18 kDa) with PET

Recently, a novel series of 2‐phenylpyrazolo[1,5‐a]pyrimidineacetamides has been reported as selective ligands of the translocator protein (18 kDa). Within this series, DPA‐714 (N,N‐diethyl‐2‐(2‐(4‐(2‐fluoroethoxy)phenyl)‐5,7‐dimethylpyrazolo[1,5‐a]pyrimidin‐3‐yl)acetamide, K_i=7.0 nM) is a compound, which had been designed with a fluorine atom in its structure, allowing labelling with fluorine‐18 (half‐life: 109.8 min) and in vivo imaging using positron emission tomography. DPA‐714 and its tosyloxy derivative (N,N‐diethyl‐2‐(2‐(4‐(2‐toluenesulfonyloxyethoxy)phenyl)‐5,7‐dimethylpyrazolo[1,5‐a]pyrimidin‐3‐yl)acetamide) as precursor for the labelling with fluorine‐18 were synthesized in two steps from DPA‐713 (N,N‐diethyl‐2‐(2‐(4‐methoxyphenyl)‐5,7‐dimethylpyrazolo[1,5‐a]pyrimidin‐3‐yl)acetamide) and obtained in 32 and 42% yields, respectively. [¹⁸F]DPA‐714 was synthesized using a simple one‐step process (a tosyloxy‐for‐fluorine nucleophilic aliphatic substitution), which has been fully automated on our Zymate‐XP robotic system. It involves: (A) reaction of K[¹⁸F]F‐Kryptofix^®222 with the tosyloxy precursor (4.5–5.0 mg, 8.2–9.1 µmol) at 165°C for 5 min in dimethyl sufloxide (0.6 mL) followed by (B) C18 PrepSep cartridge pre‐purification and finally (C) semi‐preparative high‐performance liquid chromatography (HPLC) purification on a Waters X‐Terra? RP18. Typically, 5.6–7.4 GBq of [¹⁸F]DPA‐714 (>95% chemically and radiochemically pure) could be obtained with specific radioactivities ranging from 37 to 111 GBq/µmol within 85–90 min (HPLC purification and SepPak^®‐based formulation included), starting from a 37 GBq [¹⁸F]fluoride batch (overall non‐decay‐corrected and isolated radiochemical yield: 15–20%). Copyright © 2008 John Wiley & Sons, Ltd.     

A new approach for 11C–C bond formation: Synthesis of 17α‐(3′‐[11C]prop‐1‐yn‐1‐yl)‐3‐methoxy‐3,17β‐estradiol

A new approach for ¹¹C–C bond formation via a Sonogashira‐like cross‐coupling reaction of terminal alkynes with [¹¹C]methyl iodide was exemplified by the synthesis of 17α‐(3′‐[¹¹C]prop‐1‐yn‐1‐yl)‐3‐methoxy‐3,17β‐estradiol. The LC‐purified title compound was obtained in decay‐corrected radiochemical yields of 27–47% (n=8) based on [¹¹C]methyl iodide within 21–27 min after EOB. In a typical synthesis starting from 9.6 GBq [¹¹C]methyl iodide, 1.87 GBq of 17α‐(3′‐[¹¹C]prop‐1‐yn‐1‐yl)‐3‐methoxy‐3,17β‐estradiol was synthesized in radiochemical purity >99%. The specific radioactivity ranged between 10 and 19 GBq/µmol, and the labeling position was verified by ¹³C‐NMR analysis of the corresponding ¹³C‐labeled compound. Copyright © 2003 John Wiley & Sons, Ltd.     

Synthesis of an 18F‐labeled cyclin‐dependent kinase‐2 inhibitor

The radiosynthesis of N‐(5‐(((5‐(tert‐butyl)oxazol‐2‐yl)methyl)thio)thiazol‐2‐yl)‐4‐[¹⁸F]fluoro‐benzamide [¹⁸F]2 as a potential radiotracer for molecular imaging of cyclin‐dependent kinase‐2 (CDK‐2) expression in vivo by positron emission tomography is described. Two different synthesis routes were envisaged. The first approach followed direct radiofluorination of respective nitro‐ and trimethylammonium substituted benzamides as labeling precursors with no‐carrier‐added (n.c.a.) [¹⁸F]fluoride. A second synthesis route was based on the acylation reaction of 2‐aminothiazole derivative with labeling agent [¹⁸F]SFB. Direct radiofluorination afforded ¹⁸ F‐labeled CDK‐2 inhibitor in very low yields of 1%–3%, whereas acylation reaction with [¹⁸F]SFB gave ¹⁸ F‐labeled CDK‐2 inhibitor [¹⁸ F]2 in high yields of up to 85% based upon [¹⁸ F]SFB during the optimization experiments. Large scale preparation afforded radiotracer [¹⁸ F]2 in isolated radiochemical yields of 37%–44% (n = 3, decay‐corrected) after HPLC purification within 75 min based upon [¹⁸ F]SFB. This corresponds to a decay‐corrected radiochemical yield of 13%–16% based upon [¹⁸F]fluoride. The radiochemical purity exceeded 95% and the specific activity was determined to be 20 GBq/µmol. Copyright © 2011 John Wiley & Sons, Ltd.