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.     

Automated commercial synthesis system for preparation of O‐(2‐[18F]fluoroethyl)‐L‐tyrosine by direct nucleophilic displacement on a resin column

A slightly modified automated commercial synthesis system for preparation of O‐(2‐[¹⁸F]fluoroethyl)‐l‐tyrosine (FET), an amino acid tracer for tumor imaging with positron emission tomography, is described. Direct nucleophilic fluorination of [¹⁸F]fluoride with 1,2‐di(4‐methylphenylsulfonyloxy)ethane on a quaternary 4‐(4‐methylpiperidinyl)‐pyridinium functionalized polystyrene anion exchange resin gave 1‐[¹⁸F]‐2‐(4‐methylphenylsulfonyloxy)ethane, then [¹⁸F]fluoroalkylation of l‐tyrosine yielded FET. The overall radiochemical yield with no decay correction was about 8–10%, the whole synthesis time was about 52 min, and the radiochemical purity was above 95%. Copyright © 2003 John Wiley & Sons, Ltd.     

Radiosynthesis of the HIV integrase inhibitor [18F]MK‐0518 (Isentress)

The human immunodeficiency virus integrase inhibitor, [¹⁸F]MK‐0518, was prepared via a three‐step, one‐pot radiosynthesis. [¹⁸F]4‐Fluorobenzylamine was produced from the fluorination of 4‐cyano‐N,N,N‐trimethylammonium triflate with [¹⁸F]fluoride and reduction with borane methylsulfide complex in 50–68% radiochemical yield. The final step, the coupling of [¹⁸F]4‐fluorobenzylamine with an ester coupling partner, achieved an overall uncorrected radiochemical yield after HPLC purification of ～2%, based on the starting [¹⁸F]fluoride. In a typical run, the total synthesis time was about 90 min and gave 0.37–1.74 GBq (10–47 mCi) of [¹⁸F]MK‐0518. The radiochemical purity of [¹⁸F]MK‐0518 was>98% and the specific activity was 243–1275 Ci/mmol (EOS, n=4). A convenient three‐step, one‐pot radiosynthesis of [¹⁸F]MK‐0518 via [¹⁸F]4‐fluorobenzylamine has been developed, giving sufficient quantities of [¹⁸F]MK‐0518 for animal positron emission tomography studies. Copyright © 2010 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.     

Automated synthesis of N‐(2‐[18F]Fluoropropionyl)‐l‐glutamic acid as an amino acid tracer for tumor imaging on a modified [18F]FDG synthesis module

N‐(2‐[¹⁸F]Fluoropropionyl)‐l ‐glutamic acid ([¹⁸F]FPGLU) is a potential amino acid tracer for tumor imaging with positron emission tomography. However, due to the complicated multistep synthesis, the routine production of [¹⁸F]FPGLU presents many challenging laboratory requirements. To simplify the synthesis process of this interesting radiopharmaceutical, an efficient automated synthesis of [¹⁸F]FPGLU was performed on a modified commercial fluorodeoxyglucose synthesizer via a 2‐step on‐column hydrolysis procedure, including ¹⁸F‐fluorination and on‐column hydrolysis reaction. [¹⁸F]FPGLU was synthesized in 12 ± 2% (n = 10, uncorrected) radiochemical yield based on [¹⁸F]fluoride using the tosylated precursor 2 . The radiochemical purity was ≥98%, and the overall synthesis time was 35 minutes. To further optimize the radiosynthesis conditions of [¹⁸F]FPGLU, a brominated precursor 3 was also used for the preparation of [¹⁸F]FPGLU, and the improved radiochemical yield was up to 20 ± 3% (n  = 10, uncorrected) in 35 minutes. Moreover, all these results were achieved using the similar on‐column hydrolysis procedure on the modified fluorodeoxyglucose synthesis module.     

A facile automated synthesis of N‐succinimidyl 4‐[18F]fluorobenzoate ([18F]SFB) for 18F‐labeled cell‐penetrating peptide as PET tracer

A fully automated synthesis of N‐succinimidyl 4‐[¹⁸F]fluorobenzoate ([¹⁸F]SFB) was carried out by a convenient three‐step, one‐pot procedure on the modified TRACERlab FX_FN synthesizer, including [¹⁸F]fluorination of ethyl 4‐(trimethylammonium triflate)benzoate as the precursor, saponification of the ethyl 4‐[¹⁸F]fluorobenzoate with aqueous tetrapropylammonium hydroxide instead of sodium hydroxide, and conversion of 4‐[¹⁸F]fluorobenzoate salt ([¹⁸F]FBA) to [¹⁸F]SFB treated with N,N,N′,N′‐tetramethyl‐O‐(N‐succinimidyl)uranium tetrafluoroborate (TSTU). The purified [¹⁸F]SFB was used for the labeling of Tat membrane‐penetrating peptide (containing the Arg‐Lys‐Lys‐Arg‐Arg‐Arg‐Arg‐Arg‐Arg‐Arg‐Arg‐Pro‐Leu‐Gly‐Leu‐Ala‐Gly‐Glu‐Glu‐Glu‐Glu‐Glu‐Glu‐Glu sequence, [¹⁸F]CPP) through radiofluorination of lysine amino groups. The uncorrected radiochemical yields of [¹⁸F]SFB were as high as 25–35% (based on [¹⁸F]fluoride) (n=10) with a synthesis time of～40 min. [¹⁸F]CPP was produced in an uncorrected radiochemical yields of 10–20% (n=5) within 30 min (based on [¹⁸F]SFB). The radiochemical purities of [¹⁸F]SFB and [¹⁸F]CPP were greater than 95%. Copyright © 2010 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.     

Initial experience in synthesis of (2S,4R)‐4‐[18F]fluoroglutamine for clinical application

We report initial experience in synthesis of (2S,4R)‐4‐[¹⁸F]fluoroglutamine, [¹⁸F]FGln, which has been used as a tool for monitoring glutamine metabolism in cancer patients. [¹⁸F]FGln was prepared by a fully automated PET‐MF‐2V‐IT‐I synthesizer under GMP‐compliant conditions for routine clinical studies. The total radiosynthesis time was about 65 minutes, the decay‐corrected radiochemical yield was 18.0 ± 4.2% (n = 59; failure n = 15), and the radiochemical purity was greater than 90%. In some situations, the yields were low (less than 5%), and the most likely cause of this problem is the initial fluorination step; the fluoride ion might not have been fully activated. In other occasions, low final radiochemical purity was often associated with the failure of the second step—removal of protection groups by anhydrous trifluoroacetic acid. A trace amount of water led to production of undesired 4‐[¹⁸F]fluoroglutamic acid. Knowledge learned from the successes and failures of synthesis may be helpful to identify critical steps and pitfalls for preparation of this clinically useful metabolic probe, [¹⁸F]FGln, for imaging glutamine utilization in tumor of cancer patients.     

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.     

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.     

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 fully automated synthesis of [18F]‐FEAU and [18F]‐FMAU using a novel dual reactor radiosynthesis module

2′‐Deoxy‐2′‐[¹⁸F]fluoro‐5‐substituted‐1‐β‐D ‐arabinofuranosyluracils, including 2′‐deoxy‐2′‐[¹⁸F]fluoro‐5‐methyl‐1‐β‐D ‐arabinofuranosyluracil [¹⁸F]FMAU and [¹⁸F]FEAU are established radiolabeled probes to monitor cellular proliferation and herpes simplex virus type 1 thymidine kinase (HSV1‐tk) reporter gene expression with positron emission tomography. For clinical applications, a fully automated CGMP‐compliant radiosynthesis is necessary for production of these probes. However, due to multiple steps in the synthesis, no such automated synthetic protocols have been developed. We report here a fully automated synthesis of [¹⁸F]‐FEAU and [¹⁸F]‐FMAU on a prototype dual reactor module TRACERlab FX FN. The synthesis was performed by using a computer‐programmed standard operating procedure, and the product was purified on a semipreparative high‐performance liquid chromatography (HPLC) integrated with the synthesis module using 12% EtOH in 50 mM Na₂HPO₄. Finally, the percentage of alcohol was adjusted to 7% by adding Na₂HPO₄ and filtered through a Millipore filter to make dose for human. The radiochemical yield on the fluorination was 40±10% (n=10), and the overall yields were 4±1% (d. c.), from the end of the bombardment; [¹⁸F]FEAU (n=7) and [¹⁸F]FMAU (n=3). The radiochemical purity was >99%, specific activity was 1200–1300 mCi/µmol. The synthesis time was 2.5 h. This automated synthesis should be suitable for production of [¹⁸F]FIAU, [¹⁸F]FFAU, [¹⁸F]FCAU, [¹⁸F]FBAU and other 5‐substitued thymidine analogues. Copyright © 2009 John Wiley & Sons, Ltd.     

N3‐Substituted thymidine analogues III: radiosynthesis of N3‐[(4‐[18F]fluoromethyl‐phenyl)butyl]thymidine ([18F]‐FMPBT) and N3‐[(4‐[18F]fluoromethyl‐phenyl)pentyl] thymidine ([18F]‐FMPPT) for PET

Radiosyntheses of two N³‐substituted thymidine analogues, N³‐[(4[¹⁸F]fluoromethyl‐phenyl)butyl]thymidine ([¹⁸F]‐FMPBT) and N³‐[(4[¹⁸F]fluoromethyl‐phenyl)pentyl]thymidine ([¹⁸F]‐FMPPT), are reported. The precursor compounds 9 and 10 were synthesized in six steps and the standard compounds 13 and 14 were synthesized from these precursors. For radiosynthesis, compounds 9 and 10 were fluorinated with n‐Bu₄N[¹⁸F] to produce [¹⁸F]‐ 11 and [¹⁸F]‐ 12 , which by acid hydrolysis yielded [¹⁸F]‐ 13 and [¹⁸F]‐ 14 , respectively. The crude products were purified by high‐performance liquid chromatography to obtain [¹⁸F]‐FMPBT and [¹⁸F]‐FMPPT. The average decay‐corrected radiochemical yield for [¹⁸F]‐ 13 was 15% in five runs, and that for [¹⁸F]‐ 14 was 10% in four runs. The radiochemical purity was >99% and the specific activity was >74 GBq/µmol at the end of synthesis. The synthesis time was 80–90 min from the end of bombardment. Copyright © 2007 John Wiley & Sons, Ltd.     

Fully automated,high yielding production of N‐succinimidyl 4‐[18F]fluorobenzoate ([18F]SFB), and its use in microwave‐enhanced radiochemical coupling reactions

A General Electric Medical Systems (GEMS) Tracerlab FX_FN fluorine‐18 synthesis module has been reconfigured to allow rapid (45 min), fully automated production of N‐succinimidyl 4‐[¹⁸F]fluorobenzoate ([¹⁸F]SFB) using the established three‐step, one‐pot synthesis procedure. Purification is by sep‐pak only and [¹⁸F]SFB is routinely obtained in 38% non‐decay corrected yield,>1 Ci/µmol specific activity, and >95% radiochemical purity (n=20). Moreover, this report includes our preliminary research efforts into improving peptide coupling reactions with [¹⁸F]SFB using microwave‐enhanced radiochemistry. Reaction times can be reduced by>90%, when compared with traditional thermal reactions, with no significant effect on radiochemical reaction yield. Copyright © 2010 John Wiley & Sons, Ltd.     

Automated synthesis and purification of [18F]fluoro‐[di‐deutero]methyl tosylate

Automated synthetic procedures of [¹⁸F]fluoro‐[di‐deutero]methyl tosylate on a GE TRACERlab FX F‐N module and a non‐commercial synthesis module have been developed. The syntheses included azeotropic drying of the [¹⁸F]fluoride, nucleophilic ¹⁸F‐fluorination of bis(tosyloxy)‐[di‐deutero]methane, HPLC purification and subsequent formulation of the synthesized [¹⁸F]fluoro‐[di‐deutero]methyl tosylate (d₂‐[¹⁸F]FMT) in organic solvents. Automation shortened the total synthesis time to 50 min, resulting in an average radiochemical yield of about 50% and high radiochemical purity (>98%). The possible application of this procedure to commercially available synthesis modules might be of significance for the production of deuterated ¹⁸F‐fluoromethylated imaging probes in the future. Copyright © 2013 John Wiley & Sons, Ltd.     

A simplified radiosynthesis of [18F]MK‐6240 for tau PET imaging

[¹⁸F]MK‐6240 (6‐(fluoro)‐3‐(1H‐pyrrolo[2,3‐c]pyridin‐1‐yl)isoquinolin‐5‐amine) is a highly selective PET radiotracer for the in vivo imaging of neurofibrillary tangles (NFTs). [¹⁸F]MK‐6240 was synthesized in one step from its bis‐Boc protected precursor N‐[(tert‐butoxy)carbonyl]‐N‐(6‐nitro‐3‐[1H‐pyrrolo[2,3‐c]pyridin‐1‐yl]isoquinolin‐5‐yl) carbamate in DMSO using [¹⁸F] fluoride with TEA HCO₃ with step‐wise heating up to 150°C, resulting in an isolated radiochemical yield of 9.8% ± 1.8% (n = 3) calculated from the end of bombardment (5.2% ± 1.0% calculated from the end of synthesis). This new synthetic approach eliminates the acidic deprotection of the bis‐Boc ¹⁸F‐labeled intermediate, which reduces the number of operations necessary for the synthesis as well as losses, which occur during deprotection and neutralization of the crude product mixture prior to the HPLC purification. The synthesis was performed automatically with a single‐use cassette on an IBA Synthera+ synthesis module. This synthesis method affords the radioligand with a reliable radiochemical yield, high radiochemical purity, and a high molar activity. [¹⁸F]MK‐6240 synthesized with this method has been regularly (n > 60) used in our ongoing human and animal PET imaging studies.     

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.     

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 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.