Trifluoromethanesulfonic acid,an alternative solvent medium for the direct electrophilic fluorination of DOPA: new syntheses of 6‐[18F]fluoro‐L‐DOPA and 6‐[18F]fluoro‐D‐DOPA

Previous work from this laboratory has shown that the direct fluorination of 3, 4‐dihydroxy‐phenyl‐L ‐alanine (L ‐DOPA) in anhydrous HF (aHF) or BF₃/HF with F₂ is an efficient method for the synthesis of 6‐fluoro‐L ‐DOPA. Since then, ¹⁸F‐labeled 6‐fluoro‐L ‐DOPA ([¹⁸F]6‐fluoro‐L ‐DOPA) has been used to study presynaptic dopaminergic function in the human brain and to monitor gastrointestinal carcinoid tumors. This work demonstrates that the reactivity and selectivity of F₂ toward L ‐DOPA in CF₃SO₃H is comparable with that in aHF. This new synthetic procedure has led to the production of [¹⁸F]fluoro‐L ‐DOPA and [¹⁸F]fluoro‐D‐DOPA isomers in 17±2% radiochemical yields (decay corrected with respect to [¹⁸F]F₂). The 2‐ and 6‐FDOPA isomers were separated by HPLC and subsequently characterized by ¹⁹F NMR spectroscopy. The corresponding [¹⁸F]‐FDOPA enantiomers have been obtained in clinically useful quantities by a synthetic approach that avoids the use of aHF. Copyright © 2007 John Wiley & Sons, Ltd.     

Automated production at the curie level of no‐carrier‐added 6‐[18F]fluoro‐ l‐dopa and 2‐[18F]fluoro‐ l‐tyrosine on a FASTlab synthesizer

An efficient, fully automated, enantioselective multi‐step synthesis of no‐carrier‐added (nca) 6‐[¹⁸F]fluoro‐L‐dopa ([¹⁸F]FDOPA) and 2‐[¹⁸F]fluoro‐L‐tyrosine ([¹⁸F]FTYR) on a GE FASTlab synthesizer in conjunction with an additional high‐ performance liquid chromatography (HPLC) purification has been developed. A PTC (phase‐transfer catalyst) strategy was used to synthesize these two important radiopharmaceuticals. According to recent chemistry improvements, automation of the whole process was implemented in a commercially available GE FASTlab module, with slight hardware modification using single use cassettes and stand‐alone HPLC. [¹⁸F]FDOPA and [¹⁸F]FTYR were produced in 36.3 ± 3.0 % (n = 8) and 50.5 ± 2.7 % (n = 10) FASTlab radiochemical yield (decay corrected). The automated radiosynthesis on the FASTlab module requires about 52 min. Total synthesis time including HPLC purification and formulation was about 62 min. Enantiomeric excesses for these two aromatic amino acids were always >95 %, and the specific activity of was >740 GBq/µmol. This automated synthesis provides high amount of [¹⁸F]FDOPA and [¹⁸F]FTYR (>37 GBq end of synthesis (EOS)). The process, fully adaptable for reliable production across multiple PET sites, could be readily implemented into a clinical good manufacturing process (GMP) environment.     

One‐step reductive etherification of 4‐[18F]fluoro‐benzaldehyde with decaborane

Reductive coupling reactions between 4‐[¹⁸F]fluoro‐benzaldehyde ([¹⁸F] 1 ) and different alcohols by use of decaborane (B₁₀H₁₄) as reducing agent have the potential to synthesize 4‐[¹⁸F]fluoro‐benzylethers in one step. [¹⁸F] 1 was synthesized from 4‐trimethylammonium benzaldehyde (triflate salt) via a standard fluorination procedure (K[¹⁸F]F/Kryptofix^® 222) in dimethylformamide at 90°C for 25 min and purified by solid‐phase extraction. Subsequently, reductive etherifications of [¹⁸F] 1 were performed as one‐step reactions with primary and secondary alcohols, mediated by B₁₀H₁₄ in acetonitrile at 60°C. Various 4‐[¹⁸F]fluorobenzyl ethers (6 examples are shown) were obtained within 1–2 h reaction time in decay‐corrected radiochemical yields of 12–45%. Copyright © 2006 John Wiley & Sons, Ltd.     

Synthesis of 3′‐deoxy‐3′‐[18F]fluoro‐1‐β‐D‐xylofuranosyluracil ([18F]‐FMXU) for PET

The synthesis of a pyrimidine analog, 3′‐deoxy‐3′‐[¹⁸F]‐fluoro‐1‐β‐D ‐xylofuranosyluracil ([¹⁸F]‐FMXU) is reported. 5‐Methyluridine 1 was converted to its di‐methoxytrityl derivatives 2 and 3 as a mixture. After separation the 2′,5′‐di‐methoxytrityluridine 2 was converted to its 3′‐triflate 4 followed by derivatization to the respective N³‐t‐Boc product 5 . The triflate 5 was reacted with tetrabutylammonium[¹⁸F]fluoride to produce 6 , which by acid hydrolysis yielded compound 7 . The crude preparation was purified by HPLC to obtain the desired product [¹⁸F]‐FMXU. The radiochemical yields were 25–40% decay corrected (d. c.) with an average of 33% in four runs. Radiochemical purity was >99% and specific activity was >74 GBq/µmol at the end of synthesis (EOS). The synthesis time was 67–75 min from the end of bombardment (EOB). Copyright © 2005 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.     

2‐, 3‐ and 4‐[18F]Fluoropyridine by no‐carrier‐added nucleophilic aromatic substitution with K[18F]F‐K222 – a comparative study

Compared to homoaromatic and aliphatic nucleophilic radiofluorinations, only few references can be found in the literature describing nucleophilic substitutions with [¹⁸F]fluoride ion of heteroaromatic compounds such as pyridines and only reactions involving fluorination processes at the ortho‐position (2‐position) have been more intensively studied. In the present paper, the scope of the nucleophilic aromatic fluorinations at the meta‐ and para‐position of the pyridine ring with no‐carrier‐added [¹⁸F]fluoride ion as its activated K[¹⁸F]F‐K₂₂₂ complex has been evaluated and compared to the nucleophilic aromatic fluorinations at the ortho‐position in this pyridine series. The syntheses of 3‐ and 4‐[¹⁸F]fluoropyridines were chosen as model reactions and compared to the radiosynthesis of 2‐[¹⁸F]fluoropyridine. The parameters studied include the influence of the position of the leaving group at the pyridine ring, as well as the quantity of the precursor used, the type of activation (conventional heating, microwave irradiation), the solvent, the temperature and the reaction time. Using the corresponding nitro precursor, high yields were obtained at the 2‐position (94% yield) using microwaves (100 W) for 2 min in DMSO. Good yields (up to 72%) were observed at the 4‐position using the same conditions while practically no reaction was observed at the 3‐position. About 60% yield was also obtained at both the 2‐ and 4‐position using the corresponding nitro precursor at 145°C for 10 min in DMSO. Copyright © 2003 John Wiley & Sons, Ltd.     

Ortho‐[18F]Fluoronitrobenzenes by no‐carrier‐added nucleophilic aromatic substitution with K[18F]F–K222—A comparative study

The scope of the nucleophilic aromatic ortho‐fluorinations from the corresponding ortho‐halonitrobenzene precursors (halo‐to‐fluoro substitutions) with no‐carrier‐added [¹⁸F]fluoride ion as its activated K[¹⁸F]F–K₂₂₂ complex has been evaluated via the radiosynthesis of ortho‐[¹⁸F]fluoronitrobenzene, chosen as a model reaction. The parameters studied include the influence of the leaving group in the ortho position of the phenyl ring (–Cl, –Br, –l), the quantity of precursor used, the type of activation (conventional heating or microwave irradiations), the solvent, the temperature and the reaction time. The iodo‐precursor was completely unreactive and the bromo‐precursor gave only low incorporation (<10%) in the optimal conditions used (conventional heating at 145°C or microwave activation, 100 W for 120 s). Only the chloro‐precursor was found reactive in the conditions described above and up to 70% yield was observed for the formation of ortho‐[¹⁸F]fluoronitrobenzene ([¹⁸F]‐ 1 ). In all the experiments, the unwanted ortho‐[¹⁸F]fluoro‐halobenzenes, potentially resulting from the nitro‐to‐fluoro substitution, could not be detected. These results will be applied for the radiosynthesis of 5‐[¹⁸F]fluoro‐6‐nitroquipazine, a potent radioligand for the imaging of the serotonin transporter with PET. Copyright © 2002 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.     

A novel method for stereospecific fluorination at the 2′‐arabino‐position of pyrimidine nucleoside: synthesis of [18F]‐FMAU

Direct fluorination of a pyrimidine nucleoside at the 2′‐arabino‐position has been deemed to be extremely difficult, if not impossible. The conventional synthesis of 2′‐deoxy‐2′‐fluoro‐5‐methy‐1‐β‐D ‐arabinofuranosyluracil (FMAU) and its 5‐substituted analogs involves stereospecific fluorination of the 1,3,5‐tri‐O‐benzoyl‐α‐D ‐ribofuranose‐2‐sulfonate ester followed by bromination at the C₁‐postion, and then coupling with pyrimidine‐bis‐trimethylsilyl ether. Several radiolabeled nucleoside analogs, including [¹⁸F]FMAU, and other 5‐substituted analogs, were developed according to this methodology. However, routine production of these compounds using this multi‐step process is inconvenient and limits their clinical application. We developed a novel precursor and method for direct fluorination of preformed nucleoside analogs at the 2′‐arabino position, exemplified via radiosynthesis of [¹⁸F]FMAU. The 2′‐methylsulfonyl‐3′,5′‐O‐tetrahydropyranyl‐N³‐Boc‐5‐methyl‐1‐β‐D ‐ribofuranosiluracil was synthesized in multiple steps. Radiofluorination of this precursor with K¹⁸F/kryptofix produced 2′‐deoxy‐2′‐[¹⁸F]fluoro‐3′,5′‐O‐tetrahydropyranyl‐N³‐Boc‐5‐methyl‐1‐β‐D ‐arabinofuranosiluracil. Acid hydrolysis followed by high‐performance liquid chromatography purification produced the desired [¹⁸F]FMAU. The average radiochemical yield was 2.0% (decay corrected, n=6), from the end of bombardment. Radiochemical purity was >99%, and specific activity was >1800 mCi/µmol. Synthesis time was 95–100 min from the end of bombardment. This direct fluorination is a novel method for synthesis of [¹⁸F]FMAU, and the method should be suitable for production of other 5‐substituted pyrimidine analogs, including [¹⁸F]FEAU, [¹⁸F]FIAU, [¹⁸F]FFAU, [¹⁸F]FCAU, and [¹⁸F]FBAU. Copyright © 2010 John Wiley & Sons, Ltd.     

The first enzymatic method for C–18F bond formation: the synthesis of 5′‐[18F]‐fluoro‐5′‐deoxyadenosine for imaging with PET

The use of the key enzyme involved in carbon–fluorine bond formation in Streptomyces cattleya catalysing the formation of 5′‐fluoro‐5′‐deoxyadenosine (5′‐FDA) from fluoride ion and S‐adenosyl‐l‐methionine (SAM) was explored for its potential application in fluorine‐18 labelling of the adenosine derivative. Enzymatic radiolabelling of [¹⁸F]‐5′‐FDA was successfully carried out starting from SAM and [¹⁸F]HF when the concentration of the enzyme preparation was increased from sub‐mg/ml values to mg/ml values. The purity of the enzyme had no measurable effect on the radiochemical yield of the reaction and the radiochemical purity of [¹⁸F]‐5′‐FDA. Copyright © 2003 John Wiley & Sons, Ltd.     

An efficient new method for the synthesis of 3‐[18F]fluoro‐4‐aminopyridine via Yamada‐Curtius rearrangement

4‐Aminopyridine is a clinically approved drug to improve motor symptoms in multiple sclerosis . A fluorine‐18‐labeled derivative of this drug, 3‐[¹⁸F]fluoro‐4‐aminopyridine, is currently under investigation for positron emission tomography (PET) imaging of demyelination. Herein, the Yamada‐Curtius reaction has been successfully applied for the preparation of this PET radioligand with a better radiochemical yield and improved specific activity. The overall radiochemical yield was 5 to 15% (n = 12, uncorrected) with a specific activity of 37 to 148 GBq/μmol (end of synthesis) in a 90 minute synthesis time. It is expected that this 1 pot Yamada‐Curtius reaction can be used to prepare similar fluorine‐18‐labeled amino substituted heterocycles.     

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.     

Use of perfluoro groups in nucleophilic 18F‐fluorination

Substrates with leaving groups that contained perfluoro moieties were investigated in labelling chemistry in order to exploit their properties to improve reactivity and purification. [¹⁸F](Fluoromethyl)benzene was used as the model target compound. Precursors containing perfluoroalkyl and perfluoroaryl sulfonate moieties were subjected to nucleophilic ¹⁸F‐fluorination, and the impact of perfluoro groups on the substitution reaction and product purification was investigated. [¹⁸F]Fluoride interacted with perfluoroalkyl chains, precluding nucleophilic substitution. When perfluoroaryl groups were used, the substitution proceeded, and the separation of product was explored. The radiolabelled product was obtained in 32% analytical yield and the radiochemical purity was increased to approximately 77% using fluorous solid phase extraction purification. Copyright © 2009 John Wiley & Sons, Ltd.     

Radiosynthesis of 3‐[18F]fluoropropyl and 4‐[18F]fluorobenzyl triarylphosphonium ions

3‐[¹⁸F]Fluoropropyl‐, 4‐[¹⁸F]fluorobenzyl‐triphenylphosphonium and 4‐[¹⁸F]fluorobenzyltris‐4‐dimethylaminophenylphosphonium cations were synthesized in multi‐step reactions from no carrier added (nca) [¹⁸F]fluoride. The time for synthesis, purification, and formulation was 56, 82, and 79 min with an average radiochemical yield of 12, 6 and 15%, respectively (not corrected for decay). The average specific radioactivity for the three radiolabeled compounds was 14.9 GB q/µmole (403 mCi/µmole) at end of synthesis (EOS). Copyright © 2004 John Wiley & Sons, Ltd.     

Synthesis of [18F]‐6‐deoxy‐6‐fluoro‐D‐glucose ([18F]6FDG), a potential tracer of glucose transport

With the goal of developing a PET radioligand for the in vivo assessment of glucose transport, 6-deoxy-6-[¹⁸F]fluoro-D -glucose ([¹⁸F]6FDG) was prepared in two steps from ¹⁸F⁻. Starting with D -glucose, the tosyl- and mesyl-derivatives of 3,5-O-benzylidene-1,2-O-isopropylidene-α-D -glucofuranose were prepared by known methods. Reaction of either of these precursors with ¹⁸F⁻ resulted in the formation of 3,5-O-benzylidene-6-deoxy-6-[¹⁸F]-fluoro-1,2-O-isopropylidene-α-D -glucofuranose in high yield. Subsequent hydrolysis resulted in the production of [¹⁸F]6FDG. Under optimal conditions, [¹⁸F]6FDG is produced 60–70 min after end of bombardment (EOB) in 71 ± 12% yield (decay corrected, based upon fluoride) with a radiochemical purity of ⩾96%. Preliminary experiments have indicated that [¹⁸F]6FDG may be a more representative in vivo tracer for the glucose transporter than 2FDG. Copyright © 2005 John Wiley & Sons, Ltd.     

19F/18F exchange synthesis for a novel [18F]S1P3‐radiopharmaceutical

¹⁹F/¹⁸F isotope exchange is a useful method to label drug molecules containing ¹⁹F‐fluorine with ¹⁸F without modifying the drug molecule itself. Sphingosine‐1‐phosphate (S1P) is an important cellular mediator that functions by signaling through cell surface receptors. S1P is involved in several cell responses and may be related to many central nervous system disorders, including neural malfunction in Alzheimer's disease. In this study, [¹⁸F]1‐benzyl‐N‐(3,4‐difluorobenzyl)‐2‐isopropyl‐6‐(2‐methoxyethoxy)‐1H‐indole‐3‐carboxamide, a novel ¹⁸F‐labeled positron emission tomography tracer for the S1P₃ receptor, was successfully synthesized using the ¹⁹F/¹⁸F isotope exchange reaction. Parameters of the reaction kinetics were studied, and correlations between the initial ¹⁸F‐activity, the amount of precursor, radiochemical yield and specific activity (SA) were determined. Contrary to expectations, high initial ¹⁸F‐activity decreased the radiochemical yield, and only a minor increase of SA occurred. This is most probably due to the complexity of the molecule and the subsequent susceptibility to radiolytic bond disruption. On the basis of the present results, a convenient condition for the ¹⁹F/¹⁸F exchange reaction is the use of 2 µmol precursor with 20 GBq of ¹⁸F‐activity. This afforded a radiochemical yield of ~10% with an SA of 0.3 GBq/µmol. Results from this study are of interest for new tracer development where high initial ¹⁸F‐activity and ¹⁹F/¹⁸F isotope exchange is used.     

Radiosynthesis of the fluorinated sucrose analogue, 1′‐[18F]fluoro‐1′‐deoxysucrose

Fluorinated and deoxysucrose analogues have been proven useful in probing the substrate specificity and roles of sucrose processing enzymes and transporters in plants. To synthesize an ¹⁸F‐labeled fluorodeoxysucrose analogue suitable for in vivo studies, an acyl‐protected, disaccharide‐based radiofluorination precursor (sucrose 1′‐O‐trifluoromethanesulfonyl‐2,3,4,6,3′,4′,6′‐hepta‐O‐acetate; 2) was prepared by regioselective mono‐deacetylation of sucrose octaacetate using a commercial esterase enzyme followed by conversion of the resultant sucrose heptaacetate to the corresponding triflate. Reaction of this triflate precursor with [¹⁸F]fluoride followed by base hydrolysis to remove the acetate groups and HPLC purification gave 1′‐[¹⁸F]fluoro‐1′‐deoxysucrose (4) in an overall synthesis time of 80 min and with a median decay corrected yield of 26% (n = 4). This study demonstrates the use of an enzymatic approach to aid the synthesis of a regiospecific radiofluorination precursor starting from the readily available fully acetylated sugar, thus avoiding the need for a complex classical carbohydrate protection strategy to individually protect each hydroxyl group in the molecule. Copyright © 2012 John Wiley & Sons, Ltd.     

A general synthesis of 2′‐deoxy‐2′‐[18F]fluoro‐1‐β‐D‐arabinofuranosyluracil and its 5‐substituted nucleosides

Several 2′‐deoxy‐2′‐[¹⁸F]fluoro‐1‐β‐D‐arabinofuranosyluracil derivatives have been synthesized. Coupling of 1‐bromo‐2‐deoxy‐2‐[¹⁸F]fluoro‐3,5‐di‐O‐benzoyl‐α‐D‐arabinofuranose 2 with protected uracil derivatives 3a–e followed by hydrolysis and high‐performance liquid chromatography purification produced the radiolabeled nucleosides 4a–e in 15–30% yield (d. c.), >99% radiochemical purity and 55.5–103.6 GBq/µmol specific activities. Copyright © 2003 John Wiley & Sons, Ltd.     

A microwave radiosynthesis of the 4‐[18F]‐fluorobenzyltriphenylphosphonium ion

The 4‐[¹⁸F]‐fluorobenzyltriphenylphosphonium cation was synthesized by a series of microwave reactions from no carrier added [¹⁸F]‐fluoride. The microwave procedure reduced the quantity of reagents used and synthesis time when compared with the original synthesis. In addition, problematic solid phase extraction, sodium borohydride reduction by column and inconsistent yields with excessive precipitate formation during the bromination step were eliminated. The 4‐[¹⁸F]‐fluorobenzyltriphenylphosphonium cation was produced radiochemically pure in 8.3% yield with a specific radioactivity of 534.5 ± 371.4 GBq/µmole at end of synthesis.     

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.