Application of n.c.a. 4‐[18F]fluorophenol in diaryl ether syntheses of 2‐(4‐[18F]fluorophenoxy)‐benzylamines

The availability of no‐carrier‐added (n.c.a.) 4‐[¹⁸F]fluorophenol offers the possibility of introducing the 4‐[¹⁸F]fluorophenoxy moiety into potential radiopharmaceuticals. Besides alkyl–aryl ether synthesis using n.c.a. 4‐[¹⁸F]fluorophenol the diaryl ether coupling is an attractive synthetic method to enlarge the spectrum of interesting labelling procedures. As examples the syntheses of n.c.a. 2‐(4‐[¹⁸F]fluorophenoxy)‐N,N‐dimethylbenzylamine and n.c.a. 2‐(4‐[¹⁸F]fluorophenoxy)‐N‐methylbenzylamine were realized by an Ullmann ether synthesis of corresponding 2‐bromobenzoic acid amides using tetrakis(acetonitrile)copper(I) hexafluorophosphate as catalyst and a subsequent reduction of the amides formed. The radiochemical yield of the coupling varied between 5 and 65% based on labelled 4‐[¹⁸F]fluorophenol. Both compounds are structural analogues of recently published radiotracers for imaging the serotonin reuptake transporter sites (SERT). However, in vitro binding assays of both molecules showed only a low affinity towards monoamine transporters. Copyright © 2004 John Wiley & Sons, Ltd.     

Hydroacylation of 4‐[18F]fluorobenzaldehyde: a novel method for the preparation of 4′‐[18F]phenylketones

To assess the potential of intermolecular hydroacylation reactions as a new fluorine‐18 labeling method, model reactions of [¹⁸F]fluorobenzaldehyde with three different olefins (1‐hexene ( 2a ), allylbenzene ( 2b ), and 3‐phenoxypropene ( 2c )) in the presence of Wilkinson's catalyst were performed. The procedure gave high radiochemical yields (38–62%) of [¹⁸F]fluorophenylketones with short reaction times (15 min). The intermolecular hydroacylation reaction provides a new method for the preparation of fluorine‐18 labeled compounds. Copyright © 2002 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 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.     

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.     

Synthesis,radiofluorination, and preliminary evaluation of the potential 5‐HT2A receptor agonists [18F]Cimbi‐92 and [18F]Cimbi‐150

An agonist PET tracer is of key interest for the imaging of the 5‐HT_2A receptor, as exemplified by the previously reported success of [¹¹C]Cimbi‐36. Fluorine‐18 holds several advantages over carbon‐11, making it the radionuclide of choice for clinical purposes. In this respect, an ¹⁸F‐labelled agonist 5‐HT_2A receptor (5‐HT_2AR) tracer is highly sought after. Herein, we report a 2‐step, 1‐pot labelling methodology of 2 tracer candidates. Both ligands display high in vitro affinities for the 5‐HT_2AR. The compounds were synthesised from easily accessible labelling precursors, and radiolabelled in acceptable radiochemical yields, sufficient for in vivo studies in domestic pigs. PET images partially conformed to the expected brain distribution of the 5‐HT_2AR; a notable exception however being significant uptake in the striatum and thalamus. Additionally, a within‐scan displacement challenge with a 5‐HT_2AR antagonist was unsuccessful, indicating that the tracers cannot be considered optimal for neuroimaging of the 5‐HT_2AR.     

N‐2‐(4‐N‐(4‐[18F]Fluorobenzamido)phenyl)‐propyl‐2‐propanesulphonamide: synthesis and radiofluorination of a putative AMPA receptor ligand

Arylpropylsulphonamides are in the focus of research as α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolpropionic acid (AMPA) receptor ligands. A new fluorine‐18‐labelled potentiator of AMPA receptors was synthesized as a potential radiotracer for cerebral imaging with positron emission tomography. Using N‐2‐(4‐N‐(4‐nitrobenzamido)phenyl)‐propyl‐2‐propanesulphonamide ( 7 ) as labelling precursor for a Kryptofix 2.2.2^®/K₂CO₃‐activated nucleophilic radiofluorination, the putative AMPA receptor ligand N‐2‐(4‐N‐(4‐[¹⁸F]fluorobenzamido)phenyl)‐propyl‐2‐propanesulphonamide [¹⁸F] 8 was obtained in one step. Optimization of the reaction parameters time, temperature, solvent and concentration gave a radiochemical yield of 38±8% at 180°C in dimethylsulphoxide within 30‐min reaction time. After a solid‐phase extraction followed by a high‐performance liquid chromatography separation, the product could be obtained in radiochemical yields of 5±1.5%. Radiochemical purity was higher than 95% and the specific activity amounted to 77±40 GBq/µmol. First in vitro assays with rat brain slices revealed a high non‐specific binding and a uniform distribution of [¹⁸F] 8 not lending it for in vivo imaging purposes. Copyright © 2007 John Wiley & Sons, Ltd.     

Radiochemical synthesis of 2′‐[18F]‐labelled and 3′‐[18F]‐labelled nucleosides for positron emission tomography imaging

This review article considers 2′‐labelled and 3′‐labelled nucleosides, which are of great importance as positron emission tomography (PET) probes in clinical diagnostics and PET research. Although the radiochemical preparation of several [¹⁸F]‐labelled nucleosides such as [¹⁸F]fluorothymidine or [¹⁸F](fluoroarabinofuranosyl)cytosine has been accomplished within the last two decades, a number of potentially interesting nucleoside‐based biomarkers are not yet available for automated good manufacturing practice production due to the lack of fast and efficient synthetic methods for late‐stage [¹⁸F]‐introduction. In order to meet recent demands for new PET‐based biomarkers in various clinical applications, appropriate precursors that can easily be fluorinated and deprotected need to be developed.     

Alternative solvents for electrophilic synthesis of 6‐[18F]fluoro‐L‐DOPA

Owing to the ozone layer‐depleting properties of chlorofluorocarbon compounds, alternative solvents for electrophilic fluorination reactions are desirable. Chloroform, dichloromethane, acetone or their deuterated analogues were examined as substitutes for Freon‐11 in the electrophilic synthesis of 6‐[¹⁸F]fluoro‐L ‐DOPA ([¹⁸F]FDOPA). CDCl₃, CD₂Cl₂ and C₃D₆O were found to be suitable solvents in this reaction, with the deuterated solvents providing significantly higher yields than Freon‐11. There were no differences among the solvents in the specific radioactivity, the radiochemical purity, the chemical purity or the microbiological quality of the final product. However, the radiochemical yield of [¹⁸F]FDOPA was increased when acetic acid was added to the precursor solution prior to the fluorination reaction. Copyright © 2009 John Wiley & Sons, Ltd.     

Baeyer‐Villiger oxidation tuned to chemoselective conversion of non‐activated [18F]fluorobenzaldehydes to [18F]fluorophenols

A reaction pathway via oxidation of [¹⁸F]fluorobenzaldehydes offers a very useful tool for the no‐carrier‐added radiosynthesis of [¹⁸F]fluorophenols, a structural motive of several potential radiopharmaceuticals. A considerably improved chemoselectivity of the Baeyer‐Villiger oxidation (BVO) towards phenols was achieved, employing 2,2,2‐trifluoroethanol as reaction solvent in combination with Oxone or m‐CPBA as oxidation agent. The studies showed the necessity of H₂SO₄ addition, which appears to have a dual effect, acting as catalyst and desiccant. For example, 2‐[¹⁸F]fluorophenol was obtained with a RCY of 97% under optimised conditions of 80°C and 30‐minute reaction time. The changed performance of the BVO, which is in agreement with known reaction mechanisms via Criegee intermediates, provided the best results with regard to radiochemical yield (RCY) and chemoselectivity, i.e. formation of [¹⁸F]fluorophenols rather than [¹⁸F]fluorobenzoic acids. Thus, after a long history of the BVO, the new modification now allows an almost specific formation of phenols, even from electron‐deficient benzaldehydes. Further, the applicability of the tuned, chemoselective BVO to the n.c.a. level and to more complex compounds was demonstrated for the products n.c.a. 4‐[¹⁸F]fluorophenol (RCY 95%; relating to 4‐[¹⁸F]fluorobenzaldehyde) and 4‐[¹⁸F]fluoro‐m‐tyramine (RCY 32%; relating to [¹⁸F]fluoride), respectively.     

Microfluidic radiosynthesis and biodistribution of [18F] 2‐(5‐fluoro‐pentyl)‐2‐methyl malonic acid

Microfluidics technology has emerged as a powerful tool for the radiosynthesis of positron emission tomography (PET) and single‐photon emission computed tomography radiolabeled compounds. In this work, we have exploited a continuous flow microfluidic system (Advion, Inc., USA) for the [¹⁸F]‐fluorine radiolabeling of the malonic acid derivative, [¹⁸F] 2‐(5‐fluoro‐pentyl)‐2‐methyl malonic acid ([¹⁸F]‐FPMA), also known as [¹⁸F]‐ML‐10, a radiotracer proposed as a potential apoptosis PET imaging agent. The radiosynthesis was developed using a new tosylated precursor. Radiofluorination was initially optimized by manual synthesis and served as a basis to optimize reaction parameters for the microfluidic radiosynthesis. Under optimized conditions, radio‐thin‐layer chromatography analysis showed 79% [¹⁸F]‐fluorine incorporation prior to hydrolysis and purification. Following hydrolysis, the [¹⁸F]‐FPMA was purified by C18 Sep‐Pak, and the final product was analyzed by radio‐HPLC (high‐performance liquid chromatography). This resulted in a decay‐corrected 60% radiochemical yield and ≥98% radiochemical purity. Biodistribution data demonstrated rapid blood clearance with less than 2% of intact [¹⁸F]‐FPMA radioactivity remaining in the circulation 60 min post‐injection. Most organs showed low accumulation of the radiotracer, and radioactivity was predominately cleared through kidneys (95% in 1 h). Radio‐HPLC analysis of plasma and urine samples showed a stable radiotracer at least up to 60 min post‐injection.     

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.     

How to increase the reactivity of [18F]fluoroethyl bromide: [18F]fluoroethylation of amine,phenol and amide functional groups with [18F]FEtBr, [18F]FEtBr/NaI and [18F]FEtOTf

[¹⁸F]Fluoroethyl bromide ([¹⁸F]FEtBr) is a useful synthetic precursor to synthesize ¹⁸F‐labeled compounds. However, the lower reactivity of [¹⁸F]FEtBr with amine, phenol and amide functional groups than that of [¹¹C]CH₃I partly limits its wide application in the synthesis of [¹⁸F]fluoroethylated compounds. The aim of this study was to increase the reactivity of [¹⁸F]FEtBr with various nucleophilic substrates for PET tracers containing amine, phenol and amide moieties. The present strategies included (1) adding NaI into the reaction mixture of [¹⁸F]FEtBr and substrate, where [¹⁸F]FEtI is reversibly formed and becomes more reactive; (2) converting [¹⁸F]FEtBr into much more reactive [¹⁸F]FEtOTf, similar to conversion of [¹¹C]CH₃I into [¹¹C]CH₃OTf. By these efforts, the [¹⁸F]fluoroethylation efficiency of various substrates containing amine, phenol and amide groups with [¹⁸F]FEtBr/NaI and [¹⁸F]FEtOTf was significantly improved, compared with the corresponding reaction efficiency with [¹⁸F]FEtBr. Copyright © 2003 John Wiley & Sons, Ltd.     

Radiosynthesis of 4‐[18F]fluoromethyl‐L‐phenylalanine and [18F]FET via a same strategy and automated synthesis module

Currently there is still a need for more potent amino acid analogues as tumour imaging agents for peripheral tumour imaging with PET as it was recently reported that the success of O‐(2′‐[¹⁸F]fluoroethyl)‐L ‐tyrosine ([¹⁸F]FET) is limited to brain, head and neck tumours. As the earlier described 2‐Amino‐3‐(2‐[¹⁸F]fluoromethyl‐phenyl)‐propionic acid (2‐[¹⁸F]FMP) suffered from intramolecular‐catalysed defluorination, we synthesized 2‐Amino‐3‐(4‐[¹⁸F]fluoromethyl‐phenyl)‐propionic acid (4‐[¹⁸F]FMP) as an alternative for tumour imaging with PET. Radiosynthesis of 4‐[¹⁸F]FMP, based on Br for [¹⁸F] aliphatic nucleophilic exchange, was performed with a customized modular Scintomics automatic synthesis hotbox^three system in a high overall yield of 30% and with a radiochemical purity of \gt 99%. 4‐[¹⁸F]FMP was found to be stable in its radiopharmaceutical formulation, even at high radioactivity concentrations. Additionally, for a comparative study, [¹⁸F]FET was synthesized using the same setup in 40% overall yield, with a radiochemical purity \gt 99%. The described automated radiosynthesis allows the production of two different amino acid analogues with minor alternations to the parameter settings of the automated system, rendering this unit versatile for both research and clinical practice. Copyright © 2009 John Wiley & Sons, Ltd.     

Radiosynthesis and ‘click’ conjugation of ethynyl‐4‐[18F]fluorobenzene — an improved [18F]synthon for indirect radiolabeling

Reproducible methods for [¹⁸F]radiolabeling of biological vectors are essential for the development of new [¹⁸F]radiopharmaceuticals. Molecules such as carbohydrates, peptides and proteins are challenging substrates that often require multi‐step indirect radiolabeling methods. With the goal of developing more robust, time saving, and less expensive procedures for indirect [¹⁸F]radiolabeling of such molecules, our group has synthesized ethynyl‐4‐[¹⁸F]fluorobenzene ([¹⁸F]2, [¹⁸F]EYFB) in a single step (14 ± 2% non‐decay corrected radiochemical yield (ndc RCY)) from a readily synthesized, shelf stable, inexpensive precursor. The alkyne‐functionalized synthon [¹⁸F]2 was then conjugated to two azido‐functionalized vector molecules via CuAAC reactions. The first ‘proof of principle’ conjugation of [¹⁸F]2 to 1‐azido‐1‐deoxy‐β‐d ‐glucopyranoside (3) gave the desired radiolabeled product [¹⁸F]4 in excellent radiochemical yield (76 ± 4% ndc RCY (11% overall)). As a second example, the conjugation of [¹⁸F]2 to matrix‐metalloproteinase inhibitor (5), which has potential in tumor imaging, gave the radiolabeled product [¹⁸F]6 in very good radiochemical yield (56 ± 12% ndc RCY (8% overall)). Total preparation time for [¹⁸F]4 and [¹⁸F]6 including [¹⁸F]F^? drying, two‐step reaction (nucleophilic substitution and CuAAC conjugation), two HPLC purifications, and two solid phase extractions did not exceed 70 min. The radiochemical purity of synthon [¹⁸F]2 and the conjugated products, [¹⁸F]4 and [¹⁸F]6, were all greater than 98%. The specific activities of [¹⁸F]2 and [¹⁸F]6 were low, 5.97 and 0.17 MBq nmol^?1, respectively.     

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.     

C‐Terminal 18F‐fluoroethylamidation exemplified on [Gly‐OH9] oxytocin

The no‐carrier‐added (n.c.a.) ¹⁸F‐fluoroethylamidation of the acid function of the protected nonapeptide Boc–Cys–Tyr(tBu)–Ile–Gln(Mtt)–Asn(Mtt)–Cys–Pro–Leu–Gly–OH forming the labelled peptide hormone derivative [Gly‐(2‐[¹⁸F]fluoroethyl)NH⁹]‐oxytocin is described. The labelling conditions were elaborated using a protected tripeptide, identical to the C‐terminal sequence of oxytocin. The prosthetic group n.c.a. 2‐[¹⁸F]fluoroethylamine was synthesised via cryptate mediated n.c.a. ¹⁸F‐fluorination of N‐Boc‐2‐(p‐toluenesulfonyloxy)ethylamine in DMSO (RCY: ca. 60%) and subsequent deprotection with a radiochemical yield of 46±5%. [¹⁸F]Fluoroethylamine was reacted with Z–Pro–Leu–Gly–OH in presence of the coupling reagent TBTU or with activated esters of the model‐tripeptide. The activated ester method as well as the condensation in presence of TBTU yielded ?90% of the ¹⁸F‐fluoroethyl‐amidated tripeptide. TBTU‐mediated condensation of n.c.a. 2‐[¹⁸F]fluoro‐ethylamine with the C‐terminal free acid group of protected oxytocin gave the radiochemical yield of about 75%. Deprotection under acidic conditions led to the formation of [Gly–(2‐[¹⁸F]fluoroethyl)NH⁹]oxytocin within 75 min with a radiochemical yield of about 30% as measured by analytical HPLC. Copyright © 2002 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.     

Synthesis,labelling and first evaluation of [18F]R91150 as a serotonin 5‐HT2A receptor antagonist for PET

In psychiatric disorders such as anxiety, depression and schizophrenia, 5‐HT_2A receptors play an important role. In order to investigate them in vivo there is an increasing interest in selective and high‐affinity radioligands for receptor binding studies using positron emission tomography (PET). Since available radioligands have disadvantages, R91150, which is a selective and high‐affinity ligand for 5‐HT_2A receptors, was labelled with fluorine‐18. This was accomplished in six steps via 4‐[¹⁸F]fluorophenol and 1‐(3‐bromopropoxy)‐4‐[¹⁸F]fluorobenzene within 190 min starting from no‐carrier‐added [¹⁸F]fluoride. The overall radiochemical yield was 3.8±2% and the specific activity was at least 335 GBq/µmol at the end of the synthesis. First ex vivo studies in mice proved the uptake of [¹⁸F]R91150 in the brain. Radiometabolite studies revealed no radiometabolites in the brain, whereas in the plasma at least two could be detected 30 min p.i. Further preclinical studies are encouraged to evaluate the potential of this new 5‐HT_2A ligand as a radiotracer for PET. Copyright © 2008 John Wiley & Sons, Ltd.     

Synthesis of 18F‐labelled biphenyls via SUZUKI cross‐coupling with 4‐[18F]fluoroiodobenzene

The SUZUKI reaction of organoboron compounds with 4‐[¹⁸F]fluoroiodobenzene has been developed as a novel radiolabelling technique in ¹⁸F chemistry. The cross‐coupling reaction of p‐tolylboronic acid with 4‐[¹⁸F]fluoroiodobenzene was used to screen different palladium complexes, bases and solvents. Optimized reaction conditions (Pd₂(dba)₃, Cs₂CO₃, acetonitrile, 60°C for 5 min) were further applied to the synthesis of various ¹⁸F‐labelled biphenyls bearing different functional groups. The reaction proceeded in excellent radiochemical yields of up to 94% within 5 min while showing good compatibility to many functional groups. Copyright © 2006 John Wiley & Sons, Ltd.