Efficient alkali iodide promoted F-fluoroethylations with 2-[F]fluoroethyl tosylate and 1-bromo-2-[F]fluoroethane

Radiochemical ¹⁸F-fluorination yields of several compounds using the secondary labelling precursors 2-[¹⁸F]fluoroethyl tosylate ([¹⁸F]FETos) and 1-bromo-2-[¹⁸F]fluoroethane ([¹⁸F]BFE) could be considerably enhanced by the addition of an alkali iodide. The radiochemical yield of [¹⁸F]fluoroethyl choline for example could be doubled with [¹⁸F]BFE and increased from 13% to ≈80% with [¹⁸F]FETos. By addition of alkali iodide to the precursor, the ¹⁸F-fluoroethylation yields of established radiopharmaceuticals, especially in the case of automated syntheses, could be significantly increased without major changes of the reaction conditions.     

Enantioselective syntheses of no-carrier-added (n.c.a.) (s)-4-chloro-2-[f] fluorophenylalanine and (s)-(α-methyl) -4-chloro-2-[f]fluorophenylalanine

(S)-4-Chloro-2-fluorophenylalanine and (S)-(α-methy)-4-chloro-2-fluorophenylalanine were synthesized and labeled with no carrier added (n.c.a.) fluorine-18 through a radiochemical synthesis relying on the highly enantioselective reaction between 4-chloro-2-[¹⁸F]fluorobenzyl iodide and the lithium enolate of (2S)-1-(tert-butyloxycarbonyl)-2-(tert-butyl)-3-methyl-1,3-imidazolidine-4-one for (S)-4-chloro-2-[¹⁸F]fluorophenylalanine and (2S,5S)-1-(tert-butyloxycarbonyl)-2-(tert-butyl)-3,5-dimethyl-1,3-imidazolidine-4-one for (S)-(α-methyl) -4-chloro-2-[¹⁸F] fluorophenylalanine. Quantities of about 20–25 mCi were obtained at the end of sy nthesi s, ready for injection after hydrolysis and high performance liquid chromatography (HPLC) purification, with a radiochemical yield of 17%–20% corrected to the end of bombardment after a total synthesis time of 90–105 min from [¹⁸F] fluoride. The enantiomeric excesses were shown to be 97% or more for both molecules without chiral separation and the radiochemical and chemical purities were 98% or better.     

[F]Fluoromethyl iodide ([F]FCH2I): preparation and reactions with phenol, thiophenol, amide and amine functional groups

In this study, we report the synthesis and reactivity of [¹⁸F]fluoromethyl iodide ([¹⁸F]FCH₂I) with various nucleophilic substrates and the stabilities of [¹⁸F]fluoromethylated compounds. [¹⁸F]FCH₂I was prepared by reacting diiodomethane (CH₂I₂) with [¹⁸F]KF, and purified by distillation in radiochemical yields of 14-31% (n = 25). [¹⁸F]FCH₂I was stable in organic solvents commonly used for labeling and aqueous solution with pH 1-7, but was unstable in basic solutions. [¹⁸F]FCH₂I displayed a high reactivity with various nucleophilic substrates such as phenol, thiophenol, amide and amine. The [¹⁸F]fluoromethylated compounds synthesized by the reactions of phenol, thiophenol and tertiary amine with [¹⁸F]FCH₂I were stable for purification, formulation and storage. In contrast, the [¹⁸F]fluoromethylated compounds synthesized by the reactions of primary or secondary amines, and amide with [¹⁸F]FCH₂I were too unstable to be detected or purified from the reaction mixtures. Defluorination of these [¹⁸F]fluoromethyl compounds was a main decomposition route.     

An Improved Synthesis of N-(4-[18F]Fluorobenzoyl)-Interleukin-2 for the Preclinical PET Imaging of Tumour-Infiltrating T-cells in CT26 and MC38 Colon Cancer Models

Positron emission tomography (PET) imaging of activated T-cells with N-(4-[¹⁸F]fluorobenzoyl)-interleukin-2 ([¹⁸F]FB-IL-2) may be a promising tool for patient management to aid in the assessment of clinical responses to immune therapeutics. Unfortunately, existing radiosynthetic methods are very low yielding due to complex and time-consuming chemical processes. Herein, we report an improved method for the synthesis of [¹⁸F]FB-IL-2, which reduces synthesis time and improves radiochemical yield. With this optimized approach, [¹⁸F]FB-IL-2 was prepared with a non-decay-corrected radiochemical yield of 3.8 ± 0.7% from [¹⁸F]fluoride, 3.8 times higher than previously reported methods. In vitro experiments showed that the radiotracer was stable with good radiochemical purity (>95%), confirmed its identity and showed preferential binding to activated mouse peripheral blood mononuclear cells. Dynamic PET imaging and ex vivo biodistribution studies in naïve Balb/c mice showed organ distribution and kinetics comparable to earlier published data on [¹⁸F]FB-IL-2. Significant improvements in the radiochemical manufacture of [¹⁸F]FB-IL-2 facilitates access to this promising PET imaging radiopharmaceutical, which may, in turn, provide useful insights into different tumour phenotypes and a greater understanding of the cellular nature and differential immune microenvironments that are critical to understand and develop new treatments for cancers.     

Alpha selective epoxide opening with F: synthesis of 4-(3-[F]fluoro-2-hydroxypropoxy)benzaldehyde ([F]FPB) for peptide labeling

Strained tricyclic ring systems such as epoxides are rarely used as precursors for the introduction of anionic fluorine-18 into organic compounds intended for positron emission tomography (PET). Here we report the alpha selective ring opening of epoxides for the introduction of fluorine-18 into small as well as larger biomolecules via 1- and 2-step protocols. [¹⁸F]fluoromisonidazole ([¹⁸F]MISO), a tracer for hypoxia imaging, and the tumor targeting peptide Tyr³-octreotate (TATE) were radiolabeled using epoxide opening reactions. In the latter case, the new prosthetic labeling synthon 4-(3-[¹⁸F]fluoro-2-hydroxypropoxy)benzaldehyde ([¹⁸F]FPB) has been used for ¹⁸F-introduction.     

Preparation of the novel fluorine-18-labeled VIP analog for PET imaging studies using two different synthesis methods

Vasoactive intestinal peptide (VIP) receptors are expressed on various tumor cells in much higher density than somatostatin receptors, which provides the basis for radiolabeling VIP as tumor diagnostic agent. However, fast proteolytic degradation of VIP in vivo limits its clinical application. With the aim to develop and evaluate new ligands for depicting the VIP receptors with positron emission tomography (PET), the structure modified [R^8,15,21, L¹⁷]-VIP analog was radiolabeled with ¹⁸F using two different methods. With the first method, N-4-[¹⁸F]fluorobenzoyl-[R^8,15,21, L¹⁷]-VIP ([¹⁸F]FB-[R^8,15,21, L¹⁷]-VIP 7) was produced in a decay-corrected radiochemical yield (RCY) of 33.6 ± 3%, a specific radioactivity of 255 GBq/μmol (n = 5) within 100 min in four steps. Similarly, N-4-[¹⁸F](fluoromethyl)-benzoyl-[R^8,15,21, L¹⁷]-VIP ([¹⁸F]FMB-[R^8,15,21, L¹⁷]-VIP 8) was synthesized in a RCY of 34.85 ± 5%, a specific radioactivity of 180 GBq/μmol (n = 5) within 60 min in only one step. The two products 7 and 8 were both shown good stability in HSA. Moreover, the low bone uptakes of 7 and 8 in vivo of mice showed good defluorination stability.     

Nucleophilic substitution of nitro groups by [F]fluoride in methoxy-substituted ortho-nitrobenzaldehydes—A systematic study

As model reactions for the introduction of [¹⁸F]fluorine into aromatic amino acids, the replacement of NO₂ by [¹⁸F]fluoride ion in mono- to tetra-methoxy-substituted ortho-nitrobenzaldehydes was systematically investigated. Unexpectedly, the highly methoxylated precursors 2,3,4-trimethoxy-6-nitrobenzaldehyde and 2,3,4,5-tetramethoxy-6-nitrobenzaldehyde showed high maximum radiochemical yields (82% and 48% respectively). When the electrophilicity of the leaving group substituted carbon atom is expressed by its ¹³C NMR chemical shift a good correlation with the reaction rate at the beginning of the reaction (first min) was found (R² = 0.89), whereas the maximum radiochemical yields correlated much poorer with this electrophilicity parameter. This may be caused by side reactions becoming influencial in the further reaction course. As possible side reactions the demethylation of methoxy groups and intramolecular redox reactions could be detected by HPLC/MS.     

Rapid Detection of the Residual Kryptofix 2.2.2 Levels in [18F]-Labeled Radiopharmaceuticals by Ultra-Performance Liquid Chromatography Tandem Mass Spectrometry

A fast and sensitive ultra-performance liquid chromatography-tandem mass spectrometric (UPLC/MS/MS) method was developed and validated for determination of the residual levels of Kryptofix 2.2.2 (K222) in [¹⁸F]-labeled radiopharmaceuticals. The analytical time was only 3 min, and the injection volume was 5 μL. An electrospray ionization source was used in the positive mode (ESI⁺) for UPLC/MS/MS. The analytical measurements were performed in the multiple reaction monitoring (MRM) mode. The calibration curve at the spiked concentrations of 2–500 ng/mL for K222 showed good linearity. The intra- and inter-day precisions were not more than 5%. The accuracy satisfied the requirement of quality control analysis, the recoveries were found to be 80–120%. This method was successfully applied to detect the residue of K222 in [¹⁸F]-fluorodeoxyglucose [(¹⁸F)FDG], [¹⁸F]-fluoromisonizole[(¹⁸F)FMISO], 3′-deoxy-3′-[¹⁸F]-fluorothymidine [(¹⁸F)FLT], and two new [¹⁸F]-labeled radiopharmaceuticals 4-[-(2-[¹⁸F]fluoroethoxy) methyl]-1-[2-(2-methyl-5-nitro-1H- imidazol-1-yl) ethyl]-1H-1,2,3-triazole (named as ¹⁸F-BNU-1) and 4-[-(2-[¹⁸F] fluoroethoxy) methyl]-1-[2-(2-nitro-1H-imidazol-1-yl) ethyl]-1H-1,2,3-triazole (named as ¹⁸F-BNU-2) produced in our lab.     

Nucleophilic Radiofluorination Using Tri-tert-Butanol Ammonium as a Bifunctional Organocatalyst: Mechanism and Energetics

We present a quantum chemical analysis of the ¹⁸F-fluorination of 1,3-ditosylpropane, promoted by a quaternary ammonium salt (tri-(tert-butanol)-methylammonium iodide (TBMA-I) with moderate to good radiochemical yields (RCYs), experimentally observed by Shinde et al. We obtained the mechanism of the S_N2 process, focusing on the role of the –OH functional groups facilitating the reactions. We found that the counter-cation TBMA⁺ acts as a bifunctional promoter: the –OH groups function as a bidentate ‘anchor’ bridging the nucleophile [¹⁸F]F⁻ and the –OTs leaving group or the third –OH. These electrostatic interactions cooperate for the formation of the transition states of a very compact configuration for facile S_N2 ¹⁸F-fluorination.     

Production of 6-l-[18F]Fluoro-m-tyrosine in an Automated Synthesis Module for 11C-Labeling

6-l-[¹⁸F]Fluoro-m-tyrosine (6-l-[¹⁸F]FMT) represents a valuable alternative to 6-l-[¹⁸F]FDOPA which is conventionally used for the diagnosis and staging of Parkinson’s disease. However, clinical applications of 6-l-[¹⁸F]FMT have been limited by the paucity of practical production methods for its automated production. Herein we describe the practical preparation of 6-l-[¹⁸F]FMT using alcohol-enhanced Cu-mediated radiofluorination of Bpin-substituted chiral Ni(II) complex in the presence of non-basic Bu₄ONTf using a volatile iPrOH/MeCN mixture as reaction solvent. A simple and fast radiolabeling procedure afforded the tracer in 20.0 ± 3.0% activity yield within 70 min. The developed method was directly implemented onto a modified TracerLab FX C Pro platform originally designed for ¹¹C-labeling. This method enables an uncomplicated switch between ¹¹C- and ¹⁸F-labeling. The simplicity of the developed procedure enables its easy adaptation to other commercially available remote-controlled synthesis units and paves the way for a widespread application of 6-l-[¹⁸F]FMT in the clinic.     

Synthesis of [F]xenon difluoride as a radiolabeling reagent from [F]fluoride ion in a micro-reactor and at production scale

[¹⁸F]Xenon difluoride ([¹⁸F]XeF₂), was produced by treating xenon difluoride with cyclotron-produced [¹⁸F]fluoride ion to provide a potentially useful agent for labeling novel radiotracers with fluorine-18 (t_1/2 = 109.7 min) for imaging applications with positron emission tomography. Firstly, the effects of various reaction parameters, for example, vessel material, solvent, cation and base on this process were studied at room temperature. Glass vials facilitated the reaction more readily than polypropylene vials. The reaction was less efficient in acetonitrile than in dichloromethane. Cs⁺ or K⁺ with or without the cryptand, K 2.2.2, was acceptable as counter cation. The production of [¹⁸F]XeF₂ was retarded by K₂CO₃, suggesting that generation of hydrogen fluoride in the reaction milieu promoted the incorporation of fluorine-18 into xenon difluoride. Secondly, the effect of temperature was studied using a microfluidic platform in which [¹⁸F]XeF₂ was produced in acetonitrile at elevated temperature (≥85 °C) over 94 s. These results enabled us to develop a method for obtaining [¹⁸F]XeF₂ on a production scale (up to 25 mCi) through reaction of [¹⁸F]fluoride ion with xenon difluoride in acetonitrile at 90 °C for 10 min. [¹⁸F]XeF₂ was separated from the reaction mixture by distillation at 110 °C. Furthermore, [¹⁸F]XeF₂ was shown to be reactive towards substrates, such as 1-((trimethylsilyl)oxy)cyclohexene and fluorene.     

Synthesis of [18F]F-γ-T-3, a Redox-Silent γ-Tocotrienol (γ-T-3) Vitamin E Analogue for Image-Based In Vivo Studies of Vitamin E Biodistribution and Dynamics

Vitamin E, a natural antioxidant, is of interest to scientists, health care pundits and faddists; its nutritional and biomedical attributes may be validated, anecdotal or fantasy. Vitamin E is a mixture of tocopherols (TPs) and tocotrienols (T-3s), each class having four substitutional isomers (α-, β-, γ-, δ-). Vitamin E analogues attain only low concentrations in most tissues, necessitating exacting invasive techniques for analytical research. Quantitative positron emission tomography (PET) with an F-18-labeled molecular probe would expedite access to Vitamin E’s biodistributions and pharmacokinetics via non-invasive temporal imaging. (R)-6-(3-[¹⁸F]Fluoropropoxy)-2,7,8-trimethyl-2-(4,8,12-trimethyltrideca-3,7,11-trien-1-yl)-chromane ([¹⁸F]F-γ-T-3) was prepared for this purpose. [¹⁸F]F-γ-T-3 was synthesized from γ-T-3 in two steps: (i) 1,3-di-O-tosylpropane was introduced at C6-O to form TsO-γ-T-3, and (ii) reaction of this tosylate with [¹⁸F]fluoride in DMF/K₂₂₂. Non-radioactive F-γ-T-3 was synthesized by reaction of γ-T-3 with 3-fluoropropyl methanesulfonate. [¹⁸F]F-γ-T-3 biodistribution in a murine tumor model was imaged using a small-animal PET scanner. F-γ-T-3 was prepared in 61% chemical yield. [¹⁸F]F-γ-T-3 was synthesized in acceptable radiochemical yield (RCY 12%) with high radiochemical purity (>99% RCP) in 45 min. Preliminary F-18 PET images in mice showed upper abdominal accumulation with evidence of renal clearance, only low concentrations in the thorax (lung/heart) and head, and rapid clearance from blood. [¹⁸F]F-γ-T-3 shows promise as an F-18 PET tracer for detailed in vivo studies of Vitamin E. The labeling procedure provides acceptable RCY, high RCP and pertinence to all eight Vitamin E analogues.     

Synthesis of <Emphasis Type="Italic">O</Emphasis>-(2-[<Superscript>18</Superscript>F]fluoroethyl)-<Emphasis Type="Italic">L</Emphasis>-tyrosine and its biological evaluation in B16 melanoma-bearing mice as PET tracer for tumor imaging

O-(2-[¹⁸F]fluoroethyl)-L-tyrosine ([¹⁸F]FET), a fluorine-18 labeled analogue of tyrosine, has been synthesized and biologically evaluated in tumor-bearing mice. The whole synthesis procedure is completed within 50 min. The radiochemical yield is about 40% (no decay corrected) and radiochemical purity more than 97% after simplified solid phase extraction. [¹⁸F]FET shows rapid, high uptake and long retention in the tumor as well as low uptake in the brain. The ratios of tumor-to-muscle (T/M) and tumor-to-blood (T/B) of [¹⁸F]FET are similar to those of [¹⁸F]FDG, but the ratios of tumor-to-brain (T/Br) are 2–3 times higher than that of [¹⁸F]FDG. Autoradiography of [¹⁸F]FET demonstrates a remarkable accumulation in melanoma with high contrast. It appears to be a probable competitive candidate for melanoma imaging with PET. Supported by the Knowledge Innovation Project of Chinese Academy of Sciences (No. KJCX1-SW-08) and the National Natural Science Foundation of China (Grant No. 30371634)     

Alternate HPLC method for the analysis of tetrabutylammonium hydroxide in [18F]fluorodeoxythymidine (FLT)

Tetrabutylammonium hydroxide is a common reagent used in the synthesis of [¹⁸F]Fluorodeoxythymidine (FLT) for positron emission tomography imaging. The British Pharmacopeia monograph for the analysis of [¹⁸F]FLT was released in 2015 incorporating a HPLC method for the analysis of tetrabutylammonium hydroxide. We describe alternate HPLC conditions that mitigate the challenges in fulfilling the system suitability requirements such as signal to noise and symmetry factor that are specified in the monograph. Our method was validated by analyzing tetrabutylammonium hydroxide at a range of concentrations to determine the linearity (R²?=?0.994), accuracy (≤9.2%) and precision (≤3.2%). Our method does not affect the analysis of [¹⁸F]FLT and it complies with all requirements in the BP monograph.     

Preliminary Assessment of the Anti-inflammatory Activity of New Structural Honokiol Analogs with a 4′-O-(2-Fluoroethyl) Moiety and the Potential of Their 18F-Labeled Derivatives for Neuroinflammation Imaging

Neolignans honokiol and 4′-O-methylhonokiol (MH) and their derivatives have pronounced anti-inflammatory activity, as evidenced by numerous pharmacological studies. Literature data suggested that cyclooxygenase type 2 (COX-2) may be a target for these compounds in vitro and in vivo. Recent studies of [¹¹C]MPbP (4′-[¹¹C]methoxy-5-propyl-1,1′-biphenyl-2-ol) biodistribution in LPS (lipopolysaccharide)-treated rats have confirmed the high potential of MH derivatives for imaging neuroinflammation. Here, we report the synthesis of four structural analogs of honokiol, of which 4′-(2-fluoroethoxy)-2-hydroxy-5-propyl-1, 1′-biphenyl (F-IV) was selected for labeling with fluorine-18 (T_1/2 = 109.8 min) due to its high anti-inflammatory activity confirmed by enzyme immunoassays (EIA) and neuromorphological studies. The high inhibitory potency of F-IV to COX-2 and its moderate lipophilicity and chemical stability are favorable factors for the preliminary evaluation of the radioligand [¹⁸F]F-IV in a rodent model of neuroinflammation. [¹⁸F]F-IV was prepared with good radiochemical yield and high molar activity and radiochemical purity by ¹⁸F-fluoroethylation of the precursor with Boc-protecting group (15) with [¹⁸F]2-fluoro-1-bromoethane ([¹⁸F]FEB). Ex vivo biodistribution studies revealed a small to moderate increase in radioligand uptake in the brain and peripheral organs of LPS-induced rats compared to control animals. Pretreatment with celecoxib resulted in significant blocking of radioactivity uptake in the brain (pons and medulla), heart, lungs, and kidneys, indicating that [¹⁸F]F-IV is likely to specifically bind to COX-2 in a rat model of neuroinflammation. However, in comparison with [¹¹C]MPbP, the new radioligand showed decreased brain uptake in LPS rats and high retention in the blood pool, which apparently could be explained by its high plasma protein binding. We believe that the structure of [¹⁸F]F-IV can be optimized by replacing the substituents in the biphenyl core to eliminate these disadvantages and develop new radioligands for imaging activated microglia.     

Synthesis and biological evaluation of 3-{[4-(4-[18F]fluorophenyl)methyl] piperazin-1-yl}-methyl-1H-pyrrolo[2,3-b]pyridine for in vivo studies of dopamine D4 receptor

The compound 3-{[4-(4-[¹⁸F]fluorophenyl)methyl]piperazin-1-yl}-methyl-1H-pyrrolo[2,3-b]pyridine ([¹⁸F]3), which is an analogue of L-745,870 binding D₄ This revised version was published online in July 2006 with corrections to the Cover Date.     

Cover Picture: A Practical One-Pot Synthesis of Positron Emission Tomography (PET) Tracers via Nickel-Mediated Radiofluorination (ChemistryOpen 4/2015)

Invited for this months cover picture is the group of Professor Bernd Neumaier at the Institute of Radiochemistry and Experimental Molecular Imaging at the University Clinic of Cologne. The cover picture shows the differences in brain metabolism of a healthy young and a healthy old subject, as well as a patient suffering from Parkinsons disease (left to right) uncovered by 6-[¹⁸F]FDOPA-positron emission tomography (PET). Morbus Parkinson occurs when nerve cells that produce dopamine begin to die. The shortage of dopamine leads to movement problems in affected individuals. 6-[¹⁸F]FDOPA is extensively used to evaluate the progression of Parkinsons disease. Bold stick projections of this PET tracer, as well as a neuronal network, are seen in the background. Unfortunately, conventional procedures to produce 6-[¹⁸F]FDOPA are cumbersome. Thus, several recent developments aim at the simplification of this radiosynthesis. In our work, we studied the applicability of the recently reported Ni-mediated radiofluorination approach for daily routine production of 6-[¹⁸F]FDOPA. For more details, see the Full Paper on p. 457 ff.     

Lymph Nodes Draining Infections Investigated by PET and Immunohistochemistry in a Juvenile Porcine Model

Background: [¹⁸F]FDG and [¹¹C]methionine accumulate in lymph nodes draining S. aureus -infected foci. The lymph nodes were characterized by weight, [¹¹C]methionine- and [¹⁸F]FDG-positron emissions tomography (PET)/computed tomography (CT), and immunohistochemical (IHC)-staining. Methods: 20 pigs inoculated with S. aureus into the right femoral artery were PET/CT-scanned with [¹⁸F]FDG, and nine of the pigs were additionally scanned with [¹¹C]methionine. Mammary, medial iliac, and popliteal lymph nodes from the left and right hind limbs were weighed. IHC-staining for calculations of area fractions of Ki-67, L1, and IL-8 positive cells was done in mammary and popliteal lymph nodes from the nine pigs. Results: The pigs developed one to six osteomyelitis foci. Some pigs developed contiguous infections of peri-osseous tissue and inoculation-site abscesses. Weights of mammary and medial iliac lymph nodes and their [¹⁸F]FDG maximum Standardized Uptake Values (SUV_FDGmax) showed a significant increase in the inoculated limb compared to the left limb. Popliteal lymph node weight and their FDG uptake did not differ significantly between hind limbs. Area fractions of Ki-67 and IL-8 in the right mammary lymph nodes and SUV_Metmax in the right popliteal lymph nodes were significantly increased compared with the left side. Conclusion: The PET-tracers [¹⁸F]FDG and [¹¹C]methionine, and the IHC- markers Ki-67 and IL-8, but not L1, showed increased values in lymph nodes draining soft tissues infected with S. aureus. The increase in [¹¹C]methionine may indicate a more acute lymph node response, whereas an increase in [¹⁸F]FDG may indicate a more chronic response.     

Synthesis and Derivatization of 1,1‐[18F]Difluorinated Alkenes

A general method for the synthesis of 1,1‐[¹⁸F]difluorinated alkenes from [¹⁸F]fluoride is reported. This transformation is highly regioselective giving the desired ¹⁸F‐fluoroalkenes with radiochemical purities of up to 77 % within 20 minutes and a molar activity (A_m) of 1 GBq μmol^?1. The transformations are operationally simple to perform and were readily translated onto a commercial automated synthesis unit. The resultant 1,1‐[¹⁸F]difluorinated alkene motif is prevalent in numerous drug molecules, and this is the first general method to synthesize this motif with fluorine‐18. ¹⁸F‐fluorinated alkenes are excellent building blocks and participate in a number of post‐labeling transformations to access a range of ¹⁸F‐perfluorinated functional groups that have never before been radiolabeled with non‐carrier‐added [¹⁸F]fluoride. This method considerably expands the range of ¹⁸F‐motifs accessible to radiochemists.     

Radiosynthesis of [18F]-5-[2-(2-chlorophenoxy)phenyl]-1,3,4-oxadiazole-2-yl-4-fluorobenzoate: A labeled ligand for benzodiazepine receptors

5-[2-(2-Chlorophenoxy)phenyl]-1,3,4-oxadiazole-2-yl-4-fluorobenzoate 6a, the non-classic benzodiazepine ligand, has been shown to elicit a significant anticonvulsant activity against pentylenetetrazole-induced convulsion. In order to perform biological studies, we decided to prepare the [¹⁸F]-labeled compound. This compound was prepared in no-carrier-added (n.c.a) form from 5-[2-(2-chlorophenoxy)phenyl]-1,3,4-oxadiazole-2-yl-4-N,N,N-trimethylanilinium triflate 5 in one step at 125 °C in Kryptofix 2.2.2/[¹⁸F] and DMSO as the solvent followed by column chromatography. The synthesis took 20 minutes with an overall radiochemical yield of 70-75% (EOS) and a specific activity about 74 GBq/mmole and chemical-radiochemical purity more than 95%. This revised version was published online in July 2006 with corrections to the Cover Date.