Efficient in‐loop synthesis of high specific radioactivity [11C]carfentanil

The synthesis of the precursor for [¹¹C]carfentanil and the precursor labelling with ¹¹C have both been improved. The problem ‘bottleneck’ step in the carfentanil precursor synthesis, due to low chemical yield (14%) of intermediates nitrile into amide conversion, has been solved. Application of a H₂O₂/K₂CO₃/DMSO reaction method significantly increased the yield of this chemical transformation (up to 84%). A simple and straight‐forward synthesis of [¹¹C]carfentanil was achieved by combining in‐loop methylation of the ammonia salt of the precursor by [¹¹C]CH₃I, using tetrabutylammonium hydroxide as a base, with a previously developed product purification procedure using a C2 extraction disc. A decay corrected yield with respect to [¹¹C]CH₃I of [¹¹C]carfentanil was 64±12% (n=6) with the synthesis time of 21 min. The radiochemical purity was >98%. Comparatively high specific radioactivity of [¹¹C]carfentanil [11.2±4.8 Ci/μmol (EOS, n=5)] was partially attributed to the use of [¹¹C]methane target gas for production of carbon‐11 methyl iodide. Copyright © 2003 John Wiley & Sons, Ltd.     

Synthesis of [18F]anginex with high specific activity [18F]fluorobenzaldehyde for targeting angiogenic activity in solid tumors

Anginex is a 33‐residue peptide that has been previously demonstrated to possess antiangiogenic properties. To provide a tool to evaluate the regional biodistribution and pharmacokinetics of anginex, and possibly to provide a useful angiogenesis‐targeted radiotracer, we have radiolabeled anginex with fluorine‐18. High specific activity [¹⁸F]fluorobenzaldehyde (1.5–4.8 TBq (40–130 Ci)/µmol) was used to label anginex via reductive amination in 76% yield. The effective specific activity of the product was lower because unlabeled anginex was not separated. However, the high specific activity labeling reagent increased the labeling yield and reduced the amount of anginex required for labeling. Regional pharmacokinetics were measured by PET scanning in mice, demonstrating tumor uptake and low background, with up to 30% of total injected dose localized in some tumors. Copyright © 2011 John Wiley & Sons, Ltd.     

N1'‐(p‐[18F]Fluorobenzyl)naltrindole (p‐[18F]BNTI) as a potential PET imaging agent for DOP receptors

The N1'‐(p‐fluorobenzyl)naltrindole 5 has been synthesized by reaction of 3‐O‐benzyl NTI 3 with p‐fluorobenzylbromide under phase transfer catalysis. The subsequent 3‐O‐benzyldeprotection of 4 in HBr/CH₃COOH gave the target compound 5 in three steps from naltrindole 2 . p‐FBNTI 5 is a novel delta opioid receptor antagonist (K_i=0.00312 nM) and antagonizes the delta opioid (DOP) agonist, DPDPE, with a K_e=1.55 nM in the mouse vas deferens preparation. Using the same synthetic strategy the synthesis of p‐[¹⁸F]BNTI 10 was undertaken. The final yield was 4% and the specific activity varied in a range of 250–400 mCi/µmol. Copyright © 2006 John Wiley & Sons, Ltd.     

Synthesis and preliminary evaluation of a 18F‐labeled ethisterone derivative [18F]EAEF for progesterone receptor targeting

To develop a novel progesterone receptor‐targeting probe for positron emission tomography imaging, an ethisterone derivative [¹⁸F]EAEF was designed and prepared in high decay‐corrected radiochemical yield (30–35%) with good radiochemical purity (>98%). [¹⁸F]EAEF is a lipophilic tracer (logP = 0.53 ± 0.06) with very good stability in saline and serum. In the biodistribution study, high radioactivity accumulation of [¹⁸F]EAEF were found in uterus (5.73 ± 1.83% ID/g) and ovary (4.05 ± 0.73% ID/g) at 2 hr postinjection (p.i.), which have high progesterone receptor expression after treated with estradiol, while the muscle background has very low uptake (0.50 ± 0.17% ID/g). For positron emission tomography imaging, [¹⁸F]EAEF showed high uptake in progesterone receptor‐positive MCF‐7 tumor (3.15 ± 0.07% ID/g at 2 hr p.i.) with good tumor to muscle ratio (2.90), and obvious lower tumor uptakes were observed in MCF‐7 with EAEF blocking (1.84 ± 0.05% ID/g at 2 hr p.i.) or in progesterone receptor‐negative MDA‐MB‐231 tumor (1.80 ± 0.03% ID/g at 2 hr p.i.). Based on the good stability and specificity of [¹⁸F]EAEF, it may be a good candidate for imaging progesterone receptor and worth further investigation.     

Utility of azetidinium methanesulfonates for radiosynthesis of 3‐[18F]fluoropropyl amines

3‐Methanesulfonyloxypropyl tertiary amines were observed to cyclize to form azetidinium methanesulfonate moieties. Heat‐induced cyclization of 3‐methanesulfonyloxypropyl amines was utilized for preparation of azetidinium methanesulfonates. The azetidinium methanesulfonates were found to incorporate radioactive [¹⁸F]fluoride (decay‐corrected yields >60%) efficiently, resulting in an efficient synthesis of 3‐[¹⁸F]fluoropropyl tertiary amines. Copyright © 2004 John Wiley & Sons, Ltd.     

Synthesis of [18F]‐labeled adenosine analogues as potential PET imaging agents

The syntheses of adenosine analogues, 2′‐deoxy‐2′‐[¹⁸F]fluoro‐9‐β‐D ‐arabinofuranosyladenine ([¹⁸F]‐FAA) and 3′‐deoxy‐3′‐[¹⁸F]fluoro‐9‐β‐D ‐xylofuranosyladenine ([¹⁸F]‐FXA) are reported. Adenosine ( 1 ) was converted to its methoxytrityl derivatives 2 and 3 as a mixture. After separation, these derivatives were converted to their respective triflates 4 and 5 . Each triflate was reacted with tetrabutylammonium[¹⁸F]fluoride to produce 6b or 7b , which by acidic hydrolysis yielded compounds 8b and 9b . Crude preparations were purified by HPLC to obtain the desired pure products. The radiochemical yields were 10‐18% decay corrected (d. c.) for 8b and 30‐40% (d. c.) for 9b in 4 and 3 runs, respectively. Radiochemical purity was >99% and specific activity was >74 GBq/μmol at the end of synthesis (EOS). The synthesis time was 90‐95 min from the end of bombardment (EOB). Copyright © 2003 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 and quality control of [18F]T807 for tau PET imaging

The detailed synthesis and quality control of [¹⁸F]T807, radiotracer for tau protein aggregate imaging, are described. The radiotracer synthesis was accomplished in an average of 48 min with an average specific activity at end‐of‐synthesis of over 4.4 TBq/µmole (120 Ci/µmole) and an average radiochemical yield of 32%. Compliance with all standard US Pharmacopeia Chapter <823> acceptance tests was observed.     

Synthesis,bioconjugation and stability studies of [18F]ethenesulfonyl fluoride

Fluorine‐18 labelled prosthetic groups (PGs) are often necessary for radiolabelling sensitive biological molecules such as peptides and proteins. Several shortcomings, however, often diminish the final yield of radiotracer. In an attempt to provide higher yielding and operationally efficient tools for radiolabelling biological molecules, we describe herein the first radiochemical synthesis of [¹⁸F]ethenesulfonyl fluoride ([¹⁸F]ESF) and its Michael conjugation with amino acids and proteins. The synthesis of [¹⁸F]ESF was optimised using a microfluidic reactor under both carrier‐added (c.a.) and no‐carrier‐added (n.c.a.) conditions, affording, in a straightforward procedure, 30‐50% radiochemical yield (RCY) for c.a. [¹⁸F]ESF and 60‐70% RCY for n.c.a. [¹⁸F]ESF. The conjugation reactions were performed at room temperature using 10 mg/mL precursor in aqueous/organic solvent mixtures for 15 min. The radiochemical stability of the final conjugates was evaluated in injectable formulation and rat serum, and resulted strongly substrate dependent and generally poor in rat serum. Therefore, in this work we have optimised a straightforward synthesis of [¹⁸F]ESF and its Michael conjugation with model compounds, without requiring chromatographic purification. However, given the general low stability of the final products, further studies will be required for improving conjugate stability, before assessing the use of this PG for PET imaging.     

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.     

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.     

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.     

Radiosynthesis of [18F]ATPFU: a potential PET ligand for mTOR

Mammalian target of rapamycin (mTOR) plays a pivotal role in many aspects of cellular proliferation, and recent evidence suggests that an altered mTOR signaling pathway plays a central role in the pathogenesis of aging, tumor progression, neuropsychiatric, and major depressive disorder. Availability of a mTOR‐specific PET tracer will facilitate monitoring early response to treatment with mTOR inhibitors that are under clinical development. Towards this we have developed the radiosynthesis of [¹⁸F]1‐(4‐(4‐(8‐oxa‐3‐azabicyclo[3.2.1]octan‐3‐yl)‐1‐(2,2,2‐trifluoroethyl)‐1H‐pyrazolo[3,4‐d]pyrimidin‐6‐yl)phenyl)‐3‐(2‐fluoroethyl)urea [¹⁸F]ATPFU ([¹⁸F]1) as an mTOR PET ligand. Synthesis of reference 1 and the precursor for radiolabeling, 4‐(4‐8‐oxa‐3‐azabicyclo[3.2.1]‐octan‐3yl)‐1‐(2,2,2‐trifluoroethyl)‐1H‐pyrazolo[3,4‐d]pyrimidin‐6yl)aniline (10), were achieved from beta‐chloroaldehyde 3 in 4 and 5 steps, respectively, with an overall yield of 25–28%. [¹⁸F]Fluoroethylamine was prepared by heating N‐[2‐(toluene‐4‐sulfonyloxy)ethyl]phthalimide with [¹⁸F]fluoride ion in acetonitrile. [¹⁸F]1 was obtained by slow distillation under argon of [¹⁸F]FCH₂CH₂NH₂ into amine 10 that was pre‐treated with triphosgene at 0–5 °C. The total time required for the two‐step radiosynthesis including semi‐preparative HPLC purification was 90 min, and the overall radiochemical yield of [¹⁸F]1 for the process was 15 ± 5% based on [¹⁸F]fluoride ion (decay corrected). At the end of synthesis (EOS), the specific activity was 37–74 GBq/µmol (N = 6).     

Rapid and efficient synthesis of [18F]fluoronicotinamides, [18F]fluoroisonicotinamides and [18F]fluorobenzamides as potential pet radiopharmaceuticals for melanoma imaging

In an attempt to simplify nucleophilic radiofluorination reactions to be amenable for automation, a series of [¹⁸F]fluoronicotinamides, [¹⁸F]fluoroisonicotinamides and [¹⁸F]fluorobenzamides were synthesized using one‐step synthetic approach involving displacement reactions on trimethylammonium‐nicotinamide, trimethylammonium‐isonicotinamide and trimethylammonium‐benzamide precursors. Based on starting [¹⁸F]‐fluoride, radiochemical yields and purities were found to be greater than 90 and 97%, respectively, within 20 min synthesis time and, without high‐performance liquid chromatography purification. This synthetic approach holds great promise as a rapid and simple method for the automated radiofluorination of [¹⁸F]fluoronicotinamides, [¹⁸F]fluoroisonicotinamides and [¹⁸F]fluorobenzamides with high radiochemical yield and very short preparation time. Copyright © 2011 John Wiley & Sons, Ltd.     

A concise radiosynthesis of the tau radiopharmaceutical, [18F]T807

Fluorine‐18 labeled 7‐(6‐fluoropyridin‐3‐yl)‐5H‐pyrido[4,3‐b]indole ([¹⁸F]T807) is a potent and selective agent for imaging paired helical filaments of tau and is among the most promising PET radiopharmaceuticals for this target in early clinical trials. The present study reports a simplified one‐step method for the synthesis of [¹⁸F]T807 that is broadly applicable for routine clinical production using a GE TRACERlab? FX_FN radiosynthesis module. Key facets of our optimized radiosynthesis include development and use of a more soluble protected precursor, tert‐butyl 7‐(6‐nitropyridin‐3‐yl)‐5H‐pyrido[4,3‐b]indole‐5‐carboxylate, as well as new HPLC separation conditions that enable a facile one‐step synthesis. During the nucleophilic fluorinating reaction with potassium cryptand [¹⁸F]fluoride (K[¹⁸F]/K₂₂₂) in DMSO at 130 °C over 10 min the precursor is concurrently deprotected. Formulated [¹⁸F]T807 was prepared in an uncorrected radiochemical yield of 14 ± 3%, with a specific activity of 216 ± 60 GBq/µmol (5837 ± 1621 mCi/µmol) at the end of synthesis (60 min; n = 3) and validated for human use. This methodology offers the advantage of faster synthesis in fewer steps, with simpler automation that we anticipate will facilitate widespread clinical use of [¹⁸F]T807. Copyright © 2013 John Wiley & Sons, Ltd.     

Radiosyntheses and reactivities of novel [18F]2‐fluoroethyl arylsulfonates

[¹⁸F]2‐Fluoroethyl tosylate ([¹⁸F]FEOX, X=Ts) is widely used for labeling radiotracers for positron emission tomography (PET). Little work has been reported on syntheses of other [¹⁸F]2‐fluoroethyl arylsulfonates ([¹⁸F]FEOX) that bear a less electron‐rich aryl group, even though these might offer enhanced reactivities. Thus, a series of novel [¹⁸F]FEOX (X=benzenesulfonyl, brosyl, nosyl, 3,4‐dibromobenzenesulfonyl) were synthesized and reactivities compared to [¹⁸F]FEOTs. Precursors for radiolabeling (bis‐ethylene glycol arylsulfonates) and reference FEOX were synthesized (alcohol+arylsulfonyl chloride+KOSiMe₃ in THF). Regardless of substitution pattern, [¹⁸F]FEOX (110°C, 5 min, acetonitrile) were obtained in similar decay‐corrected isolated radiochemical yields (RCY; 47–53%). All [¹⁸F]FEOX gave excellent RCYs (64–87%) of the dopamine uptake radioligand, [¹⁸F]FECNT (130°C, 10 min, acetonitrile). The 3,4‐dibromobenzensulfonate gave the highest RCY of [¹⁸F]FECNT (87%) and this HPLC‐purified labeling agent was used directly for efficient [¹⁸F]FECNT production. When the secondary aniline of an amyloid probe (HM‐IMPY) or p‐nitrophenol was reacted with [¹⁸F]FEOX, RCYs were appreciably higher for brosylate and nosylate than for tosylate, while 3,4‐dibromobenzenesulfonate again gave the highest RCY. Owing to the high reactivity of the new [¹⁸F]FEOX and their ease of syntheses via stable precursors, such agents (particularly 3,4‐dibromobenzenesulfonate) should be considered as alternatives to [¹⁸F]FEOTs. Copyright © 2005 John Wiley & Sons, Ltd.     

Synthesis of [18F]fluoroacetaldehyde. Application to [18F]fluoroethylation of benzylamine under reductive alkylation conditions

The radiosynthesis of a new [¹⁸F]fluoroalkylating agent, [¹⁸F]fluoroacetaldehyde, is described. It was produced using the Kornblum method by oxidation with dimethyl sulphoxide of 2‐[¹⁸F]fluoroethyl p‐toluenesulphonate ([¹⁸F]FETos). In these conditions the oxidation proceeds smoothly and rapidly to the selective conversion of tosyl esters of primary alcohols to aldehydes with no carboxylic acids being produced. The chemical identity of [¹⁸F]fluoroacetaldehyde was determined by comparing its chromatographic properties as well as those of its 2,4‐dinitrophenylhydrazone (2,4‐DNPH) derivative with those of, respectively, the standard fluoroacetaldehyde and its 2,4‐DNPH derivative. Standard fluoroacetaldehyde was prepared by oxidation of fluoroethanol with pyridinium dichromate and characterized as its 2,4‐DNPH derivative by mass spectrometry. To test its reactivity with amines under reductive alkylation conditions, [¹⁸F]fluoroacetaldehyde was reacted with benzylamine used as model substrate. The chemical identity of the resulting radiolabelled product was determined to be [¹⁸F]N‐(2‐fluoroethyl)‐benzylamine by comparing its chromatographic properties with those of the synthesized standard N‐(2‐fluoroethyl)‐benzylamine characterized by ¹⁹F and ¹H NMR spectroscopy and mass spectrometry. This new fluorine‐18 labelled synthon may find applications in radiolabelling peptide, protein and antibody fragments as well as in aldol condensation or in the Mannich reaction. Copyright © 2008 John Wiley & Sons, Ltd.     

Two‐step radiosynthesis of [18F]FE‐β‐CIT and [18F]PR04.MZ

The cocaine‐derived dopamine reuptake inhibitors FE‐β‐CIT (8‐(2‐fluoroethyl)‐3‐(4‐iodophenyl)‐8‐azabicyclo[3.2.1]octane‐2‐carboxylic acid methyl ester) (1) and PR04.MZ(8‐(4‐fluorobut‐2‐ynyl)‐3‐p‐tolyl‐8‐azabicyclo[3.2.1]octane‐2‐carboxylic acid methyl ester) (2) were labelled with ¹⁸F‐fluorine using a two‐step route. 2‐[¹⁸F]Fluoroethyltosylate and 4‐[¹⁸F]fluorobut‐2‐yne‐1‐yl tosylate were used as labelling reagents, respectively. Radiochemically pure (>98%) [¹⁸F]FE‐β‐CIT and [¹⁸F]PRD04.MZ (32–86 GBq/µmol) were obtained after a synthesis time of 100 min in about 25% non‐decay‐corrected overall yield.     

Improved synthesis of [18F]fluoromethyl tosylate,a convenient reagent for radiofluoromethylations

The utility of [¹⁸F]fluoromethyl tosylate as an [¹⁸F]fluoromethylation reagent has been reexamined. The preparation of this potentially useful compound from the reaction of bis(tosyloxy) methane with ¹⁸F‐ was reported several years ago, but it had not found use as a labeling reagent. When the reported reaction of bis(tosyloxy) methane with ¹⁸F‐ was carried out, [¹⁸F]fluoromethyl tosylate was formed along with [¹⁸F]tosyl fluoride. The product ratio depended upon reaction conditions, with the yield of [¹⁸F]fluoromethyl tosylate usually in the range of 25–40%. Addition of a small amount of water to the reaction mixture resulted in a significant increase in the yield of [¹⁸F]fluoromethyl tosylate. Reaction conditions were defined that produced a yield of 71±6% of [¹⁸F]fluoromethyl tosylate (decay corrected). The product was conveniently purified by alumina chromatography. Reaction of [¹⁸F]fluoromethyl tosylate with the (des‐fluoromethyl) fluticasone propionate thioacid precursor produced [¹⁸F]fluticasone propionate in improved yield (16%, from fluoride in production‐scale runs) over other synthesis methods. Similarly, formation of [¹⁸F]choline, [¹⁸F]fluoromethionine and N‐([¹⁸F]fluoromethyl)spiperone from the reaction of [¹⁸F]fluoromethyl tosylate with corresponding precursors was examined. Copyright © 2005 John Wiley & Sons, Ltd.     

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.