Radiosynthesis and in vivo study of [18F]1‐(2‐fluoroethyl)‐4‐[(4‐cyanophenoxy)methyl]piperidine: a promising new sigma‐1 receptor ligand

The novel sigma‐1 receptor PET radiotracer [¹⁸F]1‐(2‐fluoroethyl)‐4‐[(4‐cyanophenoxy)methyl]piperidine ([¹⁸F]WLS1.002, [¹⁸F]‐2) was synthesized (n=6) by heating the corresponding N‐ethylmesylate precursor in an anhydrous acetonitrile solution containing [¹⁸F]fluoride, Kryptofix K₂₂₂ and potassium carbonate for 15 min. Purification was accomplished by reverse‐phase HPLC methods, providing [¹⁸F]‐2 in 59±8% radiochemical yield (EOB), with specific activity of 2.89±0.80 Ci/µmol (EOS) and radiochemical purity of 98.3±2.1%. Rat biodistribution studies revealed relatively high uptake in many organs known to contain sigma‐1 receptors, including the lungs, kidney, heart, spleen, and brain. Good clearance from normal tissues was observed over time. Blocking studies (60 min) demonstrated high (>80%) specific binding of [¹⁸F]‐2 in the brain, with reduction also noted in other organs known to express these sites. Copyright © 2005 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 6‐([18F]fluoroacetamido)‐1‐hexanoicanilide ([18F]FAHA) for PET imaging of histone deacetylase (HDAC)

Radiosynthesis of a novel substrate for histone deacetylase (HDAC), 6‐([¹⁸F]fluoroacetamido)‐1‐hexanoicanilide ([¹⁸F]FAHA, [¹⁸F]‐ 3 ) is reported. For precursor synthesis, compound 1 (6‐amino‐1‐hexanoicanilide) was prepared by the reaction of 6‐amino hexanoic acid with thionyl chloride in dichloroethane followed by addition of aniline. Compound 1 was reacted with bromoacetic anhydride in tetrahydrofuran (THF) in the presence of triethylamine to produce the precursor compound 6‐(bromoacetamido)‐1‐hexanoicanilide 2 . Fluorination reactions were performed using tetrabutylammonium fluoride in various solvents at 80°C to prepare the unlabeled reference compound 3 . Radiofluorinations were performed using either n‐Bu₄N¹⁸F or K¹⁸F/kryptofix, and the crude product was purified by high performance liquid chromatography (HPLC). The radiochemical yields were 9–13% decay corrected (d.c.) with an average of 11% using K¹⁸F/kryptofix, and specific activity >2 GBq/µmol at the end of synthesis. The synthesis time was 67–75 min from the end of bombardment (EOB). Copyright © 2006 John Wiley & Sons, Ltd.     

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

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

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.     

Radiosynthesis of [18F]PBR111, a selective radioligand for imaging the translocator protein (18 kDa) with PET

PBR111 (2‐(6‐chloro‐2‐(4‐(3‐fluoropropoxy)phenyl)imidazo[1,2‐a]pyridin‐3‐yl)‐N,N‐diethylacetamide) is a novel, reported, high‐affinity and selective ligand for the translocator protein (18 kDa). PBR111 has been labelled with fluorine‐18 (half‐life: 109.8 min) using our Zymate‐XP robotic system. The process involves (A) a simple one‐step tosyloxy‐for‐fluorine nucleophilic aliphatic substitution (performed at 165°C for 5 min in DMSO using K[¹⁸F]F‐Kryptofix^®222 and 6.8–7.6 µmol of the corresponding tosylate as precursor for labelling) followed by (B) C‐18 PrepSep cartridge pre‐purification and (C) semi‐preparative HPLC purification on a Waters Symmetry^® C‐18. Up to 4.8 GBq (130 mCi) of [¹⁸F]PBR111 could be obtained with specific radioactivities ranging from 74 to 148 GBq/µmol (2–4 Ci/µmol) in 75–80 min (HPLC purification and SepPak^®‐based formulation included), starting from a 37.0 GBq (1.0 Ci) [¹⁸F]fluoride batch. Overall non‐decay‐corrected isolated yields were 8–13% (13–21% decay‐corrected). Copyright © 2008 John Wiley & Sons, Ltd.     

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.     

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.     

Radiosynthesis of [18F]DPA‐714, a selective radioligand for imaging the translocator protein (18 kDa) with PET

Recently, a novel series of 2‐phenylpyrazolo[1,5‐a]pyrimidineacetamides has been reported as selective ligands of the translocator protein (18 kDa). Within this series, DPA‐714 (N,N‐diethyl‐2‐(2‐(4‐(2‐fluoroethoxy)phenyl)‐5,7‐dimethylpyrazolo[1,5‐a]pyrimidin‐3‐yl)acetamide, K_i=7.0 nM) is a compound, which had been designed with a fluorine atom in its structure, allowing labelling with fluorine‐18 (half‐life: 109.8 min) and in vivo imaging using positron emission tomography. DPA‐714 and its tosyloxy derivative (N,N‐diethyl‐2‐(2‐(4‐(2‐toluenesulfonyloxyethoxy)phenyl)‐5,7‐dimethylpyrazolo[1,5‐a]pyrimidin‐3‐yl)acetamide) as precursor for the labelling with fluorine‐18 were synthesized in two steps from DPA‐713 (N,N‐diethyl‐2‐(2‐(4‐methoxyphenyl)‐5,7‐dimethylpyrazolo[1,5‐a]pyrimidin‐3‐yl)acetamide) and obtained in 32 and 42% yields, respectively. [¹⁸F]DPA‐714 was synthesized using a simple one‐step process (a tosyloxy‐for‐fluorine nucleophilic aliphatic substitution), which has been fully automated on our Zymate‐XP robotic system. It involves: (A) reaction of K[¹⁸F]F‐Kryptofix^®222 with the tosyloxy precursor (4.5–5.0 mg, 8.2–9.1 µmol) at 165°C for 5 min in dimethyl sufloxide (0.6 mL) followed by (B) C18 PrepSep cartridge pre‐purification and finally (C) semi‐preparative high‐performance liquid chromatography (HPLC) purification on a Waters X‐Terra? RP18. Typically, 5.6–7.4 GBq of [¹⁸F]DPA‐714 (>95% chemically and radiochemically pure) could be obtained with specific radioactivities ranging from 37 to 111 GBq/µmol within 85–90 min (HPLC purification and SepPak^®‐based formulation included), starting from a 37 GBq [¹⁸F]fluoride batch (overall non‐decay‐corrected and isolated radiochemical yield: 15–20%). Copyright © 2008 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.     

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.     

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 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 11‐[18F]fluoroundecyltriphenylphosphonium (MitoF) as a potential mitochondria‐specific positron emission tomography radiotracer

Changes in the magnitude of the mitochondrial membrane potential occur in a range of important pathologies. To assess changes in membrane potential in patients, we set out to develop an improved mitochondria‐targeted positron emission tomography probe comprising a lipophilic triphenylphosphonium cation attached to a fluorine‐18 radionuclide via an 11‐carbon alkyl chain, which is well‐established to effectively transport to and localise within mitochondria. Here, we describe the radiosynthesis of this probe, 11‐[¹⁸F]fluoroundecyl‐triphenylphosphonium (MitoF), from no‐carrier‐added [¹⁸F]fluoride and a fully automated synthetic protocol to prepare it in good radiochemical yields (2–3 GBq at end‐of‐synthesis) and radiochemical purity (97–99%). Copyright © 2013 John Wiley & Sons, Ltd.     

Radiosynthesis of 3‐(3‐[18F]fluoropropoxy)‐4‐(benzyloxy)‐N‐[(1‐dimethylaminocyclopentyl)methyl]‐5‐methoxybenzamide,a potential PET radiotracer for the glycine transporter GlyT‐2

The recently described selective and potent GlyT2 antagonist, 4‐benzyloxy‐3,5‐dimethoxy‐N‐[(1‐dimethylaminocyclopentyl) methyl]benzamide (IC₅₀=16 nM) provided an important additional tool to further characterize GlyT2 pharmacology. In order to identify an effective PET radioligand for in vivo assessment of the GlyT‐2 transporter, 3‐(3‐[¹⁸F]fluoropropoxy)‐4‐(benzyloxy)‐N‐((1‐dimethylaminocyclopentyl) methyl)‐5‐methoxybenzamide ([¹⁸F] 3 ), a novel analog of 4‐benzyloxy‐3,5‐dimethoxy‐N‐[(1‐dimethylaminocyclopentyl) methyl]benzamide was synthesized using a one‐pot, two‐step method. The NCA radiofluorination of 1,3‐propanediol di‐p‐tosylate in the presence of K₂CO₃ and Kryptofix‐222 in acetonitrile gave 81% 3‐[¹⁸F]fluoropropyl tosylate, which was subsequently coupled with 4‐benzyloxy‐3‐hydroxy‐5‐methoxy‐N‐[(1‐dimethylaminocyclopentyl) methyl]benzamide in the same reaction vessel. Solvent extraction and HPLC (Eclipse XDB‐C8 column, 80/20/0.1 MeOH/H₂O/Et₃N, 3.0 ml/min) gave [¹⁸F] 3 in 98.5% radiochemical purity. The radiochemical yield was determined to be 14.0–16.2% at EOS, and the specific activity was 1462±342 GBq/µmol. The time of synthesis and purification was 128 min. The final product was prepared as a sterile saline solution suitable for in vivo use. Copyright © 2006 John Wiley & Sons, Ltd.     

[18F]Fluoropropylsulfonyl chloride: a new reagent for radiolabeling primary and secondary amines for PET imaging

In vivo molecular imaging with positron emission tomography (PET) requires the preparation of an appropriate positron‐emitting radiotracer. New methods for the introduction of F‐18 into biologically interesting molecules could increase the availability of specific PET radiotracers and increase the application of PET to the study of human diseases. In this work, [¹⁸F]fluoropropylsulfonyl chloride was synthesized from 3‐toluenesulfonyloxypropyl thiocyanate in two steps and was successfully incorporated into molecules containing a reactive amino group. Both a primary amine, L‐phenylalanine ethyl ester hydrochloride, and a secondary amine, 1‐(2‐methoxyphenyl)‐piperazine, were successfully radiolabeled by this method. The entire radiochemical synthesis required 90 min. The products were obtained in 25.7±2.3% (n=3) and 22.8±9.1% (n=6) (EOB). This method provides a useful and easy way to make new F‐18 labeled radiopharmaceuticals for PET imaging. Copyright © 2008 John Wiley & Sons, Ltd.     

Synthesis of [18F]Fluoroclofilium as a potential cardiac imaging agent for PET studies

N‐4‐(4‐chlorophenyl)butyl‐N,N‐diethyl‐7‐[¹⁸F]fluoroheptylammonium ([¹⁸F]‐fluoroclofilium) has been prepared as a potential cardiac imaging agent. For the synthesis of this radiolabelled ammonium salt, its tosyloxylated analogue was prepared as a precursor, and the non‐radioactive fluorine analogue was synthesized as a reference compound. Radiofluorination was achieved by the treatment of N‐4‐(4‐chlorophenyl)butyl‐N,N‐diethyl‐7‐(p‐toluenesulfonyloxy)heptylammonium p‐toluenesulfonate with ¹⁸F^? in the presence of Kryptofix‐2.2.2 in acetonitrile. Copyright © 2003 John Wiley & Sons, Ltd.     

Fluorine‐18 labelling of a series of potential EGFRvIII targeting peptides with a parallel labelling approach using [18F]FPyME

There is growing interest in the use of radiolabelled peptides as receptor targeting agents for diagnostic imaging of various cancer types using positron emission tomography. In this work, 1‐[3‐(2‐[¹⁸F]fluoropyridin‐3‐yloxy)propyl]pyrrole‐2,5‐dione ([¹⁸F]FPyME) has been used for parallel fluorine‐18 labelling of PEPHC1, a peptide selective towards the cancer‐specific mutation of the epidermal growth factor receptor (EGFRvIII), and a number of truncated and mutated analogues. Conjugation of the peptides with [¹⁸F]FPyME was achieved within 10 min in non‐decay‐corrected radiochemical yields of 30–50%. The high yield of the conjugation reaction combined with its short synthesis time allows the labelling of several peptides from a single batch of [¹⁸F]FPyME. Copyright © 2010 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.     

[18F]Fluoropyruvate: radiosynthesis and initial biological evaluation

The radiosynthesis of [¹⁸F]fluoropyruvate was investigated using numerous precursors were synthesized from ethyl 2,2‐diethoxy‐3‐hydroxypropanoate (5) containing different leaving groups: mesylate, tosylate, triflate, and nonaflate. These precursors were evaluated for [¹⁸F]fluoride incorporation with triflate being superior. The subsequent hydrolysis step was investigated, and an acidic hydrolysis was optimized. After establishing suitable purification and formulation methods, the [¹⁸F]fluoropyruvate could be isolated in ca. 50% d.c. yield. The [¹⁸F]fluoropyruvate was evaluated in vitro for its uptake into tumor cells using adenocarcinomic human alveolar basal epithelial cells (A549) and unfortunately showed an uptake of approximately 0.1% of the applied dose per 100,000 cells after 30 min. Initial pharmacokinetic properties were assessed in vivo using nude mice showed a high degree of bone uptake from defluorination, which will limit its potential as an imaging agent for metabolic processes. Copyright © 2014 John Wiley & Sons, Ltd.