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

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

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‐(2′‐[18F]fluoro)‐flumazenil ([18F]FFMZ)

Recently, two fluorine‐18 labelled derivatives of flumazenil were described: 5‐(2′‐[¹⁸F]fluoroethyl)‐5‐desmethylflumazenil (ethyl 8‐fluoro‐5‐[¹⁸F]fluoroethyl‐6‐oxo‐5,6‐dihydro‐4H‐benzo‐[f]imidazo[1,5‐a] [1,4]diazepine‐3‐carboxylate; [¹⁸F]FEFMZ) and 3‐(2′‐[¹⁸F]fluoro)‐flumazenil (2′‐[¹⁸F]fluoroethyl 8‐fluoro‐5‐methyl‐6‐oxo‐5,6‐dihydro‐4H‐benzo‐[f]imidazo[1,5‐a]‐[1,4]diazepine‐3‐carbo‐ xylate; [¹⁸F]FFMZ). Since the biodistribution data of the latter were superior to those of the former we developed a synthetic approach for [¹⁸F]FFMZ starting from a commercially available precursor, thereby obviating the need to prepare a precursor by ourselves. The following two‐step procedure was developed: First, [¹⁸F]fluoride was reacted with 2‐bromoethyl triflate using the kryptofix/acetonitrile method to yield 2‐bromo‐[¹⁸F]fluoroethane ([¹⁸F]BFE). In the second step, distilled [¹⁸F]BFE was reacted with the tetrabutylammonium salt of 3‐desethylflumazenil (8‐fluoro‐5‐methyl‐6‐oxo‐5,6‐dihydro‐4H‐benzo‐[f]imidazo[1,5‐a] [1,4]diazepine‐3‐carboxylic acid) to yield [¹⁸F]FFMZ. The synthesis of [¹⁸F]FFMZ allows for the production of up to 7 GBq of this PET‐tracer, enough to serve several patients. [¹⁸F]FFMZ synthesis was completed in less than 80 min and the radiochemical purity exceeded 98%. 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.     

N3‐Substituted thymidine analogues III: radiosynthesis of N3‐[(4‐[18F]fluoromethyl‐phenyl)butyl]thymidine ([18F]‐FMPBT) and N3‐[(4‐[18F]fluoromethyl‐phenyl)pentyl] thymidine ([18F]‐FMPPT) for PET

Radiosyntheses of two N³‐substituted thymidine analogues, N³‐[(4[¹⁸F]fluoromethyl‐phenyl)butyl]thymidine ([¹⁸F]‐FMPBT) and N³‐[(4[¹⁸F]fluoromethyl‐phenyl)pentyl]thymidine ([¹⁸F]‐FMPPT), are reported. The precursor compounds 9 and 10 were synthesized in six steps and the standard compounds 13 and 14 were synthesized from these precursors. For radiosynthesis, compounds 9 and 10 were fluorinated with n‐Bu₄N[¹⁸F] to produce [¹⁸F]‐ 11 and [¹⁸F]‐ 12 , which by acid hydrolysis yielded [¹⁸F]‐ 13 and [¹⁸F]‐ 14 , respectively. The crude products were purified by high‐performance liquid chromatography to obtain [¹⁸F]‐FMPBT and [¹⁸F]‐FMPPT. The average decay‐corrected radiochemical yield for [¹⁸F]‐ 13 was 15% in five runs, and that for [¹⁸F]‐ 14 was 10% in four runs. The radiochemical purity was >99% and the specific activity was >74 GBq/µmol at the end of synthesis. The synthesis time was 80–90 min from the end of bombardment. Copyright © 2007 John Wiley & Sons, Ltd.     

Synthesis of [18F]‐labeled 2′‐deoxy‐2′‐fluoro‐5‐methyl‐1‐β‐D‐arabinofuranosyluracil ([18F]‐FMAU)

Synthesis of 2′‐deoxy‐2′‐[¹⁸F]fluoro‐5‐methyl‐1‐β‐D‐arabinofuranosyluracil ([¹⁸F]‐FMAU) is reported. 2‐Deoxy‐2‐[¹⁸F]fluoro‐1,3,5‐tri‐O‐benzoyl‐α‐D‐arabinofuranose 2 was prepared by the reaction of the respective triflate 1 with tetrabutylammonium[¹⁸F]fluoride. The fluorosugar 2 was converted to its 1‐bromo‐derivative 3 and coupled with protected thymine 4 . The crude product mixture ( 5a and 5b ) was hydrolyzed in base and purified by HPLC to obtain the radiolabeled FMAU 6a . The radiochemical yield of 6a was 20–30% decay corrected (d.c.) in four steps with an average of 25% in four runs. Radiochemical purity was >99% and average specific activity was 2300 mCi/μmol at the end of synthesis (EOS). The synthesis time was 3.5–4.0 h from the end of bombardment (EOB). Copyright © 2002 John Wiley & Sons, Ltd.     

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

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

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

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

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 2‐exo‐(2′‐[18F]Fluoro‐3′‐(4‐fluorophenyl)‐pyridin‐5′‐yl)‐7‐azabicyclo[2.2.1]heptane ([18F]F2PhEP), a potent epibatidine‐based radioligand for nicotinic acetylcholine receptor PET imaging

2‐exo‐(2′‐Fluoro‐3′‐(4‐fluorophenyl)‐pyridin‐5′‐yl)‐7‐azabicyclo[2.2.1]heptane (F₂PhEP), a novel, epibatidine‐based, α4β2‐selective nicotinic acetylcholine receptor antagonist of low toxicity, as well as the corresponding N‐Boc‐protected chloro‐ and bromo derivatives as precursors for labelling with fluorine‐18 were synthesized from 7‐tert‐butoxycarbonyl‐7‐azabicyclo[2.2.1]hept‐2‐ene in 13, 19 and 8% overall yield, respectively. [¹⁸F]F₂PhEP was prepared in 8–9% overall yield (non‐decay‐corrected) using 1 mg of the bromo derivative in the following two‐step radiochemical process: (1) no‐carrier‐added nucleophilic heteroaromatic ortho‐radiofluorination with the activated K[¹⁸F]F‐Kryptofix^®₂₂₂ complex in DMSO using microwave activation at 250 W for 90 s, followed by (2) quantitative TFA‐induced removal of the N‐Boc protective group. Radiochemically pure (>95%) [¹⁸F]F₂PhEP (1.48–1.66 GBq, 74–148 GBq/µmol) was obtained after semi‐preparative HPLC (Symmetry^® C18, eluent aqueous 0.05 M NaH₂PO₄ CH₃CN: 78/22 (v:v)) in 75–80 min starting from an 18.5 GBq aliquot of a cyclotron‐produced [¹⁸F]fluoride production batch. Copyright © 2006 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.     

Synthesis of 2‐[(2‐chloro‐2′‐[18F]fluoroethyl)amino]‐2H‐1,3,2‐oxazaphosphorinane‐2‐oxide (18F‐fluorocyclophosphamide), a potential tracer for breast tumor prognostic imaging with PET

A fluorine‐18 labeled analog of the widely used chemotherapeutic agent cyclophosphamide was synthesized as a tracer for prognostic imaging with positron emission tomography. 2‐[(2‐Chloro‐2′‐[¹⁸F]fluoroethyl)amino]‐2H‐1,3,2‐oxazaphosphorinane‐2‐oxide (¹⁸F‐fluorocyclophosphamide), was prepared by direct halogen exchange reaction from the parent cyclophosphamide. In small‐scale syntheses, radiochemical yields of up to 4.9% and specific activities of 960 Ci/mmol were achieved in a total synthesis time of 60–75 min. The [¹⁸F]‐labeled cyclophosphamide analog with radioactive purity >99% and chemical purity >96% was suitable for in vivo (microPET imaging) and ex vivo studies of a murine model of human breast tumors. Copyright © 2005 John Wiley & Sons, Ltd.     

Copper‐mediated reduction of 2‐[18F]fluoroethyl azide to 2‐[18F]fluoroethylamine

¹⁸F‐labelled fluoroalkylamines are attractive reagents for the preparation of positron emission tomography tracers containing amine, amide, and N‐heterocyclic moieties. Herein, we report that 2‐[¹⁸F]fluoroethylamine can be obtained from 2‐[¹⁸F]fluoroethyl azide by reduction with elemental copper under acidic conditions. Azide to amine reduction was achieved in near quantitative analytical yields within 30 min by heating a solution of 2‐[¹⁸F]fluoroethyl azide in the presence of copper wire and aqueous trifluoroacetic acid. Subsequent reaction of 2‐[¹⁸F]fluoroethylamine with benzoyl chloride in the presence of triethylamine provided N‐[¹⁸F]fluoroethyl benzamide in 63% decay‐corrected radiochemical yield from 2‐[¹⁸F]fluoroethyl azide. The utility of the Cu(0)/H⁺ azide reduction method was further exemplified by preparation of the potential GABA_A tracer 9H‐β‐carboline N‐2‐[¹⁸F]fluoroethylamide, which was obtained in 46% decay‐corrected radiochemical yield by reaction of 2‐[¹⁸F]fluoroethylamine with the corresponding 9H‐β‐carboline pentafluorophenyl ester. Copyright © 2012 John Wiley & Sons, Ltd.     

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.     

Two‐step radiosynthesis of [18F]N‐succinimidyl‐4‐fluorobenzoate ([18F]SFB)

The acylation reagent [¹⁸F]N‐succinimidyl‐4‐fluorobenzoate (¹⁸F‐SFB) has been prepared using a new two‐step approach. The starting material p‐[¹⁸F]fluorobenzaldehyde (¹⁸F‐FBA) was obtained by an improved radiosynthesis with a decay‐corrected radiochemical yield of 66±6 % (n=3). Reaction of ¹⁸F‐FBA with (diacetoxyiodine)benzene and N‐hydroxysuccinimide and preparative HPLC purification furnished ¹⁸F‐SFB in an r.c.y. of 49±6 % (n=3), based on the starting radioactivity of ¹⁸F‐FBA. The radiochemical purity of ¹⁸F‐SFB was >99%. Alternatively, purification by solid phase extraction gave ¹⁸F‐SFB with an r.c.y. of 77±9% (n=4) and a radiochemical purity of 89±5% (n=4). This radiochemical synthesis only used non‐aqueous solvents, which simplifies the method and facilitates subsequent applications of ¹⁸F‐SFB. 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 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 N‐(3‐[18F]Fluoropropyl)‐2β‐carbomethoxy‐3β‐(4‐iodophenyl)nortropane ([18F]FP‐β‐CIT)

N‐(3‐[¹⁸F]fluoropropyl)‐2β‐carbomethoxy‐3β‐(4‐iodophenyl)nortropane ([¹⁸F]FP‐β‐CIT) was synthesized in a two‐step reaction sequence. In the first reaction, 1‐bromo‐3‐(nitrobenzene‐4‐sulfonyloxy)‐propane was fluorinated with no‐carrier‐added fluorine‐18. The resulting product, 1‐bromo‐3‐[¹⁸F]‐fluoropropane, was distilled into a cooled reaction vessel containing 2β‐carbomethoxy‐3β‐(4‐iodophenyl)‐nortropane, diisopropylethylamine and potassium iodide. After 30 min, the reaction mixture was subjected to a preparative HPLC purification. The product, [¹⁸F]FP‐β‐CIT, was isolated from the HPLC eluent with solid‐phase extraction and formulated to yield an isotonic, pyrogen‐free and sterile solution of [¹⁸F]FP‐β‐CIT. The overall decay‐corrected radiochemical yield was 25 ± 5%. Radiochemical purity was > 98% and the specific activity was 94 ± 50 GBq/µmol at the end of synthesis. Copyright © 2006 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).