Synthesis procedure for routine production of [carbonyl-11C]desmethyl-WAY-100635.

An improved one-pot synthesis procedure for routine production of [carbonyl-(11)C]desmethyl-WAY-100635 ([(11)C]DWAY) is described. An efficient purification of the crude product has also been developed and was accomplished by C-18 reversed-phase semi-preparative HPLC using 55/45 EtOH-NaH(2)PO(4) buffer (20 mM, pH=6.5) as the eluent. The desired product fraction was collected in a 2.0-2.5 mL volume and formulated with 11 mL of 0.9% saline. The radioligand was ready for human use in 45 min (EOB). The product was obtained with a radiochemical yield of 11.1+/-1.8% (EOB, n=15) with a radiochemical purity of >99%. Specific activity was 133.2-185.0 GBq/micromol (3.6-5.0 Ci/micromol, EOS, n=2) when ca. 37.0 GBq (ca. 1.0 Ci) of starting [(11)C]CO(2) was used. Unlabeled mass of [(11)C]DWAY was found to be 0.15-0.24 microg/mL and the precursor was present in less than 50 ng/mL in final production solution.     

Fully automated synthesis system of 3'-deoxy-3'-[18F]fluorothymidine

We developed a new fully automated method for the synthesis of 3'-deoxy-3'-[18F]fluorothymidine ([18F]FLT), by modifying a commercial FDG synthesizer and its disposable fluid pathway. Optimal labeling condition was that 40 mg of precursor in acetonitrile (2 mL) was heated at 150 degrees C for 100 sec, followed by heating at 85 degrees C for 450 sec and hydrolysis with 1 N HCl at 105 degrees C for 300 sec. Using 3.7 GBq of [18F]F- as starting activity, [18F]FLT was obtained with a yield of 50.5 +/- 5.2% (n = 28, decay corrected) within 60.0 +/- 5.4 min including HPLC purification. With 37.0 GBq, we obtained 48.7 +/- 5.6% (n = 10). The [18F]FLT showed the good stability for 6 h. This new automated synthesis procedure combines high and reproducible yields with the benefits of a disposable cassette system.     

Efficient radiosynthesis of carbon-11 labelled uncharged Thioflavin T derivatives using [11C]methyl triflate for beta-amyloid imaging in Alzheimer's Disease with PET.

The synthesis of carbon-11 amino function labelled uncharged Thioflavin T derivatives is known to be performed by reaction of the demethyl-precursors with [11C]methyl iodide but the labelling yields are only mediocre. The use of [11C]methyl triflate improved the radiochemical yield of three potential beta-amyloid imaging PET-radiotracers significantly. Performance of the labelling reaction by reacting the corresponding precursor molecules with [11C]methyl triflate for 1 min at 80 degrees C led to radiochemical yields of 44+/-10% (n=5) for [11C]6-Me-BTA-1, 68+/-4% (n=10) for [11C]BTA-1 and 58+/-2% (n=5) for [11C]6-OH-BTA-1 with respect to [11C]methyl triflate. In production runs (60 min, 50 microA) up to 6500 MBq (mean: 4000+/-1900 MBq) of [11C]6-Me-BTA-1, 7900 MBq (mean: 6000+/-1000 MBq) of [11C]BTA-1 and 7100 MBq (mean: 6300+/-600 MBq) of [11C]6-OH-BTA-1 could be obtained ready for intravenous injection. The radiochemical purity was >95% with specific activities in the range of 80-120 GBq/micromol (EOS) within a total synthesis time of less than 40 min after EOB.     

Preliminary evaluation of 2-[4-[3-tert-butylamino)-2-hydroxypropoxy]phenyl]-3-methyl-6-me thoxy-4(3H)-quinazolinone ([+/-]HX-CH 44) as a selective beta1-adrenoceptor ligand for PET

(+/-)-3-[11C]Methyl-2-[4-[3-(tert-butylamino)-2-hydroxypropoxy]phenyl]-6 -methoxy-4(3H) quinazolinone ([+/-]-[11C]HX-CH 44) was labeled with carbon-11 using [11C]iodomethane with the corresponding N-demethylated precursor. Then, 30-90 mCi (1.10-3.33 GBq) of pure [11C]HX-CH 44 were obtained 30 min after end of bombardment with specific radioactivities of 500-1,400 mCi/micromol (18.5-51.8 GBq/micromol). Myocardial uptake in dogs was 0.340+/-0.043 pmol/mL tissue per nanomole injected, 10-15 min postinjection. Heart-to-lung ratio was 3 from the 5th to the 30th minute. Only 35% of the myocardial radioactivity could be displaced. Tissue uptake could not be blocked with appropriate compounds. Therefore, (+/-)-[11C]HX-CH 44 does not appear to be a suitable ligand for the study of myocardial beta1-adrenoceptors in positron emission tomography.     

In vitro binding of [(11)C]raclopride with ultrahigh specific activity in rat brain determined by homogenate assay and autoradiography

OBJECTIVE: The aim of this study was to characterize the in vitro binding of [(11)C]raclopride with ultrahigh specific activity (SA) in the striatum and cerebral cortex of rat brain. METHODS: [(11)C]Raclopride, a dopamine D(2) receptor ligand, with an ultrahigh SA of 4880+/-2360 GBq/micromol (132+/-64 Ci/micromol, n=25) was synthesized. In vitro binding experiment was performed using brain homogenate assay and autoradiography (ARG). RESULTS: In vitro homogenate assay demonstrated that high SA [(11)C]raclopride (2520-6340 GBq/micromol; 68-171 Ci/micromol) had two-affinity (high and low) binding sites in the striatum and cerebral cortex of rat brain. In the striatum, K(d,high) and B(max,high) values were 0.005+/-0.002 nM and 0.19+/-0.04 fmol/mg tissue, respectively, while K(d,low) and B(max,low) values were 2.2+/-1.0 nM and 35.8+/-16.4 fmol/mg tissue, respectively. In the cerebral cortex, K(d,high) and B(max,high) values were 0.061+/-0.087 nM and 0.2+/-0.2 fmol/mg tissue, respectively, while K(d,low) and B(max,low) values were 2.5+/-3.2 nM and 5.5+/-4.8 fmol/mg tissue, respectively. On the other hand, only one binding site was found in the striatum and no binding site was identified in the cerebral cortex using low SA [(11)C]raclopride (44 GBq/micromol; 1.2 Ci/micromol). In vitro ARG for the rat brain using high SA [(11)C]raclopride (6212 GBq/micromol; 168 Ci/micromol) gave a coronal image of the striatum and cerebral cortex with a higher signal/noise ratio than using low SA [(11)C]raclopride (40 GBq/micromol; 1.1 Ci/micromol). CONCLUSION: Using ultrahigh SA [(11)C]raclopride for the in vitro homogenate assay, we succeeded in detecting two-affinity binding sites of [(11)C]raclopride, not only in the striatum but also in the cerebral cortex of rat brain.     

An automated radiosynthesis of 2-[11C]thymidine using anhydrous [11C]urea derived from [11C]phosgene.

2-[11C]Thymidine has been produced from [11C]methane via [11C]phosgene and [11C]urea. Anhydrous [11C]urea was prepared from [11C]phosgene by reaction with liquid ammonia. This novel approach avoids the problems associated with the synthesis of anhydrous [11C]urea from [11C]cyanide. A fully automated system based on a modular approach and under PLC control has been developed. The system provides 2-[11C]thymidine reliably and reproducibly for clinical PET studies. The radiosynthesis takes 45-50 min from [11C]methane and the average yield was 1.5-3.3 GBq (40-90 mCi). The specific radioactivity was typically in the range 29.6-51.8 GBq mumol-1 (0.8-1.4 Ci mumol-1) at EOS corresponding to 6-12 micrograms of stable thymidine. The radiochemical yield of 2-[11C]thymidine was ca. 14% from [11C]methane.     

Synthesis and autoradiographic localization of muscarinic cholinergic antagonist (+)N-[11C]methyl-3-piperidyl benzilate as a potent radioligand for positron emission tomography.

(+)N-[11C]methyl-3-piperidyl benzilate, a relatively low affinity muscarinic cholinergic receptor antagonist was synthesized by N-[11C]methylation of (+)3-piperidyl benzilate using [11C]methyl iodide. The product was isolated by HPLC, and obtained with radiochemical yield of 60-70% from [11C]methyl iodide, and a specific activity of 500-1000 Ci mmol-1 (18.5-37 GBq mumol-1) at EOS and radiochemical purity of > 98%. In vitro autoradiographic studies showed selective binding for this radiotracer in the different regions of the rat brain: high in corpus striatum, hippocampus and cerebral cortex, and low in cerebellum, consistent with muscarinic cholinergic receptor distributions. This radiotracer thus had potential as radioligand for positron emission tomography.     

Synthesis of ethyl 8-fluoro-5,6-dihydro-5-[11C]methyl-6-oxo-4H-imidazo [1,5-a] [1,4]benzodiazepine-3-carboxylate (RO 15.1788-11C): a specific radioligand for the in vivo study of central benzodiazepine receptors by positron emission tomography

A method of labelling ethyl 8-fluoro-5,6-dihydro-5-[11C]methyl-6-oxo-4H-imidazo[1,5-a][1,4] benzodiazepine-3-carboxylate (RO 15.1788 11C), a benzodiazepine antagonist with carbon-11 has been developed. RO 15.1788-11C was prepared by methylation of the nor derivative by I11CH3. About 100 mCi (maximum 153 mCi, 5.66 GBq) of the chemically and radiochemically pure labelled product were obtained within 25 min with a specific activity on average of 1100 mCi/mumol (maximum 1740 mCi/mu mol--64.4 GBq/mu mol). Preliminary results obtained after i.v. administration in the baboon have shown RO 15.1788-11C to be of interest as a benzodiazepine radioligand for the in vivo study of benzodiazepine receptors by positron emission tomography.     

Enzymatic synthesis of [1-11C]pyruvic acid, L-[1-11C]lactic acid and L-[1-11C]alanine via DL-[1-11C]alanine

L-[1-11C]Lactic acid was prepared enzymatically from [1-11C]pyruvic acid by way of DL-[1-11C]alanine, using remote, semiautomated procedures. The DL isomers of alanine were prepared by a modification of the Bucherer-Strecker reaction from no-carrier-added (NCA) hydrogen [11C]cyanide. The enantiomer mixture was transformed to [1-11C]pyruvic acid by successive elution through columns of (a) immobilized D-amino acid oxidase (D-AAO)/catalase and (b) immobilized L-alanine dehydrogenase (L-AID) or L-amino acid oxidase (L-AAO/catalase). [1-11C]-Pyruvic acid was subsequently converted to L-[1-11C]lactic acid by passage through a L-lactic dehydrogenase (L-LDH) column. L-[1-11C]Alanine and [1-11C]-pyruvic acid were separated chromatographically by way of a cation-exchange column (AG50W-X2, H+ form). Typically the synthesis time was 35-40 min after cyclotron production of hydrogen [11C]cyanide (400 mCi), with radiochemical yields of 25 mCi (25%) for L-[1-11C]lactic acid, 35 mCi (29%) for [1-11C]pyruvic acid, and 20 mCi (20%) for L-[1-11C]alanine. The use of immobilized enzymes eliminates the possibility of protein contamination and assures the production of sterile, pyrogen-free products, allowing for rapid and effective regio- and stereo-specific transformations.     

Automated synthesis of the ultra high specific activity of [11C]Ro15-4513 and its application in an extremely low concentration region to an ARG study

We have designed and constructed an automated device for the production of ultra-high specific activity (11)C-labeled compounds via [(11)C]CH(3)I synthesized by the single pass I(2) method. The optimum condition for the production of [(11)C]CH(3)I was determined to be 630 degrees C for oven-1 (reaction column), 50 degrees C for oven-2 (iodine column) and 50 ml/min for the He gas flow rate, and gave the maximum conversion ratio of [(11)C]CH(3)I, 44%. [(11)C]Ro15-4513, known as an inverse agonist of the benzodiazepine receptor, was produced under optimized conditions. An i.v. injectable [(11)C]Ro15-4513 solution of 1500 +/- 490 MBq (n = 6) with specific activity 4700 +/- 2500 GBq/micromol and a radiochemical purity of 98.2 +/- 2% was obtained automatically within 25 minutes (from EOB) by irradiating nitrogen gas containing 5% H(2) with 18 MeV protons (14.2 MeV on target) at 20 microA for 20 minutes. The highest specific activity of 9700 GBq/micromol (at EOS) could be achieved, although the radiochemical purity was 92.4%. By the use of the ultra-high specific activity [(11)C]Ro15-4513, the super high affinity binding sites in the rat brain hippocampus could be clearly visualized even at the extremely low concentration of 0.66 pM Ro15-4513 by in vitro autoradiography.     

A remotely controlled production system for routine preparation of [methyl-11C]thymidine

A remotely controlled system has been developed for the routine production of [methyl-¹¹C]thymidine starting from [¹¹C]methyl iodide.The system features semi-automated operation from [¹¹C]methyl iodide production over the [¹¹C] methylation reaction, HPLC purification to filtration of the final product and collection in a sterile vial.The preparations are completed within 45 min after irradiation and ca 7.4 GBq (0.2 Ci) chemically and radiochemically pure [methyl-¹¹C]thymidine are produced with a sp. act. of 11 GBq μmol⁻¹ (0.3 Ci μmol⁻¹) at the end of production.Sterile and pyrogen free [methyl-¹¹C]thymidine suitable for animal and human injections is prepared routinely using this synthesis system.The technical set up is also useful for the production of other nucleosides like: 5-ethyl-[¹¹C]-2′-deoxyuridine and 6-methyl-[¹¹C]-2′-deoxyuridine.     

Preparation and pharmaceutical evaluation for clinical application of high specific activity S-(-)[11C]CGP-12177, a radioligand for beta-adrenoreceptors

BACKGROUND: Although S-(-)[C]CGP-12177 is a useful positron emission tomography (PET) ligand for beta-adrenoreceptors, the difficulty in radiolabelling the compound has prevented its extensive clinical application. Recently, we have developed a simple synthesis method for S-(-)[C]CGP-12177. In the present study, we attempted to prepare S-(-)[C]CGP-12177 with a high specific activity for intravenous injection which is feasible for the clinical evaluation of beta-adrenoreceptors. METHODS: The [C]methane produced during irradiation of a N2--H2 (95/5) mixture with an 18 MeV proton beam (20 microA, 30 min) was chlorinated using Cl2 to yield [C]carbon tetrachloride. S-(-)[C]CGP-12177 was synthesized by reacting the diamino precursor with [C]phosgene produced by oxidizing [C]carbon tetrachloride on a Fe--Fe2O3 column. The product was purified by using reversed phase, high-performance liquid chromatography (RP-HPLC) and the radioactive fraction containing S-(-)[C]CGP-12177 was collected and evaporated to dryness. S-(-)[C]CGP-12177 dissolved in physiological saline was sterilized through a 0.22 microm membrane filter. The radiochemical purity and the mass of the compound were determined with RP-HPLC. The residual organic solvents were determined with GC. Tests for sterility and the presence of bacterial endotoxins were also performed. RESULTS: S-(-)[C]CGP-12177 for intravenous injection was prepared in 25 min after the end of bombardment with a yield of 1.5+/-0.2 GBq. Specific activity was found to be 385.4+/-133.0 GBq/ micromol at the end of synthesis (EOS) (n=3). Radiochemical purity was found to be more than 99%. Toluene was not detected in the solution. The ethanol concentration was determined to be 60.3+/-52.5 ppm. Tests for sterility and bacterial endotoxins showed negative results. CONCLUSION: We successfully prepared S-(-)[C]CGP-12177 formulated for intravenous injection with high purity and high specific activity, which is feasible for the clinical evaluation of beta-adrenoreceptors.     

A semi-automated synthesis system for routine preparation of [11C]YM-09151-2 and [11C]pyrilamine from [11C]methyl iodide

A synthesis system has been developed for routine preparation of the ¹¹C-labeled receptor ligands, [¹¹C]YM-09151-2 and [¹¹C]pyrilamine, from [¹¹C]methyl iodide produced automatically. The system features semi-automated operation, from the reaction of the desmethyl derivative with [¹¹C]methyl iodide to filtration with a specifically developed syringe pump of the final product in saline into a sterile vial. The preparations were completed within 45 min after irradiation and approx. 1 GBq (27 mCi) of [¹¹C]YM-09151-2 or [¹¹C]pyrilamine was obtained with a radiochemical and chemical purity of >99% and an average specific activity of 44 GBq/μmol (1.2 Ci/μmol) at the end of synthesis. Sterile and pyrogen-free ¹¹C-labeled receptor ligands suitable for human injection are routinely prepared using the present synthesis system.     

Automated synthesis of [11C]choline, a positron-emitting tracer for tumor imaging.

(beta-Hydroxyethyl)tri([11C]methyl)ammonium ([11C]choline) is a tracer very effective in imaging various human tumors using positron emission tomography (PET). We have constructed a computer-controlled [11C]choline synthetic apparatus which carries out the whole process of synthesis and product purification automatically. The setup is simple and the process quick. In 20 min, 11 GBq of [11C]choline (chloride) is obtainable from 26 GBq of [11C]CO2. The final product is a sterile and pyrogen-free [11C]choline "injection".     

Synthesis of L-[β-11C]amino acids using immobilized enzymes

L-[β-¹¹C]-3,4-dihydroxyphenylalanine(L-[β-¹¹C]DOPA) and L-[β-¹¹C]-5-hydroxytryptophan(L-[β-¹¹C]-5-HTP) were synthesized in one step with immobilized thermostable enzymes (alanine racemase, D-amino acid oxidase, and β-tyrosinase or tryptophanase) on an aminopropyl-CPG carrier in a single column and by passing D,L-[3-¹¹C]alanine through the column with coenzymes and other substrates. L-[β-¹¹C]DOPA and L-[β-¹¹C]-5-HTP could be obtained at yields of 53% and 60%, respectively, by optimizing the amounts and the ratios of the enzymes used, the reaction temperature, the pH, and the flow rate. Moreover, the same immobilized enzyme column could be used repeatedly.     

Synthesis and evaluation of 6-[11C]methoxy-3-[2-[1-(phenylmethyl)-4-piperidinyl]ethyl]-1,2- benzisoxazole as an in vivo radioligand for acetylcholinesterase

6-Methoxy-3-[2-[1-(phenylmethyl)-4-piperidinyl]ethyl]-1,2-benzisoxazole is a high affinity (K(i) = 8.2 nM) reversible inhibitor of acetylcholinesterase (AChE). The carbon-11 labeled form was prepared in high (>97%) radiochemical purity and with specific activities of 37+/-20 GBq/micromol at end of synthesis, by the alkylation of the desmethyl precursor with [11C]methyl trifluoromethanesulfonate in N,N-dimethyl-formamide at room temperature. In vivo studies in mice demonstrated good blood brain permeability but essentially uniform regional brain distribution. Thus, despite in vitro and in vivo activity as an AChE inhibitor, 6-[11C]methoxy-3-[2-[1-(phenylmethyl)-4-piperidinyl]ethyl]-1,2-benzis oxa zole does not appear to be a good candidate for in vivo imaging studies of AChE in the mammalian brain.     

Synthesis and radiolabeling of N-[4-[4-(2-[11C]methoxyphenyl)piperazin-1-yl]butyl]benzo[b]thiophene-2-carboxamide -- a potential radiotracer for D3 receptor imaging with PET

FAUC346 (N-[4-[4-(2-methoxyphenyl)piperazin-1-yl]butyl]benzo[b]thiophene-2-carboxamide), an in vitro D(3)-selective ligand, and its normethyl derivative have been synthesized from commercially available 1-(2-substituted-phenyl)piperazines. FAUC346 has been labeled using [(11)C]methyl triflate in acetone containing aqueous NaOH (5 Eq) at -10 degrees C for 1 min, purified on semipreparative reverse-phase high-performance liquid chromatography (HPLC) and formulated as an intravenous injectable solution using a Sep-Pak Plus C(18) device. Up to 5.5 GBq of [(11)C]FAUC346 (N-[4-[4-(2-[methyl-(11)C]methoxyphenyl)piperazin-1-yl]butyl]benzo[b]thiophene-2-carboxamide), with a specific radioactivity of 45-75 GBq/micromol, could be obtained in 30-35 min, including HPLC purification and formulation starting from 44.4 GBq of [(11)C]carbon dioxide. Preliminary pharmacological evaluation of [(11)C]FAUC346 in rat brain clearly demonstrated in vivo selectivity for D(3) receptors and the absence of radiolabeled metabolite within the brain. These encouraging results, however, could not be confirmed in nonhuman primates; therefore, this radioligand does not appear to have the required pharmacological profile for a positron emission tomography probe for imaging D(3) receptors.     

No-carrier-added carbon-11-labeled sn-1,2- and sn-1,3-diacylglycerols by [11C]propyl ketene method

This article describes the preparation of sn-1,2-[11C]diacylglycerols and sn-1,3-[11C]diacylglycerols by a no-carrier-added reaction based on a labeling method using [1-11C]propyl ketene, which is one of the most potent acylating agents. [1-11C]Propyl ketene was produced by pyrolytic decomposition of [1-11C]butyric acid and was trapped in pyridine containing L-alpha-palmitoyl-lysophosphatidylcholine, producing L-alpha-palmitoyl-2-[1-11C]butyryl-sn-glycero-3-phosphorylcholine. We adopted an enzymatic reaction to remove the phosphorylcholine, in which L-alpha-palmitoyl-2-[1-11C]butyryl-sn-glycero-3-phosphorylcholine was incubated with phospholipase C, hydrolyzing to produce 1-palmitoyl-sn-2-[1-11C]butyrylglycerol. Total synthesis time was about 50 minutes and the specific activity was estimated at 93 GBq/mumol (2.5 Ci/mumol) at end of synthesis. Radiochemical yield was 3.8% based on the trapped 11CO2. sn-1,3-[11C]Diacylglycerol was also synthesized by [1-11C]propyl ketene reaction with 1-palmitoyl-sn-glycerol in a single procedure. The regional brain tissue radioactivities obtained in sn-1,2-[11C]diacylglycerol were higher than those of sn-1,3-[11C]diacylglycerol, and the regional values varied widely. In autoradiography of brain slices from conscious rats, sn-1,2-[11C]diacylglycerol incorporation sites were discretely localized, especially in the amygdala, cerebral cortex, and hippocampus, suggesting that intensive neuronal processing occurred in these areas on the basis of phosphatidylinositol turnover.     

Automatic synthesis of 16 alpha-[(18)F]fluoro-17beta-estradiol using a cassette-type [(18)F]fluorodeoxyglucose synthesizer

16 alpha-[(18)F]fluoro-17beta-estradiol ([(18)F]FES) is a radiotracer for imaging estrogen receptors by positron emission tomography. We developed a clinically applicable automatic preparation system for [(18)F]FES by modifying a cassette-type [(18)F]fluorodeoxyglucose synthesizer. Two milligrams of 3-O-methoxymethyl-16,17-O-sulfuryl-16-epiestriol in acetonitrile was heated at 105 degrees C for 10 min with dried [(18)F]fluoride. The resultant solution was evaporated and hydrolyzed with 0.2 N HCl in 90% acetonitrile/water at 95 degrees C for 10 min under pressurized condition. The neutralization was carried out with 2.8% NaHCO(3), and then the high-performance liquid chromatography (HPLC) purification was performed. The desired radioactive fraction was collected and the solvent was replaced by 10 ml of saline, and then passed through a 0.22-microm filter into a pyrogen-free vial as the final product. The HPLC purification data demonstrated that [(18)F]FES was synthesized with a yield of 76.4+/-1.9% (n=5). The yield as the final product for clinical use was 42.4+/-3.2% (n=5, decay corrected). The total preparation time was 88.2+/-6.4 min, including the HPLC purification and the solvent replacement process. The radiochemical purity of the final product was >99%, and the specific activity was more than 111 GBq/micromol. The final product was stable for more than 6 h in saline containing sodium ascorbate. This new preparation system enables us to produce [(18)F]FES safe for clinical use with high and reproducible yield.     

Facile synthesis of new carbon-11 labeled conformationally restricted rivastigmine analogues as potential PET agents for imaging AChE and BChE enzymes.

Rivastigmine is a newer-generation inhibitor with a dual inhibitory action on both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes, and is used for the treatment of AChE- and BChE-related diseases such as brain Alzheimer's disease and cardiovascular disease. New carbon-11 labeled conformationally restricted rivastigmine analogues radiolabeled quaternary ammonium triflate salts, (3aR,9bS)-1-[(11)C]methyl-1-methyl-6-(methylcarbamoyloxy)-2,3,3a,4,5,9b-hexahydro-1H-benzo[g]indolium triflate ([(11)C]8) and (3aR,9bS)-1-[(11)C]methyl-1-methyl-6-(heptylcarbamoyloxy)-2,3,3a,4,5,9b-hexahydro-1H-benzo[g]indolium triflate ([(11)C]9), were designed and synthesized as potential positron emission tomography (PET) agents for imaging AChE and BChE enzymes. The appropriate precursors were labeled with [(11)C]CH(3)OTf through N-[(11)C]methylation, and the target tracers were isolated by solid-phase extraction (SPE) using a cation-exchange CM Sep-Pak cartridge in 40-50% radiochemical yields decay corrected to end of bombardment (EOB), 15-20 min overall synthesis time, and 148-222 GBq/micromol specific activity at EOB.