End Of Bombardment Research Articles

Synthesis and biological evaluation of [carboxyl‐11C]eprosartan

AbstractEssential hypertension occurs in approximately 25% of the adult population and one cause of hypertension is primary aldosteronism. Targeting the angiotensin II AT1 receptor using PET and an appropriate tracer may offer a diagnostic method for adrenocortical tissue. This report describes the synthesis of the selective AT1 receptor antagonist [carboxyl‐11C]eprosartan 10, 4‐[2‐butyl‐5‐((E)‐2‐carboxy‐3‐thiophen‐2‐yl‐propenyl)‐imidazol‐1‐ylmethyl]‐[carboxyl‐11C]benzoic acid, and its precursor (E)‐3‐[2‐butyl‐3‐(4‐iodo‐benzyl)‐3H‐imidazol‐4‐yl]‐2‐thiophen‐2‐ylmethyl‐acrylic acid 9. 11C‐carboxylation of the iodobenzyl moiety was performed using a palladium‐mediated reaction with [11C]carbon monoxide in the presence of tetra‐n‐butyl‐ammonium hydroxide in a micro‐autoclave using a temperature gradient from 25 to 140°C over 5 min. After purification by semipreparative HPLC, [carboxyl‐11C]eprosartan 10 was obtained in 37–54% decay‐corrected radiochemical yield (from [11C]carbon monoxide) with a radiochemical purity >95% within 35 min of the end of bombardment (EOB). A 5‐µAh bombardment gave 2.04 GBq of 10 (50% rcy from [11C]carbon monoxide) with a specific activity of 160 GBq µmol−1 at 34 min after EOB. Frozen‐section autoradiography shows specific binding in kidney, lung and adrenal cortex. In vivo experiments in rats demonstrate a high accumulation in kidney, liver and intestinal wall. Copyright © 2009 John Wiley & Sons, Ltd.

Undesired radionuclides in 18F2 production by deuterons

In this paper, radionuclidic impurities generated during the bombardment of an 20Ne gaseous matrix in the routine production of [18F]-fluorodopa were studied. 18F2 is produced by the GE PETtrace cyclotron capable of accelerating negative deuteron ions to an energy of 8.4 MeV. The materials of the target and of the Havar foil, the stable fluorine added as carrier and the natural isotope composition of neon may interact with deuterons and produce undesired radionuclides. To measure them, a sampling system has been realized. Samples of the irradiated gas have been measured by gamma-ray spectrometry. The results show how the radionuclidic purity obtained is very high after a short time from the end of bombardment (EOB).

Investigation of the 68Zn(p, 2p)67Cu nuclear reaction: New measurements up to 40 MeV and compilation up to 100 MeV

The excitation function was measured for the 68Zn(p,2p)67Cu nuclear reaction from its threshold energy up to 40MeV. Nine pieces of highly enriched 68Zn (>98%) metal foils were irradiated to obtain reliable cross-sections using the usual stacked-foil technique. All foils were subjected to high efficiency radiochemical separation before the activity measurements. A critical compilation of the available experimental cross-section results was also performed. Thick target yields of 67Cu and the longer-lived copper radio-contaminants (61Cu and 64Cu) were calculated using the reliable literature results up to 100MeV. Additionally, EOB (End Of Bombardment) contamination levels as a function of bombarding energy and irradiation time were deduced.

Dependence of the cross sections for Ir isotopes on the values of Qgg in the heavy ion collision

197Au were irradiated with 47 MeV/u 12C ions. Iridium was produced via the multinucleon transfer reactions in bombardments of 197Au with 12C. and was separated radiochemically from Au and the mixture of the reaction products. The γ radioactivities of Ir isotopes were measured by using a HPGe detector. The production cross sections of Ir isotopes were determined from activities of Ir isotopes at the end of bombardment and the other relative data. It has been found that the cross sections for neutron-rich isotopes of iridium show an exponential dependence on the values of Qgg. Our experimental results also demonstrate lack of correlation between the cross sections and Qgg in the case of neutron-deficient isotopes of iridium. The fact can be explained from that neutron-rich isotopes of iridium were produced in the deep inelastic transfer reactions.

Synthesis and PET studies of [11C-cyano]letrozole (Femara), an aromatase inhibitor drug

Aromatase, a member of the cytochrome P450 family, converts androgens such as androstenedione and testosterone into estrone and estradiol, respectively. Letrozole (1-[bis-(4-cyanophenyl)methyl]-1H-1,2,4-triazole; Femara) is a high-affinity aromatase inhibitor (K(i)=11.5 nM) that has Food and Drug Administration approval for breast cancer treatment. Here we report the synthesis of carbon-11-labeled letrozole and its assessment as a radiotracer for brain aromatase in the baboon. Letrozole and its precursor (4-[(4-bromophenyl)-1H-1,2,4-triazol-1-ylmethyl]benzonitrile) were prepared in a two-step synthesis from 4-cyanobenzyl bromide and 4-bromobenzyl bromide, respectively. The [(11)C]cyano group was introduced via tetrakis(triphenylphosphine)palladium(0)-catalyzed coupling of [(11)C]cyanide with the bromo precursor. Positron emission tomography (PET) studies in the baboon brain were carried out to assess regional distribution and kinetics, reproducibility of repeated measures and saturability. Log D, the free fraction of letrozole in plasma and the [(11)C-cyano]letrozole fraction in arterial plasma were also measured. [(11)C-cyano]Letrozole was synthesized in 60 min with a radiochemical yield of 79-80%, with a radiochemical purity greater than 98% and a specific activity of 4.16+/-2.21 Ci/mumol at the end of bombardment (n=4). PET studies in the baboon revealed initial rapid and high uptake and initial rapid clearance, followed by slow clearance of carbon-11 from the brain, with no difference between brain regions. Brain kinetics was not affected by coinjection of unlabeled letrozole (0.1 mg/kg). The free fraction of letrozole in plasma was 48.9%, and log D was 1.84. [(11)C-cyano]Letrozole is readily synthesized via a palladium-catalyzed coupling reaction with [(11)C]cyanide. Although it is unsuitable as a PET radiotracer for brain aromatase, as revealed by the absence of regional specificity and saturability in brain regions such as amygdala, which are known to contain aromatase, it may be useful in measuring letrozole distribution and pharmacokinetics in the brain and peripheral organs.

N3-Substituted Thymidine Analogues: Radiosyntheses of N3-[4-(4-(2-[18F] fluoroethyl)phenyl)butyl]thymidine and N3-[5-(4-(2-[18F]fluoroethyl)- phenyl)pentyl]thymidine for PET

Radiosyntheses of two new N3-substituted analogues of thymidine, N3-[4-(4-(2-[18F]fluoroethyl)phenyl)butyl] thymidine ([18F]-FEPBT) and N3-[5-(4-(2-[18F]fluoroethyl)phenyl)pentyl]thymidine ([18F]-FEPPT) are reported. Synthesesof the precursor compounds, 3,5-O-bis-tetrahydropyranyl-N3-[4-(4-(2-methanesulfonyl-ethyl)phenyl)butyl]thymidine and 3,5-O-bis-tetrahydropyranyl-N3-[5-(4-(2-methanesulfonyl-ethyl)phenyl)pentyl]thymidine are described. Radiofluorination of these precursors was performed using K[18F]/kryptofix 2.2.2. in dry MeCN. Hydrolysis of the protecting groups followed by HPLC purification yielded the desired products [18F]-FEPBT and [18F]-FEPPT. The radiochemical yields of [18F]-FEPBT were 35%-48% decay corrected (d. c.) with an average of 44%; and those of [18F]-FEPPT were 32%-40% (d. c.) with an average of 37% in three runs per compound. Radiochemical purity was > 99% and specific activity was > 74 GBq/μmol at the end of synthesis. The synthesis time was 80-90 min from the end of bombardment (EOB).

New [11C]Phosgene Based Synthesis of [11C]Pyrimidines for Positron Emission Tomography

Thymine, 5-FU, and uracil were successfully synthesized through a procedure involving a cyclocondensation of triphosgene with newly developed α-substituted β-aminoacrylamides intermediates (la, X= Me; 1b, X= F; 1c, X= H). The radioligands [2- 11 C]thymine and [2- 11 C]5-fluorouracil were synthesized in high radiochemical yields in 16-17 minutes from the end of bombardment by applying the cyclocondensation method with [ 11 C]COCl 2 .

Dopamine transporter binding in rat striatum: a comparison of [O-methyl-11C]β-CFT and [N-methyl-11C]β-CFT

Positron emission tomography scanning with radiolabeled phenyltropane cocaine analogs is important for quantifying the in vivo density of monoamine transporters, including the dopamine transporter (DAT). [(11)C]beta-CFT is useful for studying DAT as a marker of dopaminergic innervation in animal models of psychiatric and neurological disorders. [(11)C]beta-CFT is commonly labeled at the N-methyl position. However, labeling of [(11)C]beta-CFT at the O-methyl position is a simpler procedure and results in a shorter synthesis time [desirable in small-animal studies, where specific activity (SA) is crucial]. In this study, we sought to validate that the O-methylated form of [(11)C]beta-CFT provides equivalent quantitative results to that of the more commonly reported N-methyl form. Four female Sprague-Dawley rats were scanned twice on the IndyPET II small-animal scanner, once with [N-methyl-(11)C]beta-CFT and once with [O-methyl-(11)C]beta-CFT. DAT binding potentials (BP identical withB'(avail)/K(d)) were estimated for right and left striata with a nonlinear least-squares algorithm, using a reference region (cerebellum) as the input function. [N-Methyl-(11)C]beta-CFT and [O-methyl-(11)C]beta-CFT were synthesized with 40-50% radiochemical yields (HPLC purification). Radiochemical purity was >99%. SA at end of bombardment was 258+/-30 GBq/micromol. Average BP values for right and left striata with [N-methyl-(11)C]beta-CFT were 1.16+/-0.08 and 1.23+/-0.14, respectively. BP values for [O-methyl-(11)C]beta-CFT were 1.18+/-0.08 (right) and 1.22+/-0.16 (left). Paired t tests demonstrated that labeling position did not affect striatal DAT BP. These results suggest that [O-methyl-(11)C]beta-CFT is quantitatively equivalent to [N-methyl-(11)C]beta-CFT in the rat striatum.

Radiosynthesis and radiopharmacological evaluation of [ N-methyl- 11C]Org 34850 as a glucocorticoid receptor (GR)-binding radiotracer

The radiosynthesis of [ N-methyl- 11C]Org 34850 as a potential brain glucocorticoid receptor (GR)-binding radiotracer is described. The radiosynthesis was accomplished via N-methylation of the corresponding desmethyl precursor with [ 11C]methyl triflate in a remotely controlled synthesis module to give the desired compound in a radiochemical yield of 23±5% (decay-corrected, based upon [ 11C]CO 2) at a specific activity of 47±12 GBq/μmol ( n=15) at the end-of-synthesis (EOS). The radiochemical purity after semi-preparative HPLC purification exceeded 95%. The total synthesis time was 35–40 min after end-of-bombardment (EOB). The radiotracer is rapidly metabolized in rat plasma leading to the formation of two more hydrophilic metabolites as the major metabolites. Radiopharmacological evaluation involving biodistribution and small animal PET imaging in normal Wistar rats showed that the compound [ N-methyl- 11C]Org 34850 is not able to sufficiently penetrate the blood–brain barrier. Therefore, compound [ N-methyl- 11C]Org 34850 seems not to be a suitable PET radiotracer for imaging rat brain GRs. However, involvement of Pgp or species differences requires further clarification to establish whether the radiotracer [ N-methyl- 11C]Org 34850 may still represent a suitable candidate for imaging GRs in humans.

Synthesis of S-[ 13N]nitrosoglutathione ( 13N-GSNO) as a new potential PET imaging agent

In the present paper, a fast and reproducible method for the synthesis of S-[ 13N]nitrosoglutathione is reported for the first time. The labeling strategy is based on the production of [ 13N]NO 3 − via the 16O( p, α) 13N nuclear reaction in water, as opposed to the standardized production of [ 13N]NH 4 + in 2 mM aqueous ethanol. Following the reduction of [ 13N]NO 3 − to [ 13N]NO 2 −, the reaction with glutathione in the presence of hydrochloric acid led to the desired radiotracer with a good radiochemical yield (24.2±2.0% end of synthesis, n=5) in a short production time (3 min from the end of bombardment).

Synthesis of [ 11C]FEDAA1106 as a new PET imaging probe of peripheral benzodiazepine receptor expression

Peripheral benzodiazepine receptor (PBR) is associated with neuroinflammation and tumor progression. [ 11C]DAA1106 and [ 18F]FEDAA1106 are two promising radioligands for positron emission tomography (PET) imaging of PBR. This study was designed to develop a new radiolabeled analog of [ 11C]DAA1106 and [ 18F]FEDAA1106, [ 11C]FEDAA1106, for PET imaging of PBR expression in brain and cancer. Precursor N-(5-fluoro-2-phenoxyphenyl)- N-(2-(2-fluoroethoxy)-5-hydroxybenzyl)acetamide ( 9) was synthesized in multiple steps with moderate to high chemical yields. Precursor 9 was labeled by [ 11C]CH 3OTf and isolated by high pressure liquid chromatography (HPLC) purification to provide target radioligand N-(5-fluoro-2-phenoxyphenyl)- N-(2-(2-fluoroethoxy)-5-[ 11C]methoxybenzyl)acetamide ([ 11C]FEDAA1106, [ 11C] 10) in 60–70% radiochemical yields, decay corrected to end of bombardment (EOB), based on [ 11C]CO 2. The specific activity of the target radiotracer [ 11C] 10 was in a range of 111–185 GBq/μmol at the end of synthesis (EOS).

Synthesis of new carbon-11-labeled carboxamide derivatives as potential PET dopamine D 3 receptor radioligands

Carbon-11-labeled carboxamide derivatives, ( E)-4-fluoro- N-(4-(4-(2-[ 11C]methoxyphenyl)piperazin-1-yl)butyl)cinnamoylamide, ([ 11C] 3a), ( E)-4-chloro- N-(4-(4-(2-[ 11C]methoxyphenyl)piperazin-1-yl)butyl)cinnamoylamide ([ 11C] 3b), ( E)-4-bromo- N-(4-(4-(2-[ 11C]methoxyphenyl)piperazin-1-yl)butyl)cinnamoylamide, ([ 11C] 3c), ( E)-4-methoxy- N-(4-(4-(2-[ 11C]methoxyphenyl)piperazin-1-yl)butyl)cinnamoylamide ([ 11C] 3d), N-(4-(4-(2-[ 11C]methoxyphenyl)piperazin-1-yl)butyl)naphthyl-2-carboxamide ([ 11C]BP897, [ 11C] 3e), and N-(4-(4-(2-[ 11C]methoxyphenyl)piperazin-1-yl)butyl)biphenyl-4-carboxamide ([ 11C] 3f), have been synthesized as new potential PET radioligands for imaging of dopamine D 3 receptors. The target tracers were prepared by O-[ 11C]methylation of their corresponding precursors using [ 11C]CH 3OTf and isolated by a simplified solid-phase extraction (SPE) purification procedure in 50–65% radiochemical yields decay corrected to end of bombardment (EOB), 20 min overall synthesis time, and 111–148 GBq/μmol specific activity at end of synthesis (EOS).

Synthesis of new carbon-11 labeled naphthalene-sulfonamides for PET imaging of human CCR8

Carbon-11 labeled naphthalene-sulfonamides, N-(4-( N-(4-[ 11C]methoxyphenyl)sulfamoyl)naphthalene-1-yl)benzamide ([ 11C] 5a), N-(4-( N-(4-[ 11C]methoxyphenyl)sulfamoyl)naphthalene-1-yl)-2-methylbenzamide ([ 11C] 5b), N-(4-( N-(4-[ 11C]methoxyphenyl)sulfamoyl)naphthalene-1-yl)-3-methylbenzamide ([ 11C] 5c), N-[ 11C]methyl- N-methyl-4-(4-benzamidonaphthalene-1-sulfonamido)piperidine-1-carboxamide ([ 11C] 9a) and N-[ 11C]methyl- N-methyl-4-(4-(2-methylbenzamido)naphthalene-1-sulfonamido)piperidine-1-carboxamide ([ 11C] 9b), have been synthesized as new potential positron emission tomography (PET) agents for imaging of human CCR8. The target tracers were prepared by either O-[ 11C]methylation or N-[ 11C]methylation of their corresponding precursors using [ 11C]CH 3OTf and isolated by either a simplified solid-phase extraction (SPE) purification procedure or a high pressure liquid chromatography (HPLC) method in 30–50% radiochemical yields decay corrected to end of bombardment (EOB), 20–25 min overall synthesis time, and 74–111 GBq/μmol specific activity at end of synthesis (EOS).

Enantiomeric radiochemical synthesis of R and S (1‐(6‐amino‐9H‐purin‐9‐yl)‐3‐fluoropropan‐2‐yloxy)methylphosphonic acid (FPMPA)

Therapy for human immunodeficiency virus (HIV)-infected patients requires chronic multidrug administration. The eventual failure of therapy in some patients has brought into question the tissue concentration of the drugs. With an appropriately radiolabeled compound, we could utilize positron emission tomography to provide quantitative time-activity curves for various tissues. We have developed a fluorine-18 labeled analog of Tenofovir, the active metabolite of Tenofovir DF, a commonly prescribed component of multidrug therapy. Because (1-(6-amino-9H-purin-9-yl)-3-fluoropropan-2-yloxy)methylphosphonic acid (FPMPA) has a chiral center, we prepared both enantiomers and confirmed that the S-isomer exhibited significantly higher antiviral activity than the R-isomer. In viral replication inhibition assays in human MT4 cells infected with SHIV(DH12R), S-FPMPA had an IC(50) of 1.85 muM (95% CI; 0.8-5.53), while the R-isomer was inactive. An appropriate chiral precursor was prepared to allow the incorporation of fluorine-18. The [(18)F]FPMPA in racemic, R, or S form was prepared in a 50 min synthesis in 38+/-5% yield (n = 23, corrected for decay). The product was of high radiochemical and enantiomeric purity. The specific activity of the final product was 4.0+/-1.8 Ci/mumol at EOB (end of bombardment). This product may provide information about drug tissue distribution in animal models under chronic drug treatment.

Simple synthesis of carbon-11 labeled styryl dyes as new potential PET RNA-specific, living cell imaging probes

A new type of styryl dyes have been developed as RNA-specific, live cell imaging probes for fluorescent microscopy technology to study nuclear structure and function. This study was designed to develop carbon-11 labeled styryl dyes as new probes for biomedical imaging technique positron emission tomography (PET) imaging of RNA in living cells. Precursors ( E)-2-(2-(1-(triisopropylsilyl)-1 H-indol-3-yl)vinyl)quinoline ( 2), ( E)-2-(2,4,6-trimethoxystyryl)quinoline ( 3) and ( E)-4-(2-(6-methoxyquinolin-2-yl)vinyl)- N, N-diemthylaniline ( 4), and standards styryl dyes E36 ( 6), E144 ( 7) and F22 ( 9) were synthesized in multiple steps with moderate to high chemical yields. Precursor 2 was labeled by [ 11C]CH 3OTf, trapped on a cation-exchange CM Sep-Pak cartridge following a quick deprotecting reaction by addition of ( n-Bu) 4NF in THF, and isolated by solid-phase extraction (SPE) purification to provide target tracer [ 11C]E36 ([ 11C] 6) in 40–50% radiochemical yields, decay corrected to end of bombardment (EOB), based on [ 11C]CO 2. The target tracers [ 11C]E144 ([ 11C] 7) and [ 11C]F22 ([ 11C] 9) were prepared by N-[ 11C]methylation of the precursors 3 and 4, respectively, using [ 11C]CH 3OTf and isolated by SPE method in 50–70% radiochemical yields at EOB. The specific activity of the target tracers [ 11C] 6, [ 11C] 7 and [ 11C] 9 was in a range of 74–111 GBq/μmol at the end of synthesis (EOS).

Synthesis and preliminary biological evaluation of new carbon-11 labeled tetrahydroisoquinoline derivatives as SERM radioligands for PET imaging of ER expression in breast cancer

The estrogen receptors (ERs) are attractive targets in the treatment of breast cancer and the development of receptor-based breast cancer imaging agents for diagnostic use in biomedical imaging technique positron emission tomography (PET). Tetrahydroisoquinoline derivatives are a class of selective estrogen receptor modulators (SERMs) with high binding affinity and specificity exhibiting up to 50 folds for ERα over ERβ. New carbon-11 labeled tetrahydroisoquinoline derivatives, [ 11C]methyl 1-(2-(4-(2-(4-fluorophenyl)-6-hydroxy-1-methyl-1,2,3,4-tetrahydroisoquinolin-1-yl)phenoxy)ethyl)piperidine-4-carboxylate ([ 11C] 10a) and [ 11C]methyl 1-(2-(4-(2-(4-chlorophenyl)-6-hydroxy-1-methyl-1,2,3,4-tetrahydroisoquinolin-1-yl)phenoxy)ethyl)piperidine-4-carboxylate ([ 11C] 10b), have been first designed, synthesized and evaluated. The target tracers were prepared by O-[ 11C]methylation of their corresponding precursors using [ 11C]CH 3OTf and isolated by solid-phase extraction (SPE) purification procedure in 40–60% radiochemical yields, which were decay corrected to the end of bombardment (EOB), based on [ 11C]CO 2. The overall synthesis time was 15–20 min from EOB. The radiochemical purity was >99%, and specific activity was in a range of 74–111 GBq/μmol at the end of synthesis (EOS). Preliminary findings from in vitro biological assay indicate that the synthesized derivatives displayed similar potencies in the MCF-7 human breast cancer cell line in comparison with 4-hydroxytamoxifen, a well-known potent SERM. These results encourage further in vivo evaluation of carbon-11 labeled tetrahydroisoquinoline derivatives as new potential SERM radioligands for PET imaging of ER expression in breast cancer.

Synthesis of new carbon‐11‐labeled 7‐aroyl‐aminoindoline‐1‐sulfonamides as potential PET agents for imaging of tubulin polymerization in cancers

AbstractThe tubulin polymerization is an attractive target for anticancer therapy and in the development of cancer imaging agents for use in biomedical imaging technique positron emission tomography (PET). 7‐Aroyl‐aminoindoline‐1‐sulfonamides are a novel class of potent antitublin agents. Carbon‐11‐labeled 7‐aroyl‐aminoindoline‐1‐sulfonamides have been synthesized as new potential PET agents for imaging of tubulin polymerization in cancers. The target tracers were prepared by O‐[11C]methylation of their corresponding precursors using [11C]CH3OTf and isolated by a simplified solid‐phase extraction purification procedure in 40–55% radiochemical yields based on [11C]CO2 and decay corrected to the end of bombardment (EOB), 15–20 min overall synthesis time from EOB, >98% radiochemical purity, and 74–111 GBq/µmol specific activity at the end of synthesis. Copyright © 2008 John Wiley & Sons, Ltd.

Feasibility studies of 4′-[methyl-11C]thiothymidine as a tumor proliferation imaging agent in mice

This study reports on the radiosynthesis and feasibility studies of 4'-[methyl-(11)C]thiothymidine ([methyl-(11)C]S-dThd) as a tumor proliferation imaging agent. [Methyl-(11)C]S-dThd was synthesized by rapid methylation of corresponding 5-trimethylstannyl- or 5-tributylstannyl-precursor via a palladium-promoted Stille cross-coupling reaction with [(11)C]methyl iodide. The decay-corrected radiochemical yields of [methyl-(11)C]S-dThd synthesized by the corresponding 5-trimethylstannyl-precursor and 5-tributylstannyl-precursor based on [(11)C]CO(2) were 18.9% and 14.5%, respectively. The radiochemical purity of [methyl-(11)C]S-dThd was always greater than 99%. The specific activities of [methyl-(11)C]S-dThd synthesized by the corresponding 5-trimethylstannyl-precursor and 5-tributylstannyl-precursor were 47 GBq/mumol and 121 GBq/mumol, respectively, at the end of the synthesis. The total synthesis time was 30 min after the end of bombardment. The comparison between in vivo distribution of [methyl-(14)C]S-dThd and that of [methyl-(3)H]FLT showed that tracer uptake was comparable in nonproliferating tissues. In contrast, [methyl-(14)C]S-dThd showed significantly higher uptake in proliferating tissues than did [methyl-(3)H]FLT. [Methyl-(11)C]S-dThd uptake levels in five different tumor tissues were well correlated with the DNA synthesis levels determined by [2-(14)C]thymidine DNA incorporation. At 30 min after injection, plasma analysis found 95% of the activity in unmetabolized form. The microPET imaging of the C6 glioma xenograft showed significantly high uptake in the tumor and urinary bladder, followed by the intestine and marrow. Our results demonstrated that the tumor uptake of [methyl-(11)C]S-dThd was higher than that of [methyl-(3)H]FLT and was well correlated with the DNA synthesis level. Consequently, 4'-[methyl-(11)C]thiothymidine has promise for the imaging of tumor cell proliferation by positron emission tomography.

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, (3a R,9b S)-1-[ 11C]methyl-1-methyl-6-(methylcarbamoyloxy)-2,3,3a,4,5,9b-hexahydro-1 H-benzo[g]indolium triflate ([ 11C] 8) and (3a R,9b S)-1-[ 11C]methyl-1-methyl-6-(heptylcarbamoyloxy)-2,3,3a,4,5,9b-hexahydro-1 H-benzo[g]indolium triflate ([ 11C] 9), were designed and synthesized as potential positron emission tomography (PET) agents for imaging AChE and BChE enzymes. The appropriate precursors were labeled with [ 11C]CH 3OTf through N-[ 11C]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/μmol specific activity at EOB.

Synthesis of new carbon-11 labeled benzoxazole derivatives for PET imaging of 5-HT 3 receptor

5-HT 3 receptor is an attractive target for the development of therapeutic agents for use in brain, heart and cancer diseases, and imaging agents for use in biomedical imaging technique PET. Benzoxazole derivatives are a novel class of 5-HT 3 receptor partial agonists with high binding affinity. Carbon-11 labeled benzoxazole derivatives have been synthesized as new potential PET radioligands for imaging 5-HT 3 receptor. The target tracers were prepared by N-[ 11C]methylation of their corresponding precursors using [ 11C]CH 3OTf and isolated by HPLC purification procedure in 40–50% radiochemical yields, which were decay corrected to the end of bombardment (EOB), based on [ 11C]CO 2. The overall synthesis time was 20–25 min from EOB. The radiochemical purity was >99%, and specific activity was in a range of 74–111 GBq/μmol at the end of synthesis (EOS).