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Sample records for newly formed c-11

  1. Cross-Linking Mast Cell Specific Gangliosides Stimulates the Release of Newly Formed Lipid Mediators and Newly Synthesized Cytokines

    Directory of Open Access Journals (Sweden)

    Edismauro Garcia Freitas Filho

    2016-01-01

    Full Text Available Mast cells are immunoregulatory cells that participate in inflammatory processes. Cross-linking mast cell specific GD1b derived gangliosides by mAbAA4 results in partial activation of mast cells without the release of preformed mediators. The present study examines the release of newly formed and newly synthesized mediators following ganglioside cross-linking. Cross-linking the gangliosides with mAbAA4 released the newly formed lipid mediators, prostaglandins D2 and E2, without release of leukotrienes B4 and C4. The effect of cross-linking these gangliosides on the activation of enzymes in the arachidonate cascade was then investigated. Ganglioside cross-linking resulted in phosphorylation of cytosolic phospholipase A2 and increased expression of cyclooxygenase-2. Translocation of 5-lipoxygenase from the cytosol to the nucleus was not induced by ganglioside cross-linking. Cross-linking of GD1b derived gangliosides also resulted in the release of the newly synthesized mediators, interleukin-4, interleukin-6, and TNF-α. The effect of cross-linking the gangliosides on the MAP kinase pathway was then investigated. Cross-linking the gangliosides induced the phosphorylation of ERK1/2, JNK1/2, and p38 as well as activating both NFκB and NFAT in a Syk-dependent manner. Therefore, cross-linking the mast cell specific GD1b derived gangliosides results in the activation of signaling pathways that culminate with the release of newly formed and newly synthesized mediators.

  2. Enzymatic synthesis of 11C-pyruvic acid and 11C-L-lactic acid

    International Nuclear Information System (INIS)

    Cohen, M.B.; Spolter, L.; Chang, C.C.; Cook, J.S.; Macdonald, N.S.

    1980-01-01

    L-Lactic acid is formed as the end product of glycolysis under anaerobic conditions in all cells, but this reaction is of special significance in the myocardium. L-Lactic acid is reversibly formed from and is in equilibrium with myocardial pyruvic acid, which is its sole metabolic pathway. 11 C-Pyruvic acid is synthesized from 11 C carbon dioxide using pyruvate-ferredoxin oxidoreductase and coenzymes. The 11 C-pyruvic acid is then converted to 11 -L-lactic acid by lactic acid dehydrogenase. The availability of 11 C-pyruvic acid and 11 C-L-lactic acid will permit the in vivo investigation of lactate metabolism. (author)

  3. Synthesis of [11C]cyanoalkyltriphenylphosphoranes via [11C]cyanide substitution on haloalkylphosphonium salts

    International Nuclear Information System (INIS)

    Hoernfeldt, K.

    1994-01-01

    The synthesis of the 11 C-labelled bifunctional precursors 3-[ 11 C]cyanoethyltriphenylphosphonium bromide (1'), 4-[ 11 C]cyanopropyltriphenylphosphonium bromide (2'), 5-[ 11 C]cyanobutyltriphenylphosphonium bromide (3'), 4-[ 11 C]cyanopropyltriphenylphosphonium iodide (4') and 5-[ 11 C]cyanobutyltriphenylphosphonium iodide (5') is presented. The label was introduced using [ 11 C]cyanide in a substitution reaction on the ω-halo-alkyltriphenylphosphonium salt (bromide or iodide salt). The phosphonium salts 1'-5' were formed in 33-99% radiochemical yield in 5-10 min reaction time. After addition of epichlorohydrin as generator of base, the precursors 1-3 were formed. The potential of the intermediates 1-3 in Wittig reactions was shown in model reactions with aromatic and aliphatic aldehydes. The aromatic olefins obtained from 1'-5' were formed in 85-96% radiochemical yield, with Z/E ratios between 67/33-75/25. The aliphatic olefins were obtained in 60-78% radiochemical yield from 4' and 5'. In the reaction with 1' and an aliphatic aldehyde, the yield decreased to 5-10%. The Z/E ratios were 100/0 for the aliphatic olefins. In an experiment starting with 2,7 GBq (73 mCi) hydrogen [ 11 C]cyanide, 451 MBq (12.2 mCi) olefin from 3' and 4-nitrobenzaldehyde was obtained in 44 min from hydrogen [ 11 C]cyanide production, with a 55% decay corrected radiochemical yield, the radiochemical purity was 96%. (Author)

  4. Assessment of the Quality of Newly Formed Bone around Titanium Alloy Implants by Using X-Ray Photoelectron Spectroscopy

    Directory of Open Access Journals (Sweden)

    Hiroshi Nakada

    2012-01-01

    Full Text Available The aim of this study was to evaluate differences in bones quality between newly formed bone and cortical bone formed around titanium alloy implants by using X-ray photoelectron spectroscopy. As a result of narrow scan measurement at 4 weeks, the newly formed bone of C1s, P2p, O1s, and Ca2p were observed at a different peak range and strength compared with a cortical bone. At 8 weeks, the peak range and strength of newly formed bone were similar to those of cortical bone at C1s, P2p, and Ca2p, but not O1s. The results from this analysis indicate that the peaks and quantities of each element of newly formed bone were similar to those of cortical bone at 8 weeks, suggestive of a strong physicochemical resemblance.

  5. Observation of the bone mineral density of newly formed bone using rabbits. Compared with newly formed bone around implants and cortical bone

    International Nuclear Information System (INIS)

    Nakada, Hiroshi; Numata, Yasuko; Sakae, Toshiro; Tamaki, Hiroyuki; Kato, Takao

    2009-01-01

    There have been many studies reporting that newly formed bone around implants is spongy bone. However, although the morphology is reported as being like spongy bone, it is difficult to discriminate whether the bone quality of newly formed bone appears similar to osteoid or cortical bone; therefore, evaluation of bone quality is required. The aims of this study were to measure the bone mineral density (BMD) values of newly formed bone around implants after 4, 8, 16, 24 and 48 weeks, to represent these values on three-dimensional color mapping (3Dmap), and to evaluate the change in bone quality associated with newly formed bone around implants. The animal experimental protocol of this study was approved by the Ethics Committee for Animal Experiments of our University. This experiment used 20 surface treatment implants (Ti-6Al-4V alloy: 3.1 mm in diameter and 30.0 mm in length) by grit-blasting. They were embedded into surgically created flaws in femurs of 20 New Zealand white rabbits (16 weeks old, male). The rabbits were sacrificed with an ear intravenous overdose of pentobarbital sodium under general anesthesia each period, and the femurs were resected. We measured BMD of newly formed bone around implants and cortical bone using Micro-CT, and the BMD distribution map of 3Dmap (TRI/3D Bon BMD, Ratoc System Engineering). The BMD of cortical bone was 1,026.3±44.3 mg/cm 3 at 4 weeks, 1,023.8±40.9 mg/cm 3 at 8 weeks, 1,048.2±45.6 mg/cm 3 at 16 weeks, 1,067.2±60.2 mg/cm 3 at 24 weeks, and 1,069.3±50.7 mg/cm 3 at 48 weeks after implantation, showing a non-significant increase each period. The BMD of newly formed bone around implants was 296.8±25.6 mg/cm 3 at 4 weeks, 525.0±72.4 mg/cm 3 at 8 weeks, 691.2±26.0 mg/cm 3 at 16 weeks, 776.9±27.7 mg/cm 3 at 24 weeks, and 845.2±23.1 mg/cm 3 at 48 weeks after implantation, showing a significant increase after each period. It was revealed that the color scale of newly formed bone was Low level at 4 weeks, and then it

  6. Conversion of no-carrier-added [11C]carbon dioxide to [11C]carbon monoxide on molybdenum for the synthesis of 11C-labelled aromatic ketones

    International Nuclear Information System (INIS)

    Zeisler, S.K.; Nader, M.; Theobald, A.; Oberdorfer, F.

    1997-01-01

    A new method for the efficient conversion of no-carrier-added [ 11 C]carbon dioxide into [ 11 C]carbon monoxide is described. [ 11 C]Carbon dioxide produced by proton bombardment of ultra high purity nitrogen is pre-concentrated in a cryo trap and then passed through a quartz tube filled with a mesh of thin molybdenum wire heated to 850 o C. [ 11 C]Carbon dioxide readily reacts with molybdenum to form [ 11 C]carbon monoxide and molybdenum(IV) oxide. The latter also reduces carbon dioxide to carbon monoxide and helps improve the performance of the converter. [ 11 C]Carbon monoxide is purified from remaining [ 11 C]carbon dioxide and collected in a small silica trap from which it is eluted into a reaction mixture for the palladium-mediated synthesis of a 11 C-labelled aromatic ketone. Radiochemical yields of up to 81% (decay-corrected) for [ 11 C]carbon monoxide were obtained. Radiochemical purity and specific radioactivity of both [ 11 C]carbon monoxide and the 11 C-labelled ketone are sufficient for nuclear medical studies with PET. (Author)

  7. Newly-formed emotional memories guide selective attention processes: Evidence from event-related potentials.

    Science.gov (United States)

    Schupp, Harald T; Kirmse, Ursula; Schmälzle, Ralf; Flaisch, Tobias; Renner, Britta

    2016-06-20

    Emotional cues can guide selective attention processes. However, emotional stimuli can both activate long-term memory representations reflecting general world knowledge and engage newly formed memory representations representing specific knowledge from the immediate past. Here, the self-completion feature of associative memory was utilized to assess the regulation of attention processes by newly-formed emotional memory. First, new memory representations were formed by presenting pictures depicting a person either in an erotic pose or as a portrait. Afterwards, to activate newly-built memory traces, edited pictures were presented showing only the head region of the person. ERP recordings revealed the emotional regulation of attention by newly-formed memories. Specifically, edited pictures from the erotic compared to the portrait category elicited an early posterior negativity and late positive potential, similar to the findings observed for the original pictures. A control condition showed that the effect was dependent on newly-formed memory traces. Given the large number of new memories formed each day, they presumably make an important contribution to the regulation of attention in everyday life.

  8. Newly-formed emotional memories guide selective attention processes: Evidence from event-related potentials

    Science.gov (United States)

    Schupp, Harald T.; Kirmse, Ursula; Schmälzle, Ralf; Flaisch, Tobias; Renner, Britta

    2016-01-01

    Emotional cues can guide selective attention processes. However, emotional stimuli can both activate long-term memory representations reflecting general world knowledge and engage newly formed memory representations representing specific knowledge from the immediate past. Here, the self-completion feature of associative memory was utilized to assess the regulation of attention processes by newly-formed emotional memory. First, new memory representations were formed by presenting pictures depicting a person either in an erotic pose or as a portrait. Afterwards, to activate newly-built memory traces, edited pictures were presented showing only the head region of the person. ERP recordings revealed the emotional regulation of attention by newly-formed memories. Specifically, edited pictures from the erotic compared to the portrait category elicited an early posterior negativity and late positive potential, similar to the findings observed for the original pictures. A control condition showed that the effect was dependent on newly-formed memory traces. Given the large number of new memories formed each day, they presumably make an important contribution to the regulation of attention in everyday life. PMID:27321471

  9. 11 CFR 104.6 - Form and content of internal communications reports (2 U.S.C. 431(9)(B)(iii)).

    Science.gov (United States)

    2010-01-01

    ... internal communications reports (2 U.S.C. 431(9)(B)(iii)). (a) Form. Every membership organization or corporation which makes disbursements for communications pursuant to 11 CFR 100.134(a) and 114.3 shall report... 11 Federal Elections 1 2010-01-01 2010-01-01 false Form and content of internal communications...

  10. C-11 cyanide production system

    Science.gov (United States)

    Kim, Dohyun; Alexoff, David; Kim, Sung Won; Hooker, Jacob M.; Ferrieri, Richard A.

    2017-11-21

    A method for providing .sup.11C-labeled cyanides from .sup.11C labeled oxides in a target gas stream retrieved from an irradiated high pressure gaseous target containing O.sub.2, wherein .sup.11C labeled oxides are reduced with H.sub.2 in the presence of a nickel catalyst under a pressure and a temperature sufficient to form a product stream comprising at least about 95% .sup.11CH.sub.4, the .sup.11CH.sub.4 is then combined with an excess of NH.sub.3 in a carrier/reaction stream flowing at an accelerated velocity and the combined .sup.11CH4 carrier/reaction stream is then contacted with a platinum (Pt) catalyst particulate supported on a substantially-chemically-nonreactive heat-stable support at a temperature of at least about 900.degree. C., whereby a product stream comprising at least about 60% H.sup.11CN is provided in less than 10 minutes from retrieval of the .sup.11C labeled oxide.

  11. The synthesis of [1-11C]-butanol

    International Nuclear Information System (INIS)

    Helus, F.; Maier-Borst, W.; Oberdorfer, F.; Silvester, D.J.

    1982-01-01

    11 C-labelled butanol has been synthesised for use as a tracer in the assessment of regional blood supply for substrate utilisation in tumors. 11 CO 2 was produced by the 14 N(p,a) 11 C reactions in a cyclotron. 11 C-butanol was formed by the carboxylation of n-propyl magnesium chlorides with 11 CO 2 , and reduction of the resulting 11 C-butyric acid with LiAlH 4 . (U.K.)

  12. Newly-formed emotional memories guide selective attention processes: Evidence from event-related potentials

    OpenAIRE

    Harald T. Schupp; Ursula Kirmse; Ralf Schmälzle; Tobias Flaisch; Britta Renner

    2016-01-01

    Emotional cues can guide selective attention processes. However, emotional stimuli can both activate long-term memory representations reflecting general world knowledge and engage newly formed memory representations representing specific knowledge from the immediate past. Here, the self-completion feature of associative memory was utilized to assess the regulation of attention processes by newly-formed emotional memory. First, new memory representations were formed by presenting pictures depi...

  13. Caffeine-11C, ephedrine-11C and methylephedrine-11C: synthesis and distribution in mice

    International Nuclear Information System (INIS)

    Saji, Hideo; Ido, Tatsuo; Iwata, Ren; Suzuki, Kazutoshi; Tamate, Kazuhiko

    1978-01-01

    Caffeine, ephedrine and methylephedrine were labeled with carbon-11 by the action of methyliodide- 11 C on theophylline, norephedrine and ephedrine, respectively. Caffeine- 11 C was prepared in 44 min. with a radiochemical yield of 40%, ephedrine- 11 C in 45 min. with a 11% radiochemical yield and methylephedrine- 11 C in 36 min. with a 43% radiochemical yield. When injected in mice intravenously, these products show a high uptake in the liver, the kidney and the blood for caffeine- 11 C and in the liver and the kidney for ephedrine- 11 C and methylephedrine- 11 C. The brain uptake for these products was found to be 2.4 to 3.9% of the injected dose per gram at 5 min. after injection. These studies in mice have demonstrated that these products are potentially useful agents for the dynamic studies of the brain. (auth.)

  14. A simple, versatile, low-cost and remotely operated apparatus for [11C]acetate, [11C]choline, [11C]methionine and [11C]PIB synthesis

    International Nuclear Information System (INIS)

    Cheung Manki; Ho Chilai

    2009-01-01

    A simple, efficient and remotely operated synthesis apparatus for carrying out routine [ 11 C]carboxylation, on-column and bubbling [ 11 C]methylation was essential for reliable, day-to-day production of [ 11 C]-labelled PET radiopharmaceuticals. We developed an in-house apparatus specifically applied to the synthesis of [ 11 C]acetate, [ 11 C]choline, [ 11 C]methionine and 2-(4'-N-[ 11 C]methylaminophenyl)-6-hydroxybenzothiazole ([ 11 C]PIB), where high radiochemical purity (≥97%) and moderate radiochemical yields (18% for [ 11 C]PIB, 41-55% for the others) could be achieved. These findings provided evidence that this was a fast, versatile and reliable apparatus suitable for a PET/CT centre with limited financial budget and hot cell space for synthesis of [ 11 C]-labelled radiopharmaceuticals

  15. Production of [11C]CO2 with gas target at low proton energies

    International Nuclear Information System (INIS)

    Sansaloni, Francesc; Lagares, Juan Ignacio; Llop, Jordi; Arce, Pedro; Díaz, Carlos; Pérez-Morales, José Manuel

    2013-01-01

    Nowadays the demand and the installation of self-shielded low-energy cyclotrons is growing, allowing the use of 11 C in many more centers. The aim of this study was the design of a new target and the evaluation of the production of 11 C as [ 11 C]CO 2 at low proton energies. The target was coupled to an IBA Cyclone-18/9 and the energy was decreased to 4–16 MeV. The newly designed target allowed the production of [ 11 C]CO 2 at different proton energies, and the results suggest that the cyclotron energy of Cyclone-18/9 is slightly higher than the nominal 18 MeV

  16. Total Synthesis of Zoanthamine Alkaloids, Part 2. Construction of the C1-C5, C6-C10 and C11-C24 Fragments of Zoanthamine

    DEFF Research Database (Denmark)

    Tanner, David Ackland; Tedenborg, Lars; Somfai, Peter

    1997-01-01

    This paper describes the construction of three key intermediates for a projected total synthesis of the marine alkaloid zoanthamine. These building blocks, corresponding to the C1-C5, C6-C10 and C11-C24 fragments of the target molecule, are synthesised efficiently form (R)-hydroxymethyl-butyrolac......This paper describes the construction of three key intermediates for a projected total synthesis of the marine alkaloid zoanthamine. These building blocks, corresponding to the C1-C5, C6-C10 and C11-C24 fragments of the target molecule, are synthesised efficiently form (R...

  17. Synthesis of 1-[11c]methylpiperidin-4-yl propionate ([11c]pmp) for in vivo measurements of acetylcholinesterase activity

    International Nuclear Information System (INIS)

    Snyder, Scott E.; Tluczek, Louis; Jewett, Douglas M.; Nguyen, Thinh B.; Kuhl, David E.; Kilbourn, Michael R.

    1998-01-01

    Synthesis of 1-[ 11 C]methylpiperidin-4-yl propionate ([ 11 C]PMP), an in vivo substrate for acetylcholinesterase, is reported. An improved preparation of 4-piperidinyl propionate (PHP), the immediate precursor for radiolabeling, was accomplished in three steps from 4-hydroxypiperidine by (a) protection of the amine as the benzyl carbamate, (b) acylation with propionyl chloride, and (c) deprotection of the carbamate by catalytic hydrogenation. The final product was obtained in an overall 82% yield. Reaction of the free base form of PHP with [ 11 C]methyl trifluoromethanesulfonate at room temperature in N,N-dimethylformamide, followed by high performance liquid chromatography (HPLC) purification, provided [ 11 C]PMP in 57% radiochemical yield, >99% radiochemical purity, and >1500 Ci/mmol at the end of synthesis. The total synthesis time from end-of-bombardment was 35 min. [ 11 C]PMP can thus be reliably prepared for routine clinical studies of acetylcholinesterase in human brain using positron emission tomography

  18. Catalytic conversion of 11CO2 and 11CO into synthesis precursors for 11C labelling

    International Nuclear Information System (INIS)

    Patt, J.T.

    1994-03-01

    The positron emitter carbon-11 (T 1/2 =20.3 min) is an ideal radio nuclide for tracers in positron emission tomography (PET). In this study catalytic methods for the synthesis of [ 11 C]alcohols have been investigated. The formation of [ 11 C]methanol has been studied on Pd/Al 2 O 3 and Cu/ZnO/Al 2 O 3 catalysts with respect to CO and CO 2 carrier addition to the synthesis gas. Carbon monoxide was identified as the precursor of methanol formation on the Pd/Al 2 O 3 -catalyst. In contrast on the Cu/ZnO/Al 2 O 3 -catalyst methanol was formed on a reaction pathway via an adsorbed CO 2 -species. A n.c.a.-[ 11 C]methanol synthesis basing on the Cu/ZnO/Al 2 O 3 -catalyst has been developed by substitution of the oxygen containing components CO and CO 2 in the synthesis gas by N 2 O. The radiochemical yield, the low selectivity of [ 11 C]methanol production and the rather slow kinetics of this process were arguments against the practical use of this process in the synthesis of 11 C-labelling agents. (orig.)

  19. A Comparison of Traditional and Newly Emerging Forms of Cooperative Capitalization

    OpenAIRE

    Barton, David G.

    2004-01-01

    This paper compares the traditional forms of capitalization used by American co-ops to newly emerging forms. It is based on an in-depth review of several case co-ops. A broad framework is provided that may be beneficial in more extensive studies of capitalization practices of cooperatives and similar organizations. It is divided into three parts. Part One outlines the alternative capitalization forms being used by cooperatives and their antecedents, where conversions to other structures and f...

  20. Synthesis of racemic [3-11C]phenylalanine and [3-11C] DOPA

    International Nuclear Information System (INIS)

    Halldin, C.; Laangstroem, B.

    1984-01-01

    The synthesis of racemic [3- 11 C]phenylalanine and [3- 11 C]DOPA is reported. The [ 11 C]benzaldehyde and [ 11 C]veratraldehyde prepared in a two-step reaction from the corresponding [ 11 C]acid salt and [ 11 C]alcohol, by means of selective oxidation with tetrabutylammonium hydrogen chromate, were reacted with 2-phenyl-5-oxazolone or 2-(4-chloro)phenyl-5-oxazolone in the presence of a tertiary amine to give the corresponding [α- 11 C]-4-arylene-2-aryl-5-oxazolones. Ring opening of these olefins, hydrogenation, and removal of protecting groups was carried out in one step using hydroiodic cid/phosphorus, with the production of the racemic [3- 11 C]amino acids in 8-30% radiochemical yield (starting with 11 CO 2 ) within 52-60 min (including LC separation). (author)

  1. E3 Ligase cIAP2 Mediates Downregulation of MRE11 and Radiosensitization in Response to HDAC Inhibition in Bladder Cancer.

    Science.gov (United States)

    Nicholson, Judith; Jevons, Sarah J; Groselj, Blaz; Ellermann, Sophie; Konietzny, Rebecca; Kerr, Martin; Kessler, Benedikt M; Kiltie, Anne E

    2017-06-01

    The MRE11/RAD50/NBS1 (MRN) complex mediates DNA repair pathways, including double-strand breaks induced by radiotherapy. Meiotic recombination 11 homolog (MRE11) is downregulated by histone deacetylase inhibition (HDACi), resulting in reduced levels of DNA repair in bladder cancer cells and radiosensitization. In this study, we show that the mechanism of this downregulation is posttranslational and identify a C-terminally truncated MRE11, which is formed after HDAC inhibition as full-length MRE11 is downregulated. Truncated MRE11 was stabilized by proteasome inhibition, exhibited a decreased half-life after treatment with panobinostat, and therefore represents a newly identified intermediate induced and degraded in response to HDAC inhibition. The E3 ligase cellular inhibitor of apoptosis protein 2 (cIAP2) was upregulated in response to HDAC inhibition and was validated as a new MRE11 binding partner whose upregulation had similar effects to HDAC inhibition. cIAP2 overexpression resulted in downregulation and altered ubiquitination patterns of MRE11 and mediated radiosensitization in response to HDAC inhibition. These results highlight cIAP2 as a player in the DNA damage response as a posttranscriptional regulator of MRE11 and identify cIAP2 as a potential target for biomarker discovery or chemoradiation strategies in bladder cancer. Cancer Res; 77(11); 3027-39. ©2017 AACR . ©2017 American Association for Cancer Research.

  2. The synthesis of no-carrier-added [11C]urea from [11C]carbon dioxide and application to [11C]uracil synthesis

    International Nuclear Information System (INIS)

    Chakraborty, P.K.; Mangner, T.J.; Chugani, H.T.

    1997-01-01

    No-carrier-added [ 11 C]urea has been synthesized by bubbling cyclotron-produced [ 11 C]-carbon dioxide directly into a tetrahydrofuran solution of lithium bis(trimethylsilyl)amide, followed by hydrolysis of the C-11 labeled adduct with aqueous ammonium chloride. Using this simple, one-pot method, [ 11 C]urea was produced in 55-70% radiochemical yield (decay-corrected) in 16 min following end-of-bombardment (or in 10 min following the introduction of the [ 11 C]carbon dioxide. The [ 11 C]urea thus produced was converted to [ 11 C]uracil (carrier-added) in 40-75% decay-corrected radiochemical yield by condensation with diethyl malate in presence of fuming sulfuric acid. (author)

  3. Tumor imaging with PET and C-11 thymidine

    International Nuclear Information System (INIS)

    Conti, P.S.; Hilton, J.; Magee, C.A.; Anderson, J.H.

    1989-01-01

    Accurate interpretation of kinetic positron-emission tomographic (PET) data obtained following administration of C-11 thymidine requires identification of radiolabeled metabolites. The authors goal is to quantitate rapidly formed metabolites of C-11 thymidine by using reproducible high-pressure liquid chromatography (HPLC). Following coinjection of methyl-C-11 and methyl-C-14 thymidine, dogs bearing implanted glioblastoma were imaged with PET. Plasma samples were collected, and dogs were sacrificed at 60 minutes. Tissues were prepared for quantitative autoradiography and analysis of radioactivity associated with DNA, RNA protein, and acid soluble extracts. Plasma and tissue extracts were analyzed by HPLC by using C-18 reverse phase and dilute buffer mobile phase systems for the separation of catabolites and phosphorylated nucleotides

  4. Newly formed skeletal muscle fibers are prone to false positive immunostaining by rabbit antibodies

    DEFF Research Database (Denmark)

    Andersen, Ditte C; Kliem, Anette; Schrøder, Henrik Daa

    2011-01-01

    rely on controls that reveal non-specific binding by the secondary antibody and neglect that the primary rabbit antibody itself may cause false positive staining of the muscle. We suggest that reliable immuno-based protein detection in newly formed muscle fibers at least requires a nonsense rabbit......Reports on muscle biology and regeneration often implicate immuno(cyto/histo)chemical protein characterization using rabbit polyclonal antibodies. In this study we demonstrate that newly formed myofibers are especially prone to false positive staining by rabbit antibodies and this unwanted staining...

  5. Synthesis of 1-[{sup 11}c]methylpiperidin-4-yl propionate ([{sup 11}c]pmp) for in vivo measurements of acetylcholinesterase activity

    Energy Technology Data Exchange (ETDEWEB)

    Snyder, Scott E. E-mail: snyderse@umich.edu; Tluczek, Louis; Jewett, Douglas M.; Nguyen, Thinh B.; Kuhl, David E.; Kilbourn, Michael R

    1998-11-01

    Synthesis of 1-[{sup 11}C]methylpiperidin-4-yl propionate ([{sup 11}C]PMP), an in vivo substrate for acetylcholinesterase, is reported. An improved preparation of 4-piperidinyl propionate (PHP), the immediate precursor for radiolabeling, was accomplished in three steps from 4-hydroxypiperidine by (a) protection of the amine as the benzyl carbamate, (b) acylation with propionyl chloride, and (c) deprotection of the carbamate by catalytic hydrogenation. The final product was obtained in an overall 82% yield. Reaction of the free base form of PHP with [{sup 11}C]methyl trifluoromethanesulfonate at room temperature in N,N-dimethylformamide, followed by high performance liquid chromatography (HPLC) purification, provided [{sup 11}C]PMP in 57% radiochemical yield, >99% radiochemical purity, and >1500 Ci/mmol at the end of synthesis. The total synthesis time from end-of-bombardment was 35 min. [{sup 11}C]PMP can thus be reliably prepared for routine clinical studies of acetylcholinesterase in human brain using positron emission tomography.

  6. Positron emission tomography (PET) study of the alterations in brain distribution of [11C]dethamphetamine in methamphetamine sensitized dog

    International Nuclear Information System (INIS)

    Mizugaki, Michinao; Nakamura, Hitoshi; Hishinuma, Takanori; Tomioka, Yoshihisa; Ishiwata, Shunji; Suzuki, Hideaki; Ido, Tatsuo; Iwata, Ren; Funaki, Yoshihito; Itoh, Masatoshi; Fujiwara, Takehiko; Yanai, Kazuhiko; Sato, Mitsumoto; Numachi, Yohtaro; Yoshida, Sumiko

    1995-01-01

    [ 11 C]Methamphetamine ([ 11 C]MAP) was synthesized by an automated on-line [ 11 C]methylation system for positron emission tomography (PET) study. We newly produced a MAP sensitized dog by repeated MAP treatment and studied the brain distribution of [ 11 C]MAP in the normal and the MAP sensitized dog. The maximal level of accumulation of [ 11 C]MAP in the sensitized dog brain was 1.4 times higher than that in the control. No difference was found in the metabolism of MAP between the two conditions. The significant increase of [ 11 C]MAP in the MAP sensitized brain indicates that subchronic MAP administration causes some functional change in uptake site of MAP

  7. Dopamine transporter binding in rat striatum: a comparison of [O-methyl-{sup 11}C]{beta}-CFT and [N-methyl-{sup 11}C]{beta}-CFT

    Energy Technology Data Exchange (ETDEWEB)

    Yoder, Karmen K.; Hutchins, Gary D.; Mock, Bruce H.; Fei, Xiangshu; Winkle, Wendy L. [Department of Radiology, Indiana University School of Medicine, L3-208, Indianapolis, IN 46202 (United States); Gitter, Bruce D.; Territo, Paul R. [Lilly Center for Anatomical and Molecular Imaging, Integrative Biology Division, Lilly Research Laboratories, Greenfield, IN 46140 (United States); Zheng Qihuang [Department of Radiology, Indiana University School of Medicine, L3-208, Indianapolis, IN 46202 (United States)], E-mail: qzheng@iupui.edu

    2009-01-15

    Introduction: 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). [{sup 11}C]{beta}-CFT is useful for studying DAT as a marker of dopaminergic innervation in animal models of psychiatric and neurological disorders. [{sup 11}C]{beta}-CFT is commonly labeled at the N-methyl position. However, labeling of [{sup 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 [{sup 11}C]{beta}-CFT provides equivalent quantitative results to that of the more commonly reported N-methyl form. Methods: Four female Sprague-Dawley rats were scanned twice on the IndyPET II small-animal scanner, once with [N-methyl-{sup 11}C]{beta}-CFT and once with [O-methyl-{sup 11}C]{beta}-CFT. DAT binding potentials (BP{identical_to}B'{sub avail}/K{sub d}) were estimated for right and left striata with a nonlinear least-squares algorithm, using a reference region (cerebellum) as the input function. Results: [N-Methyl-{sup 11}C]{beta}-CFT and [O-methyl-{sup 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/{mu}mol. Average BP values for right and left striata with [N-methyl-{sup 11}C]{beta}-CFT were 1.16{+-}0.08 and 1.23{+-}0.14, respectively. BP values for [O-methyl-{sup 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. Conclusions: These results suggest that [O-methyl-{sup 11}C]{beta}-CFT is quantitatively equivalent to [N-methyl-{sup 11}C]{beta}-CFT in the rat striatum.

  8. Synthesis of [(11)C]Am80 via Novel Pd(0)-Mediated Rapid [(11)C]Carbonylation Using Arylboronate and [(11)C]Carbon Monoxide.

    Science.gov (United States)

    Takashima-Hirano, Misato; Ishii, Hideki; Suzuki, Masaaki

    2012-10-11

    (11)C-labeled methylbenzoates [(11)C]4a-d were synthesized using Pd(0)-mediated rapid cross-coupling reactions employing [(11)C]carbon monoxide and arylboronic acid neopentyl glycol esters 3a-d under atmospheric pressure in methanol-dimethylformamide (MeOH-DMF), in radiochemical yields of 12 ± 5-26 ± 13% (decay-corrected based on [(11)C]O). The reaction conditions were highly favorable for the synthesis of [(11)C]Am80 ([(11)C]2) and [(11)C]methyl 4-((5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)carbamoyl)benzoate ([(11)C]2-Me) using 4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-N-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)benzamide (5), both of which produced a decay-corrected radiochemical yield (RCY) of 26 ± 13%, with >99% radiochemical purity and an average specific radioactivity of 44 GBq/μmol. The yields of [(11)C]4a, [(11)C]2-Me, and [(11)C]2 were improved by the use of a 2-fold excess of the solvents and reagents under the same conditions to give respective yields of 66 ± 8, 65 ± 7, and 48 ± 2%.

  9. Hadronic decay properties of newly observed $\\Omega_c$ baryons

    OpenAIRE

    Zhao, Ze; Ye, Dan-Dan; Zhang, Ailin

    2017-01-01

    Hadronic decay widths of the newly observed charmed strange baryons, $\\Omega_c(3000)^0$, $\\Omega_c(3050)^0$, $\\Omega_c(3066)^0$, $\\Omega_c(3090)^0$ and $\\Omega_c(3119)^0$ have been calculated in a $^3P_0$ model. Our results indicate that $\\Omega_c(3066)^0$ and $\\Omega_c(3090)^0$ can be interpreted as the $1P-$wave $\\Omega_{c2}(\\frac{3}{2}^-)$ or $\\Omega_{c2}(\\frac{5}{2}^-)$. Though the measured masses of $\\Omega_c(3000)^0$, $\\Omega_c(3050)^0$ and $\\Omega_c(3119)^0$ are lower than existed theo...

  10. A study of 11C-acetate production using 11C-choline commercial module

    International Nuclear Information System (INIS)

    Zhang Jinming; Tian Jiahe; Yao Shulin; Chen Yan

    2008-01-01

    Objective: 11 C-acetate is a useful PET tracer in evaluating myocardial metabolism but more interest has been focused on its application in tumor detection in recent years, especially hepatocellular carcinoma (HCC). This study was designed to evaluate the laboratory, preparation of 11 C-acetate with a modified 11 C-choline commercial module and to investigate its biodistribution in tumor (lung adenocarcinoma)-bearing mice as well as its potential as a tumor imaging agent. Methods: 11 C-acetate was synthesized with a modified 11 C choline module: Methyl magnesium bromide Grignard (0.1 ml of 1.5 mol/L) was load- ed to a Teflon loop before 11 CO 2 was recovered from the target. Cartier acetate solution (2 ml of 1 mmol/L) was pushed through the loop, SPE cartridges (mixed AG50 and IC-Ag) and then the QMA. The loop and cartridges were then rinsed with water. The product 11 C-acetate was then washed out from QMA with 0.9% NaCl solution into a collection vial containing diluted HCl. 11 C-carbonate was removed by nitrogen bubbling for 2 min. After neutralization with trisodium citrate, the injectable 11 C-acetate solution was obtained. The tumor-bearing mice were sacrificed. The percentage activity of injected dose per gram of tissue (% ID/g) for tumor and other tissues were calculated. One patient with known diagnosis of moderately differentiated HCC was injected with 11 C-acetate and imaged by PET/CT, followed by 18 F-fluorodeoxyglucose (FDG). Results: The synthesis yield of 11 C-acetate was (60.5 ± 8.7)% (decay conected, n=10); the radio-chemistry purity was > 98% and the synthesis time was 10 min from 11 CO 2 to 11 C-acetate. The radioactivity ratio for tumor/muscle was 1.76 at 30 min. A patient with known HCC showed positive 11 C-acetate accumulation in the tumor but was negative in 18 F-FDG. Conclusion: The synthesis of 11 C-acetate by modification of an 11 C-choline commercial module was feasible and it could be achieved with high yield, high radiochemical purity

  11. The determination of unchanged [11C]diprenorphine, [11C]L-deprenyl and [11C]raclopride in plasma by HPLC

    International Nuclear Information System (INIS)

    Luthra, S.K.; Turton, D.R.; Price, G.; Ahier, R.; Martin, F.; Hume, S.; Cremer, J.

    1990-01-01

    In PET studies a knowledge of the fraction of radioactivity in plasma representing unchanged 11 C-labelled ligand/tracer is essential for correction of the arterial plasma input curve. A number of different approaches (e.g. HPLC and TLC/OPTLC) to the determination of unchanged radio-ligand/tracer have been reported for 11 C-labelled carfentanil, raclopride and L-deprenyl and for 76 Br-labelled bromolisuride. The authors report here how they have applied the simple work-up and analytical procedure, originally reported for [ 11 C]carfentanil, to establish the percentage of unmchanged 11 C-labelled diprenorphine, L-deprenyl and raclopride in human and animal plasma as a function of time

  12. Reliable set-up for in-loop 11C-carboxylations using Grignard reactions for the preparation of [carbonyl-11C]WAY-100635 and [11C]-(+)-PHNO

    International Nuclear Information System (INIS)

    Rami-Mark, Christina; Ungersboeck, Johanna; Haeusler, Daniela; Nics, Lukas; Philippe, Cecile; Mitterhauser, Markus; Willeit, Matthaeus; Lanzenberger, Rupert; Karanikas, Georgios; Wadsak, Wolfgang

    2013-01-01

    Aim of this work was the implementation of a generalized in-loop synthesis for 11 C-carboxylations and subsequent 11 C-acylations on the TRACERlab FxC Pro platform. The set-up was tested using [carbonyl- 11 C]WAY-100635 and, for the first time, [ 11 C]-(+)-PHNO. Its general applicability could be demonstrated and both [carbonyl- 11 C]WAY-100635 and [ 11 C]-(+)-PHNO were prepared with high reliability and satisfying outcome. - Highlights: • Generalized method for in-loop 11 C-carboxylations implemented. • Grignard reactions successfully tested. • First in-loop procedure for [ 11 C]-(+)PHNO established. • Satisfactory synthesis outcome for both [carbonyl- 11 C]WAY-100635 and [ 11 C]-(+)PHNO. • No distillation for purification of intermediate required

  13. Positron emission tomography (PET) study of the alterations in brain distribution of [{sup 11}C]dethamphetamine in methamphetamine sensitized dog

    Energy Technology Data Exchange (ETDEWEB)

    Mizugaki, Michinao; Nakamura, Hitoshi; Hishinuma, Takanori; Tomioka, Yoshihisa; Ishiwata, Shunji; Suzuki, Hideaki; Ido, Tatsuo; Iwata, Ren; Funaki, Yoshihito; Itoh, Masatoshi; Fujiwara, Takehiko; Yanai, Kazuhiko; Sato, Mitsumoto; Numachi, Yohtaro; Yoshida, Sumiko

    1995-08-01

    [{sup 11}C]Methamphetamine ([{sup 11}C]MAP) was synthesized by an automated on-line [{sup 11}C]methylation system for positron emission tomography (PET) study. We newly produced a MAP sensitized dog by repeated MAP treatment and studied the brain distribution of [{sup 11}C]MAP in the normal and the MAP sensitized dog. The maximal level of accumulation of [{sup 11}C]MAP in the sensitized dog brain was 1.4 times higher than that in the control. No difference was found in the metabolism of MAP between the two conditions. The significant increase of [{sup 11}C]MAP in the MAP sensitized brain indicates that subchronic MAP administration causes some functional change in uptake site of MAP.

  14. Total Synthesis of Zoanthamine Alkaloids, Part 2. Construction of the C1-C5, C6-C10 and C11-C24 Fragments of Zoanthamine

    DEFF Research Database (Denmark)

    Tanner, David Ackland; Tedenborg, Lars; Somfai, Peter

    1997-01-01

    This paper describes the construction of three key intermediates for a projected total synthesis of the marine alkaloid zoanthamine. These building blocks, corresponding to the C1-C5, C6-C10 and C11-C24 fragments of the target molecule, are synthesised efficiently form (R...

  15. Reaction of 11 C-benzoyl chlorides with metalloid reagents: 11 C-labeling of benzyl alcohols, benzaldehydes, and phenyl ketones from [11 C]CO.

    Science.gov (United States)

    Roslin, Sara; Dahl, Kenneth; Nordeman, Patrik

    2018-01-26

    In this article, we describe the carbon-11 ( 11 C, t 1/2  = 20.4 minutes) labeling of benzyl alcohols, benzaldehydes, and ketones using an efficient 2-step synthesis in which 11 C-carbon monoxide is used in an initial palladium-mediated reaction to produce 11 C-benzoyl chloride as a key intermediate. In the second step, the obtained 11 C-benzoyl chloride is further treated with a metalloid reagent to furnish the final 11 C-labeled product. Benzyl alcohols were obtained in moderated to high non-isolated radiochemical yields (RCY, 35%-90%) with lithium aluminum hydride or lithium aluminum deuteride as metalloid reagent. Changing the metalloid reagent to either tributyltin hydride or sodium borohydride, allowed for the reliable syntheses of 11 C-benzaldehydes in RCYs ranging from 58% to 95%. Finally, sodium tetraphenylborate were utilized to obtain 11 C-phenyl ketones in high RCYs (77%-95%). The developed method provides a new and efficient route to 3 different classes of compounds starting from aryl iodides or aryl bromides. Copyright © 2018 John Wiley & Sons, Ltd.

  16. Automated radiochemical synthesis and biodistribution of [11C]l-α-acetylmethadol ([11C]LAAM)

    International Nuclear Information System (INIS)

    Sai, Kiran Kumar Solingapuram; Fan, Jinda; Tu, Zhude; Zerkel, Patrick; Mach, Robert H.; Kharasch, Evan D.

    2014-01-01

    Long-acting opioid agonists methadone and l-α-acetylmethadol (LAAM) prevent withdrawal in opioid-dependent persons. Attempts to synthesize [ 11 C]-methadone for PET evaluation of brain disposition were unsuccessful. Owing, however, to structural and pharmacologic similarities, we aimed to develop [ 11 C]LAAM as a PET ligand to probe the brain exposure of long-lasting opioids in humans. This manuscript describes [ 11 C]LAAM synthesis and its biodistribution in mice. The radiochemical synthetic strategy afforded high radiochemical yield, purity and specific activity, thereby making the synthesis adaptable to automated modules. - Highlights: • Radiochemical synthesis of opioid [ 11 C]l-α-acetylmethadol (LAAM) described for the first time. • High radiochemical yield, purity and specific activity. • Easily reproducible and adaptable synthesis to any C-11 automated modules. • [ 11 C]LAAM utility as a PET radiopharmaceutical for assessing brain penetration

  17. [11C]copper(I) cyanide: a new radioactive precursor or 11C-cyanation and functionalization of haloarenes

    International Nuclear Information System (INIS)

    Ponchant, M.; Hinnen, F.; Demphel, S.; Crouzel, C.

    1997-01-01

    Radiosyntheses of [cyano- 11 C]benzonitriles, [carboyxyl- 11 C]benzoic acids, [carbonyl- 11 C]benzamides and [tetrazoyl- 11 C]5-biphenyl-1H-tetrazoles are described. [Cyano- 11 C]benzonitriles were prepared using the Rosenmund-von Braun reaction in one step from [ 11 C]hydrogen cyanide via [ 11 C]copper(1) cyanide in 2 min. [Carboxyl- 11 C]benzoic acids and [carbonyl- 11 C]benzamides were prepared from [cyano- 11 C]benzonitrile-complexes using basic hydrogen peroxide for 3 min in N,N-dimethylformamide at 180 and 80 o C, respectively. [Tetrazoyl- 11 C]5-biphenyl-1H-tetrazoles were obtained from [cyano- 11 C]benzonitrile-complexes in 7 min by cyclization with trimethyltin azide followed by acid hydrolysis at 180 o C. These labelled compounds were obtained in a one-pot procedure with good average specific radioactivities [500 mCi/μmol) at the end of synthesis] and in satisfactory average radiochemical yields (24-69%) at 40 min from the end of radionuclide production. This new radioactive precursor, [ 11 C]copper(I) cyanide, should give access to new 11 C-labelled ligands for positron emission tomography. (author)

  18. Effective modern C++ 42 specific ways to improve your use of C++11 and C++14

    CERN Document Server

    Meyers, Scott

    2015-01-01

    At first glance, C++11 and C++14 are defined by the new features they introduce, e.g., auto type declarations, move semantics, lambda expressions, and concurrency support. Information on these features is easy to come by, but learning to apply them effectively (such that the resulting software is correct, efficient, maintainable, and portable) is more challenging. That’s the role of this book. It describes how to write effective software using C++11 and C++14, i.e., using modern C++. Topics include: * The pros and cons of uniform initialization, noexcept specifications, perfect forwarding, and smart pointer make functions. * The relationships among std::move, std::forward, rvalues references, and universal references. * The most effective forms of lambda capture. * How best practices in “old” C++ programming (i.e., C++98) require revision for modern C++. Effective Modern C++ follows the proven format of Scott Meyers’ earlier Effective books (Effective C++, More Effective C++, and Effective STL), but c...

  19. In vivo evaluation of alpha7 nicotinic acetylcholine receptor agonists [11C]A-582941 and [11C]A-844606 in mice and conscious monkeys.

    Directory of Open Access Journals (Sweden)

    Jun Toyohara

    Full Text Available BACKGROUND: The alpha7 nicotinic acetylcholine receptors (nAChRs play an important role in the pathophysiology of neuropsychiatric diseases such as schizophrenia and Alzheimer's disease. The goal of this study was to evaluate the two carbon-11-labeled alpha7 nAChR agonists [(11C]A-582941 and [(11C]A-844606 for their potential as novel positron emission tomography (PET tracers. METHODOLOGY/PRINCIPAL FINDINGS: The two tracers were synthesized by methylation of the corresponding desmethyl precursors using [(11C]methyl triflate. Effects of receptor blockade in mice were determined by coinjection of either tracer along with a carrier or an excess amount of a selective alpha7 nAChR agonist (SSR180711. Metabolic stability was investigated using radio-HPLC. Dynamic PET scans were performed in conscious monkeys with/without SSR180711-treatment. [(11C]A-582941 and [(11C]A-844606 showed high uptake in the mouse brain. Most radioactive compounds in the brain were detected as an unchanged form. However, regional selectivity and selective receptor blockade were not clearly observed for either compound in the mouse brain. On the other hand, the total distribution volume of [(11C]A-582941 and [(11C]A-844606 was high in the hippocampus and thalamus but low in the cerebellum in the conscious monkey brain, and reduced by pretreatment with SSR180711. CONCLUSIONS/SIGNIFICANCE: A nonhuman primate study suggests that [(11C]A-582941 and [(11C]A-844606 would be potential PET ligands for imaging alpha7 nAChRs in the human brain.

  20. Synthesis of [11C]-Sarin

    International Nuclear Information System (INIS)

    Prenant, C.; Crouzel, C.

    1990-01-01

    [ 11 C]-acetone, prepared from 11 CO 2 and methyllithium, was reduced to [ 11 C]-isopropanol. The latter reacted with methylphosphonic acid difluoride in the presence of diisopropylamine, to yield [11C]-sarin. 3.4 GBq (100 mCi) of [ 11 C]-sarin may be obtained from about 55.5 GBq (1.5 Ci) of 11 CO 2 in 40 minutes. The product purified by HPLC, is obtained with a specific radioactivity ranging from 22.2 to 33.3 GBq (600 to 900 mCi/μmol.). (author)

  1. Automated synthesis of 11C-carfentanil with 11C-choline module and micro PET imaging

    International Nuclear Information System (INIS)

    Zhang Jinming; Zhang Xiaojun; Tian Jiahe; Xu Zhihong; Xiang Xiaohui

    2011-01-01

    A simple modified home-made 11 C-choline module enabled to rapid and efficient synthesis 11 C-carfentanil ( 11 C-CFN) as CNS μ-opioid receptor imaging agent. The synthesis of 11 C-CFN was completed in a yield of 14.8 GBq within 18 min from 11 C-CO 2 on the choline module. The methylation took place from 4-piperidinecarboxylic acid, 4-[(1-oxopropyl) phenylamino]-l-(2-phenylethyl), sodium salt as precursor in DMSO solution. The radio- chemical yields were over 80% (n=55, decay-corrected and based on 11 CH 3 -triflate). The radiochemical purity was over 95% and the specific activities was over 1.4 × 10 14 Bq/g. The biologic activity of 11 C-CFN was confirmed with Micro PET/CT imaging. (authors)

  2. In vivo positron emission tomography studies on the novel nicotinic receptor agonist [11C]MPA compared with [11C]ABT-418 and (S)(-)[11C]nicotine in Rhesus monkeys

    International Nuclear Information System (INIS)

    Sihver, Wiebke; Fasth, Karl-Johan; Oegren, Matthias; Lundqvist, Hans; Bergstroem, Mats; Watanabe, Yasuyoshi; Laangstroem, Bengt; Nordberg, Agneta

    1999-01-01

    The novel 11 C-labeled nicotinic agonist (R,S)-1-[ 11 C]methyl-2(3-pyridyl)azetidine ([ 11 C]MPA) was evaluated as a positron emission tomography (PET) ligand for in vivo characterization of nicotinic acetylcholine receptors in the brain of Rhesus monkeys in comparison with the nicotinic ligands (S)-3-methyl-5-(1-[ 11 C]methyl-2-pyrrolidinyl)isoxazol ([ 11 C]ABT-418) and (S)(-)[ 11 C]nicotine. The nicotinic receptor agonist [ 11 C]MPA demonstrated rapid uptake into the brain to a similar extent as (S)(-) [ 11 C]nicotine and [ 11 C]ABT-418. When unlabeled (S)(-)nicotine (0.02 mg/kg) was administered 5 min before the radioactive tracers, the uptake of [ 11 C]MPA was decreased by 25% in the thalamus, 19% in the temporal cortex, and 11% in the cerebellum, whereas an increase was found for the uptake of (S)(-)[ 11 C]nicotine and [ 11 C]ABT-418. This finding indicates specific binding of [ 11 C]MPA to nicotinic receptors in the brain in a simple classical displacement study. [ 11 C]MPA seems to be a more promising radiotracer than (S)(-)[ 11 C]nicotine or [ 11 C]ABT-418 for PET studies to characterize nicotinic receptors in the brain

  3. Protogalaxy interactions in newly formed clusters: Galaxy luminosities, colors, and intergalactic gas

    International Nuclear Information System (INIS)

    Silk, J.

    1978-01-01

    The role of protogalaxy interactions in galactic evolution is studied during the formation of galaxy clusters. In the early stages of the collapse, coalescent encounters of protogalaxies lead to the development of a galactic luminosity function. Once galaxies acquire appreciable random motions, mutual collisions between galaxies in rich clusters will trigger the collapse of interstellar clouds to form stars. This provides both a source for enriched intracluster gas and an interpretation of the correlation between luminosity and color for cluster elliptical galaxies. Other observational consequences that are considered include optical, X-ray, and diffuse nonthermal radio emission from newly formed clusters of galaxies

  4. Cloning of cDNA encoding steroid 11β-hydroxylase (P450c11)

    International Nuclear Information System (INIS)

    Chua, S.C.; Szabo, P.; Vitek, A.; Grzeschik, K.H.; John, M.; White, P.C.

    1987-01-01

    The authors have isolated bovine and human adrenal cDNA clones encoding the adrenal cytochrome P-450 specific for 11β-hydroxylation (P450c11). A bovine adrenal cDNA library constructed in the bacteriophage λ vector gt10 was probed with a previously isolated cDNA clone corresponding to part of the 3' untranslated region of the 4.2-kilobase (kb) mRNA encoding P450c11. Several clones with 3.2-kb cDNA inserts were isolated. Sequence analysis showed that they overlapped the original probe by 300 base pairs (bp). Combined cDNA and RNA sequence data demonstrated a continuous open reading frame of 1509 bases. P450c11 is predicted to contain 479 amino acid residues in the mature protein in addition to a 24-residue amino-terminal mitochondrial signal sequence. A bovine clone was used to isolate a homologous clone with a 3.5-kb insert from a human adrenal cDNA library. A region of 1100 bp was 81% homologous to 769 bp of the coding sequence of the bovine cDNA except for a 400-bp segment presumed to be an unprocessed intron. Hybridization of the human cDNA to DNA from a panel of human-rodent somatic cell hybrid lines and in situ hybridization to metaphase spreads of human chromosomes localized the gene to the middle of the long arm of chromosome 8. These data should be useful in developing reagents for heterozygote detection and prenatal diagnosis of 11β-hydroxylase deficiency, the second most frequent cause of congenital adrenal hyperplasia

  5. Preparation of [11C]diethyl oxalate and [11C]oxalic acid and demonstration of their use in the synthesis of [11C]-2,3-dihydroxyquinoxaline

    International Nuclear Information System (INIS)

    Thorell, J.-O.; Stone-Elander, S.

    1993-01-01

    A method for the production of two new carbon-11 labelled difunctional radiolabelling precursors, [ 11 C]diethyl oxalate,2, and [ 11 C]oxalic acid, 3 is described. Methyl chloroformate was reacted with no-carrier-added [ 11 C]cyanide to generate the intermediate nitrile, methyl [ 11 C]cyanoformate. Alcoholysis with HC1 in ethanol generated 2, which could subsequently be converted to 3 with aqueous acid. The total time of preparation from end-or-trapping of [ 11 C]cyanide was 6-7 min using combined microwave and thermal treatment or, by exclusively thermal treatment, 15 and 20 min for 2 and 3, respectively. The radiochemical conversion of [ 11 C]cyanide to 2 and 3 was ∼ 80% and ∼ 70%, respectively. Both 2 and 3 were used in a model reaction with 1,2-phenylenediamine to synthesize the heterocyclic compound, 2,3-dihydroxyquinoxaline, a basic structural unit in antagonists for the excitatory amino acid receptor system. (Author)

  6. Radiosynthesis of the D2/3 agonist [3-11C]-(+)-PHNO using [11C]iodomethane

    International Nuclear Information System (INIS)

    Francisco Garcia-Arguello, Segundo; Fortt, Robin; Steel, Colin J.; Brickute, Diana; Glaser, Matthias; Turton, David R.; Robins, Edward G.; Årstad, Erik; Luthra, Sajinder K.

    2013-01-01

    We report here a radiosynthesis for the D 2/3 agonist (+)-4-([3- 11 C]propyl)-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4] oxazin-9-ol (3-[ 11 C]-(+)-PHNO) labelled at the terminal carbon of the N-propyl chain. The protocol is based on 11 C-methylation of an N-acetyl precursor. This initial step is followed by a reduction with LiAlH 4 to give ([3- 11 C]-(+)-PHNO). We first applied the method for the synthesis of a model compound, N-3-([ 11 C]propyl)-1,2,3,4-tetrahydroisoquinoline, which we obtained in 77–97% analytical radiochemical yield (n=6) in 20 min. Similarly, we prepared ([3- 11 C]-(+)-PHNO) in 55–60% analytical radiochemical yield (n=5) using a one-pot procedure. We have also been able to implement the complete process on a semi-automated module. This platform delivered purified and formulated [3- 11 C]PHNO with an average radiochemical yield of 9% (n=13, range 2–30%, non-decay corrected), a radiochemical purity >95%, and a specific radioactivity of 26.8–81.1 GBq/μmol in a total time of 63–65 min. - Highlights: ► We report an alternative method to obtain carbon-11 labelled PHNO. ► The method is based on readily available [ 11 C]methyl iodide as starting material. ► We have automated the alkylation/reduction protocol including purification and formulation

  7. Synthesis of some 11C-labelled alkaloids

    International Nuclear Information System (INIS)

    Laangstroem, B.; Antoni, G.; Halldin, H.; Svaerd, H.; Bergson, G.

    1982-01-01

    Using ( 11 C)-methyl iodide in N-alkylation reactions in dimethylformamide (DMF), the alkaloids N-( 11 C-methyl)-morphine, N-( 11 C-methyl)-codeine, 6-N(methyl)-9, 10-dihydroergotamine, 6-N-( 11 C-methyl)-bromocriptine and N-( 11 C-methyl)-nicotine have been synthesized in radiochemical yields of 50-95%, within 5-10 min of introducing ( 11 C)-methyl iodide into the reaction vial. ( 11 C)-Methyl iodide was obtained within 4-7 min from ( 11 C)-carbon dioxide prepared by the 14 N(p,α) 11 C reaction. (Authors)

  8. C-11 production with MC-50 cyclotron and synthesis of L-[11C-methyl] methionine

    International Nuclear Information System (INIS)

    Kim, Sang Wook; Hur, Min Goo; Yang, Seung Dae; Ahn, Soon Hyuk; Chun, Kweon Soo

    2003-01-01

    L-[ 11 C-methyl] methionine was prepared via no-carrier-added(nca) fast S-alkylation of L-homocysteine with [ 11 C]CH 3 I using solid support (Al 2 O 3 /KF)at room temperature in ethanol. The radiochemical yield of methylation was 90.2%. After reaction, no radiochemical impurity was detected but traces of L-homocysteine precursor were monitored by UV detector. The purification was archived by passing successively through a C 18 and alumina sep-pak. the radiochemical purity of L-[ 11 C-methyl] methionine was over 98% after purification and total elapsed time to prepare was 10min from [ 11 C]CH 3 I delivery

  9. Localization of foot-and-mouth disease - RNA synthesis on newly formed cellular smooth membranous vacuoles

    International Nuclear Information System (INIS)

    Polatnick, J.; Wool, S.H.

    1982-01-01

    Viral RNA synthesis in foot-and-mouth disease infected bovine kidney cell cultures was associated throughout the infectious period with newly formed smooth membranous vacuoles. Membrane formation was measured by choline uptake. The site of RNA synthesis was determined by electron microscopic examination of autoradiograms of incorporated [ 3 H] uridine. Both membrane formation and RNA synthesis became signifcant at 2.5 hours postinfection, but membrane formation increased steadily to 4.5 hours while RNA synthesis peaked at 3.5 hours. Percent density distributions of developed silver grains on autoradiograms showed that almost all RNA synthesis was concentrated on the smooth vacuoles of infected cells. Histogram analysis of grain density distributions established that the site of RNA synthesis was the vacuolar membrane. The newly formed smooth membrane-bound vacuoles were not seen to coalesce into the large vacuolated areas typical of poliovirus cytopathogenicity. (Author)

  10. Localization of foot-and-mouth disease - RNA synthesis on newly formed cellular smooth membranous vacuoles

    Energy Technology Data Exchange (ETDEWEB)

    Polatnick, J.; Wool, S.H. (United States Department of Agriculture, Science and Education, Greenport, New York (USA). Agricultural Research, Plum Island Animal Disease Center)

    1982-01-01

    Viral RNA synthesis in foot-and-mouth disease infected bovine kidney cell cultures was associated throughout the infectious period with newly formed smooth membranous vacuoles. Membrane formation was measured by choline uptake. The site of RNA synthesis was determined by electron microscopic examination of autoradiograms of incorporated (/sup 3/H) uridine. Both membrane formation and RNA synthesis became signifcant at 2.5 hours postinfection, but membrane formation increased steadily to 4.5 hours while RNA synthesis peaked at 3.5 hours. Percent density distributions of developed silver grains on autoradiograms showed that almost all RNA synthesis was concentrated on the smooth vacuoles of infected cells. Histogram analysis of grain density distributions established that the site of RNA synthesis was the vacuolar membrane. The newly formed smooth membrane-bound vacuoles were not seen to coalesce into the large vacuolated areas typical of poliovirus cytopathogenicity.

  11. EXPERIMENTAL INVESTIGATION OF THE ORTHO/PARA RATIO OF NEWLY FORMED MOLECULAR HYDROGEN ON AMORPHOUS SOLID WATER

    International Nuclear Information System (INIS)

    Gavilan, L.; Lemaire, J. L.; Dulieu, F.; Congiu, E.; Chaabouni, H.; Vidali, G.; Chehrouri, M.; Fillion, J.-H.

    2012-01-01

    Several astronomical observations have shown that the ortho/para ratio (OPR) of H 2 can differ from the expected statistical value of 3 or the local thermodynamic equilibrium (LTE) value at the gas or dust temperature. It is thus important to know the OPR of H 2 newly formed on dust grain surfaces, in order to clarify the dependence of the observed OPR in space on the formation process. Using an experimental setup designed to mimic interstellar medium environments, we measured the OPR of H 2 and D 2 formed on the surface of porous amorphous water ice held at 10 K. We report for the first time the OPR value for newly formed D 2 , consistent with the expected LTE value at the high-temperature limit found by previous theoretical and experimental works on the determination of the OPR upon H 2 formation on surfaces at low temperature.

  12. Carbon-11 labelling of an inhibitor of acetylcholinesterase: [11C]physostigmine

    International Nuclear Information System (INIS)

    Bonnot-Lours, S.; Crouzel, C.; Prenant, C.; Hinnen, F.

    1993-01-01

    Physostigmine, an alkaloid from calabar bean is a strong inhibitor of acetylcholinesterase and has been used clinically in the treatment of glaucoma, atropine intoxication, myasthenia gravis and more recently, in experimental trials in Alzheimer's disease. In order to study the AChE activity in the brain by positron emission tomography, we have undertaken the labelling of physostigmine with carbon-11. The synthesis involves the reaction of [ 11 C]methylisocyanate with eseroline. [ 11 C]Methylisocyanate was obtained by heating [ 11 C]acetylchloride with tetrabutylammonium azide in toluene. The synthesis of [ 11 C]CH 3 COC1 involves the carbonation of methylmagnesium bromide in THF with cyclotron produced [ 11 C]carbon dioxide and the addition of phthaloyl dichloride. The [ 11 C]methylisocyanate is distilled into a solution of eseroline in ether with a small piece of sodium. After 10 minutes at 25 o C, the solution is purified by HPLC and the appropriate fraction collected. Starting with 55.5 GBq (1.5 Ci) of [ 11 C]carbon dioxide, 0.92-1.48 GBq (25-40 mCi) of [ 11 C]Physostigmine are obtained 57 minutes after EOB. (author)

  13. Synthesis of O-[11C]acetyl CoA, O-[11C]acetyl-L-carnitine, and L-[11C]carnitine labelled in specific positions, applied in PET studies on rhesus monkey

    International Nuclear Information System (INIS)

    Jacobson, Gunilla B.; Watanabe, Yasuyoshi; Valind, Sven; Kuratsune, Hirohiko; Laangstroem, Bengt

    1997-01-01

    The syntheses of L-carnitine, O-acetyl CoA, and O-acetyl-L-carnitine labelled with 11 C at the 1- or 2-position of the acetyl group or the N-methyl position of carnitine, using the enzymes acetyl CoA synthetase and carnitine acetyltransferase, are described. With a total synthesis time of 45 min, O-[1- 11 C]acetyl CoA and O-[2- 11 C]acetyl CoA was obtained in 60-70% decay-corrected radiochemical yield, and O-[1- 11 C]acetyl-L-carnitine and O-[2- 11 C]acetyl-L-carnitine in 70-80% yield, based on [1- 11 C]acetate or [2- 11 C]acetate, respectively. By an N-methylation reaction with [ 11 C]methyl iodide, L-[methyl- 11 C]carnitine was obtained within 30 min, and O-acetyl-L-[methyl- 11 C]carnitine within 40 min, giving a decay-corrected radiochemical yield of 60% and 40-50%, respectively, based on [ 11 C]methyl iodide. Initial data of the kinetics of the different 11 C-labelled L-carnitine and acetyl-L-carnitines in renal cortex of anaesthetized monkey (Macaca mulatta) are presented

  14. Synthesis of[11C]LY186126, an inhibitor of phosphodiesterase

    International Nuclear Information System (INIS)

    Prenant, C.; Crouzel, C.; Comar, D.; Robertson, D.W.

    1992-01-01

    LY186126 [1,3-dihydro-1,3,3-trimethyl-5-(1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyriddazinyl)-2H-indol-2-one ], an analogue of the cardiotonic agent indolidan, is a potent, selective and competitive inhibitor of an isozymic form of cyclic AMP phosphodiesterase. LY186126 was labelled with carbon-11 to permit pharmacological studies in the dog myocardium by positron emission tomography. Alkylation with [ 11 C]methyl iodide of N-norLY186126 (LY-197055) allowed the production of 1.7 GBq (50mCi) of [ 11 C]LY-186126 in 40 min. The product, was purified by HPLC. (author)

  15. Semi-automated preparation of a 11C-labelled antibiotic - [N-methyl-11C]erythromycin A lactobionate

    International Nuclear Information System (INIS)

    Pike, V.W.; Palmer, A.J.; Horlock, P.L.; Liss, R.H.

    1984-01-01

    A fast semi-automated method is described for labelling the antibiotic, erythromycin A (1), with the short-lived positron-emitting radionuclide, 11 C(tsub(1/2)=20.4 min), in order to permit the non-invasive study of its tissue uptake in vivo. Labelling was achieved by the fast reductive methylation of N-demethylerythromycin A (2) with [ 11 C]formaldehyde, itself prepared from cyclotron-produced [ 11 C]-carbon dioxide. Rapid chemical and radiochemical purification of the [N-methyl- 11 C]erythromycin A (3) were achieved by HPLC and verified by TLC with autoradiography. The purified material was formulated for human i.v. injection as a sterile apyrogenic solution of the lactobionate salt. The preparation takes 42 min from the end of radionuclide production and from [ 11 C]carbon dioxide produces [N-methyl- 11 C]erythromycin A lactobionate in 4-12% radiochemical yield, corrected for radioactive decay. (author)

  16. EXPERIMENTAL INVESTIGATION OF THE ORTHO/PARA RATIO OF NEWLY FORMED MOLECULAR HYDROGEN ON AMORPHOUS SOLID WATER

    Energy Technology Data Exchange (ETDEWEB)

    Gavilan, L.; Lemaire, J. L.; Dulieu, F.; Congiu, E.; Chaabouni, H. [LERMA, UMR 8112 du CNRS, de l' Observatoire de Paris et de l' Universite de Cergy Pontoise, 5 mail Gay Lussac, F-95000 Cergy Pontoise Cedex (France); Vidali, G. [Visiting Professor. Permanent address: Physics Department, Syracuse University, Syracuse, NY 13244-1320 (United States); Chehrouri, M. [Permanent address: LEPC Universite de Saida, BP138, ENSAR, 20002 Saida (Algeria); Fillion, J.-H., E-mail: lisseth.gavilan@obspm.fr [Permanent address: LPMAA, UMR 7092, Universite Pierre et Marie Curie, F-75252 Paris Cedex 05 (France)

    2012-11-20

    Several astronomical observations have shown that the ortho/para ratio (OPR) of H{sub 2} can differ from the expected statistical value of 3 or the local thermodynamic equilibrium (LTE) value at the gas or dust temperature. It is thus important to know the OPR of H{sub 2} newly formed on dust grain surfaces, in order to clarify the dependence of the observed OPR in space on the formation process. Using an experimental setup designed to mimic interstellar medium environments, we measured the OPR of H{sub 2} and D{sub 2} formed on the surface of porous amorphous water ice held at 10 K. We report for the first time the OPR value for newly formed D{sub 2}, consistent with the expected LTE value at the high-temperature limit found by previous theoretical and experimental works on the determination of the OPR upon H{sub 2} formation on surfaces at low temperature.

  17. One column method to prepare 11C-labelled methyl iodide

    International Nuclear Information System (INIS)

    Kovacs, Z.; Priboczki, E.

    1999-01-01

    A new method in which the [ 11 C]methyl iodide is prepared on one alumina column is presented. A high specific surface alumina column, previously impregnated with lithium aluminium hydride solution, was used for direct trapping from the target gas and reduction into radiocomplex. The complex was then reacted on this column with HI to form [ 11 C]methyl iodide. The use of one alumina column, instead of a freezing trap, reaction vessel and separate unit for iodination, simplifies the apparatus, shortens the synthesis time and is well suitable for automation. (K.A.)

  18. Synthesis and preclinical evaluation of [11C]D617, a metabolite of (R)-[11C]verapamil

    NARCIS (Netherlands)

    Verbeek, Joost; Syvänen, Stina; Schuit, Robert C.; Eriksson, Jonas; de Lange, Elizabeth C M; Windhorst, Albert D.; Luurtsema, Gert; Lammertsma, Adriaan A.

    2012-01-01

    OBJECTIVES: (R)-[(11)C]verapamil is widely used as a positron emission tomography (PET) tracer to evaluate P-glycoprotein (P-gp) functionality at the blood-brain barrier in man. A disadvantage of (R)-[(11)C]verapamil is the fact that its main metabolite, [(11)C]D617, also enters the brain. For

  19. Synthesis of [11C]-ohmefentanyl, a novel, highly potent and selective agonist for opiate μ-receptors

    International Nuclear Information System (INIS)

    Zhu, Y.C.; Academia Sinica, Shangha, SH; Prenant, C.; Crouzel, C.; Comar, D.; Chi, Z.Q.

    1992-01-01

    We describe the synthesis of 11 C-ohmefentanyl, a novel, highly potent and selective agonist for opiate μ-receptors, to be visualized by Positron Emission Tomography (PET). The unlabelled cis-A-ohmefentanyl was prepared in a nine-step synthesis and two-step fractional crystallization, and the OH-precursor for [ 11 C]-ohmefentanyl labelling was obtained by hydrolysis of the 4-N-propionyl group of cis-A-ohmefentanyl in 6 N hydrochloric acid. The [ 11 C]-propionyl chloride was prepared by carbonation of ethylmagnesium bromide with cyclotron-produced [ 11 C]-carbon dioxide followed by direct treatment of the intermediate complex with phthaloyl dichloride and 2,6-di-t-butylpyridine. Reaction of the OH-precursor with [ 11 C]-propionyl chloride yields [ 11 C]-ohmefentanyl separated by HPLC, with a high specific activity of 300-400 mCi μmol -1 . The keto-precursor prepared by hydrolysis of the 4-N-propionyl group of cis-10 in 8 N hydrochloric acid, was also used for [ 11 C]-ohmefentanyl labelling. Reaction of the [ 11 C]-propionyl chloride with keto-precursor, followed by addition of sodium borohydride, yields [ 11 C]-ohmefentanyl. The [ 11 C]-labelled ohmefentanyl obtained using the OH-precursor is a cis-A form, while that obtained using the keto-precursor is a mixture of cis-A and cis-B forms. (author)

  20. Critical opalescence of the nuclear pion field: A possible evidence in the M1 (15.11 MeV) form factor of 12C

    International Nuclear Information System (INIS)

    Delorme, J.; Figureau, A.; Giraud, N.

    1980-01-01

    We have computed the nuclear pion field for the transition to the 15.11 MeV (1 + , T = 1) state of 12 C, evaluating the nuclear polarization with a large basis of nucleon- and isobar-hole excitations. The field shows an enhancement (or critical opalescence) in the momentum region beyond 1.5 msub(π) which leads to a substantial increase of the second maximum of the M1 form factor. Agreement with experiment can be obtained if the 12 C nucleus is much closer to the condensation threshold than currently expected. (orig.)

  1. Critical opalescence of the nuclear pion field: a possible evidence in the M1 (15.11 MeV) form factor of 12C

    International Nuclear Information System (INIS)

    Delorme, J.; Ericson, M.; Figureau, A.; Giraud, N.

    1979-07-01

    The nuclear pion field for the transition to the 15.11 MeV (1 + , T= 1) state of 12 C has been computed, evaluating the nuclear polarization with a large basis of nucleon- and isobar-hole excitations. The field shows an enhancement (or critical opalescence) in the momentum region beyond 1.5msub(π) which leads to a substantial increase of the second maximum of the M1 form factor. Agreement with experiment can be obtained if the 12 C nucleus is much closer to the pion condensation threshold than currently expected

  2. Preparation of [[sup 11]C]diethyl oxalate and [[sup 11]C]oxalic acid and demonstration of their use in the synthesis of [[sup 11]C]-2,3-dihydroxyquinoxaline

    Energy Technology Data Exchange (ETDEWEB)

    Thorell, J -O; Stone-Elander, S [Karolinska Pharmacy, Stockholm (Sweden) Karolinska Hospital and Institute, Stockholm (Sweden). Dept. of Clinical Neurophysiology; Elander, N [Manne Siegbahn Inst. of Physics, Stockholm (Sweden)

    1993-11-01

    A method for the production of two new carbon-11 labelled difunctional radiolabelling precursors, [[sup 11]C]diethyl oxalate,2, and [[sup 11]C]oxalic acid, 3 is described. Methyl chloroformate was reacted with no-carrier-added [[sup 11]C]cyanide to generate the intermediate nitrile, methyl [[sup 11]C]cyanoformate. Alcoholysis with HC1 in ethanol generated 2, which could subsequently be converted to 3 with aqueous acid. The total time of preparation from end-or-trapping of [[sup 11]C]cyanide was 6-7 min using combined microwave and thermal treatment or, by exclusively thermal treatment, 15 and 20 min for 2 and 3, respectively. The radiochemical conversion of [[sup 11]C]cyanide to 2 and 3 was [approx] 80% and [approx] 70%, respectively. Both 2 and 3 were used in a model reaction with 1,2-phenylenediamine to synthesize the heterocyclic compound, 2,3-dihydroxyquinoxaline, a basic structural unit in antagonists for the excitatory amino acid receptor system. (Author).

  3. 26 CFR 11.412(c)-11 - Election with respect to bonds.

    Science.gov (United States)

    2010-04-01

    ... amount payable at maturity (or, in the case of a bond which is callable prior to maturity, the earliest... 26 Internal Revenue 14 2010-04-01 2010-04-01 false Election with respect to bonds. 11.412(c)-11... OF 1974 § 11.412(c)-11 Election with respect to bonds. (a) In general. Section 412(c)(2)(B) provides...

  4. 11 CFR 100.11 - State (2 U.S.C. 431(12)).

    Science.gov (United States)

    2010-01-01

    ... 11 Federal Elections 1 2010-01-01 2010-01-01 false State (2 U.S.C. 431(12)). 100.11 Section 100.11 Federal Elections FEDERAL ELECTION COMMISSION GENERAL SCOPE AND DEFINITIONS (2 U.S.C. 431) General Definitions § 100.11 State (2 U.S.C. 431(12)). State means each State of the United States, the District of...

  5. Carbon-11 labelling of an inhibitor of acetylcholinesterase: [[sup 11]C]physostigmine

    Energy Technology Data Exchange (ETDEWEB)

    Bonnot-Lours, S.; Crouzel, C.; Prenant, C.; Hinnen, F. (CEA, 91 - Orsay (France). Service Hospitalier Frederic Joliot)

    1993-01-01

    Physostigmine, an alkaloid from calabar bean is a strong inhibitor of acetylcholinesterase and has been used clinically in the treatment of glaucoma, atropine intoxication, myasthenia gravis and more recently, in experimental trials in Alzheimer's disease. In order to study the AChE activity in the brain by positron emission tomography, we have undertaken the labelling of physostigmine with carbon-11. The synthesis involves the reaction of [[sup 11]C]methylisocyanate with eseroline. [[sup 11]C]Methylisocyanate was obtained by heating [[sup 11]C]acetylchloride with tetrabutylammonium azide in toluene. The synthesis of [[sup 11]C]CH[sub 3]COC1 involves the carbonation of methylmagnesium bromide in THF with cyclotron produced [[sup 11]C]carbon dioxide and the addition of phthaloyl dichloride. The [[sup 11]C]methylisocyanate is distilled into a solution of eseroline in ether with a small piece of sodium. After 10 minutes at 25[sup o]C, the solution is purified by HPLC and the appropriate fraction collected. Starting with 55.5 GBq (1.5 Ci) of [[sup 11]C]carbon dioxide, 0.92-1.48 GBq (25-40 mCi) of [[sup 11]C]Physostigmine are obtained 57 minutes after EOB. (author).

  6. PET imaging of focal demyelination and remyelination in a rat model of multiple sclerosis: comparison of [{sup 11}C]MeDAS, [{sup 11}C]CIC and [{sup 11}C]PIB

    Energy Technology Data Exchange (ETDEWEB)

    Paula Faria, Daniele de [University of Groningen, University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, Groningen (Netherlands); University of Groningen, University Medical Center Groningen, Department of Neuroscience, Groningen (Netherlands); University of Sao Paulo Medical School, Center of Nuclear Medicine, Sao Paulo (Brazil); Copray, Sjef [University of Groningen, University Medical Center Groningen, Department of Neuroscience, Groningen (Netherlands); Sijbesma, Jurgen W.A.; Willemsen, Antoon T.M.; Dierckx, Rudi A.J.O.; Vries, Erik F.J. de [University of Groningen, University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, Groningen (Netherlands); Buchpiguel, Carlos A. [University of Sao Paulo Medical School, Center of Nuclear Medicine, Sao Paulo (Brazil)

    2014-05-15

    In this study, we compared the ability of [{sup 11}C]CIC, [{sup 11}C]MeDAS and [{sup 11}C]PIB to reveal temporal changes in myelin content in focal lesions in the lysolecithin rat model of multiple sclerosis. Pharmacokinetic modelling was performed to determine the best method to quantify tracer uptake. Sprague-Dawley rats were stereotactically injected with either 1 % lysolecithin or saline into the corpus callosum and striatum of the right brain hemisphere. Dynamic PET imaging with simultaneous arterial blood sampling was performed 7 days after saline injection (control group), 7 days after lysolecithin injection (demyelination group) and 4 weeks after lysolecithin injection (remyelination group). The kinetics of [{sup 11}C]CIC, [{sup 11}C]MeDAS and [{sup 11}C]PIB was best fitted by Logan graphical analysis, suggesting that tracer binding is reversible. Compartment modelling revealed that all tracers were fitted best with the reversible two-tissue compartment model. Tracer uptake and distribution volume in lesions were in agreement with myelin status. However, the slow kinetics and homogeneous brain uptake of [{sup 11}C]CIC make this tracer less suitable for in vivo PET imaging. [{sup 11}C]PIB showed good uptake in the white matter in the cerebrum, but [{sup 11}C]PIB uptake in the cerebellum was low, despite high myelin density in this region. [{sup 11}C]MeDAS distribution correlated well with myelin density in different brain regions. This study showed that PET imaging of demyelination and remyelination processes in focal lesions is feasible. Our comparison of three myelin tracers showed that [{sup 11}C]MeDAS has more favourable properties for quantitative PET imaging of demyelinated and remyelinated lesions throughout the CNS than [{sup 11}C]CIC and [{sup 11}C]PIB. (orig.)

  7. Evaluation of (+)-p-[11C]methylvesamicol for mapping sigma1 receptors: a comparison with [11C]SA4503

    International Nuclear Information System (INIS)

    Ishiwata, Kiichi; Kawamura, Kazunori; Yajima, Kazuyoshi; QingGeLeTu; Mori, Hirofumi; Shiba, Kazuhiro

    2006-01-01

    Vesamicol is a leading compound for positron emission tomography (PET) and single photon emission computed tomography (SPECT) tracers for mapping the vesicular acetylcholine transporter (VAChT). Recently, we found that (+)-p-methylvesamicol ((+)-PMV) has low affinity for VAChT (K i =199 nM), but has moderate to high affinity for sigma receptors: K i =3.0 nM for sigma 1 and K i =40.7 nM for sigma 2 , and that sigma 1 -selective SA4503 (K i =4.4 nM for sigma 1 and K i =242 nM for sigma 2 ) has moderate affinity for VAChT (K i =50.2 nM). In the present study, we examined the potential of (+)-[ 11 C]PMV as a PET radioligand for mapping sigma 1 receptors as compared with [ 11 C]SA4503. In rat brain, similar regional distribution patterns of (+)-[ 11 C]PMV and [ 11 C]SA4503 were shown by tissue dissection and by ex vivo autoradiography. Blocking experiments using (±)-PMV (-)-vesamicol, SA4503, haloperidol and (±)-pentazocine showed that the two tracers specifically bound to sigma 1 receptors, and that [ 11 C]SA4503 exhibited greater specific binding than (+)-[ 11 C]PMV. No sign of VAChT-specific binding by [ 11 C]SA4503 was observed in the striatum, which is rich in VAChT sites. In conclusion, (+)-[ 11 C]PMV specifically bound to sigma 1 receptors in the brain, but to a lesser extent than [ 11 C]SA4503, suggesting that (+)-[ 11 C]PMV is a less preferable PET ligand than [ 11 C]SA4503. On the other hand, the moderate affinity of [ 11 C]SA4503 for VAChT is negligible in vivo

  8. C III] EMISSION IN STAR-FORMING GALAXIES NEAR AND FAR

    Energy Technology Data Exchange (ETDEWEB)

    Rigby, J. R. [Astrophysics Science Division, Goddard Space Flight Center, 8800 Greenbelt Road, Greenbelt, MD 20771 (United States); Bayliss, M. B. [Department of Physics, Harvard University, 17 Oxford Street, Cambridge, MA 02138 (United States); Gladders, M. D. [Department of Astronomy and Astrophysics, University of Chicago, 5640 S. Ellis Avenue, Chicago, IL 60637 (United States); Sharon, K.; Johnson, T. [Department of Astronomy, University of Michigan, 500 Church Street, Ann Arbor, MI 48109 (United States); Wuyts, E. [Max Plank Institute for Extraterrestrial Physics, Giessenbachstrasse 1, D-85748 Garching (Germany); Dahle, H. [Institute of Theoretical Astrophysics, University of Oslo, P.O. Box 1029, Blindern, NO-0315 Oslo (Norway); Peña-Guerrero, M. [Space Telescope Science Institute, 3700 San Martin Drive, Baltimore, MD 21218 (United States)

    2015-11-20

    We measure [C iii] 1907, C iii] 1909 Å emission lines in 11 gravitationally lensed star-forming galaxies at z ∼ 1.6–3, finding much lower equivalent widths than previously reported for fainter lensed galaxies. While it is not yet clear what causes some galaxies to be strong C iii] emitters, C iii] emission is not a universal property of distant star-forming galaxies. We also examine C iii] emission in 46 star-forming galaxies in the local universe, using archival spectra from GHRS, FOS, and STIS on HST and IUE. Twenty percent of these local galaxies show strong C iii] emission, with equivalent widths < −5 Å. Three nearby galaxies show C iii] emission equivalent widths as large as the most extreme emitters yet observed in the distant universe; all three are Wolf–Rayet galaxies. At all redshifts, strong C iii] emission may pick out low-metallicity galaxies experiencing intense bursts of star formation. Such local C iii] emitters may shed light on the conditions of star formation in certain extreme high-redshift galaxies.

  9. Design and Synthesis of 11C-Labelled Compound Libraries for the Molecular Imaging of EGFr, VEGFr-2, AT1 and AT2 Receptors: Transition-Metal Mediated Carbonylations Using [11C]Carbon Monoxide

    International Nuclear Information System (INIS)

    Aaberg, Ola

    2009-01-01

    This work deals with radiochemistry and new approaches to develop novel PET tracers labelled with the radionuclide 11 C. Two methods for the synthesis of 11 C-labelled acrylamides have been explored. First, [1- 11 C]-acrylic acid was obtained from a palladium(0)-mediated 11 C-carboxylation of acetylene with [ 11 C]carbon monoxide; this could be converted to the corresponding acyl chloride and then combined with benzylamine to form N-benzyl[carbonyl- 11 C]acrylamide. In the second method, the palladium(0)-mediated carbonylation of vinyl halides with [ 11 C]carbon monoxide was explored. This latter method, yielded labelled acrylamides in a single step with retention of configuration at the C=C double bond, and required less amine compared to the acetylene method. The vinyl halide method was used to synthesize a library of 11 C-labelled EGFr-inhibitors in 7-61% decay corrected radiochemical yield via a combinatorial approach. The compounds were designed to target either the active or the inactive form of EGFr, following computational docking studies. The rhodium(I)-mediated carbonylative cross-coupling of an azide and an amine was shown to be a very general reaction and was used to synthesize a library of dual VEGFr-2/PDGFrβ inhibitors that were 11 C-labelled at the urea position in 38-78% dc rcy. The angiotensin II AT 1 receptor antagonist eprosartan was 11 C-labelled at one of the carboxyl groups in one step using a palladium(0)-mediated carboxylation. Autoradiography shows specific binding in rat kidney, lung and adrenal cortex, and organ distribution shows a high accumulation in the intestines, kidneys and liver. Specific binding in frozen sections of human adrenal incidentalomas warrants further investigations of this tracer. Three angiotensin II AT 2 ligands were 11 C-labelled at the amide group in a palladium(0)-mediated aminocarbonylation in 16-36% dc rcy. One of the compounds was evaluated using in vitro using autoradiography, and in vivo using organ

  10. c-Plane oriented Bi-oxide superconductor

    International Nuclear Information System (INIS)

    Kugimiya, K.; Kawashima, S.; Inoue, O.; Adachi, S.

    1988-01-01

    A newly found Bi-Sr-Ca-Cu-O superconductor with T c =80 K was synthesized in an almost pure phase. It is a laminar oxide with an Aurivillius phase and easily breaks into thin flakes. By slip-casting the flakes under pressure or by hot-pressing sintered bodies of isostatically formed green compacts, c-planes of the phase were highly oriented by more than 95%, mostly 98.5%. Sintered compacts generally contained materials with T c of 80 and 110 K as proved by the Meissner effect. 11 refs.; 6 figs

  11. Search for [C II] emission in z = 6.5-11 star-forming galaxies

    Energy Technology Data Exchange (ETDEWEB)

    González-López, Jorge; Infante, Leopoldo [Instituto de Astrofísica, Facultad de Física, Pontificia Universidad Católica de Chile Av. Vicuña Mackenna 4860, 782-0436 Macul, Santiago (Chile); Riechers, Dominik A., E-mail: jgonzal@astro.puc.cl, E-mail: linfante@astro.puc.cl [Astronomy Department, Cornell University 220 Space Sciences Building, Ithaca, NY 14853 (United States); and others

    2014-04-01

    We present the search for the [C II] emission line in three z > 6.5 Lyα emitters (LAEs) and one J-dropout galaxy using the Combined Array for Research in Millimeter-wave Astronomy and the Plateau de Bure Interferometer. We observed three bright z ∼ 6.5-7 LAEs discovered in the Subaru Deep Field (SDF) and the multiple imaged lensed z ∼ 11 galaxy candidate found behind the galaxy cluster MACSJ0647.7+7015. For the LAEs IOK-1 (z = 6.965), SDF J132415.7+273058 (z = 6.541), and SDF J132408.3+271543 (z = 6.554) we find upper limits for the [C II] line luminosity of <2.05, <4.52, and <10.56 × 10{sup 8} L {sub ☉}, respectively. We find upper limits to the far-IR (FIR) luminosity of the galaxies using a spectral energy distribution template of the local galaxy NGC 6946 and taking into account the effects of the cosmic microwave background on the millimeter observations. For IOK-1, SDF J132415.7+273058, and SDF J132408.3+271543 we find upper limits for the FIR luminosity of <2.33, 3.79, and 7.72 × 10{sup 11} L {sub ☉}, respectively. For the lensed galaxy MACS0647-JD, one of the highest-redshift galaxy candidates to date with z{sub ph}=10.7{sub −0.4}{sup +0.6}, we put an upper limit in the [C II] emission of <1.36 × 10{sup 8} × (μ/15){sup –1} L {sub ☉} and an upper limit in the FIR luminosity of <6.1 × 10{sup 10} × (μ/15){sup –1} L {sub ☉} (where μ is the magnification factor). We explore the different conditions relevant for the search for [C II] emission in high-redshift galaxies as well as the difficulties for future observations with the Atacama Large Millimeter/submillimeter Array (ALMA) and the Cerro Chajnantor Atacama Telescope (CCAT).

  12. lemmingA encodes the Apc11 subunit of the APC/C in Drosophila melanogaster that forms a ternary complex with the E2-C type ubiquitin conjugating enzyme, Vihar and Morula/Apc2

    Directory of Open Access Journals (Sweden)

    Nagy Olga

    2012-03-01

    Full Text Available Abstract Background Ubiquitin-dependent protein degradation is a critical step in key cell cycle events, such as metaphase-anaphase transition and mitotic exit. The anaphase promoting complex/cyclosome (APC/C plays a pivotal role in these transitions by recognizing and marking regulatory proteins for proteasomal degradation. Its overall structure and function has been elucidated mostly in yeasts and mammalian cell lines. The APC/C is, however, a multisubunit assembly with at least 13 subunits and their function and interaction within the complex is still relatively uncharacterized, particularly in metazoan systems. Here, lemming (lmg mutants were used to study the APC/C subunit, Apc11, and its interaction partners in Drosophila melanogaster. Results The lmg gene was initially identified through a pharate adult lethal P element insertion mutation expressing developmental abnormalities and widespread apoptosis in larval imaginal discs and pupal abdominal histoblasts. Larval neuroblasts were observed to arrest mitosis in a metaphase-like state with highly condensed, scattered chromosomes and frequent polyploidy. These neuroblasts contain high levels of both cyclin A and cyclin B. The lmg gene was cloned by virtue of the lmg03424 P element insertion which is located in the 5' untranslated region. The lemming locus is transcribed to give a 2.0 kb mRNA that contains two ORFs, lmgA and lmgB. The lmgA ORF codes for a putative protein with more than 80% sequence homology to the APC11 subunit of the human APC/C. The 85 amino acid protein also contains a RING-finger motif characteristic of known APC11 subunits. The lmgA ORF alone was sufficient to rescue the lethal and mitotic phenotypes of the lmg138 null allele and to complement the temperature sensitive lethal phenotype of the APC11-myc9 budding yeast mutant. The LmgA protein interacts with Mr/Apc2, and they together form a binding site for Vihar, the E2-C type ubiquitin conjugating enzyme. Despite

  13. Preparation of no-carrier-added [1-11C]ethylene and [1-11C]1,2-dibromoethane as new labelling agents

    International Nuclear Information System (INIS)

    Shah, F.; Pike, V.W.; Dowsett, K.

    1997-01-01

    A method is described for the preparation of NCA [1- 11 C] ethylene based on the passage of [1- 11 C]ethanol over heated (550 o C) quartz glass in a stainless steel tube (in preference to dehydration by catalysis on γ-alumina or pyrolysis). The [1- 11 C]ethanol is prepared from cyclotron-produced NCA [ 11 C]carbon dioxide by 11 C-carboxylation of methylmagnesium bromide, freshly prepared in dibutyl ether, and reduction of the adduct with lithium aluminium hydride in diglyme. The use of involatile solvents avoids the formation of carrier ethylene and radioactive and stable diethyl ether by cracking processes over the heated catalyst. The preparation takes 21 min from the end of radionuclide production and has a radiochemical yield of 44%, decay-corrected from [ 11 C]carbon dioxide. NCA [1- 11 C] ethylene is converted quantitatively into [1- 11 C]1,2-dibromoethane when collected in a solution of bromine in carbon tetrachloride. The NCA [1- 11 C]ethylene and [1- 11 C]1,2-dibromoethane may serve as new and useful labelling agents. (Author)

  14. Correlation of biological aggressiveness assessed by 11C-methionine PET and hypoxic burden assessed by 18F-fluoromisonidazole PET in newly diagnosed glioblastoma

    International Nuclear Information System (INIS)

    Kawai, Nobuyuki; Miyake, Keisuke; Okada, Masaki; Tamiya, Takashi; Maeda, Yukito; Yamamoto, Yuka; Nishiyama, Yoshihiro; Kudomi, Nobuyuki

    2011-01-01

    Glioblastoma multiforme (GBM) is characterized by tissue hypoxia associated with resistance to radiotherapy and chemotherapy. To clarify the biological link between hypoxia and tumour-induced neovascularization and tumour aggressiveness, we analysed detailed volumetric and spatial information of viable hypoxic tissue assessed by 18 F-fluoromisonidazole (FMISO) PET relative to neovascularization in Gd-enhanced MRI and tumour aggressiveness by L-methyl- 11 C-methionine (MET) PET in newly diagnosed GBMs. Ten patients with newly diagnosed GBMs were investigated with FMISO PET, MET PET and Gd-enhanced MRI before surgery. Tumour volumes were calculated by performing a three-dimensional threshold-based volume of interest (VOI) analysis for metabolically active volume on MET PET (MET uptake indices of ≥1.3 and ≥1.5) and Gd-enhanced volume on MRI. FMISO PET was scaled to the blood FMISO activity to create tumour to blood (T/B) images. The hypoxic volume (HV) was defined as the region with T/B greater than 1.2. PET and MR images of each patient were coregistered to analyse the spatial location of viable hypoxic tissue relative to neovascularization and active tumour extension. Metabolically active tumour volumes defined using MET uptake indices of ≥1.3 and ≥1.5 and the volumes of Gd enhancement showed a strong correlation (r = 0.86, p < 0.01 for an index of ≥1.3 and r = 0.77, p < 0.05 for an index of ≥1.5). The HVs were also excellently correlated with the volumes of Gd enhancement (r = 0.94, p < 0.01). The metabolically active tumour volumes as defined by a MET uptake index of ≥1.3 and the HVs exhibited a strong correlation (r = 0.87, p < 0.01). On superimposed images, the metabolically active area on MET PET defined by a MET uptake index of ≥1.3 was usually larger than the area of the Gd enhancement and about 20-30% of the MET area extended outside the area of the enhancement. On the other hand, the surface area of viable hypoxic tissue with a T/B cutoff of

  15. Synthesis of O-[{sup 11}C]acetyl CoA, O-[{sup 11}C]acetyl-L-carnitine, and L-[{sup 11}C]carnitine labelled in specific positions, applied in PET studies on rhesus monkey

    Energy Technology Data Exchange (ETDEWEB)

    Jacobson, Gunilla B.; Watanabe, Yasuyoshi; Valind, Sven; Kuratsune, Hirohiko; Laangstroem, Bengt

    1997-07-01

    The syntheses of L-carnitine, O-acetyl CoA, and O-acetyl-L-carnitine labelled with {sup 11}C at the 1- or 2-position of the acetyl group or the N-methyl position of carnitine, using the enzymes acetyl CoA synthetase and carnitine acetyltransferase, are described. With a total synthesis time of 45 min, O-[1-{sup 11}C]acetyl CoA and O-[2-{sup 11}C]acetyl CoA was obtained in 60-70% decay-corrected radiochemical yield, and O-[1-{sup 11}C]acetyl-L-carnitine and O-[2-{sup 11}C]acetyl-L-carnitine in 70-80% yield, based on [1-{sup 11}C]acetate or [2-{sup 11}C]acetate, respectively. By an N-methylation reaction with [{sup 11}C]methyl iodide, L-[methyl-{sup 11}C]carnitine was obtained within 30 min, and O-acetyl-L-[methyl-{sup 11}C]carnitine within 40 min, giving a decay-corrected radiochemical yield of 60% and 40-50%, respectively, based on [{sup 11}C]methyl iodide. Initial data of the kinetics of the different {sup 11}C-labelled L-carnitine and acetyl-L-carnitines in renal cortex of anaesthetized monkey (Macaca mulatta) are presented.

  16. Radiosynthesis of 6-[C-11]-D-glucose

    International Nuclear Information System (INIS)

    Grierson, J.R.; Biskupiak, J.E.; Link, J.M.; Krohn, K.A.

    1993-01-01

    Availability of 6-[C-11]-D-glucose will permit positron emission tomography (PET) investigations of glucose utilization derived from the pentose shunt which supports biosynthesis in tissues. The first radiosynthesis of 6-[C-11]-D-glucose is described. As much as 1 mCi of 6-[C-11]-D-glucose, sufficient for animal studies, is obtained from [C-11]CO 2 after 100 min with a 16% radiochemical yield (EOB). The radiosynthesis has many attractive features. The method uses [C-11]CH 3 I and combines a Wittig reaction and a stereoselective OsO 4 catalyzed alkene hydroxylation. The OsO 4 hydroxylation of the [C-11]-labeled alkene (9) is accomplished in less than 10 min with high stereoselectivity (94:6) in favor of the 6-[C-11]-D-gluco-isomer. HPLC purification (C-18) of the protected labeled sugar removes the undesired 6-[C-11]-L-ido-sugar at an early stage and avoids the use of an expensive low-capacity ion-exchange HPLC column. OsO 4 , a highly toxic reagent, is removed in the process by adsorption and inactivation on polymer-bound triphenylphosphine. (Author)

  17. Rapid labelling of radiopharmaceuticals using 11CO2 and 11CH4

    International Nuclear Information System (INIS)

    Crouzel, C.

    1988-07-01

    In the past two decades, much effort has been devoted to the development of new molecules, labelled with β+ emitters usable for Positron Emission Tomography. Gaseous forms of 11 C ( 11 CO 2 or 11 CH 4 ) must be converted to a reactive form known as a ''radioactive precursor'': 11 C-methanol, 11 C-formaldehyde, 11 C-acetone, 11 C-phosgene, 11 C-diazomethane, 11 C-methylamine. These precursors are used to label radiopharmaceuticals. Few examples are given: 11 C-prazosin, 11 C-CGP 12177, 11 C-pindolol. Such synthesis procedures require strong initial activity (1.5 Ci). The processes are therefore remotely controlled or automated, and confined to shielded cells. Small laboratory robots have lately been introduced for this type of production

  18. Synthesis and characteristics in tumor-bearing mice of N-[11C]methyl-1-deoxynojirimycin and N-[11C]methyl-1-deoxymannojirimycin

    International Nuclear Information System (INIS)

    Ishiwata, Kiichi; Sasaki, Toru; Ishii, Shin-ichi; Senda, Michio; Seki, Hiroyuki; Kitasato Univ.; Nozaki, Tadashi

    1993-01-01

    N-[ 11 C]Methyl-1-deoxynojirimycin ([ 11 C]MDNM) and N-[ 11 C]methyl-1-deoxymannojirimycin ([ 11 C]MDMM) were prepared by 11 C-methylation of 1-deoxynojirimycin (DNM) and 1-deoxymannojirimycin (DMM), which are specific inhibitors of glucosidase and mannosidase, respectively. In mice bearing Ehrich ascitic tumor, the highest uptake of the [ 11 C]MDNM was observed in the kidney, followed by the liver and small intestine, while the tumour uptake was moderate. By MDNM loading, saturable uptake was observed in these tissues. In homogenates of the kidney and tumor tissues, a considerable amount of radioactivity was detected in a high-molecular weight fraction. These results demonstrate that the [ 11 C]MDNM has a potential for imaging the glucosidase activity by positron emission tomography. On the other hand, [ 11 C]MDMM showed lower uptake than [ 11 C]MDNM in the kidney, liver and small intestine and no effect of carrier DMM, suggesting that the [ 11 C]MDMM would not reflect mannosidase activity. (Author)

  19. Nuclear critical opalescence and the M1 form factors of 12C and 13C

    International Nuclear Information System (INIS)

    Delorme, J.; Figureau, A.; Guichon, P.

    1981-01-01

    It is shown that core polarization by the nuclear pion field has opposite effects on the M1 form factors of 12 C(15.11 MeV) and 13 C(g.s.). New data on 13 C are found to agree with this prediction and a common interpretation of the experiments is shown to be possible for the two nuclei in terms of critical opalescence. Discrimination from alternative explanations of the observed anomalies should await further experiments, especially photopion reactions. (orig.)

  20. Chemical Behaviour of C{sup 11} in Liquid Hydrocarbons; Comportement Chimique de {sup 11}C dans les Hydrocarbures Liquides; Khimicheskaya kharakteristika ugleroda-11 v zhidkikh uglevodorodakh; Comportamiento Quimico del {sup 11}C en Hidrocarburos Liquidos

    Energy Technology Data Exchange (ETDEWEB)

    Voigt, A. F.; Clark, D. E.; Mesich, F. G. [Institute of Atomic Research and Department of Chemistry, Iowa State University, Ames, IA (United States)

    1965-04-15

    Carbon-11 is produced by the C{sup 12} ({gamma}, n)Cu{sup 11} reaction in the Bremsstrahlung beam of a 70 MeV electron synchrotron. As target materials, liquid hydrocarbons with 5 and 6 carbons have been used, including normal, branched and alicyclic pentanes and hexanes as well as benzene. The behaviour of Cu{sup 11} has been studied by gas chromatographic separation of the products, counting the Cu{sup 11} in the gas stream in a cell placed in a well-type scintillation counter. In each experiment yields of different products were compared to the yield of acetylene as an internal standard and either to a tantalum monitor or to the total Cu{sup 11} produced as measured in the entire sample before separation. The flow counters were calibrated in terms of total Cu{sup 11} produced in experiments in which the complete sample was burned to CO{sub 2} and passed through a flow counter. Our earlier experiments were concerned only with the gaseous products that have now been well characterized for the various target molecules under different dosage conditions. Current experiments on product molecules similar in size to the target have proved very helpful in deciding on mechanisms for recombination of recoil atoms. Of particular interest is the yield of product with one carbon more than the target,the result of an addition reaction. The location of the additional atom on a target molecule having several types of addition sites gives information regarding the process itself. When the recoil atom is slowed to an energy at which it is possible for a bond to be formed, at least temporarily, the extra energy which the Cu{sup 11} atom brings into the system may cause bond rupture elsewhere within the activated complex usually leading to a two-carbon product. If the complex is able to hold together without rupturing, an additional product will result. Thus comparison of the yields of two-carbon compounds, acetylene, ethylene and ethane, and the additional products provides

  1. 21 CFR 1305.11 - Procedure for obtaining DEA Forms 222.

    Science.gov (United States)

    2010-04-01

    ... the name, address, and registration number of the registrant and the number of books of DEA Forms 222... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Procedure for obtaining DEA Forms 222. 1305.11... I AND II CONTROLLED SUBSTANCES DEA Form 222 § 1305.11 Procedure for obtaining DEA Forms 222. (a) DEA...

  2. Synthesis and positron emission tomographic (PET) baboon studies of [{sup 11}C]methadone and R-(-)-[{sup 11}C]methandone

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Y.S.; Fowler, J.S.; Volkow, N.D. [Brookhaven National Lab., Upton, NY (United States)] [and others

    1996-05-01

    Methadone (MET) maintenance has been used successfully for many years in the rehabilitation of heroin addicts. MET, a typical m{mu}-opioid receptor agonist, exists as two enantiomers and is used clinically as the racemic mixture. However, R-(-)-MET has a 10-fold higher affinity for m{mu} receptors than S-(+)-MET (IC{sub 50}: 3.0 nM and 26.4 nM, respectively) and R-(-)-MET is almost entirely responsible for the therapeutic actions of the racemate. In order to examine the pharmacokinetics and stereoselectivity of the drug, we have synthesized both [{sup 11}C]MET and R-(-)-[{sup 11}C]MET. Preparing the precursor by one-step approach to the N-demethylated methadone was precluded as other investigators cited problems with intramolecular cyclization. Therefore, a four-step synthesis using MET (or R-(-)-MET) as starting material was required to obtain the precursor, followed by a two-step radiolabeling synthesis (N-methylation followed by oxidation) to obtain [{sup 11}C]MET (or R-(-)-[{sup 11}C]MET). Comparative PET studies in the same baboon showed peak striatal uptake was 0.022%/cc at 5 minutes with a half time of clearance from peak of 100 minutes for R-(-)-[{sup 11}C]MET and a peak uptake of 0.013%/cc with a half time of 90 min for [{sup 11}C]MET. R-(-)-[{sup 11}C]MET also showed a slower disappearance in plasma. Both tracers showed higher C-11 in basal ganglia (BG), thalamus and midbrain relative to the cerebellum (CB) and occipital cortex (OC) but the BG/OC ratio was higher for R-(-)-[{sup 11}C]MET (1.3 vs 1.1). Pretreatment with naloxone (1 mg/kg, iv) increased R-(-)-[{sup 11}C]MET uptake in all brain regions whereas unlabeled MET slightly increased C-11 clearance in BG, OC and CB. These initial results show higher brain concentration and specificity of the pharmacologically active enantiomer of methadone along with significant non-specific binding.

  3. Different selective pressures lead to different genomic outcomes as newly-formed hybrid yeasts evolve

    Directory of Open Access Journals (Sweden)

    Piotrowski Jeff S

    2012-04-01

    Full Text Available Abstract Background Interspecific hybridization occurs in every eukaryotic kingdom. While hybrid progeny are frequently at a selective disadvantage, in some instances their increased genome size and complexity may result in greater stress resistance than their ancestors, which can be adaptively advantageous at the edges of their ancestors' ranges. While this phenomenon has been repeatedly documented in the field, the response of hybrid populations to long-term selection has not often been explored in the lab. To fill this knowledge gap we crossed the two most distantly related members of the Saccharomyces sensu stricto group, S. cerevisiae and S. uvarum, and established a mixed population of homoploid and aneuploid hybrids to study how different types of selection impact hybrid genome structure. Results As temperature was raised incrementally from 31°C to 46.5°C over 500 generations of continuous culture, selection favored loss of the S. uvarum genome, although the kinetics of genome loss differed among independent replicates. Temperature-selected isolates exhibited greater inherent and induced thermal tolerance than parental species and founding hybrids, and also exhibited ethanol resistance. In contrast, as exogenous ethanol was increased from 0% to 14% over 500 generations of continuous culture, selection favored euploid S. cerevisiae x S. uvarum hybrids. Ethanol-selected isolates were more ethanol tolerant than S. uvarum and one of the founding hybrids, but did not exhibit resistance to temperature stress. Relative to parental and founding hybrids, temperature-selected strains showed heritable differences in cell wall structure in the forms of increased resistance to zymolyase digestion and Micafungin, which targets cell wall biosynthesis. Conclusions This is the first study to show experimentally that the genomic fate of newly-formed interspecific hybrids depends on the type of selection they encounter during the course of evolution

  4. 9 CFR 151.11 - Form of books of record.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Form of books of record. 151.11... AGRICULTURE ANIMAL BREEDS RECOGNITION OF BREEDS AND BOOKS OF RECORD OF PUREBRED ANIMALS Recognition of Breeds and Books of Record § 151.11 Form of books of record. (a) If a registry association has not published...

  5. OSCILLATION OF NEWLY FORMED LOOPS AFTER MAGNETIC RECONNECTION IN THE SOLAR CHROMOSPHERE

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Shuhong [Key Laboratory of Solar Activity, National Astronomical Observatories, Chinese Academy of Sciences, Beijing 100012 (China); Xiang, Yongyuan, E-mail: shuhongyang@nao.cas.cn [Fuxian Solar Observatory, Yunnan Observatories, Chinese Academy of Sciences, Kunming 650011 (China)

    2016-03-10

    With the high spatial and temporal resolution Hα images from the New Vacuum Solar Telescope, we focus on two groups of loops with an X-shaped configuration in the dynamic chromosphere. We find that the anti-directed loops approach each other and reconnect continually. The connectivity of the loops is changed and new loops are formed and stack together. The stacked loops are sharply bent, implying that they are greatly impacted by the magnetic tension force. When another reconnection process takes place, one new loop is formed and stacks with the previously formed ones. Meanwhile, the stacked loops retract suddenly and move toward the balance position, performing an overshoot movement, which led to an oscillation with an average period of about 45 s. The oscillation of newly formed loops after magnetic reconnection in the chromosphere is observed for the first time. We suggest that the stability of the stacked loops is destroyed due to the attachment of the last new loop and then suddenly retract under the effect of magnetic tension. Because of the retraction, another lower loop is pushed outward and performs an oscillation with a period of about 25 s. The different oscillation periods may be due to their difference in three parameters, i.e., loop length, plasma density, and magnetic field strength.

  6. Socket Preservation with d-PTFE Membrane: Histologic Analysis of the Newly Formed Matrix at Membrane Removal.

    Science.gov (United States)

    Laurito, Domenico; Cugnetto, Riccardo; Lollobrigida, Marco; Guerra, Fabrizio; Vestri, Annarita; Gianno, Francesca; Bosco, Sandro; Lamazza, Luca; De Biase, Alberto

    This study aimed to evaluate the efficacy of an exposed high-density polytetrafluoroethylene (d-PTFE) membrane in preventing epithelial migration in postextraction sockets. For this purpose, a histologic description of the newly formed soft tissue underlying the membrane is presented. The periodontal status of the adjacent teeth was also evaluated to assess the gingival response. Ten premolar extraction sockets were treated. After tooth extraction, the sockets were filled with nanocrystalline hydroxyapatite and covered with d-PTFE membranes. Subperiosteal pockets were created to ensure the stability of the membranes. Membranes were left intentionally exposed and were atraumatically removed after 28 days. At that time, a bioptic specimen of the newly formed soft tissue under the membranes was taken. All the histologic samples showed a dense connective tissue without epithelial cells and no signs of foreign body reaction. No significant variation of the periodontal indices was observed on the teeth adjacent to the extraction sites. The study results indicate that exposed d-PTFE membranes can prevent epithelial migration in healing sockets without consequences on the periodontal health.

  7. Hepatic metabolism of 11C-methionine and secretion of 11C-protein measured by PET in pigs

    DEFF Research Database (Denmark)

    Horsager, Jacob; Lausten, Susanne Bach; Bender, Dirk

    2017-01-01

    Hepatic amino acid metabolism and protein secretion are essential liver functions that may be altered during metabolic stress, e.g. after surgery. We wished to develop a dynamic liver PET method using the radiolabeled amino acid 11C-methionine to examine this question. Eleven 40-kg pigs were...... allocated to either laparotomy or pneumoperitoneum. 24 hours after surgery a 70-min dynamic PET scanning of the liver with arterial blood sampling was performed immediately after intravenous injection of 11C-methionine. Time course of arterial plasma 11C-methionine concentration was used as input function...

  8. Synthesis and preliminary scintigraphic evaluation of in vivo distribution of 11C-hydroxyurea/isohydroxyurea and 11C-cyanate

    International Nuclear Information System (INIS)

    Winstead, M.B.; Chern, C.-I.; Lin, T.-H.; Khentigan, A.; Lamb, J.F.; Winchell, H.S.

    1978-01-01

    H 11 CN, produced directly from proton bombardment of 99% N 2 -1% H 2 [ 14 N(p, α) 11 C], was oxidized by KMn0 4 to 11 C-cyanate which was added to hydroxylamine at -5 to 0 0 C to yield a mixture of hydroxyurea and isohydroxyurea. Scintigraphic evaluation of in vivo distribution in a dog following administration of K0 11 CN showed diffuse whole-body distribution, apparently including brain, with greater activity seen in regions of the heart, liver, and kidneys. Similar evaluation of a dog given 11 C-hydroxyurea/isohydroxyurea showed early localization of activity in the region of the heart which appeared to be due to activity in the myocardium. However, tissue activity measured in rats after administration of this material failed to demonstrate concentration in the myocardium. (author)

  9. Routine production of H11CN and :11C:-1-aminocyclopentanecarboxylic acid

    International Nuclear Information System (INIS)

    Sambre, J.; Vandecasteele, C.; Geothals, P.; Rabi, N.A.; Haver, D. van; Slegers, G.

    1985-01-01

    The production of H 11 CN using the 14 N(p,α) 11 C reaction, was studied. The yield is 140 mCi/μA at saturation (EOB). From 1.8 Ci of H 11 CN 140 mCi of [ 11 C]ACPC are produced routinely and under remote-control. Chemical and pharmaceutical controls showed that the product is suitable for injection. (author)

  10. A novel approach for a C-11C bond formation: synthesis of 17α-([11C]prop-1-ynyl)-3-methoxy-3,17β-estradiol

    International Nuclear Information System (INIS)

    Wuest, F.; Zessin, J.

    2002-01-01

    A novel method for a 11 C-C bond formation was developed, employing a cross-coupling reaction between a terminal acetylene and [ 11 C]methyl iodide. The method was used for the synthesis of 17α-([ 11 C]prop-1-ynyl)-3-methoxy-3,17β-estadiol. (orig.)

  11. 1-/sup 11/C-D-glucose and related compounds

    Energy Technology Data Exchange (ETDEWEB)

    Shiue, C.Y.; Wolf, A.P.

    1982-01-26

    The novel compounds 1-/sup 11/C-D-glucose, 1-/sup 11/C-D-mannose, 1-/sup 11/C-D-galactose, 2-/sup 11/C-D-glucose, 2-/sup 11/C-D-mannose and 2-/sup 11/C-D-galactose which can be used in nuclear medicine to monitor the metabolism of glucose and galactose can be rapidly prepared by reaction of the appropriate aldose substrate with an alkali metal /sup 11/C-labeled cyanide followed by reduction with a Raney alloy in formic acid.

  12. Evaluation of (+)-p-[{sup 11}C]methylvesamicol for mapping sigma{sub 1} receptors: a comparison with [{sup 11}C]SA4503

    Energy Technology Data Exchange (ETDEWEB)

    Ishiwata, Kiichi [Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Tokyo 173-0022 (Japan)]. E-mail: ishiwata@pet.tmig.or.jp; Kawamura, Kazunori [Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Tokyo 173-0022 (Japan); SHI Accelerator Service Ltd., Tokyo 141-0032 (Japan); Yajima, Kazuyoshi [The Medical and Pharmacological Research Center Foundation, Hakui 920-0631 (Japan); QingGeLeTu [Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Tokyo 173-0022 (Japan); Mori, Hirofumi [Advanced Science Research Center, Kanazawa University, Kanazawa 920-8640 (Japan); Shiba, Kazuhiro [Advanced Science Research Center, Kanazawa University, Kanazawa 920-8640 (Japan)

    2006-05-15

    Vesamicol is a leading compound for positron emission tomography (PET) and single photon emission computed tomography (SPECT) tracers for mapping the vesicular acetylcholine transporter (VAChT). Recently, we found that (+)-p-methylvesamicol ((+)-PMV) has low affinity for VAChT (K {sub i}=199 nM), but has moderate to high affinity for sigma receptors: K {sub i}=3.0 nM for sigma{sub 1} and K {sub i}=40.7 nM for sigma{sub 2}, and that sigma{sub 1}-selective SA4503 (K {sub i}=4.4 nM for sigma{sub 1} and K {sub i}=242 nM for sigma{sub 2}) has moderate affinity for VAChT (K {sub i}=50.2 nM). In the present study, we examined the potential of (+)-[{sup 11}C]PMV as a PET radioligand for mapping sigma{sub 1} receptors as compared with [{sup 11}C]SA4503. In rat brain, similar regional distribution patterns of (+)-[{sup 11}C]PMV and [{sup 11}C]SA4503 were shown by tissue dissection and by ex vivo autoradiography. Blocking experiments using ({+-})-PMV (-)-vesamicol, SA4503, haloperidol and ({+-})-pentazocine showed that the two tracers specifically bound to sigma{sub 1} receptors, and that [{sup 11}C]SA4503 exhibited greater specific binding than (+)-[{sup 11}C]PMV. No sign of VAChT-specific binding by [{sup 11}C]SA4503 was observed in the striatum, which is rich in VAChT sites. In conclusion, (+)-[{sup 11}C]PMV specifically bound to sigma{sub 1} receptors in the brain, but to a lesser extent than [{sup 11}C]SA4503, suggesting that (+)-[{sup 11}C]PMV is a less preferable PET ligand than [{sup 11}C]SA4503. On the other hand, the moderate affinity of [{sup 11}C]SA4503 for VAChT is negligible in vivo.

  13. The NE11 experiment at SLAC and the neutron form factors

    International Nuclear Information System (INIS)

    Stuart, L.M.; Lung, A.; Bosted, P.E.

    1993-05-01

    The neutron electromagnetic form factors G En and G Mn , which reflect the charge and magnetization distributions within the neutron, are of fundamental importance for understanding nucleon structure, and are necessary for calculations of processes involving the electromagnetic interaction with complex nuclei. These quantities are functions of Q 2 , the four-momentum transfer squared. SLAC experiment NE11 has measured these form factors out to a Q 2 of 4.0 (GeV/c) 2 with high precision, and the results have been recently published. This paper provides some additional details on the extraction of G Mn and G En from the NE11 measurements. Several formalisms have been developed over the years which attempt to understand the nucleon form factors using basic physical principles. Vector Meson Dominance (VMD) models are based on superpositions of photon couplings to various vector mesons. These models generally involve free parameters which are fit to form factor data at low Q 2 , and are not expected to be valid at high Q 2 . For asymptotically large Q 2 , dimensional scaling methods and perturbative Quantum Chromodynamics (pQCD) predict form factor behavior at large Q 2 , but they do not make absolute magnitude predictions. To describe the form factor behavior at intermediate values of Q 2 , a hybrid model by Gari and Kruempelmann (GK) uses VMD constraints at low Q 2 and pQCD constraints at high Q 2 . Free parameters in the model are adjusted to fit existing form factor data. Other approaches include the use of QCD sum rules to make absolute predictions, diquark models, and relativistic constituent quark models

  14. Assessment of cerebral P-glycoprotein expression and function with PET by combined [11C]inhibitor and [11C]substrate scans in rats

    International Nuclear Information System (INIS)

    Müllauer, Julia; Karch, Rudolf; Bankstahl, Jens P.; Bankstahl, Marion; Stanek, Johann; Wanek, Thomas; Mairinger, Severin; Müller, Markus; Löscher, Wolfgang; Langer, Oliver; Kuntner, Claudia

    2013-01-01

    Introduction: The adenosine triphosphate-binding cassette (ABC) transporter P-glycoprotein (Pgp) protects the brain from accumulation of lipophilic compounds by active efflux transport across the blood–brain barrier. Changes in Pgp function/expression may occur in neurological disorders, such as epilepsy, Alzheimer’s or Parkinson’s disease. In this work we investigated the suitability of the radiolabeled Pgp inhibitors [ 11 C]elacridar and [ 11 C]tariquidar to visualize Pgp density in rat brain with PET. Methods: Rats underwent a first PET scan with [ 11 C]elacridar (n = 5) or [ 11 C]tariquidar (n = 6) followed by a second scan with the Pgp substrate (R)-[ 11 C]verapamil after administration of unlabeled tariquidar at a dose which half-maximally inhibits cerebral Pgp (3 mg/kg). Compartmental modeling using an arterial input function and Logan graphical analysis were used to estimate rate constants and volumes of distribution (V T ) of radiotracers in different brain regions. Results: Brain PET signals of [ 11 C]elacridar and [ 11 C]tariquidar were very low (∼ 0.5 standardized uptake value, SUV). There was a significant negative correlation between V T and K 1 (i.e. influx rate constant from plasma into brain) values of [ 11 C]elacridar or [ 11 C]tariquidar and V T and K 1 values of (R)-[ 11 C]verapamil in different brain regions which was consistent with binding of [ 11 C]inhibitors to Pgp and efflux of (R)-[ 11 C]verapamil by Pgp. Conclusion: The small Pgp binding signals obtained with [ 11 C]elacridar and [ 11 C]tariquidar limit the applicability of these tracers to measure cerebral Pgp density. PET tracers with higher (i.e. subnanomolar) binding affinities will be needed to visualize the low density of Pgp in brain

  15. Aziridines in the synthesis of 11C- and 18F-labelled compounds

    International Nuclear Information System (INIS)

    Gillings, N.M.

    1998-01-01

    Racemic [4- 11 C]aspartic acid, [4- 11 C]asparagine and 2,4-diamino[4- 11 C]butyric acid were synthesised by the ring-opening of an N-activated aziridine-2-carboxylate with 11 C]cyanide, followed by preparative HPLC and hydrolysis/reduction. These labelled amino acids arise from nucleophilic attack at the β-carbon of the aziridine ring. A radioactive by-product of ca. 25% was attributed to the product of α-attack. Several N-activated 2-aryl aziridines were synthesised for the attempted synthesis of β-[ 18 F] fluorophenylalanine and β-[ 18 F]fluorodopa. Ring-opening with [ 18 F]fluoride showed no evidence of β-fluorinated products and it is proposed that attack occurs exclusively at the α-carbon, giving the corresponding α-[ 18 F]fluoro-β-amino acids. Further evidence for this was the reaction of the β-unsubstituted N-activated aziridine-2-carboxylate with [ 18 F]fluoride. This reaction was totally regiospecific and afforded exclusively the α-substituted product, α-[ 18 F]fluoro-β-alanine. Aziridine precursors were resolved by chiral HPLC. On labelling the chiral aziridines, however, racemic 11 C- and 18 F-labelled amino acids were obtained. This was attributed to racemisation of the initially formed ring-opened products. The use of [ 11 C]methyl lithium as a nucleophile for aziridine ring-opening was investigated. Reaction was expected to occur at low temperature, thus potentially avoiding racemisation. No products corresponding to aziridine ring-opening with [ 11 C]methyl lithium were, however, observed. A difluorinated analogue of amphetamine was synthesised by fluorination of an azirine (via an aziridine). This racemic compound was resolved as its chiral tartarate salts and subsequently labelled by methylation with [ 11 C]methyl iodide, giving the novel compound β, β-difluoro[N-methyl- 11 C]methamphetamine in high specific activity for in vivo binding studies using positron emission tomography. The non-radioactive reference compound was also

  16. Optimization of the radiosynthesis of the Alzheimer tracer 2-(4-N-[11C]methylaminophenyl)-6-hydroxybenzothiazole ([11C]PIB)

    International Nuclear Information System (INIS)

    Philippe, C.; Haeusler, D.; Mitterhauser, M.; Ungersboeck, J.; Viernstein, H.; Dudczak, R.; Wadsak, W.

    2011-01-01

    [ 11 C]PIB is still the standard PET compound for Alzheimer imaging targeting beta-amyloid plaques. We aimed to establish a fully-automated procedure for the synthesis and purification of [ 11 C]PIB with a high degree of reliability and improved specific activity as well as a suitable and fast quality control assay. The optimum reaction conditions were 75 deg. C, 4 mg/mL precursor yielding at 48.0±2.7% (EOS, based on [ 11 C]CH 3 OTf, corrected for decay), 183±14 GBq/μmol specific activity and >99% radiochemical purity. Time consumption was kept to a minimum (40 min from EOB) and overall yields were enough to serve 2 consecutive patients with a single preparation. - Highlights: → Optimized radiosynthesis of [ 11 C]PIB in 40 min. → Optimum reaction conditions were 75 deg. C and 4 mg/mL precursor. → Radiochemical yields were 4.2±1.1 GBq. → The specific activity was 183±14 GBq/μmol.

  17. Different sensitivities to competitive inhibition of benzodiazepine receptor binding of {sup 11}C-iomazenil and {sup 11}C-flumazenil in rhesus monkey brain

    Energy Technology Data Exchange (ETDEWEB)

    Inoue, Osamu; Hosoi, Rie; Kobayashi, Kaoru [Osaka Univ., Suita (Japan). Medical School; Itoh, Takashi; Gee, A.; Suzuki, Kazutoshi

    2001-04-01

    The in vivo binding kinetics of {sup 11}C-iomazenil were compared with those of {sup 11}C-flumazenil binding in rhesus monkey brain. The monkey was anesthetized with ketamine and intravenously injected with either {sup 11}C-iomazenil or {sup 11}C-flumazenil in combination with the coadministration of different doses of non-radioactive flumazenil (0, 5 and 20 {mu}g/kg). The regional distribution of {sup 11}C-iomazenil in the brain was similar to that of {sup 11}C-flumazenil, but the sensitivity of {sup 11}C-iomazenil binding to competitive inhibition by non-radioactive flumazenil was much less than that of {sup 11}C-flumazenil binding. A significant reduction in {sup 11}C-flumazenil binding in the cerebral cortex was observed with 20 {mu}g/kg of flumazenil, whereas a relatively smaller inhibition of {sup 11}C-iomazenil binding in the same region was observed with the same dose of flumazenil. These results suggest that {sup 11}C-flumazenil may be a superior radiotracer for estimating benzodiazepine receptor occupancy in the intact brain. (author)

  18. Greater adenosine A2A receptor densities in cardiac and skeletal muscle in endurance-trained men: a [11C]TMSX PET study

    International Nuclear Information System (INIS)

    Mizuno, Masaki; Kimura, Yuichi; Tokizawa, Ken; Ishii, Kenji; Oda, Keiichi; Sasaki, Toru; Nakamura, Yoshio; Muraoka, Isao; Ishiwata, Kiichi

    2005-01-01

    We examined the densities of adenosine A 2A receptors in cardiac and skeletal muscles between untrained and endurance-trained subjects using positron emission tomography (PET) and [7-methyl- 11 C]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine ([ 11 C]TMSX), a newly developed radioligand for mapping adenosine A 2A receptors. Five untrained and five endurance-trained subjects participated in this study. The density of adenosine A 2A receptors was evaluated as the distribution volume of [ 11 C]TMSX in cardiac and triceps brachii muscles in the resting state using PET. The distribution volume of [ 11 C]TMSX in the myocardium was significantly greater than in the triceps brachii muscle in both groups. Further, distribution volumes [ 11 C]TMSX in the trained subjects were significantly grater than those in untrained subjects (myocardium, 3.6±0.3 vs. 3.1±0.4 ml g -1 ; triceps brachii muscle, 1.7±0.3 vs. 1.2±0.2 ml g -1 , respectively). These results indicate that the densities of adenosine A 2A receptors in the cardiac and skeletal muscles are greater in the endurance-trained men than in the untrained men

  19. Quality control of 11C-carfentanil

    International Nuclear Information System (INIS)

    Zhang Xiaojun; Zhang Jinming; Tian Jiahe; Xiang Xiaohui

    2013-01-01

    To study the quality control of 11 C-Carfentanil injection, physical, chemical and biological identification were used. The chemical and radiochemical purity of 11 C-Carfentanil Injection were detected by HPLC and Flower Count system; measured the quantity of product by LC-MS, specific activity was calculated later; The PTS was used to detect endotoxin, and other quality control methods were put up to guarantee the security of its clinical application. The produce appeared colorless and transparent, the radiochemical purity was more than 98%, content of the endotoxin was less than 5 EU/mL. The result showed that 11 C-Carfentanil injection had fulfilled pharmaceutical quality control request and could be applied safely to animal experiment and clinical diagnosis. (authors)

  20. Synthesis and evaluation of inhaled [11C]butane and intravenously injected [11C]acetone as potential radiotracers for studying inhalant abuse

    International Nuclear Information System (INIS)

    Gerasimov, Madina R.; Ferrieri, Richard A.; Pareto, Deborah; Logan, Jean; Alexoff, David; Ding Yushin

    2005-01-01

    The phenomenon of inhalant abuse is a growing problem in the US and many countries around the world. Yet, relatively little is known about the pharmacokinetic properties of inhalants that underlie their abuse potential. While the synthesis of 11 C-labeled toluene, acetone and butane has been proposed in the literature, none of these compounds has been developed as radiotracers for PET studies. In the present report we extend our previous studies with [ 11 C]toluene to include [ 11 C]acetone and [ 11 C]butane with the goal of comparing the pharmacokinetic profiles of these three volatile abused substances. Both [ 11 C]toluene and [ 11 C]acetone were administered intravenously and [ 11 C]butane was administered via inhalation to anesthesized baboons. Rapid and efficient uptake of radiolabeled toluene and acetone into the brain was followed by fast clearance in the case of toluene and slower kinetics in the case of acetone. [ 11 C]Butane was detected in the blood and brain following inhalation, but the levels of radioactivity in both tissues dropped to half of the maximal values over the period of less than a minute. To our knowledge, this is the first reported study of the in vivo brain pharmacokinetics of labeled acetone and butane in nonhuman primates. These data provide insight into the pharmacokinetic features possibly associated with the abuse liability of toluene, acetone and butane

  1. [11C]metaraminol, a false neurotransmitter: Preparation, metabolite studies and positron emission tomography examination in monkey

    International Nuclear Information System (INIS)

    Naagren, Kjell; Halldin, Christer; Swahn, Carl-Gunnar; Suhara, Tetsuya; Farde, Lars

    1996-01-01

    No-carrier-added racemic [ 11 C]metaraminol was prepared by a selective condensation of [ 11 C]nitroethane with 3-hydroxy-benzaldehyde using tetrabutylammonium fluoride in tetrahydrofuran (THF) as a catalyst, followed by a reduction with Raney nickel in formic acid. [ 11 C]Metaraminol was produced in 30 to 45% decay-corrected yield from [ 11 C]nitroethane (13 to 20% decay corrected from [ 11 C]CO 2 ) within 45 to 55 min total synthesis time. Reversed phase high-performance liquid chromatography (HPLC) was used for the separation of the racemic erythro- and threo-forms of [ 11 C]metaraminol. The radiochemical purity was higher than 98%, and the specific radioactivity at the end of synthesis was 500 to 800 Ci/mmol (18 to 30 GBq/μmol). Positron emission tomography (PET) examination of racemic erythro-[ 11 C]metaraminol in a Cynomolgus monkey showed a high uptake of radioactivity in the heart. Following pretreatment with the selective norepinephrine reuptake inhibitor desipramine, the radioactivity uptake in the myocardium was markedly reduced (80%), demonstrating the specificity of erythro-[ 11 C]metaraminol for the norepinephrine reuptake system of the heart. Pretreatment with desipramine had no effect on radioactivity in lung. The metabolism was rapid for [ 11 C]metaraminol. The amounts of the total radioactivity representing [ 11 C]metaraminol in plasma, determined by HPLC, were 14% at 6 min and 8% at 34 min. The high specific uptake of racemic erythro-[ 11 C]metaraminol indicates that enantiomerically pure (R,S)-[ 11 C]metaraminol has potential for detailed mapping of the sympathetic innervation of the human myocardium

  2. Rapid solid-phase extraction method to quantify [11C]-verapamil, and its [11C]-metabolites, in human and macaque plasma

    International Nuclear Information System (INIS)

    Unadkat, Jashvant D.; Chung, Francisco; Sasongko, Lucy; Whittington, Dale; Eyal, Sara; Mankoff, David; Collier, Ann C.; Muzi, Mark; Link, Jeanne

    2008-01-01

    Introduction: P-glycoprotein (P-gp), an efflux transporter, is a significant barrier to drug entry into the brain and the fetus. The positron emission tomography (PET) ligand, [ 11 C]-verapamil, has been used to measure in vivo P-gp activity at various tissue-blood barriers of humans and animals. Since verapamil is extensively metabolized in vivo, it is important to quantify the extent of verapamil metabolism in order to interpret such P-gp activity. Therefore, we developed a rapid solid-phase extraction (SPE) method to separate, and then quantify, verapamil and its radiolabeled metabolites in plasma. Methods: Using high-performance liquid chromatography (HPLC), we established that the major identifiable circulating radioactive metabolite of [ 11 C]-verapamil in plasma of humans and the nonhuman primate, Macaca nemestrina, was [ 11 C]-D-617/717. Using sequential and differential pH elution on C 8 SPE cartridges, we developed a rapid method to separate [ 11 C]-verapamil and [ 11 C]-D-617/717. Recovery was measured by spiking the samples with the corresponding nonradioactive compounds and assaying these compounds by HPLC. Results: Verapamil and D-617/717 recovery with the SPE method was >85%. When the method was applied to PET studies in humans and nonhuman primates, significant plasma concentration of D-617/717 and unknown polar metabolite(s) were observed. The SPE and the HPLC methods were not significantly different in the quantification of verapamil and D-617/717. Conclusions: The SPE method simultaneously processes multiple samples in less than 5 min. Given the short half-life of [ 11 C], this method provides a valuable tool to rapidly determine the concentration of [ 11 C]-verapamil and its [ 11 C]-metabolites in human and nonhuman primate plasma

  3. Novel synthesis of [11C]GVG (Vigabatgrin) for pharmacokinetic studies of addiction treatment

    International Nuclear Information System (INIS)

    Ding, Y.S.; Studenov, A.R.; Zhang, Z.; Gerasimov, M.; Schiffer, W.; Dewey, S.L.; Telang, F.

    2001-01-01

    We report here a novel synthetic route to prepare the precursor and to efficiently label GVG with C-11. 5-Bromo-3-(carbobenzyloxy)amino-1-pentene was synthesized in five steps from homoserine lactone. This was used in a two step radiosynthesis, displacement with [ 11 C]cyanide followed by acid hydrolysis to afford [ 11 C]GVG with high radiochemical yields (> 35%, not optimized) and high specific activity (2-5 Ci/micromol). The [ 11 C]cyanide trapping was achieved at minus5 C with a mixture of Kryptofix and K 2 CO 3 without using conventional aqueous trapping procedure [7]. At this temperature, the excess NH 3 from the target that may interfere with the synthesis would not be trapped [8]. This procedure would be advantageous to any moisture sensitive radiosynthetic steps, as it was the case for our displacement reaction. When conventional aqueous trapping procedure was used, any trace amount of water left, even after prolonged heating, resulted in either no reaction or extremely low yields for the displacement reaction. The entire synthetic procedure should be extendible to the labeling of the pharmacologically active S- form of GVG when using S-homoserine lactone

  4. Radiosynthesis of [11C]D.P.A.-713, [11C]D.P.A.-715 and [11C]clinme, selected carbon-11-labelled novel potential radioligands for imaging the peripheral benzodiazepine receptors with PET

    International Nuclear Information System (INIS)

    Dolle, F.; Thominiaux, C.; Hinnen, F.; Demphel, S.; Le helleix, S.; Chauveau, F.; Boutin, H.; Herard, A.S.; Hantraye, P.; Tavitian, B.; Kassiou, M.; James, M.; Creelman, A.; Fulton, R.; Kassiou, M.; Katsifis, A.; Greguric, I.; Mattner, F.; Loch, C.; Selleri, S.

    2008-01-01

    11 C P.K.11195 is not only the oldest, but also the most widely used PET radiotracer for in vivo imaging of the peripheral benzodiazepine receptors (P.B.R. or translocator protein (18 kDa, T.S.P.O.). With the aim of developing a new PET imaging probe for the in vivo study of the P.B.R., two pyrazol [1,5-a]pyrimidineacetamides (D.P.A.-713 and D.P.A.-715) and one imidazol[1,2-a]pyridine-acetamide (C.L.I.N.M.E.) were radiolabelled with the positron emitters carbon 11 (half life: 20.38 min) [1-5]. Briefly, C.L.I.N.M.E. (2-[6-chloro-2(4-iodophenyl)-imidazol[1,2-a]pyridin-3-yl] -N-ethyl-N-methyl-acetamide) was labelled at its methyl-acetamide moity chain from the corresponding nor-analogue using[ 11 C]methyl iodide (in D.M.S.O./D.M.F (100/200 μL) containing powdered K.O.H. (3-5 mg) at 110 degrees C for 3 min. D.P.A.-713 (N,N-diethyl-2-[2-(4-methoxy-phenyl)-5,7-dimethyl-pyrazolo[1,5-a]pyrimidin -3-yl]acetamide) and D.P.A.-715 (N,N-diethyl-2-[2-(4-methoxy-phenyl)-5,7-bis-tri-fluoro-methyl-pyrazolo [1,5-a]pyrimidin-3-yl]acetamide) were labelled at their aromatic methoxy groups from the corresponding nor-derivatives using [ 11 C]methyl triflate (in acetone (300μL) containing aq. 3 M NaOH (4μL) at 110 degrees C for 1 min). All radioligands were purified using semi preparative Zorbax reverse phase H.P.L.C., were adequately formulated for in vivo injection within 30 min and were found to be > 95% chemically and radiochemically pure. (N.C.)

  5. Synthesis of n.c.a. PET-radiotracers with carbon-11

    International Nuclear Information System (INIS)

    Schirbel, A.

    1998-11-01

    Carbon-11 offers the unique possibility of authentic labelling of molecules as radioindicators for non invasive and quantitative determination of physiological functions via positron emission tomography (PET). Therefore, the goal of this thesis was to synthesize of different n.c.a. 11 C-labelled pharmaceuticals for in vivo distribution studies with PET. For the determination of the pharmacokinetics of [1- 11 C]acetate in porcine myocardium during prolonged ischemia, n.c.a. [1- 11 C]acetate was synthesized via carboxylation of methylmagnesium bromide with in target produced n.c.a. [ 11 C]CO 2 with a radiochemical yield (RCY) of 68 ± 7%. The fast (18 min) and reliable radiosynthesis allowed for repeated tracer administration at short intervals ( R c) in humans, [1- 11 C]acetylsalicylic acid, acetyl-[carboxy- 11 C]salicylic acid and [carboxy- 11 C]salicylic acid were prepared. N.c.a. [1- 11 C]acetylsalicylic acid was synthesized via the reaction of [1- 11 C]acetylchloride with salicylic acid salts. The use of the silver salt proved to be superior to the sodium salt and resulted in radiochemical yields of 32 ± 5%. Base-line (clean) separation of the labelled product was achieved using radio-HPLC. With regard to the preparation of n.c.a. [carboxy- 11 C]salicylic acid, several protected and unprotected phenol derivates were metallated and subsequently carboxylated using n.c.a. [ 11 C]CO 2 . Best results (87 ± 3% RCY) could be achieved with 2-(methoxymethoxy)-phenylmagnesium iodide as a precursor and subsequent quantitative cleavage of the MOM-group. Acetylation of n.c.a. [carboxy- 11 C]salicylic acid to acetyl-[carboxy- 11 C]salicylic acid was performed using acetylchloride in CH 2 Cl 2 with a radiochemical yield of 65 ± 4%. (orig.)

  6. Relationship between the isotopic composition of strontium in newly formed continental clay minerals and their source material

    International Nuclear Information System (INIS)

    Clauer, N.

    1979-01-01

    The 87 Sr/ 86 Sr ratios of recent montmorillonites and kaolinites newly formed in weathering profiles of western and central Africa and of Nosy Be and La Reunion islands near Madagascar are directly related to the composition and age of the parent rocks or minerals. They may, therefore, be used as a genetic tracer. The 87 Sr/ 86 Sr ratios are about 0.704 when these clays crystallise from recent basalts and they are higher than 0.715 when the parent rocks are of sialic composition and old in age. Kaolinites newly formed in situ from feldspars contain small amounts of Sr with abnormally high 87 Sr/ 86 Sr ratios: in this study they are higher than 1.094. When these minerals crystallize from biotites, their 87 Sr/ 86 Sr ratios are much lower and can be close to the value of the primary Sr trapped in the biotites during their crystallization. On the other hand, the 87 Sr/ 86 Sr of continental montmorillonites are less scattered: they range, in this study, between 0.704 and 0.722. These low values, as well as the high adsorption capacities of these minerals in the sedimentary environment, allow the assumption that they frequently have 87 Sr/ 86 Sr ratios close to that of marine Sr during sedimentation. Therefore, montmorillonites are able to form homogeneous authigenic minerals by synsedimentary alterations. (Auth.)

  7. Radiosynthesis and in vivo evaluation of [{sup 11}C]MP-10 as a positron emission tomography radioligand for phosphodiesterase 10A

    Energy Technology Data Exchange (ETDEWEB)

    Plisson, Christophe, E-mail: Christophe.2.plisson@gsk.com [GlaxoSmithKline, Clinical Imaging Centre Hammersmith Hospital, London, W12 0NN (United Kingdom); Salinas, Cristian [GlaxoSmithKline, Clinical Imaging Centre Hammersmith Hospital, London, W12 0NN (United Kingdom); Weinzimmer, David; Labaree, David; Lin, Shu-Fei; Ding, Yu-Shin [Yale University PET Center, Yale University School of Medicine, PO Box 208048 New Haven, CT (United States); Jakobsen, Steen [Aarhus PET Centre, Aarhus Sygehus, Norrebrogade 44, DK-8000 Aarhus C (Denmark); Smith, Paul W. [GlaxoSmithKline, Clinical Imaging Centre Hammersmith Hospital, London, W12 0NN (United Kingdom); Eiji, Kawanishi [Medicinal Chemistry Research Laboratories II, Research Division, Mitsubishi Tanabe Pharma Corporation, Saitama 335-8505 (Japan); Carson, Richard E. [Yale University PET Center, Yale University School of Medicine, PO Box 208048 New Haven, CT (United States); Gunn, Roger N.; Rabiner, Eugenii A. [GlaxoSmithKline, Clinical Imaging Centre Hammersmith Hospital, London, W12 0NN (United Kingdom)

    2011-08-15

    Introduction: The aim of this study was to evaluate a newly reported positron emission tomography (PET) radioligand [{sup 11}C]MP-10, a potent and selective inhibitor of the central phosphodiesterase 10A enzyme (PDE10A) in vivo, using PET. Methods: A procedure was developed for labeling MP-10 with carbon-11. [{sup 11}C]MP-10 was evaluated in vivo both in the pig and baboon brain. Results: Alkylation of the corresponding desmethyl compound with [{sup 11}C]methyl iodide produced [{sup 11}C]MP-10 with good radiochemical yield and specific activity. PET studies in the pig showed that [{sup 11}C]MP-10 rapidly entered the brain reaching peak tissue concentration at 1-2 min postadministration, followed by washout from the tissue. Administration of a selective PDE10A inhibitor reduced the binding in all brain regions to the levels of the cerebellum, demonstrating the saturability and selectivity of [{sup 11}C]MP-10 binding. In the nonhuman primate, the brain tissue kinetics of [{sup 11}C]MP-10 were slower, reaching peak tissue concentrations at 30-60 min postadministration. In both species, the observed rank order of regional brain signal was striatum>diencephalon>cortical regions=cerebellum, consistent with the known distribution and concentration of PDE10A. [{sup 11}C]MP-10 brain kinetics were well described by a two-tissue compartment model, and estimates of total volume of distribution (V{sub T}) were obtained. Blocking studies with unlabeled MP-10 revealed the suitability of the cerebellum as a reference tissue and enabled the estimation of regional binding potential (BP{sub ND}) as the outcome measure of specific binding. Quantification of [{sup 11}C]MP-10 binding using the simplified reference tissue model with cerebellar input function produced BP{sub ND} estimates consistent with those obtained by the two-tissue compartment model. Conclusion: We demonstrated that [{sup 11}C]MP-10 possesses good characteristics for the in vivo quantification of the PDE10A in the

  8. On-line production of [11C]cyanogen bromide

    International Nuclear Information System (INIS)

    Westerberg, G.; Laangstroem, B.

    1997-01-01

    The electrophilic labelling precursor [ 11 C]cyanogen bromide was produced in 95% radiochemical yield (decay-corrected) from hydrogen [ 11 C]cyanide within 3 min from the end of bombardment using a simple and convenient solid-phase on-line procedure. The [ 11 C]cyanogen bromide has been used in the synthesis of a number of labelled compounds for use in positron emission tomography. (author)

  9. Permanent uncoupling of male-specific CYP2C11 transcription/translation by perinatal glutamate

    Energy Technology Data Exchange (ETDEWEB)

    Banerjee, Sarmistha; Das, Rajat Kumar; Giffear, Kelly A.; Shapiro, Bernard H., E-mail: shapirob@vet.upenn.edu

    2015-04-01

    Perinatal exposure of rats and mice to the typically reported 4 mg/g bd wt dose of monosodium glutamate (MSG) results in a complete block in GH secretion as well as obesity, growth retardation and a profound suppression of several cytochrome P450s, including CYP2C11, the predominant male-specific isoform — all irreversible effects. In contrast, we have found that a lower dose of the food additive, 2 mg/g bd wt on alternate days for the first 9 days of life results in a transient neonatal depletion of plasma GH, a subsequent permanent overexpression of CYP2C11 as well as subnormal (mini) GH pulse amplitudes in an otherwise normal adult masculine episodic GH profile. The overexpressed CYP2C11 was characterized by a 250% increase in mRNA, but only a 40 to 50% increase in CYP2C11 protein and its catalytic activity. Using freshly isolated hepatocytes as well as primary cultures exposed to the masculine-like episodic GH profile, we observed normal induction, activation, nuclear translocation and binding to the CYP2C11 promoter of the GH-dependent signal transducers required for CYP2C11 transcription. The disproportionately lower expression levels of CYP2C11 protein were associated with dramatically high expression levels of an aberrant, presumably nontranslated CYP2C11 mRNA, a 200% increase in CYP2C11 ubiquitination and a 70–80% decline in miRNAs associated, at normal levels, with a suppression of CYP2C expression. Whereas the GH-responsiveness of CYP2C7 and CYP2C6 as well as albumin was normal in the MSG-derived hepatocytes, the abnormal expression of CYP2C11 was permanent and irreversible. - Highlights: • A “low” neonatal dose of MSG causes an immediate but transient growth hormone depletion. • Adult circulating growth hormone contains mini pulses in an otherwise male profile. • CYP2C11 is permanently overexpressed > 250%; CYP2C6, 2C7 and albumin remain normal. • The bulk of the overexpressed CYP2C11 mRNA consists of an intron-retained form. • SOCS2

  10. Permanent uncoupling of male-specific CYP2C11 transcription/translation by perinatal glutamate

    International Nuclear Information System (INIS)

    Banerjee, Sarmistha; Das, Rajat Kumar; Giffear, Kelly A.; Shapiro, Bernard H.

    2015-01-01

    Perinatal exposure of rats and mice to the typically reported 4 mg/g bd wt dose of monosodium glutamate (MSG) results in a complete block in GH secretion as well as obesity, growth retardation and a profound suppression of several cytochrome P450s, including CYP2C11, the predominant male-specific isoform — all irreversible effects. In contrast, we have found that a lower dose of the food additive, 2 mg/g bd wt on alternate days for the first 9 days of life results in a transient neonatal depletion of plasma GH, a subsequent permanent overexpression of CYP2C11 as well as subnormal (mini) GH pulse amplitudes in an otherwise normal adult masculine episodic GH profile. The overexpressed CYP2C11 was characterized by a 250% increase in mRNA, but only a 40 to 50% increase in CYP2C11 protein and its catalytic activity. Using freshly isolated hepatocytes as well as primary cultures exposed to the masculine-like episodic GH profile, we observed normal induction, activation, nuclear translocation and binding to the CYP2C11 promoter of the GH-dependent signal transducers required for CYP2C11 transcription. The disproportionately lower expression levels of CYP2C11 protein were associated with dramatically high expression levels of an aberrant, presumably nontranslated CYP2C11 mRNA, a 200% increase in CYP2C11 ubiquitination and a 70–80% decline in miRNAs associated, at normal levels, with a suppression of CYP2C expression. Whereas the GH-responsiveness of CYP2C7 and CYP2C6 as well as albumin was normal in the MSG-derived hepatocytes, the abnormal expression of CYP2C11 was permanent and irreversible. - Highlights: • A “low” neonatal dose of MSG causes an immediate but transient growth hormone depletion. • Adult circulating growth hormone contains mini pulses in an otherwise male profile. • CYP2C11 is permanently overexpressed > 250%; CYP2C6, 2C7 and albumin remain normal. • The bulk of the overexpressed CYP2C11 mRNA consists of an intron-retained form. • SOCS2

  11. Development of miniature module for [11C] methionine synthesis

    International Nuclear Information System (INIS)

    Watanabe, Toshimitsu; Araya, Hiroshi; Ueno, Satoshi

    2006-01-01

    [ 18 F]FDG-PET has spread rapidly in the cancer diagnosis. On the other hand, [ 11 C]Methionine is paid attention as one of the PET drugs that may help cancer diagnosis by [ 18 F]FDG. Due to its short half-life, repeated preparations of [ 11 C] Methionine, two or three times a day, are generally required for the routine PET practice. Although the automatic synthesis devices for [ 11 C]Methionine were developed, it was difficult to supply [ 11 C]Methionine two times a day or more. We developed a methionine synthesis system that was able to supply [ 11 C]Methionine two times a day or more, and a new methionine synthesis unit. The new synthesis unit is able to synthesize [ 11 C]Methionine efficiently without HPLC preparation and evaporation in a short time. The new methionine synthesis unit and system are more useful for the routine synthesis of [ 11 C]Methionine. (author)

  12. Binding kinetics of 11C-N-methyl piperidyl benzilate (11C-NMPB) in a rhesus monkey brain using the cerebellum as a reference region

    International Nuclear Information System (INIS)

    Itoh, Takashi; Tanaka, Masayasu; Suzuki, Kasutoshi; Kobayashi, Kaoru; Inoue, Osamu

    2005-01-01

    The binding kinetics of' 11 C-N-methyl piperidyl benzilate ( 11 C-NMPB) in rhesus monkey brain were studied using animal positron emission tomography (PET) (SHR2000). This study is intended to assess the validity of the method using the cerebellum as a reference region, and to evaluate the effects of anesthesia on 11 C -NMPB binding. Two monkeys, anesthetized with ketamine, received intravenous 11 C-NMPB alone (370-760 MBq, 11 C-NMPB accumulated densely in the striatum and cerebral cortex with time. In contrast, the tracer accumulation significantly decreased with increased doses of nonradioactive NMPB. In the cerebellum, on the other hand, the accumulation of 11 C-NMPB remained low and the tracer was slowly eliminated from the brain following the injection. 11 C-NMPB binding in the cerebellum was barely affected by the increased dose of nonradioactive NMPB. We thus concluded that the specific 11 C-NMPB binding was negligible in the cerebellum, and performed simplified evaluation of 11 C-NMPB binding in each brain region by a graphical method using the cerebellum as a reference region. PET was conducted 26 times, in total both in ketamine-anesthetized and awake monkeys (n=3 each). Measurements of 11 C-NMPB binding showed good run-to-run reproducibility within individual animals. When 11 C-NMPB binding was compared between ketamine-treated and awake animals, a significant increase in 11 C-NMPB binding was observed in the striatum but not in other brain regions of ketamine-treated animals. (author)

  13. Synthesis of 11-14C-quetiapine, 11-14C-isoclotiapine and 10-(4-methylpiperazin-1-yl)pyrido[4,3-b][1,4]benzothiazepine[10-14C

    International Nuclear Information System (INIS)

    Naghi Saadatjoo; Mohsen Javaheri; Nuclear Science and Technology Research Institute, Tehran; Nader Saemian; Mohsen Amini

    2016-01-01

    Quetiapine is one of the most widely used antipsychotic drug which acts as an antagonist for multiple neurotransmitter receptor sites. 2-[2-(4-(Dibenzo[b,f][1,4]thiazepin-11-yl)piperazin-1-yl)ethoxy]ethanol (quetiapine) labeled with carbon-14 in 11-position has been synthesized as part of a 5-step sequence from anthranilic acid-[carboxy- 14 C]. We have presented a convenient synthetic pathway for labeling of quetiapine with carbon-14 by using one-pot procedures from a key thiazepin-11(10H)-one-[11- 14 C] by good radiochemical yield. And also isoclotiapine[11- 14 C], and 10-(4-methylpiperazin-1-yl)pyrido[4,3-b][1,4]benzothiazepine[10- 14 C], synthesized according to this route. (author)

  14. Synthesis of (1-/sup 11/C)-butanol

    Energy Technology Data Exchange (ETDEWEB)

    Oberdorfer, F; Helus, F; Maier-Borst, W [Deutsches Krebsforschungszentrum, Heidelberg (Germany, F.R.); Silvester, D J [Hammersmith Hospital, London (UK). M.R.C. Cyclotron Unit

    1982-09-20

    A method for carrier-free labelling of n-butanol with the positron emitting radionuclide carbon-11 (half-life 20.4 min) is described. Labelling was achieved by carboxylation of n-propyl magnesium chloride with /sup 11/C-labelled carbon dioxide and the subsequent reduction of the resulting free (1-/sup 11/C)-butyric acid with LiAlH/sub 4/ after hydrolysis of the Grignard complex. The procedure permits /sup 11/C-labelled butanol to be prepared in high activity and high radiochemical purity for in vivo biological studies only 25 min after the start of carboxylation of the Grignard compound. Gas chromatography and HPLC were used to assess the purity of the product. To maintain carrier-free conditions, atmospheric carbon dioxide was rigorously excluded from all reagents and every parts of the apparatus.

  15. The synthesis of [1-11C]-butanol

    International Nuclear Information System (INIS)

    Oberdorfer, F.; Helus, F.; Maier-Borst, W.; Silvester, D.J.

    1982-01-01

    A method for carrier-free labelling of n-butanol with the positron emitting radionuclide carbon-11 (half-life 20.4 min) is described. Labelling was achieved by carboxylation of n-propyl magnesium chloride with 11 C-labelled carbon dioxide and the subsequent reduction of the resulting free [1- 11 C]-butyric acid with LiAlH 4 after hydrolysis of the Grignard complex. The procedure permits 11 C-labelled butanol to be prepared in high activity and high radiochemical purity for in vivo biological studies only 25 min after the start of carboxylation of the Grignard compound. Gas chromatography and HPLC were used to assess the purity of the product. To maintain carrier-free conditions, atmospheric carbon dioxide was rigorously excluded from all reagents and every parts of the apparatus. (author)

  16. Novel synthesis of [11C]GVG (Vigabatgrin) for pharmacokinetic studies of addiction treatment

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Y.S.; Studenov, A.R.; Zhang, Z.; Gerasimov, M.; Schiffer, W.; Dewey, S.L.; Telang, F.

    2001-06-10

    We report here a novel synthetic route to prepare the precursor and to efficiently label GVG with C-11. 5-Bromo-3-(carbobenzyloxy)amino-1-pentene was synthesized in five steps from homoserine lactone. This was used in a two step radiosynthesis, displacement with [{sup 11}C]cyanide followed by acid hydrolysis to afford [{sup 11}C]GVG with high radiochemical yields (> 35%, not optimized) and high specific activity (2-5 Ci/{micro}mol). The [{sup 11}C]cyanide trapping was achieved at {minus}5 C with a mixture of Kryptofix and K{sub 2}CO{sub 3} without using conventional aqueous trapping procedure [7]. At this temperature, the excess NH{sub 3} from the target that may interfere with the synthesis would not be trapped [8]. This procedure would be advantageous to any moisture sensitive radiosynthetic steps, as it was the case for our displacement reaction. When conventional aqueous trapping procedure was used, any trace amount of water left, even after prolonged heating, resulted in either no reaction or extremely low yields for the displacement reaction. The entire synthetic procedure should be extendible to the labeling of the pharmacologically active S- form of GVG when using S-homoserine lactone.

  17. Total synthesis of [2-11C]thymidine from [11C]urea: A tracer of choice for measurement of cellular proliferation using PET

    International Nuclear Information System (INIS)

    Labar, D.; Vander Borght, T.

    1990-01-01

    In preliminary studies of cellular proliferation with [methyl- 11 C]thymidine, the labelled degradative products mask the progressive incorporation of the tracer into DNA. The authors have developed a procedure for the synthesis of [2- 11 C]thymidine to circumvent this difficulty, using a [ 11 C]urea precursor

  18. Two anti-angiogenic TKI-PET tracers, [11C]axitinib and [11C]nintedanib: Radiosynthesis, in vivo metabolism and initial biodistribution studies in rodents

    International Nuclear Information System (INIS)

    Slobbe, Paul; Poot, Alex J.; Haumann, Rianne; Schuit, Robert C.; Windhorst, Albert D.; Dongen, Guus A.M.S. van

    2016-01-01

    Introduction: Tyrosine kinase inhibitors (TKIs) are very attractive targeted drugs, although a large portion of patients remains unresponsive. PET imaging with EGFR targeting TKIs ([ 11 C]erlotinib and [ 18 F]afatinib) showed promise in identifying treatment sensitive tumors. The aim of this study was to synthesize two anti-angiogenic TKI tracers, [ 11 C]axitinib and [ 11 C]nintedanib, and to evaluate their potential for PET. Methods: Following successful tracer synthesis, biodistribution studies in VU-SCC-OE and FaDu xenograft bearing mice were performed. Furthermore, tracer stability studies in mice were performed employing (radio-)HPLC and LC–MS/MS techniques. For [ 11 C]nintedanib an LC–MS/MS method was developed to detect the primary carboxylic acid metabolite, resulting from methylester cleavage, in plasma and tumors, because this metabolite is postulated to be important for nintedanib efficacy. LC–MS/MS was also explored to assess the metabolic fate of [ 11 C]axitinib in vivo, since axitinib has an isomerizable double bond. Results: [ 11 C]axitinib and [ 11 C]nintedanib were successfully synthesized with 10.5 ± 2.6% and 25.6 ± 3.3% radiochemical yield (corrected for decay), respectively. Biodistribution studies only demonstrated tumor uptake of [ 11 C]nintedanib in FaDu xenografts of 1.66 ± 0.02% ID/g at 60 min p.i. In vivo stability analysis of [ 11 C]axitinib at 45 min p.i. revealed the formation of predominantly non-polar metabolites (36.6 ± 6.8% vs 47.1 ± 8.4% of parent tracer and 16.3 ± 2.1% of polar metabolites), while for [ 11 C]nintedanib mostly polar metabolites were found (70.9 ± 4.1 vs 26.7 ± 3.9% of parent tracer and only 2.4 ± 1.6 of a non-polar metabolites). No isomerization of [ 11 C]axtinib was observed in vivo; however, a sulfoxide metabolite could be detected using LC–MS/MS. For [ 11 C]nintedanib, LC–MS/MS revealed formation of the reported primary carboxylic acid metabolite when in vitro plasma incubations were performed

  19. Biodistribution and radiation dosimetry of the α7 nicotinic acetylcholine receptor ligand [11C]CHIBA-1001 in humans

    International Nuclear Information System (INIS)

    Sakata, Muneyuki; Wu, Jin; Toyohara, Jun; Oda, Keiichi; Ishikawa, Masatomo; Ishii, Kenji; Hashimoto, Kenji; Ishiwata, Kiichi

    2011-01-01

    Introduction: 4-[ 11 C]Methylphenyl 2,4-diazabicyclo[3.2.2]nonane-2-carboxylate ([ 11 C]CHIBA-1001) is a newly developed positron emission tomography (PET) ligand for mapping α 7 nicotinic acetylcholine receptors. We investigated whole-body biodistribution and radiation dosimetry of [ 11 C]CHIBA-1001 in humans and compared the results with those obtained in mice. Methods: Dynamic whole-body PET was carried out for three human subjects after administering a bolus injection of [ 11 C]CHIBA-1001. Emission scans were collected in two-dimensional mode over five bed positions. Regions of interest were placed over 12 organs. Radiation dosimetry was estimated from the residence times of these source organs using the OLINDA program. Biodistribution data from mice were also used for the prediction of radiation dosimetry in humans, and results with and those without accommodation of different proportions of organ-to-total-body mass were compared with the results from the human PET study. Results: In humans, the highest accumulation was observed in the liver, whereas in mice, the highest accumulation was observed in the urinary bladder. The estimated effective dose from the human PET study was 6.9 μSv/MBq, and that from mice was much underestimated. Conclusion: Effective dose estimates for [ 11 C]CHIBA-1001 were compatible with those associated with other common nuclear medicine tests. Absorption doses among several organs were considerably different between the human and mouse studies. Human dosimetry studies for the investigation of radiation safety are desirable as one of the first clinical trials of new PET probes before their application in subsequent clinical investigations.

  20. The preparation of 11C-labeled caffeine

    International Nuclear Information System (INIS)

    Denutte, H.R.; Cattoir, H.J.; Jonckheere, J.A.; Gelijkens, C.F.; Leenheer, A.P. de; Vandewalle, T.; Vandecasteele, C.; Slegers, G.

    1982-01-01

    A rapid and mild procedure for the preparation of [N-7-methyl- 11 C] caffeine is described. Gaseous 11 C-methyl iodide was led into dimethyl sulphoxide (DMSO), containing theophylline (1,3-dimethylxanthine) and sodium hydride. Purification of the reaction product was achieved by High Performance Liquid Chromatography (HPLC). (author)

  1. Effects of cocaine on [11C]norepinephrine and [11C]β-CIT uptake in the primate peripheral organs measured by PET

    International Nuclear Information System (INIS)

    Suhara, Tetsuya; Farde, L.; Halldin, C.; Karlsson, P.; Nagren, K.

    1996-01-01

    The toxic properties of cocaine are related to both the central and peripheral effects. To identify possible lethal mechanisms and the accumulation of cocaine in various organs, the effects of cocaine on [ 11 C] norepinephrine and cocaine congener [ 11 C]β-CIT uptake in Cynomolgus monkeys were measured by positron emission tomography (PET). Cocaine (5 mg/kg) noticeably inhibited [ 11 C] norepinephrine uptake in the heart. The uptake of [ 11 C]β-CIT in the heart and lung was reduced by pretreatment with cocaine. There was a significant uptake in the liver which was increased following cocaine pretreatment. The results of this study confirm that cocaine blocks the neuronal uptake of norepinephrine in sympathetic nerve terminals in the myocardium. The effect of cocaine on [ 11 C]β-CIT uptake indicates that the binding sites in the heart and lung are saturable, while the uptake mechanism in the liver is different from those of the heart and lung. (author)

  2. Biodistribution and metabolism of the anti-influenza drug [{sup 11}C]oseltamivir and its active metabolite [{sup 11}C]Ro 64-0802 in mice

    Energy Technology Data Exchange (ETDEWEB)

    Hatori, Akiko; Arai, Takuya; Yanamoto, Kazuhiko; Yamasaki, Tomoteru; Kawamura, Kazunori; Yui, Joji; Konno, Fujiko; Nakao, Ryuji; Suzuki, Kazutoshi [Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences (NIRS), Inage-ku, Chiba 263-8555 (Japan); Zhang Mingrong [Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences (NIRS), Inage-ku, Chiba 263-8555 (Japan)], E-mail: zhang@nirs.go.jp

    2009-01-15

    Introduction: Oseltamivir phosphate (Tamiflu) is an orally active anti-influenza drug, which is hydrolyzed by esterase to its carboxylate metabolite Ro 64-0802 with potent activity to inhibit the influenza virus. The abnormal behavior and death associated with the use of oseltamivir have developed into a major problem in Japan where Tamiflu is often prescribed for seasonal influenza. It is critical to determine the amount of oseltamivir and Ro 64-0802 in the human brain and to elucidate the relationship between their amounts and neuropsychiatric side effects. The aim of this study was to evaluate [{sup 11}C]oseltamivir and [{sup 11}C]Ro 64-0802 in mice as promising positron emission tomography (PET) ligands for measuring their amounts in living brains. Methods: Whole-body biodistribution of [{sup 11}C]oseltamivir and [{sup 11}C]Ro 64-0802 was determined in mice using the dissection method and micro-PET. In vitro and in vivo metabolite assay was performed in the plasma and brain of mice. Results: Between 1 and 60 min after injection of [{sup 11}C]oseltamivir and [{sup 11}C]Ro 64-0802, 0.20-0.06% and 0.39-0.03% ID/g were detected in the mouse brains, respectively (dissection method). Radioactivity concentrations in the living brains between 0 and 90 min after injection were measured at standardized uptake values of 0.25-0.05 for [{sup 11}C]oseltamivir and 0.38-0.02 for [{sup 11}C]Ro 64-0802 (micro-PET). In vivo metabolite assay demonstrated the presence of [{sup 11}C]oseltamivir and [{sup 11}C]Ro 64-0802 in the brains after [{sup 11}C]oseltamivir injection. Conclusion: This study determined the distribution and metabolism of [{sup 11}C]oseltamivir and [{sup 11}C]Ro 64-0802 in mice. PET could be used to measure their amounts in the living brain and to elucidate the relationship between the amounts in the brain and the side effects of Tamiflu in the central nervous system.

  3. 11C-methionine translocation in barley

    International Nuclear Information System (INIS)

    Nakanishi, Hiromi; Bughio, Naimatullah; Shigeta Ishioka, Noriko

    2000-01-01

    11 C-methionine was supplied to barley plants through a single leaf or via the roots and real time 11 C movement was monitored using a PETIS (positron emitting tracer imaging system). In Fe-deficient plants, 11 C-methionine was translocated from the tip of the absorbing leaf to the discrimination center' at the basal part of the shoot and then retranslocated to all the chlorotic leaves, while a negligible amount was retranslocated to the roots. In Fe-sufficient plants, methionine was translocated from the absorbing leaf to the discrimination center and then only to the newest leaf on the main shoot. A negligible amount was also retranslocated to the roots. Although, in Fe-sufficient plants, methionine translocation was observed from absorbing roots to shoots, in Fe-deficient plants, only a little amount was translocated from roots to shoots. In conclusion, methionine from the upper portion of a plant is not used as a precursor of mugineic acid under Fe-deficiency conditions. (author)

  4. Synthesis of N1'-([11C]methyl)naltrindole ([11C]MeMNTI): a radioligand for positron emission tomographic studies of delta opioid receptors

    International Nuclear Information System (INIS)

    Lever, J.R.; Dannals, R.F.; Kinter, C.M.; Mathews, W.B.

    1995-01-01

    A delta opioid receptor antagonist, Nl'-methylnaltrindole (MeNTI), has been labeled with carbon-11. The precursor for radiolabeling was prepared in 71% yield by benzylation of the phenolic moiety of naltrindole. Alkylation of the indole nitrogen using [ 11 C]iodomethane and aqueous tetra(n-butyl)ammonium hydroxide at 80 o C in dimethylformamide followed by hydrogenolysis (H 2 , 10% Pd-C) of the benzyl protecting group gave [ 11 C]MeNTI. The average (n = 10) time for radiosynthesis, HPLC purification and formulation was 24 min from end-of-bombardment. [ 11 C]MeNTI of high radiochemical purity was obtained at end-of-synthesis with an average specific activity of 2050 mCi/μmol and radiochemical yield, based on [ 11 C]iodomethane, of 6%. (Author)

  5. N-[11C]methylpiperidine esters as acetylcholinesterase substrates: an in vivo structure-reactivity study

    International Nuclear Information System (INIS)

    Kilbourn, Michael R.; Nguyen, Thinh B.; Snyder, Scott E.; Sherman, Phillip

    1998-01-01

    A series of simple esters incorporating the N-[ 11 C]methylpiperidine structure were examined as in vivo substrates for acetylcholinesterase in mouse brain. 4-N-[ 11 C]Methylpiperidinyl esters, including the acetate, propionate and isobutyrate esters, are good in vivo substrates for mammalian cholinesterases. Introduction of a methyl group at the 4-position of the 4-piperidinol esters, to form the ester of a teritary alcohol, effectively blocks enzymatic action. Methylation of 4- N-[ 11 C]methylpiperidinyl propionate at the 3-position gives a derivative with increased in vivo reactivity toward acetylcholinesterase. Esters of piperidinecarboxylic acids (nipecotic, isonipecotic and pipecolinic acid ethyl esters) are not hydrolyzed by acetylcholinesterase in vivo, nor do they act as in vivo inhibitors of the enzyme. This study has identified simple methods to both increase and decrease the in vivo reactivity of piperidinyl esters toward acetylcholinesterase

  6. Test-retest reproducibility of dopamine D{sub 2/3} receptor binding in human brain measured by PET with [{sup 11}C]MNPA and [{sup 11}C]raclopride

    Energy Technology Data Exchange (ETDEWEB)

    Kodaka, Fumitoshi [National Institute of Radiological Sciences, Molecular Neuroimaging Program, Molecular Imaging Center, Chiba (Japan); Jikei University School of Medicine, Department of Psychiatry, Tokyo (Japan); Ito, Hiroshi [National Institute of Radiological Sciences, Molecular Neuroimaging Program, Molecular Imaging Center, Chiba (Japan); National Institute of Radiological Sciences, Biophysics Program, Molecular Imaging Center, Chiba (Japan); Kimura, Yasuyuki; Fujie, Saori; Takano, Harumasa; Fujiwara, Hironobu; Sasaki, Takeshi; Suhara, Tetsuya [National Institute of Radiological Sciences, Molecular Neuroimaging Program, Molecular Imaging Center, Chiba (Japan); Nakayama, Kazuhiko [Jikei University School of Medicine, Department of Psychiatry, Tokyo (Japan); Halldin, Christer; Farde, Lars [Karolinska Institutet, Department of Clinical Neuroscience, Stockholm (Sweden)

    2013-04-15

    Dopamine D{sub 2/3} receptors (D{sub 2/3}Rs) have two affinity states for endogenous dopamine, referred to as high-affinity state (D{sub 2/3} {sup HIGH}), which has a high affinity for endogenous dopamine, and low-affinity state (D{sub 2/3} {sup LOW}). The density of D{sub 2/3} {sup HIGH} can be measured with (R)-2-{sup 11}CH{sub 3}O-N-n-propylnorapomorphine ([{sup 11}C]MNPA), while total density of D{sub 2/3} {sup HIGH} and D{sub 2/3} {sup LOW} (D{sub 2/3}Rs) can be measured with [{sup 11}C]raclopride using positron emission tomography (PET). Thus, the ratio of the binding potential (BP) of [{sup 11}C]MNPA to that of [{sup 11}C]raclopride ([{sup 11}C]MNPA/[{sup 11}C]raclopride) may reflect the proportion of the density of D{sub 2/3} {sup HIGH} to that of D{sub 2/3}Rs. In the caudate and putamen, [{sup 11}C]MNPA/[{sup 11}C]raclopride reflects the proportion of the density of D{sub 2} {sup HIGH} to that of D{sub 2}Rs. To evaluate the reliability of the PET paradigm with [{sup 11}C]MNPA and [{sup 11}C]raclopride, we investigated the test-retest reproducibility of non-displaceable BP (BP{sub ND}) measured with [{sup 11}C]MNPA and of [{sup 11}C]MNPA/[{sup 11}C]raclopride in healthy humans. Eleven healthy male volunteers underwent two sets of PET studies on separate days that each included [{sup 11}C]MNPA and [{sup 11}C]raclopride scans. BP{sub ND} values in the caudate and putamen were calculated. Test-retest reproducibility of BP{sub ND} of [{sup 11}C]MNPA and [{sup 11}C]MNPA/[{sup 11}C]raclopride was assessed by intra-subject variability (absolute variability) and test-retest reliability (intraclass correlation coefficient: ICC). The absolute variability of [{sup 11}C]MNPA BP{sub ND} was 5.30 {+-} 3.96 % and 12.3 {+-} 7.95 % and the ICC values of [{sup 11}C]MNPA BP{sub ND} were 0.72 and 0.82 in the caudate and putamen, respectively. The absolute variability of [{sup 11}C]MNPA/[{sup 11}C]raclopride was 6.11 {+-} 3.68 % and 11.60 {+-} 5.70 % and the ICC values of [{sup

  7. Aziridines in the synthesis of {sup 11}C- and {sup 18}F-labelled compounds

    Energy Technology Data Exchange (ETDEWEB)

    Gillings, N.M

    1998-07-01

    Racemic [4-{sup 11}C]aspartic acid, [4-{sup 11}C]asparagine and 2,4-diamino[4-{sup 11}C]butyric acid were synthesised by the ring-opening of an N-activated aziridine-2-carboxylate with [{sup 11}C]cyanide, followed by preparative HPLC and hydrolysis/reduction. These labelled amino acids arise from nucleophilic attack at the {beta}-carbon of the aziridine ring. A radioactive by-product of ca. 25% was attributed to the product of {alpha}-attack. Several N-activated 2-aryl aziridines were synthesised for the attempted synthesis of {beta}-[{sup 18}F] fluorophenylalanine and {beta}-[{sup 18}F]fluorodopa. Ring-opening with [{sup 18}F]fluoride showed no evidence of {beta}-fluorinated products and it is proposed that attack occurs exclusively at the {alpha}-carbon, giving the corresponding {alpha}-[{sup 18}F]fluoro-{beta}-amino acids. Further evidence for this was the reaction of the {beta}-unsubstituted N-activated aziridine-2-carboxylate with [{sup 18}F]fluoride. This reaction was totally regiospecific and afforded exclusively the {alpha}-substituted product, {alpha}-[{sup 18}F]fluoro-{beta}-alanine. Aziridine precursors were resolved by chiral HPLC. On labelling the chiral aziridines, however, racemic {sup 11}C- and {sup 18}F-labelled amino acids were obtained. This was attributed to racemisation of the initially formed ring-opened products. The use of [{sup 11}C]methyl lithium as a nucleophile for aziridine ring-opening was investigated. Reaction was expected to occur at low temperature, thus potentially avoiding racemisation. No products corresponding to aziridine ring-opening with [{sup 11}C]methyl lithium were, however, observed. A difluorinated analogue of amphetamine was synthesised by fluorination of an azirine (via an aziridine). This racemic compound was resolved as its chiral tartarate salts and subsequently labelled by methylation with [{sup 11}C]methyl iodide, giving the novel compound {beta}, {beta}-difluoro[N-methyl-{sup 11}C]methamphetamine in high

  8. On the synthesis of 11C-labelled aromatic amino acids

    International Nuclear Information System (INIS)

    Halldin, C.

    1984-01-01

    The use of 11 C-labelled aromatic amino acids in positron emission tomography (PET) and their importance in physiological studies, especially cerebral protein synthesis or their role as precursors of neurotransmitters, is discussed. The synthesis of 11 -C-labelled aromatic amino acids by various routes is presented and new 11 C-labelled precursors, aromatic and aliphatic 11 C-aldehydes, are reported. The 11 C-aldehydes were obtained in 60-95% radiochemical yield and reaction times were of the order of 5 min. The 11 C-aldehydes have been used in condensation reactions with 2-aryl-5-oxazolones in the presence of a tertiary amine, diazabicyclooctane (DABCO), to produce the corresponding [α- 11 C]-4-arylene-2-aryl-5-oxazolones. Ring opening, hydrogenation and removal of protecting groups were carried out in one step to produce the racemic [3- 11 C]-labelled aromatic amino acids in 8-30% radiochemical yield. The total reaction time was 52-60 min. L-[3- 11 C]Phenylalanine was obtained by a seven-step synthesis in 80% e.e. (enantiomeric excess) and 60% e.e., respectively, in 10-15% radiochemical yield within 60 min, by use of the chiral rhodium complex of (R)-1,2-bis(diphenylphosphino)propane ((R)-PROPHOS) or (+)-2,3-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino)butane ((+)-DIOP) in the hydrogenation reaction. Racemic [2- 11 C]-labelled aromatic amino acids were produced by a high-pressure, high-temperature modification of the Buechere-Strecker synthesis. [2- 11 C]Phenylglycine was obtained in 20% radiochemical yield within 50 min. [3- 11 C]Phenylpyruvic acid was prepared via the aldehyde-oxyzolone condensation reaction in 40% radiochemical yield within 40 min (not including LC separation). Its use in the synthesis of [3- 11 C]-phenylalanine by enzymatic transamination is also discussed. With 32 refs.(Author)

  9. 45 CFR 234.11 - Assistance in the form of money payments.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 2 2010-10-01 2010-10-01 false Assistance in the form of money payments. 234.11... FINANCIAL ASSISTANCE TO INDIVIDUALS § 234.11 Assistance in the form of money payments. (a) Federal financial participation is available in money payments made under a State plan under title I, IV-A, X, XIV, or XVI of the...

  10. 5-Fluoro-[β-11C]-L-tryptophan is a functional analogue of 5-hydroxy-[β-11C]-L-tryptophan in vitro but not in vivo

    International Nuclear Information System (INIS)

    Eriksson, Olof; Selvaraju, Ramkumar; Borg, Beatrice; Asplund, Veronika; Estrada, Sergio; Antoni, Gunnar

    2013-01-01

    Introduction: 5-Hydroxy-[β- 11 C]-L-tryptophan ([ 11 C]HTP) is an established positron emission tomography (PET) imaging agent for neuroendocrine tumors (NETs). It has also been used for other clinical research purposes in neurology and diabetes. However, its widespread use is limited by the short physical half-life of the radionuclide and a difficult radiosynthesis. Therefore, a Fluorine-18 labeled analogue, 5-[ 18 F]Fluoro-L-tryptophan ([ 18 F]FTRP), has been proposed as a functional analogue. There is no published method for the synthesis of L-[ 18 F]FTRP. We have therefore developed a synthesis of 5-fluoro-[β- 11 C]-L-tryptophan ([ 11 C]FTRP), based on the existing chemo-enzymatic method for [ 11 C]HTP and evaluated the potential usefulness of radiolabeled FTRP as a substitute for [ 11 C]HTP. Methods: The in vitro and in vivo behavior of [ 11 C]FTRP, including the dependence of key enzymes in the serotonergic metabolic pathway, was investigated in NET cell lines, NET xenograft carrying immunodeficient mice, normal rats and in non-human primate. [ 11 C]HTP was used for direct comparison. Results: Uptake of [ 11 C]FTRP in NET cell lines in vitro was mediated by enzymes involved in serotonin synthesis and metabolism, similar to [ 11 C]HTP. In vivo biodistribution, either in rodent or non-human primate, was not affected by selectively inhibiting enzymatic steps in the serotonergic metabolic pathway. Conclusion: [ 11 C]FTRP has in vitro biological function similar to that of [ 11 C]HTP. However, this function is not retained in vivo as shown by biodistribution and PET/CT studies. Radiolabeled FTRP is thus not likely to provide an advantage over [ 11 C]HTP in PET imaging in oncology, neurology or diabetes

  11. Simple and rapid preparation of [11C]DASB with high quality and reliability for routine applications

    International Nuclear Information System (INIS)

    Haeusler, D.; Mien, L.-K.; Nics, L.; Ungersboeck, J.; Philippe, C.; Lanzenberger, R.R.; Kletter, K.; Dudczak, R.; Mitterhauser, M.; Wadsak, W.

    2009-01-01

    [ 11 C]DASB combines all major prerequisites for a successful SERT-ligand, providing excellent biological properties and in-vivo behaviour. Thus, we aimed to establish a fully automated procedure for the synthesis and purification of [ 11 C]DASB with a high degree of reliability reducing the overall synthesis time while conserving high yields and purity. The optimized [ 11 C]DASB synthesis was applied in more than 60 applications with a very low failure rate (3.2%). We obtained yields up to 8.9 GBq (average 5.3±1.6 GBq). Radiochemical yields based on [ 11 C]CH 3 I, (corrected for decay) were 66.3±6.9% with a specific radioactivity (A s ) of 86.8±24.3 GBq/μmol (both at the end of synthesis, EOS). Time consumption was kept to a minimum, resulting in 43 min from end of bombardment to release of the product after quality control. Form our data, it is evident that the presented method can be implemented for routine preparations of [ 11 C]DASB with high reliability.

  12. Comparison of halo of 11Be, 15C, and 19C

    Science.gov (United States)

    Kharab, R.; Kumar, R.; Singh, P.; Sharma, H. C.

    2007-12-01

    We have compared the halo of 11Be, 15C, and 19C nuclei by analyzing the one-neutron stripping reaction data on the Be target at 60-, 54-, and 57-MeV/ A beam energies, respectively, within the framework of the eikonal approximation approach. The determination of effective range through the comparison of the total cross section data and prediction has revealed that the halo of 19C is the well developed, while that of 15C is the least and that of 11Be lies in between these two. The longitudinal momentum distribution data also strengthen these observations.

  13. Towards the total synthesis of stawamycin. Synthesis of C11-C21 fragment.

    OpenAIRE

    Dias, LC; Jardim, LSA; Ferreira, AA; Soarez, HU

    2001-01-01

    The carbocyclic (C11-C21) fragment of Stawamycin has been prepared by a sequence involving 11 steps (10% overall yield) from methyl (R)-(-)-3-hydroxy-2-methylpropionate. Key steps are Pd-catalyzed Stille coupling reaction between a vinyl iodide and a vinylstannane followed by an intramolecular Diels-Alder cycloaddition reaction to afford the desired adduct as the major isomer together with three other possible adducts in 78% overall yield. A porção carbocíclica (C11-C21) da Estavamicina fo...

  14. Automated photosynthesis of 11C-glucose

    International Nuclear Information System (INIS)

    Ishiwata, K.; Monma, M.; Iwata, R.; Ido, T.

    1982-01-01

    Glucose and fructose, labelled with 11 C, were produced by passing 11 CO 2 into an evacuated chamber containing spinach leaves. Photosynthesis was carried out by day light lamp illumination. 75-95% of the 11 CO 2 was absorbed by the leaves and the radioactivity in the leaves was extracted in ethanol as sugars. Radiochemical purity was determined by HPLC. The automated system was controlled by timers. (U.K.)

  15. Rapid solid-phase extraction method to quantify [{sup 11}C]-verapamil, and its [{sup 11}C]-metabolites, in human and macaque plasma

    Energy Technology Data Exchange (ETDEWEB)

    Unadkat, Jashvant D. [Department of Pharmaceutics, University of Washington, Box 357610, Seattle, WA 98195 (United States)], E-mail: jash@u.washington.edu; Chung, Francisco; Sasongko, Lucy; Whittington, Dale; Eyal, Sara [Department of Pharmaceutics, University of Washington, Box 357610, Seattle, WA 98195 (United States); Mankoff, David [Department of Radiology, University of Washington, Box 356004, Seattle, WA 98195 (United States); Collier, Ann C. [Department of Medicine, University of Washington, Box 359929, Seattle, WA 98195 (United States); Muzi, Mark; Link, Jeanne [Department of Radiology, University of Washington, Box 356004, Seattle, WA 98195 (United States)

    2008-11-15

    Introduction: P-glycoprotein (P-gp), an efflux transporter, is a significant barrier to drug entry into the brain and the fetus. The positron emission tomography (PET) ligand, [{sup 11}C]-verapamil, has been used to measure in vivo P-gp activity at various tissue-blood barriers of humans and animals. Since verapamil is extensively metabolized in vivo, it is important to quantify the extent of verapamil metabolism in order to interpret such P-gp activity. Therefore, we developed a rapid solid-phase extraction (SPE) method to separate, and then quantify, verapamil and its radiolabeled metabolites in plasma. Methods: Using high-performance liquid chromatography (HPLC), we established that the major identifiable circulating radioactive metabolite of [{sup 11}C]-verapamil in plasma of humans and the nonhuman primate, Macaca nemestrina, was [{sup 11}C]-D-617/717. Using sequential and differential pH elution on C{sub 8} SPE cartridges, we developed a rapid method to separate [{sup 11}C]-verapamil and [{sup 11}C]-D-617/717. Recovery was measured by spiking the samples with the corresponding nonradioactive compounds and assaying these compounds by HPLC. Results: Verapamil and D-617/717 recovery with the SPE method was >85%. When the method was applied to PET studies in humans and nonhuman primates, significant plasma concentration of D-617/717 and unknown polar metabolite(s) were observed. The SPE and the HPLC methods were not significantly different in the quantification of verapamil and D-617/717. Conclusions: The SPE method simultaneously processes multiple samples in less than 5 min. Given the short half-life of [{sup 11}C], this method provides a valuable tool to rapidly determine the concentration of [{sup 11}C]-verapamil and its [{sup 11}C]-metabolites in human and nonhuman primate plasma.

  16. Strategy for improved [11C]DAA1106 radiosynthesis and in vivo peripheral benzodiazepine receptor imaging using microPET, evaluation of [11C]DAA1106

    International Nuclear Information System (INIS)

    Probst, Katrin C.; Izquierdo, David; Bird, Joseph L.E.; Brichard, Laurent; Franck, Dominic; Davies, John R.; Fryer, Tim D.; Richards, Hugh K.; Clark, John C.; Davenport, Anthony P.; Weissberg, Peter L.; Warburton, Elizabeth A.

    2007-01-01

    Introduction: The peripheral benzodiazepine receptor (PBR) has shown considerable potential as a clinical marker of neuroinflammation and tumour progression. [ 11 C]DAA1106 ([ 11 C]N-(2,5-dimethoxybenzyl)-N-(5-fluoro-2-phenoxyphenyl)-acetamide) is a promising positron emission tomography (PET) radioligand for imaging PBRs. Methods: A four-step synthetic route was devised to prepare DAA1123, the precursor for [ 11 C]DAA1106. Two robust, high yielding methods for radiosynthesis based on [ 11 C]-O-methylation of DAA1123 were developed and implemented on a nuclear interface methylation module, producing [ 11 C]DAA1106 with up to 25% radiochemical yields at end-of-synthesis based on [ 11 C]CH 3 I trapped. Evaluation of [ 11 C]DAA1106 for in vivo imaging was performed in a rabbit model with microPET, and the presence of PBR receptor in the target organ was further corroborated by immunohistochemistry. Results: The standard solution method produced 2.6-5.2 GBq (n=19) of [ 11 C]DAA1106, whilst the captive solvent method produced 1.6-6.3 GBq (n=10) of [ 11 C]DAA1106. Radiochemical purities obtained were 99% and specific radioactivity at end-of-synthesis was up to 200 GBq/μmol for both methods. Based on radiochemical product, shorter preparation times and simplicity of synthesis, the captive solvent method was chosen for routine productions of [ 11 C]DAA1106. In vivo microPET [ 11 C]DAA1106 scans of rabbit kidney demonstrated high levels of binding in the cortex. The subsequent introduction of nonradioactive DAA1106 (0.2 μmol) produced considerable displacement of the radioactive signal in this region. The presence of PBR in kidney cortex was further corroborated by immunohistochemistry. Conclusions: A robust, high yielding captive solvent method of [ 11 C]DAA1106 production was developed which enabled efficacious in vivo imaging of PBR expressing tissues in an animal model

  17. Tracers development for the PET study of nicotinic receptors: [11C]-mecamylamine and [11C]-SIB 1553A. Tritium and carbon-11 radiolabelling of a serine proteinase inhibitor: the t-PAstop

    International Nuclear Information System (INIS)

    Sobrio, F.

    2002-12-01

    In order to develop radiotracers for the Positron Emission Tomography (PET), we labelled both the mecamylamine and SIB-1553A with carbon-11 to study the nicotinic cholinergic receptors (nAChRs). The radiosynthesis of [ 11 C]-t-PA stop and the labelling with tritium of one analogue were realized for cerebral ischemia PET studies. The [ 11 C]-mecamylamine, a non-competitive and non-selective nAChRs antagonist was synthesized in 45 min via a N-[ 11 C]-methylation reaction. In the rat brain, the ex vivo studies showed no radio-metabolite 45 min after the injection of [ 11 C]-mecamylamine. The uptake kinetics in the rat brain or in vivo by PET in the anesthetized baboon or in the conscious monkey, reached a plateau around 45-50 min after injection. However, the saturation or displacement experiments did not permit to exhibit nor a significant difference of labelling between the different cerebral regions nor a specific uptake. In consequence, the [ 11 C]-mecamylamine was not an appropriate radioligand for nAChRs PET study. The labelling of [ 11 C]-SIB 1553A, a selective agonist for the nicotinic β4 subunit, required the synthesis in 5 steps (56% overall yield) of precursor for the incorporation of carbon-11. The radiosynthesis was performed in 36 min by a N-[ 11 C]-methylation reaction (yield: 75%). The [ 11 C]-t-PA stop was obtained from [ 11 C]-KCN with yields from 80 to 90%. For the first time with carbon-11, the formation of an amidine group was realized from a nitrile group. The labelling by isotopic exchange of hydrogen by tritium of the t-PA stop did not permit to obtain the [ 3 H]-t-PA stop but a tritiated analogue. This compound will be used to study its vectorization by micro-encapsulation. (author)

  18. Synthesis of n. c. a. PET-radiotracers with carbon-11. Zur Synthese traegerarme PET-Radiotracer mit Kohlenstoff-11

    Energy Technology Data Exchange (ETDEWEB)

    Schirbel, A.

    1998-11-01

    Carbon-11 offers the unique possibility of authentic labelling of molecules as radioindicators for non invasive and quantitative determination of physiological functions via positron emission tomography (PET). Therefore, the goal of this thesis was to synthesize of different n.c.a. [sup 11]C-labelled pharmaceuticals for in vivo distribution studies with PET. For the determination of the pharmacokinetics of [1-[sup 11]C]acetate in porcine myocardium during prolonged ischemia, n.c.a. [1-[sup 11]C]acetate was synthesized via carboxylation of methylmagnesium bromide with in target produced n.c.a. [[sup 11]C]CO[sub 2] with a radiochemical yield (RCY) of 68 [+-] 7%. The fast (18 min) and reliable radiosynthesis allowed for repeated tracer administration at short intervals (<20 min). In order to study the pharmacokinetics and metabolism of acetylsalicylic acid (Aspirin[sup R]c) in humans, [1-[sup 11]C]acetylsalicylic acid, acetyl-[carboxy-[sup 11]C]salicylic acid and [carboxy-[sup 11]C]salicylic acid were prepared. N.c.a. [1-[sup 11]C]acetylsalicylic acid was synthesized via the reaction of [1-[sup 11]C]acetylchloride with salicylic acid salts. The use of the silver salt proved to be superior to the sodium salt and resulted in radiochemical yields of 32 [+-] 5%. Base-line (clean) separation of the labelled product was achieved using radio-HPLC. With regard to the preparation of n.c.a. [carboxy-[sup 11]C]salicylic acid, several protected and unprotected phenol derivates were metallated and subsequently carboxylated using n.c.a. [[sup 11]C]CO[sub 2]. Best results (87 [+-] 3% RCY) could be achieved with 2-(methoxymethoxy)-phenylmagnesium iodide as a precursor and subsequent quantitative cleavage of the MOM-group. Acetylation of n.c.a. [carboxy-[sup 11]C]salicylic acid to acetyl-[carboxy-[sup 11]C]salicylic acid was performed using acetylchloride in CH[sub 2]Cl[sub 2] with a radiochemical yield of 65 [+-] 4%. (orig.)

  19. Radiosynthesis of [{sup 11}C]D.P.A.-713, [{sup 11}C]D.P.A.-715 and [{sup 11}C]clinme, selected carbon-11-labelled novel potential radioligands for imaging the peripheral benzodiazepine receptors with PET

    Energy Technology Data Exchange (ETDEWEB)

    Dolle, F.; Thominiaux, C.; Hinnen, F.; Demphel, S.; Le helleix, S.; Chauveau, F.; Boutin, H.; Herard, A.S.; Hantraye, P.; Tavitian, B. [Service Hospitalier Frederic Joliot, I2BM/DSV, 91 - Orsay (France); Kassiou, M.; James, M.; Creelman, A.; Fulton, R. [Sydney Univ., Brain and Mind Research Institute, NSW (Australia); Kassiou, M. [Sydney Univ., Discipline of Medical Radiations, Sciences and School of Chemistry, NSW (Australia); Katsifis, A.; Greguric, I.; Mattner, F.; Loch, C. [Radiopharmaceuticals Research Institute, ANSTO, NSW (Australia); Selleri, S. [Degli Studi di Firenze Univ., Dipt. di Scienze Farmaceutiche (Italy)

    2008-02-15

    {sup 11}C P.K.11195 is not only the oldest, but also the most widely used PET radiotracer for in vivo imaging of the peripheral benzodiazepine receptors (P.B.R. or translocator protein (18 kDa, T.S.P.O.). With the aim of developing a new PET imaging probe for the in vivo study of the P.B.R., two pyrazol [1,5-a]pyrimidineacetamides (D.P.A.-713 and D.P.A.-715) and one imidazol[1,2-a]pyridine-acetamide (C.L.I.N.M.E.) were radiolabelled with the positron emitters carbon{sup 11} (half life: 20.38 min) [1-5]. Briefly, C.L.I.N.M.E. (2-[6-chloro-2(4-iodophenyl)-imidazol[1,2-a]pyridin-3-yl] -N-ethyl-N-methyl-acetamide) was labelled at its methyl-acetamide moity chain from the corresponding nor-analogue using[{sup 11}C]methyl iodide (in D.M.S.O./D.M.F (100/200 {mu}L) containing powdered K.O.H. (3-5 mg) at 110 degrees C for 3 min. D.P.A.-713 (N,N-diethyl-2-[2-(4-methoxy-phenyl)-5,7-dimethyl-pyrazolo[1,5-a]pyrimidin -3-yl]acetamide) and D.P.A.-715 (N,N-diethyl-2-[2-(4-methoxy-phenyl)-5,7-bis-tri-fluoro-methyl-pyrazolo [1,5-a]pyrimidin-3-yl]acetamide) were labelled at their aromatic methoxy groups from the corresponding nor-derivatives using [{sup 11}C]methyl triflate (in acetone (300{mu}L) containing aq. 3 M NaOH (4{mu}L) at 110 degrees C for 1 min). All radioligands were purified using semi preparative Zorbax reverse phase H.P.L.C., were adequately formulated for in vivo injection within 30 min and were found to be > 95% chemically and radiochemically pure. (N.C.)

  20. The balancing act of transcription factors C-1-1 and Runx2 in articular cartilage development

    International Nuclear Information System (INIS)

    Iwamoto, Masahiro; Koyama, Eiki; Enomoto-Iwamoto, Motomi; Pacifici, Maurizio

    2005-01-01

    In previous studies we found that the ets transcription factor C-1-1 is involved in articular chondrocyte development, and we and others found that the transcription factor Runx2 is required for growth plate chondrocyte maturation and ossification. We determined here whether the two factors exert reciprocal influences on their expression and function and in so doing, steer chondrocyte developmental paths. Virally driven Runx2 over-expression in cultured chick chondrocytes did indeed lead to decreased C-1-1 expression, accompanied by decreased expression of articular cartilage marker tenascin-C, decreased proliferation, and increased expression of maturation marker collagen X. In good agreement, over-expression of a dominant-negative Runx2 form had opposite phenotypic consequences. When C-1-1 itself was over-expressed in chondrocytes already undergoing maturation, maturation was halted and the cells became small, rich in tenascin-C, and mitotically quite active. To extend these observations, we misexpressed C-1-1 in mouse cartilage and found that it caused a severe inhibition of chondrocyte maturation and widespread tenascin-C expression. In sum, C-1-1 and Runx2 do influence their respective expression patterns. The factors are powerful chondrocyte regulators and their functional interrelationships may be important for steering the cells toward alternative developmental paths

  1. Enzymatic synthesis of C-11 formaldehyde: concise communication

    International Nuclear Information System (INIS)

    Slegers, G.; Lambrecht, R.H.D.; Vandewalle, T.; Meulewaeter, L.; Vandecasteele, C.

    1984-01-01

    An enzymatic synthesis of C-11 formaldehyde from C-11 methanol is presented, with immobilized alcohol oxidase and catalase: a rapid, simple procedure, with a high and reproducible yield. Carbon-11 methanol is oxidized to C-11 formaldehyde by passage over a column on which the enzymes alcohol oxidase and catalase are immobilized. The catalase increases reaction velocity by recycling the oxygen, and prevents destruction of the alcohol oxidase by eliminating the excess of hydrogen peroxide. The yield of the enzyme-catalyzed oxidation was 80-95%. A specific activity of 400-450 mCi/μmole was obtained at EOB + 20 min. Various immobilization techniques and the optimal reaction conditions of the immobilized enzymes are investigated

  2. 21 CFR 82.1261 - D&C Orange No. 11.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false D&C Orange No. 11. 82.1261 Section 82.1261 Food... CERTIFIED PROVISIONALLY LISTED COLORS AND SPECIFICATIONS Drugs and Cosmetics § 82.1261 D&C Orange No. 11. The color additive D&C Orange No. 11 shall conform in identity and specifications to the requirements...

  3. 21 CFR 74.2261 - D&C Orange No. 11.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false D&C Orange No. 11. 74.2261 Section 74.2261 Food... COLOR ADDITIVES SUBJECT TO CERTIFICATION Cosmetics § 74.2261 D&C Orange No. 11. (a) Identity and specifications. The color additive D&C Orange No. 11 shall conform in identity and specifications to the...

  4. N-[11C]methyl-3,4-methylenedioxyamphetamine (Ecstasy) and 2-methyl-N-[11C]methyl-4,5-methylenedioxyamphetamine. Synthesis and biodistribution studies

    International Nuclear Information System (INIS)

    Patt, M.; Machulla, H.J.; Guendisch, D.; Kovar, K.A.; Wuellner, U.; Blocher, A.

    1999-01-01

    In order to evaluate the neurobiological mechanism causing the psychogenic effects of methylenedioxy-derivatives of amphetamine, the carbon-11 labeled analogues of 3,4-methylenedioxymethamphetamine (MDMA), 2 and 2,N-dimethyl-4,5-methylenedioxyamphetamine (MADAM-6) 4 were prepared for application in in-vivo PET studies by methylation of 3,4-methylenedioxyamphetamine (MDA) 1 and 2-methyl-4,5-methylenedioxyamphetamine 3 with [ 11 C]CH 3 I. The radiochemical yield was determined in dependence on time, temperature and amount of precursor. The best conditions for a fast labeling reaction with carbon-11 on a preparative scale were found to be a reaction time of 10 min using 1 mg of the corresponding dimethyl-precursors 1 or 3, thus obtaining radiochemical yields of 60% (based on produced [ 11 C]CH 3 I). Biodistribution studies were performed in rats, a high brain to blood ratio of 7.5 was observed for [ 11 C]MDMA in contrast to a ratio of 3.7 for [ 11 C]MADAM-6. (author)

  5. Synthesis of γ-amino[4-11C]butyric acid (GABA)

    International Nuclear Information System (INIS)

    Antoni, G.; Laangstroem, B.

    1989-01-01

    A one-pot synthesis of no-carrier added γ-amino[4- 11 C]butyric acid (GABA) starting with hydrogen [ 11 C]cyanide prepared from [ 11 C]carbon dioxide, is presented. Hydrogen [ 11 C]cyanide was trapped in tetrahydrofuran/potassium hydroxide in the presence of the amino polyether Krytofix 2.2.2. A Michael addition with ethyl acrylate followed by a selective reduction and hydrolysis of the resulting amino ester gave [4- 11 C]GABA. The radiochemical purity of GABA was higher than 99% and the decay corrected radiochemical yield was 60-65% based on the amount of H[ 11 C]CN used. The total synthesis time including purification was around 40 min, counted from the start of the Michael addition reaction. (Author)

  6. Species differences in [11C]clorgyline binding in brain

    International Nuclear Information System (INIS)

    Fowler, Joanna S.; Ding, Yu-Shin; Logan, Jean; MacGregor, Robert R.; Shea, Colleen; Garza, Victor; Gimi, Raomond; Volkow, Nora D.; Wang, Gene-Jack; Schlyer, David; Ferrieri, Richard; Gatley, S. John; Alexoff, David; Carter, Pauline; King, Payton; Pappas, Naomi; Arnett, Carroll D.

    2001-01-01

    [ 11 C]Clorgyline selectively binds to MAO A in the human brain. This contrasts with a recent report that [ 11 C]clorgyline (in contrast to other labeled MAO A inhibitors) is not retained in the rhesus monkey brain . To explore this difference, we compared [ 11 C]clorgyline in the baboon brain before and after clorgyline pretreatment and we also synthesized deuterium substituted [ 11 C]clorgyline (and its nor-precursor) for comparison. [ 11 C]Clorgyline was not retained in the baboon brain nor was it influenced by clorgyline pretreatment or by deuterium substitution, contrasting to results in humans. This suggests a species difference in the susceptibility of MAO A to inhibition by clorgyline and represents an unusual example of where the behavior of a radiotracer in the baboon brain does not predict its behavior in the human brain

  7. 21 CFR 74.1261 - D&C Orange No. 11.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false D&C Orange No. 11. 74.1261 Section 74.1261 Food... COLOR ADDITIVES SUBJECT TO CERTIFICATION Drugs § 74.1261 D&C Orange No. 11. (a) Identity. (1) The color additive D&C Orange No. 11 is a mixture consisting principally of the disodium salts of 4′,5...

  8. Peripheral metabolism of (R)-[11C]verapamil in epilepsy patients

    International Nuclear Information System (INIS)

    Abrahim, Aiman; Langer, Oliver; Luurtsema, Gert; Lubberink, Mark; Lammertsma, Adriaan A.; Bauer, Martin; Joukhadar, Christian; Mueller, Markus; Karch, Rudolf; Pataraia, Ekaterina; Baumgartner, Christoph; Kletter, Kurt

    2008-01-01

    (R)-[ 11 C]verapamil is a new PET tracer for P-glycoprotein-mediated transport at the blood-brain barrier. For kinetic analysis of (R)-[ 11 C]verapamil PET data the measurement of a metabolite-corrected arterial input function is required. The aim of this study was to assess peripheral (R)-[ 11 C]verapamil metabolism in patients with temporal lobe epilepsy and compare these data with previously reported data from healthy volunteers. Arterial blood samples were collected from eight patients undergoing (R)-[ 11 C]verapamil PET and selected samples were analysed for radiolabelled metabolites of (R)-[ 11 C]verapamil by using an assay that measures polar N-demethylation metabolites by solid-phase extraction and lipophilic N-dealkylation metabolites by HPLC. Peripheral metabolism of (R)-[ 11 C]verapamil was significantly faster in patients compared to healthy volunteers (AUC of (R)-[ 11 C]verapamil fraction in plasma: 29.4 ± 3.9 min for patients versus 40.8 ± 5.0 min for healthy volunteers; p 11 C]verapamil plasma concentrations (AUC of (R)-[ 11 C]verapamil concentration, normalised to injected dose per body weight: 25.5 ± 2.1 min for patients and 30.5 ± 5.9 min for healthy volunteers; p = 0.038). Faster metabolism appeared to be mainly due to increased N-demethylation as the polar [ 11 C]metabolite fraction was up to two-fold greater in patients. Faster metabolism of (R)-[ 11 C]verapamil in epilepsy patients may be caused by hepatic cytochrome P450 enzyme induction by antiepileptic drugs. Based on these data caution is warranted when using an averaged arterial input function derived from healthy volunteers for the analysis of patient data. Moreover, our data illustrate how antiepileptic drugs may decrease serum levels of concomitant medication, which may eventually lead to a loss of therapeutic efficacy. (orig.)

  9. An asymmetric approach to the radiosynthesis of both enantiomers of α-[11C]methyldopa and α-[11C]methyltyrosine for positron emission tomography

    Science.gov (United States)

    Popkov, A.; Nádvorník, M.; Jirman, J.; Kružberská, P.; Lyčka, A.; Weidlich, T.; Kožíšek, J.; Breza, M.; Lehel, S.; Gillings, N. M.

    2006-01-01

    In PET, α-methyl amino acids can play a dual role: a) precursors of neurotransmitters analogues for the study of neurodegenerative diseases; b) non-metabolised analogues of proteinogenic amino acids for the study of amino acids uptake into normal and cancer cells. The difference in the uptake rates during a PET scan could visualise cancer cells in a human body. Clinical applications of such amino acids are strongly limited due to their poor availability. For the synthesis of α-[11C]methyl-tryptohan, an industrial procedure was adopted. All attempts to prepare enantiomerically pure α-[11C]methylated tyrosine failed. We carried out [11C]methylation of metalocomplex synthons derived from protected DOPA or tyrosine. Individual diastereomers were successfully separated by preparative HPLC, diluted with excess of water and extracted on C18 cartridges. Optimisation of the procedure followed by hydrolysis of the complexes and purification of the enantiomers of α-[11C]methylDOPA and α-[11C]methyltyrosine is underway.

  10. Synthesis of 13N and/or 11C single or doubly labelled urea

    International Nuclear Information System (INIS)

    Emran, A.M.

    1989-01-01

    Utilization of nitrogen by plants encounters two important problems which are denitrification and deficiency or inactivation of certain enzyme. In the first process the fertilizer is affected by certain bacteria to produce nitrogen or its oxides which cannot be utilized by plants. In the second process, transformation of urea nitrogen into forms usable by plants depends on abundance and activity of the enzyme urease. Study of inorganic nitrogen transport has been underway using 13 N-nitrate as a tracer. Behavior of organic nitrogen can be studied using labelled urea. [ 13 N] and/or [ 11 C] single or doubly labelled urea are good tracers for this purpose. Reaction of trace amounts of potassium cyanate with 13 N-ammonium sulfate produced 13 N-ammonium cyanate which was thermally transformed into [ 13 N]-urea with no added carrier. Similarly, [ 11 C]-potassium cyanate reacted with 13 N-ammonium sulfate to produce 13 N/ 11 C-doubly labelled urea. Thin layer and high performance liquid chromatography were used to identify the products and determine the yields

  11. Synthesis and pharmacological characterization of a new PET ligand for the serotonin transporter: [{sup 11}C]5-bromo-2-[2-(dimethylaminomethylphenylsulfanyl)]phenylamine ([{sup 11}C]DAPA)

    Energy Technology Data Exchange (ETDEWEB)

    Huang Yiyun E-mail: hh285@columbia.edu; Hwang, D.-R.; Zhu Zhihong; Bae, S.-A.; Guo Ningning; Sudo, Yasuhiko; Kegeles, Lawrence S.; Laruelle, Marc

    2002-10-01

    A new PET radioligand for the serotonin transporter (SERT), [{sup 11}C]-5-bromo-2-[2-(dimethylaminomethylphenylsulfanyl)]phenylamine ([{sup 11}C]DAPA (10), was synthesized and evaluated in vivo in rats and baboons. [{sup 11}C]DAPA (10) was prepared from its monomethylamino precursor 8 by reaction with high specific activity [{sup 11}C]methyl iodide. Radiochemical yield was 24{+-}5% based on [{sup 11}C]methyl iodide at end of bombardment (EOB, n=10) and specific activity was 1553{+-}939 Ci/mmol at end of synthesis (EOS, n=10). Binding assays indicated that [{sup 11}C]DAPA displays high affinity (Ki 1.49{+-}0.28 nM for hSERT) and good selectivity for the SERT in vitro. Biodistribution studies in rats indicated that [{sup 11}C]DAPA enters into the brain readily and localizes in brain regions known to contain high concentrations of SERT, such as the thalamus, hypothalamus, frontal cortex and striatum. Moreover, such binding in SERT-rich regions of the brain are blocked by pretreatment with either the selective serotonin reuptake inhibitor (SSRI) citalopram and by the cold compound itself, demonstrating that [{sup 11}C]DAPA binding in the rat brain is saturable and specific to SERT. Imaging experiments in baboons indicated that [{sup 11}C]DAPA binding is consistent with the known distribution of SERT in the baboon brain, with highest levels of radioactivity detected in the midbrain and thalamus, intermediate levels in the hippocampus and striatum, and lower levels in the cortical regions. Pretreatment of the baboon with citalopram 10 min before radioactivity injection blocked the binding of [{sup 11}C]DAPA in all brain regions that contain SERT. Kinetic analysis revealed that, in all brain regions examined, [{sup 11}C]DAPA specific to nonspecific distribution volume ratios (V{sub 3}'') are higher than [{sup 11}C](+)-McN 5652 and similar to [{sup 11}C]DASB. In summary, [{sup 11}C]DAPA appears to be a promising radioligand suitable for the visualization of SERT

  12. Robotic synthesis of L-[1-11C]tyrosine

    International Nuclear Information System (INIS)

    Luurtsema, Gert; Medema, Jitze; Elsinga, P.H.; Visser, G.M.; Vaalburg, Willem

    1994-01-01

    L-[1- 11 C]tyrosine promises to become an important tracer for determination of the protein synthesis rate (PSR) in tumor tissue and brain. The commercially available Anatech RB-86 robotic system is utilized for the automation of the L-[1- 11 C]tyrosine production via the isocyanide method as reported by Bolster et al. (Eur. J. Nucl. Med. 12, 321-324, 1986). The total synthesis time, including HPLC-purification and enantiomeric separation is 60 min. With a practical yield of 20 mCi L-[1- 11 C]tyrosine at a specific activity > 1000 Ci/mmol. (author)

  13. Simple and rapid preparation of [{sup 11}C]DASB with high quality and reliability for routine applications

    Energy Technology Data Exchange (ETDEWEB)

    Haeusler, D.; Mien, L.-K. [Department of Nuclear Medicine, PET, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, A-1090 Vienna (Austria); Nics, L. [Department of Nuclear Medicine, PET, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Department of Nutritional Sciences, University of Vienna, A-1090 Vienna (Austria); Ungersboeck, J. [Department of Nuclear Medicine, PET, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Department of Inorganic Chemistry, University of Vienna, A-1090 Vienna (Austria); Philippe, C. [Department of Nuclear Medicine, PET, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, A-1090 Vienna (Austria); Lanzenberger, R.R. [Department of Psychiatry and Psychotherapy, Medical University of Vienna, A-1090 Vienna (Austria); Kletter, K.; Dudczak, R. [Department of Nuclear Medicine, PET, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Mitterhauser, M. [Department of Nuclear Medicine, PET, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, A-1090 Vienna (Austria); Hospital Pharmacy of the General Hospital of Vienna, A-1090 Vienna (Austria); Wadsak, W. [Department of Nuclear Medicine, PET, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Department of Inorganic Chemistry, University of Vienna, A-1090 Vienna (Austria)], E-mail: wolfgang.wadsak@meduniwien.ac.at

    2009-09-15

    [{sup 11}C]DASB combines all major prerequisites for a successful SERT-ligand, providing excellent biological properties and in-vivo behaviour. Thus, we aimed to establish a fully automated procedure for the synthesis and purification of [{sup 11}C]DASB with a high degree of reliability reducing the overall synthesis time while conserving high yields and purity. The optimized [{sup 11}C]DASB synthesis was applied in more than 60 applications with a very low failure rate (3.2%). We obtained yields up to 8.9 GBq (average 5.3{+-}1.6 GBq). Radiochemical yields based on [{sup 11}C]CH{sub 3}I, (corrected for decay) were 66.3{+-}6.9% with a specific radioactivity (A{sub s}) of 86.8{+-}24.3 GBq/{mu}mol (both at the end of synthesis, EOS). Time consumption was kept to a minimum, resulting in 43 min from end of bombardment to release of the product after quality control. Form our data, it is evident that the presented method can be implemented for routine preparations of [{sup 11}C]DASB with high reliability.

  14. Characterization of hepatic tumors using [11C]metomidate through positron emission tomography

    DEFF Research Database (Denmark)

    Roivainen, Anne; Naum, Alexandru; Nuutinen, Heikki

    2013-01-01

    ABSTRACT: BACKGROUND: Using positron emission tomography (PET), we compared two tracers, [11C]metomidate ([11C]MTO) and [11C]acetate ([11C]ACE), for the characterization of hepatic tumors. METHODS: Thirty-three patients underwent PET with [11C]MTO and [11C]ACE and magnetic resonance imaging (MRI...

  15. 11beta-hydroxysteroid dehydrogenase type 2 expression in the newly formed Leydig cells after ethane dimethanesulphonate treatment of adult rats.

    Directory of Open Access Journals (Sweden)

    Katerina Georgieva

    2008-01-01

    Full Text Available The enzyme 11beta-hydroxysteroid dehydrogenase (11beta-HSD catalyzes the reversible conversion of physiologically active corticosterone to the biologically inert 11beta-dehydrocorticosterone in rat testis and protect the Leydig cells (LCs against the suppressive effect of glucocorticoids. The developmental pathway of the adult LCs population is accompanied with an increase in the 11beta-HDS activity. Thus, 11beta-HDS together with its role in controlling the toxicological effect of glucocorticoids on LCs can be used as a marker for their functional maturity. Ethane 1,2-dimethanesulphonate (EDS treatment of adult rats become unique appropriate model, which enable to answer many questions related to the differentiation of adult LCs in the prepubertal rat testis. The aim of the present study was to investigate the specific changes in the 11beta-HDS type 2 immunoreactivity in tandem with the expression of androgen receptor (AR during renewal of LCs population after EDS treatment. In the present study, we observed the first appearance of immunostaining for 11beta-HSD2 in new LCs population on day 14 after EDS administration when the progenitor LCs were detected. Our immunohistochemical analysis revealed progressive increases in the 11beta-HSD2 reaction intensity on 21 days after EDS treatment and reached a maximum on day 35. AR immunoexpression was found in new LCs on day 14 and 21 after EDS injection with an increasing curve of intensity. The most prominent AR immunostaining in new population LCs was evident by 35 days after EDS and that coincided with the increased number of LCs and restoration of adult LCs population. Our results demonstrated similar pattern of immunoreactivity for 11beta-HSD2 and AR in new LCs population after EDS treatment and suggested that the changes in 11beta-HSD2 expression can be used for evaluation of adult LCs differentiation in rat testis.

  16. Biodistribution and radiation dosimetry of the {alpha}{sub 7} nicotinic acetylcholine receptor ligand [{sup 11}C]CHIBA-1001 in humans

    Energy Technology Data Exchange (ETDEWEB)

    Sakata, Muneyuki [Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, 1-1 Naka-cho, Itabashi-ku, Tokyo 173-0022 (Japan); Wu, Jin; Toyohara, Jun [Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, 1-1 Naka-cho, Itabashi-ku, Tokyo 173-0022 (Japan); Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670 (Japan); Oda, Keiichi [Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, 1-1 Naka-cho, Itabashi-ku, Tokyo 173-0022 (Japan); Ishikawa, Masatomo [Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, 1-1 Naka-cho, Itabashi-ku, Tokyo 173-0022 (Japan); Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670 (Japan); Ishii, Kenji [Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, 1-1 Naka-cho, Itabashi-ku, Tokyo 173-0022 (Japan); Hashimoto, Kenji [Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670 (Japan); Ishiwata, Kiichi, E-mail: ishiwata@pet.tmig.or.j [Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, 1-1 Naka-cho, Itabashi-ku, Tokyo 173-0022 (Japan)

    2011-04-15

    Introduction: 4-[{sup 11}C]Methylphenyl 2,4-diazabicyclo[3.2.2]nonane-2-carboxylate ([{sup 11}C]CHIBA-1001) is a newly developed positron emission tomography (PET) ligand for mapping {alpha}{sub 7} nicotinic acetylcholine receptors. We investigated whole-body biodistribution and radiation dosimetry of [{sup 11}C]CHIBA-1001 in humans and compared the results with those obtained in mice. Methods: Dynamic whole-body PET was carried out for three human subjects after administering a bolus injection of [{sup 11}C]CHIBA-1001. Emission scans were collected in two-dimensional mode over five bed positions. Regions of interest were placed over 12 organs. Radiation dosimetry was estimated from the residence times of these source organs using the OLINDA program. Biodistribution data from mice were also used for the prediction of radiation dosimetry in humans, and results with and those without accommodation of different proportions of organ-to-total-body mass were compared with the results from the human PET study. Results: In humans, the highest accumulation was observed in the liver, whereas in mice, the highest accumulation was observed in the urinary bladder. The estimated effective dose from the human PET study was 6.9 {mu}Sv/MBq, and that from mice was much underestimated. Conclusion: Effective dose estimates for [{sup 11}C]CHIBA-1001 were compatible with those associated with other common nuclear medicine tests. Absorption doses among several organs were considerably different between the human and mouse studies. Human dosimetry studies for the investigation of radiation safety are desirable as one of the first clinical trials of new PET probes before their application in subsequent clinical investigations.

  17. Effects of ketoconazole on the biodistribution and metabolism of [{sup 11}C]loperamide and [{sup 11}C]N-desmethyl-loperamide in wild-type and P-gp knockout mice

    Energy Technology Data Exchange (ETDEWEB)

    Seneca, Nicholas; Zoghbi, Sami S.; Shetty, H. Umesha; Tuan, Edward; Kannan, Pavitra; Taku, Andrew; Innis, Robert B. [Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892 (United States); Pike, Victor W. [Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892 (United States)], E-mail: pikev@mail.nih.gov

    2010-04-15

    Introduction: [{sup 11}C]Loperamide and [{sup 11}C]N-desmethyl-loperamide ([{sup 11}C]dLop) have been proposed as radiotracers for imaging brain P-glycoprotein (P-gp) function. A major route of [{sup 11}C]loperamide metabolism is N-demethylation to [{sup 11}C]dLop. We aimed to test whether inhibition of CYP3A4 with ketoconazole might reduce the metabolism of [{sup 11}C]loperamide and [{sup 11}C]dLop in mice, and thereby improve the quality of these radiotracers. Methods: Studies were performed in wild-type and P-gp knockout (mdr-1a/b -/-) mice. During each of seven study sessions, one pair of mice, comprising one wild-type and one knockout mouse, was pretreated with ketoconazole (50 mg/kg, ip), while another such pair was left untreated. Mice were sacrificed at 30 min after injection of [{sup 11}C]loperamide or [{sup 11}C]dLop. Whole brain and plasma samples were measured for radioactivity and analyzed with radio-high-performance liquid chromatography. Results: Ketoconazole increased the plasma concentrations of [{sup 11}C]loperamide and its main radiometabolite, [{sup 11}C]dLop, by about twofold in both wild-type and knockout mice, whereas the most polar radiometabolite was decreased threefold. Furthermore, ketoconazole increased the brain concentrations of [{sup 11}C]loperamide and the radiometabolite [{sup 11}C]dLop by about twofold in knockout mice, and decreased the brain concentrations of the major and most polar radiometabolite in wild-type and knockout mice by 82% and 49%, respectively. In contrast, ketoconazole had no effect on plasma and brain distribution of administered [{sup 11}C]dLop and its radiometabolites in either wild-type or knockout mice, except to increase the low plasma [{sup 11}C]dLop concentration. The least polar radiometabolite of [{sup 11}C]dLop was identified with LC-MS{sup n} as the N-hydroxymethyl analog of [{sup 11}C]dLop and this also behaved as a P-gp substrate. Conclusion: In this study, ketoconazole (50 mg/kg, ip) proved

  18. Synthesis of two potential NK1-receptor ligands using [1-11C]ethyl iodide and [1-11C]propyl iodide and initial PET-imaging

    Directory of Open Access Journals (Sweden)

    Genchel Tove

    2007-07-01

    Full Text Available Abstract Background The previously validated NK1-receptor ligand [O-methyl-11C]GR205171 binds with a high affinity to the NK1-receptor and displays a slow dissociation from the receptor. Hence, it cannot be used in vivo for detecting concentration changes in substance P, the endogenous ligand for the NK1-receptor. A radioligand used for monitoring these changes has to enable displacement by the endogenous ligand and thus bind reversibly to the receptor. Small changes in the structure of a receptor ligand can lead to changes in binding characteristics and also in the ability to penetrate the blood-brain barrier. The aim of this study was to use carbon-11 labelled ethyl and propyl iodide with high specific radioactivity in the synthesis of two new and potentially reversible NK1-receptor ligands with chemical structures based on [O-methyl-11C]GR205171. Methods [1-11C]Ethyl and [1-11C]propyl iodide with specific radioactivities of 90 GBq/μmol and 270 GBq/μmol, respectively, were used in the synthesis of [O-methyl-11C]GR205171 analogues by alkylation of O-desmethyl GR205171. The brain uptake of the obtained (2S,3S-N-(1-(2- [1-11C]ethoxy-5-(3-(trifluoromethyl-4H-1,2,4-triazol-4-ylphenylethyl-2-phenylpiperidin-3-amine (I and (2S,3S-2-phenyl-N-(1-(2- [1-11C]propoxy-5-(3-(trifluoromethyl-4H-1,2,4-triazol-4-ylphenylethylpiperidin-3-amine (II was studied with PET in guinea pigs and rhesus monkeys and compared to the uptake of [O-methyl-11C]GR205171. Results All ligands had similar uptake distribution in the guinea pig brain. The PET-studies in rhesus monkeys showed that (II had no specific binding in striatum. Ligand (I had moderate specific binding compared to the [O-methyl-11C]GR205171. The ethyl analogue (I displayed reversible binding characteristics contrary to the slow dissociation rate shown by [O-methyl-11C]GR205171. Conclusion The propyl-analogue (II cannot be used for detecting changes in NK1-ligand levels, while further studies should be

  19. Evaluation of clinial usefulness of 11C-methionine positron emission tomography (11C-MET-PET) as a tool for liver functional imaging

    International Nuclear Information System (INIS)

    Enomoto, Kazuo; Matsui, Yoshifumi; Okazumi, Shinichi

    1994-01-01

    We studied 11 C-MET-PET in 17 clinical cases, 10 patients with obstructive jaundice and 7 normal volunteers, and analyzed its efficacy for the evaluation of hepatic functional reserve in major hepatectomy candidates. Differential absorption ratio (DAR) of 11 C was compared to the hepatic protein synthesis rate (HPS), which is measured as the incorporation rate of 3 H-labeled leucine in protein fraction, using needle biopsied liver specimen obtained from each hepatic segment. In the cases of normal liver function, DAR was well correlated with HPS. Also in jaundice cases with two exceptions, low HPS segment was demonstrated as low DAR segment. Consequently, MET-PET images could clearly provide functional liver imaging. After injection of 11 C-MET, the increase in rate of radioactivity of 11 C in plasma protein fraction was higher in jaundice cases than in normal volunteers, which is in accord with the results of our former study that cholestatic liver has accelerated protein synthesis rate. In summary, since 11 C-MET-PET could demonstrate liver functional imaging, it might be a possible tool for liver function assessment in major hepatectomy candidates. (author)

  20. Seizures beget seizures in temporal lobe epilepsies: the boomerang effects of newly formed aberrant kainatergic synapses.

    Science.gov (United States)

    Ben-Ari, Yehezkel; Crepel, Valérie; Represa, Alfonso

    2008-01-01

    Do temporal lobe epilepsy (TLE) seizures in adults promote further seizures? Clinical and experimental data suggest that new synapses are formed after an initial episode of status epilepticus, however their contribution to the transformation of a naive network to an epileptogenic one has been debated. Recent experimental data show that newly formed aberrant excitatory synapses on the granule cells of the fascia dentate operate by means of kainate receptor-operated signals that are not present on naive granule cells. Therefore, genuine epileptic networks rely on signaling cascades that differentiate them from naive networks. Recurrent limbic seizures generated by the activation of kainate receptors and synapses in naive animals lead to the formation of novel synapses that facilitate the emergence of further seizures. This negative, vicious cycle illustrates the central role of reactive plasticity in neurological disorders.

  1. [11C] Methionine as PET radiopharmaceutical produced at CDTN/CNEN

    International Nuclear Information System (INIS)

    Silveira, Marina B.; Ferreira, Soraya Z.; Carvalho, Tiago F.; Silva, Juliana B. da

    2013-01-01

    Carbon-11 ( 11 C) is an attractive radionuclide used in positron emission tomography (PET) since carbon is a ubiquitous element in biomolecules. Positron emitter-labeled amino acids are being widely used as indicators of tumor activity due to enhanced expression of amino acid transporter systems in cancer cells. L-[Methyl-( 11 C)] Methionine or [ 11 C]Methionine is being used in neuro-oncology and, unlike 2-[ 18 F]fluoro-2-deoxy-D-glucose ( 18 FDG), gives more contrast images and improves brain tumor diagnosis. The aim of this work was to develop the synthesis and quality control of [ 11 C]Methionine at the Radiopharmaceuticals Research and Production Facility (UPPR) of CDTN/CNEN. The synthesis of [ 11 C] Methionine was performed using two Sep-Pak tC18 plus cartridges one as solid support for the 11 C-methylation of the precursor L-homocysteine thiolactone hydrochloride and another for purification. The pH, radionuclidic identity and purity, residual solvents, radiochemical and chemical purity of the final product were evaluated as described on the European Pharmacopoeia 7.0 monograph. Total synthesis time was 18 minutes, the radiochemical yield was approximately 15% (non-decay corrected) and radiochemical purity was greater than 95%. [ 11 C]Methionine was successfully synthesized at CDTN using the described procedures and complied with quality requirements. Due to the rapid growth of oncologic PET scans in last decade, 11 C labelling holds great promises in the next few years with the application of other tracers beyond 18 FDG. This pioneering work of UPPR/CDTN represents a response to the demands of a growing nuclear medicine in the country focused on achieving better diagnostic imaging. (author)

  2. Utility of (11)C-methionine and (11)C-donepezil for imaging of Staphylococcus aureus induced osteomyelitis in a juvenile porcine model

    DEFF Research Database (Denmark)

    Afzelius, Pia; Alstrup, Aage Ko; Schønheyder, Henrik C

    2016-01-01

    in the right femoral artery with a porcine strain of Staphylococcus aureus. The sequential scan protocol included Computed Tomography, (11)C-methionine and (11)C-donepezil PET, (99m) Tc-DPD and (111)In-labelled leukocytes scintigraphy, and (18)F-FDG PET. This was followed by necropsy of the pigs and gross...

  3. Automatic synthesis of [11C]NKY-722 with high specific activity, using anhydrous [11C] methanol as a precursor

    International Nuclear Information System (INIS)

    Suzuki, Kazutoshi; Inoue, Osamu; Itoh, Takashi; Nemoto, Kazuyoshi; Oosumi, Seimei; Miwa, Soichi.

    1992-01-01

    3-(4-allyl-1-piperazinyl)-2,2-dimethylpropyl methyl 1,4-dihydro-2,6-dimethyl- 4-(3-nitrophenyl)-3,5-pyridine dicarboxylate (NKY-722) was labeled with carbon-11 using anhydrous [ 11 C] methanol. Using a computer controlled equipment, a few GBq of [ 11 C] NKY-722 with the specific activity of 120 - 180 GBq/μmol could by synthesized at the radiochemical purity of > 99% in 10 ml of physiological saline containing Polysolvate-80 (1.5 vol%) and ethyl alcohol (0.75 vol%). Preliminary PET experiments using rats and a rhesus monkey have bee done, and very low accumulation of the compound into the brain, however comparatively higher accumulation in the heart were observed. (author)

  4. Preparation of 11C-labelled methanol on alumina column

    International Nuclear Information System (INIS)

    Sarkadi, E.; Kovacs, Z.; Horvath, G.

    1998-01-01

    The [ 11 C]methyl iodide is an important intermedia to synthesize 11 C-labelled radiopharmaceuticals for medical diagnostics in positron emission tomography. Recently a new method has been developed to produce [ 11 C]methanol intermedia. The advantage of this method of radiomethanol preparation is the application of an alumina column at room temperature instead of a complicated cooling unit used with the conventional reaction vessel. The yield and purity of radiomethanol was the same as in the previous methods. (K.A.)

  5. PET Imaging of CRF1 with [11C]R121920 and [11C]DMP696: is the target of sufficient density?

    International Nuclear Information System (INIS)

    Sullivan, Gregory M.; Parsey, Ramin V.; Kumar, J.S. Dileep; Arango, Victoria; Kassir, Suham A.; Huang, Yung-yu; Simpson, Norman R.; Van Heertum, Ronald L.; Mann, J. John

    2007-01-01

    Aim: Overstimulation of the CRF type 1 receptor (CRF1) is implicated in anxiety and depressive disorders. The aim of this study was to investigate the in vivo binding characteristics of [ 11 C]R121920 and [ 11 C]DMP696 in the nonhuman primate for application in positron emission tomography (PET) studies of CRF1. Methods: PET imaging with the two novel CRF1 radioligands was performed in baboon. In vitro binding studies for CRF1 were performed in postmortem brain tissue of baboon and human to assess sufficiency of receptor density for PET. Results: Both [ 11 C]R121920 and [ 11 C]DMP696 distributed rapidly and uniformly throughout the brain. Washout was comparable across brain regions, without differences in volume of distribution between regions reported to have high and low in vitro CRF1 binding. Membrane-enriched tissue homogenate assay using [ 125 I]Tyr 0 -sauvagine and specific CRF1 antagonists CP154,526 and SN003 in human occipital cortex yielded maximal binding (B max ) of 63.3 and 147.3 fmol/mg protein, respectively, and in human cerebellar cortex yielded B max of 103.6 and 64.6 fmol/mg protein, respectively. Dissociation constants (K D ) were subnanomolar. In baboon, specific binding was not detectable in the same regions; therefore, B max and K D were not measurable. Autoradiographic results were consistent except there was also detectable CRF1-specific binding in baboon cerebellum. Conclusion: Neither [ 11 C]R121920 nor [ 11 C]DMP696 demonstrated quantifiable regional binding in vivo in baboon. In vitro results suggest CRF1 density in baboon may be insufficient for PET. Studies in man may generate more promising results due to the higher CRF1 density compared with baboon in cerebral cortex and cerebellum

  6. Synthesis of dimethyl-1,1 guanylguanidine-{sup 14}C-2,4 (dimethyl-1-1 biguanide) hydrochloride; Synthese du chlorhydrate de dimethyl-1,1 guanylguanidine {sup 14}C-2,4 (dimethyl-1-1 biguanide)

    Energy Technology Data Exchange (ETDEWEB)

    Herbert, M; Pichat, L [Commissariat a l' Energie Atomique, Saclay (France).Centre d' Etudes Nucleaires

    1961-07-01

    A description of the synthesis of dimethyl-1,1 guanylguanidine-{sup 14}C-2,4 hydrochloride passing through the {sup 14}C{sub 2} dicyandiamide. The overall yield with respect to Ba{sup 14}CO{sub 3} is 38 per cent. (author) [French] Description de la synthese du chlorhydrate de dimethyl-1,1 guanylguanidine {sup 14}C-2,4 par l'intermediaire de la dicyandiamide {sup 14}C{sub 2}. Le rendement global par rapport a {sup 14}CO{sub 3}Ba est de 38 pour cent. (auteur)

  7. A radiometabolite study of the serotonin transporter PET radioligand [11C]MADAM

    International Nuclear Information System (INIS)

    Gourand, F.; Emond, P.; Bergström, J.P.; Takano, A.; Gulyás, B.; Guilloteau, D.; Barré, L.; Halldin, C.

    2014-01-01

    Introduction: 11 C]MADAM is a radioligand suitable for PET studies of the serotonin transporter (SERT). Metabolite analysis in human and non-human plasma samples using HPLC separation has shown that [ 11 C]MADAM was rapidly metabolized. A possible metabolic pathway is the S-oxidation which could lead to SOMADAM and SO 2 MADAM. In vitro evaluation of these two potential metabolites has shown that SOMADAM exhibited a good affinity for SERT and a good selectivity for SERT over NET and DAT. Methods: Comparative PET imaging studies in non-human primate brain with [ 11 C]MADAM and [ 11 C]SOMADAM were carried out, and plasma samples were analyzed using reverse phase HPLC. We have explored the metabolism of [ 11 C]MADAM in rat brain with a view to understand its possible interference for brain imaging with PET. Results: PET imaging studies in non-human primate brain using [ 11 C]SOMADAM indicated that this tracer does not bind with high amounts to brain regions known to be rich in SERT. The fraction of [ 11 C]SOMADAM in non-human primate plasma was approximately 5% at 4 min and 1% at 15 min after [ 11 C]MADAM injection. HPLC analysis of brain sample after [ 11 C]MADAM injection to rats demonstrated that [ 11 C]SOMADAM was not detected in the brain. Conclusions: 11 C]SOMADAM is not superior over [ 11 C]MADAM as a SERT PET radioligand. Nevertheless, [ 11 C]SOMADAM has been identified as a minor labeled metabolite of [ 11 C]MADAM measured in monkey plasma. [ 11 C]SOMADAM was not detected in rat brain

  8. [11C] Methionine as PET radiopharmaceutical produced at CDTN/CNEN

    Energy Technology Data Exchange (ETDEWEB)

    Silveira, Marina B.; Ferreira, Soraya Z.; Carvalho, Tiago F.; Silva, Juliana B. da, E-mail: mbs@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil). Unidade de Pesquisa e Producao de Radiofarmacos

    2013-07-01

    Carbon-11 ({sup 11}C) is an attractive radionuclide used in positron emission tomography (PET) since carbon is a ubiquitous element in biomolecules. Positron emitter-labeled amino acids are being widely used as indicators of tumor activity due to enhanced expression of amino acid transporter systems in cancer cells. L-[Methyl-({sup 11}C)] Methionine or [{sup 11}C]Methionine is being used in neuro-oncology and, unlike 2-[{sup 18}F]fluoro-2-deoxy-D-glucose ({sup 18}FDG), gives more contrast images and improves brain tumor diagnosis. The aim of this work was to develop the synthesis and quality control of [{sup 11}C]Methionine at the Radiopharmaceuticals Research and Production Facility (UPPR) of CDTN/CNEN. The synthesis of [{sup 11}C] Methionine was performed using two Sep-Pak tC18 plus cartridges one as solid support for the {sup 11}C-methylation of the precursor L-homocysteine thiolactone hydrochloride and another for purification. The pH, radionuclidic identity and purity, residual solvents, radiochemical and chemical purity of the final product were evaluated as described on the European Pharmacopoeia 7.0 monograph. Total synthesis time was 18 minutes, the radiochemical yield was approximately 15% (non-decay corrected) and radiochemical purity was greater than 95%. [{sup 11}C]Methionine was successfully synthesized at CDTN using the described procedures and complied with quality requirements. Due to the rapid growth of oncologic PET scans in last decade, {sup 11}C labelling holds great promises in the next few years with the application of other tracers beyond {sup 18}FDG. This pioneering work of UPPR/CDTN represents a response to the demands of a growing nuclear medicine in the country focused on achieving better diagnostic imaging. (author)

  9. 11C-MET PET/MRI for detection of recurrent glioma.

    Science.gov (United States)

    Deuschl, C; Kirchner, J; Poeppel, T D; Schaarschmidt, B; Kebir, S; El Hindy, N; Hense, J; Quick, H H; Glas, M; Herrmann, K; Umutlu, L; Moenninghoff, C; Radbruch, A; Forsting, M; Schlamann, M

    2018-04-01

    Radiological assessment of brain tumors is widely based on the Radiology Assessment of Neuro-Oncology (RANO) criteria that consider non-specific T1 and T2 weighted images. Limitation of the RANO criteria is that they do not include metabolic imaging techniques that have been reported to be helpful to differentiate treatment related changes from true tumor progression. In the current study, we assessed if the combined use of MRI and PET with hybrid 11 C-MET PET/MRI can improve diagnostic accuracy and diagnostic confidence of the readers to differentiate treatment related changes from true progression in recurrent glioma. Fifty consecutive patients with histopathologically proven glioma were prospectively enrolled for a hybrid 11 C-MET PET/MRI to differentiate recurrent glioma from treatment induced changes. Sole MRI data were analyzed based on RANO. Sole PET data and in a third evaluation hybrid 11 C-MET-PET/MRI data were assessed for metabolic respectively metabolic and morphologic glioma recurrence. Diagnostic performance and diagnostic confidence of the reader were calculated for the different modalities, and the McNemar test and Mann-Whitney U Test were applied for statistical analysis. Hybrid 11 C-MET PET/MRI was successfully performed in all 50 patients. Glioma recurrence was diagnosed in 35 of the 50 patients (70%). Sensitivity and specificity were calculated for MRI (86.11% and 71.43%), for 11 C-MET PET (96.77% and 73.68%), and for hybrid 11 C-MET-PET/MRI (97.14% and 93.33%). For diagnostic accuracy hybrid 11 C-MET-PET/MRI (96%) showed significantly higher values than MRI alone (82%), whereas no significant difference was found for 11C-MET PET (88%). Furthermore, by rating on a five-point Likert scale significantly higher scores were found for diagnostic confidence when comparing 11 C-MET PET/MRI (4.26 ± 0,777) to either PET alone (3.44 ± 0.705) or MRI alone (3.56 ± 0.733). This feasibility study showed that hybrid PET/MRI might strengthen

  10. Stereocontrolled Synthesis of the C(1)-C(11) Subunit of the Iejimalides

    DEFF Research Database (Denmark)

    Mendlik, Matthew T.; Cottard, Muriel; Rein, Tobias

    1997-01-01

    An enantioselective synthesis of the C(1)-C(11) subunit of the iejimalides has been accomplished through a combination of an asymmetric Homer-Wadsworth-Emmons condensation and a chiral pool approach. (C) 1997 Elsevier Science Ltd....

  11. Modified synthesis of 11-[14C]-clozapine

    International Nuclear Information System (INIS)

    Matloubi, Hojatollah; Ghandi, Mehdi; Zarrindast, M.-R.; Saemian, Nader

    2001-01-01

    The reported synthetic pathway of 8-chloro-11-(4-methyl-1-piperazinyl)-11-[ 14 C]-5H-dibenzo[b,e][1,4]diazapine (clozapine) was modified in several steps. The synthetic pathway was shortened by 60% and the total yield was increased from 6% to 23%

  12. 33 CFR 125.11 - Form of Coast Guard Port Security Card.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Form of Coast Guard Port Security... WATERFRONT FACILITIES OR VESSELS § 125.11 Form of Coast Guard Port Security Card. The Coast Guard Port... data. ...

  13. 11 CFR 102.11 - Petty cash fund (2 U.S.C. 432(h)(2)).

    Science.gov (United States)

    2010-01-01

    ... 11 Federal Elections 1 2010-01-01 2010-01-01 false Petty cash fund (2 U.S.C. 432(h)(2)). 102.11 Section 102.11 Federal Elections FEDERAL ELECTION COMMISSION GENERAL REGISTRATION, ORGANIZATION, AND... and Congressional district) sought by such candidate. ...

  14. 42 CFR 1005.11 - Form, filing and service of papers.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Form, filing and service of papers. 1005.11 Section... and service of papers. (a) Forms. (1) Unless the ALJ directs the parties to do otherwise, documents filed with the ALJ will include an original and two copies. (2) Every pleading and paper filed in the...

  15. Species differences in [{sup 11}C]clorgyline binding in brain

    Energy Technology Data Exchange (ETDEWEB)

    Fowler, Joanna S. E-mail: fowler@bnl.gov; Ding, Yu-Shin; Logan, Jean; MacGregor, Robert R.; Shea, Colleen; Garza, Victor; Gimi, Raomond; Volkow, Nora D.; Wang, Gene-Jack; Schlyer, David; Ferrieri, Richard; Gatley, S. John; Alexoff, David; Carter, Pauline; King, Payton; Pappas, Naomi; Arnett, Carroll D

    2001-10-01

    [{sup 11}C]Clorgyline selectively binds to MAO A in the human brain. This contrasts with a recent report that [{sup 11}C]clorgyline (in contrast to other labeled MAO A inhibitors) is not retained in the rhesus monkey brain . To explore this difference, we compared [{sup 11}C]clorgyline in the baboon brain before and after clorgyline pretreatment and we also synthesized deuterium substituted [{sup 11}C]clorgyline (and its nor-precursor) for comparison. [{sup 11}C]Clorgyline was not retained in the baboon brain nor was it influenced by clorgyline pretreatment or by deuterium substitution, contrasting to results in humans. This suggests a species difference in the susceptibility of MAO A to inhibition by clorgyline and represents an unusual example of where the behavior of a radiotracer in the baboon brain does not predict its behavior in the human brain.

  16. A new form of the rotating C-metric

    International Nuclear Information System (INIS)

    Hong, Kenneth; Teo, Edward

    2005-01-01

    In a previous paper, we showed that the traditional form of the charged C-metric can be transformed, by a change of coordinates, into one with an explicitly factorizable structure function. This new form of the C-metric has the advantage that its properties become much simpler to analyse. In this paper, we propose an analogous new form for the rotating charged C-metric, with structure function G(ξ) = (1 - ξ 2 )(1 + r + Aξ)(1 + r - Aξ), where r ± are the usual locations of the horizons in the Kerr-Newman black hole. Unlike the non-rotating case, this new form is not related to the traditional one by a coordinate transformation. We show that the physical distinction between these two forms of the rotating C-metric lies in the nature of the conical singularities causing the black holes to accelerate apart: the new form is free of torsion singularities and therefore does not contain any closed timelike curves. We claim that this new form should be considered the natural generalization of the C-metric with rotation

  17. Strategies for the generation of parametric images of [11C]PIB with plasma input functions considering discriminations and reproducibility.

    Science.gov (United States)

    Edison, Paul; Brooks, David J; Turkheimer, Federico E; Archer, Hilary A; Hinz, Rainer

    2009-11-01

    Pittsburgh compound B or [11C]PIB is an amyloid imaging agent which shows a clear differentiation between subjects with Alzheimer's disease (AD) and controls. However the observed signal difference in other forms of dementia such as dementia with Lewy bodies (DLB) is smaller, and mild cognitively impaired (MCI) subjects and some healthy elderly normals may show intermediate levels of [11C]PIB binding. The cerebellum, a commonly used reference region for non-specific tracer uptake in [11C]PIB studies in AD may not be valid in Prion disorders or monogenic forms of AD. The aim of this work was to: 1-compare methods for generating parametric maps of [11C]PIB retention in tissue using a plasma input function in respect of their ability to discriminate between AD subjects and controls and 2-estimate the test-retest reproducibility in AD subjects. 12 AD subjects (5 of which underwent a repeat scan within 6 weeks) and 10 control subjects had 90 minute [11C]PIB dynamic PET scans, and arterial plasma input functions were measured. Parametric maps were generated with graphical analysis of reversible binding (Logan plot), irreversible binding (Patlak plot), and spectral analysis. Between group differentiation was calculated using Student's t-test and comparisons between different methods were made using p values. Reproducibility was assessed by intraclass correlation coefficients (ICC). We found that the 75 min value of the impulse response function showed the best group differentiation and had a higher ICC than volume of distribution maps generated from Logan and spectral analysis. Patlak analysis of [11C]PIB binding was the least reproducible.

  18. (S)- and (R)-[11C]nicotine and the metabolite (R/S)-[11C]cotinine. Preparation, metabolite studies and in vivo distribution in the human brain using PET

    International Nuclear Information System (INIS)

    Halldin, C.; Swahn, C.-G.; Nybaeck, H.; Naagren, K.; Laangstroem, B.

    1992-01-01

    In order to investigate [ 11 C]nicotine binding and metabolism in the living human brain by PET, routine protocols were developed for the preparation and purification of (S)-and (R)-[ 11 C]nicotine and the metabolite (R/S)-[ 11 C]cotinine. (S)- and (R)-[ 11 C]nicotine were prepared by N-methylation with [ 11 C]methyl iodide of the appropriate secondary amine, which was liberated in situ by 2,2,6,6,-tetramethylpiperidine (TMP) from its corresponding biscamsylate-salt. (R/S)-[ 11 C]Cotinine was prepared by N-methylation of the amide precursor using tetrabutylammonium hydroxide as a phase transfer catalyst. Straight-phase semipreparative HPLC was in all purifications found to be superior to reversed-phase since the contamination by the norcompounds was eliminated. Reaction in acetonitrile for both (S)- and (R)-[ 11 C]nicotine and (R/S)-[ 11 C]cotinine with subsequent straight-phase HPLC purification resulted in 35-45% radiochemical yield with a total synthesis time of 30-35 min, a specific radioactivity of 1000-1500 Ci/mmol (37-55 GBq/μmol, EOS) and a radiochemical purity >99%. The uptake and distribution of these tracers in the human brain was studied in healthy volunteers by PET. The metabolite (R/S)-[ 11 C]cotinine did not cross the blood-brain barrier to any significant degree. (author)

  19. The Impact of HbA1c Testing on Total Annual Healthcare Expenditures Among Newly Diagnosed Patients with Diabetes.

    Science.gov (United States)

    Bhounsule, Prajakta; Peterson, Andrew M

    2015-09-01

    In 2010, diabetes was the seventh leading cause of death in the United States. Diabetes also imposes a huge financial burden on the US economy. In 2009, the American Diabetes Association International Expert Committee recommended the use of the glycated hemoglobin (HbA1c) test as a uniform diagnostic measure to identify patients with diabetes. Although HbA1c is a convenient diagnostic test, it is also more expensive than older tests and could, therefore, have an impact on patients' healthcare expenditures. To determine if HbA1c testing has an impact on total annual healthcare expenditures among newly diagnosed patients with diabetes and to analyze the factors that are associated with the total healthcare expenditures among diabetic patients before and after HbA1c was implemented as a standard diagnostic factor. This was an observational, retrospective, cross-sectional study. The Medical Expenditure Panel Survey-Household Component 2009 and 2011 databases were used to form the study cohort of patients with diabetes. The total mean healthcare expenditures among patients with diabetes formed the dependent variable. A proxy variable representing a diagnosis of diabetes with and without the use of HbA1c testing in 2009 and in 2011, respectively, formed the main independent variable along with demographic factors, comorbidities, and healthcare services utilization in both years. A generalized linear regression was conducted to determine the association of HbA1c testing with total diabetes-related healthcare expenditures. The mean total healthcare expenditure decreased in 2011 compared with 2009. The HbA1c test did not show an association with the total healthcare expenditures versus earlier diabetes-related diagnostic factors. The total expenditures were associated with private insurance, the incidence of a previous heart attack, prescription drug refills, inpatient hospital stays, home care, hospital discharges, and visits to outpatient providers and physicians in both

  20. Evaluation of internal and external doses from $^{11}C$ produced in the air in high energy proton accelerator tunnels

    CERN Document Server

    Endo, A; Kanda, Y; Oishi, T; Kondo, K

    2001-01-01

    Air has been irradiated with high energy protons at the 12 GeV proton synchrotron to obtain the following parameters essential for the internal dose evaluation from airborne /sup 11/C produced through nuclear spallation reactions: the abundance of gaseous and particulate /sup 11/C, chemical forms, and particle size distribution. It was found that more than 98% of /sup 11/C is present as gas and the rest is aerosol. The gaseous components were only /sup 11/CO and /sup 11/CO/sub 2/ and their proportions were approximately 80% and 20%, respectively. The particulate /sup 11/C was found to be sulphate and/or nitrate aerosols having a log-normal size distribution; the measurement using a diffusion battery showed a geometric mean radius of 0.035 mu m and a geometric standard deviation of 1.8 at a beam intensity of 6.8*10/sup 11/ proton.pulse /sup -1/ and an irradiation time of 9.6 min. By taking the chemical composition and particle size into account, effective doses both from internal and from external exposures pe...

  1. The synthesis of 5-[1-11C]ethyl barbiturates from labelled malonic esters

    International Nuclear Information System (INIS)

    Gee, A.; Laangstroem, B.

    1991-01-01

    The synthesis of [ 11 C]phenobarbital, [ 11 C]pentobarbital and[ 11 C]amobarbital labelled in the 5-[1- 11 C]ethyl position is reported. The malonic esters R- CH(CO 2 Et) 2 [R phenyl-, 1-methylbutyl-, and 3- methylbutyl- were alkylated with [1- 11 C]ethyl iodide prepared from [ 11 C]carbon dioxide. Ring closure of the 2-[1- 11 C]ethyl-labelled malonic esters with urea afforded 5-[1- 11 C]ethyl-phenobarbital,-phenobarbital, -pentobarbital and -amobarbital synthesis times of 42-47 min, counted from [ 11 C] carbon dioxide. In typical syntheses starting with 3 GBq pentobarbitol and (81 mCi) [ 11 C]carbon dioxide, 150-215 MBq (4-6 mCi) were produced in 25-30% decay corrected -amobarbital radiochemical yields with radiochemical purities greater than 98%. (author)

  2. [11 C]Rhodamine-123: Synthesis and biodistribution in rodents

    International Nuclear Information System (INIS)

    Bao Xiaofeng; Lu Shuiyu; Liow, Jeih-San; Morse, Cheryl L.; Anderson, Kacey B.; Zoghbi, Sami S.; Innis, Robert B.; Pike, Victor W.

    2012-01-01

    Introduction: Rhodamine-123 is a known substrate for the efflux transporter, P-glycoprotein (P-gp). We wished to assess whether rhodamine-123 might serve as a useful substrate for developing probes for imaging efflux transporters in vivo with positron emission tomography (PET). For this purpose, we aimed to label rhodamine-123 with carbon-11 (t 1/2 = 20.4 min) and to study its biodistribution in rodents. Methods: [ 11 C]Rhodamine-123 was prepared by treating rhodamine-110 (desmethyl-rhodamine-123) with [ 11 C]methyl iodide. The biodistribution of this radiotracer was studied with PET in wild-type mice and rats, in efflux transporter knockout mice, in wild-type rats pretreated with DCPQ (an inhibitor of P-gp) or with cimetidine (an inhibitor of organic cation transporters; OCT), and in P-gp knockout mice pretreated with cimetidine. Unchanged radiotracer in forebrain, plasma and peripheral tissues was also measured ex vivo at 30 min after radiotracer administration to wild-type and efflux transporter knockout rodents. Results: [ 11 C]Rhodamine-123 was obtained in 4.4% decay-corrected radiochemical yield from cyclotron-produced [ 11 C]carbon dioxide. After intravenous administration of [ 11 C]rhodamine-123 to wild-type rodents, PET and ex vivo measurements showed radioactivity uptake was very low in brain, but relatively high in some other organs such as heart, and especially liver and kidney. Inhibition of P-gp increased uptake in brain, heart, kidney and liver, but only by up to twofold. Secretion of radioactivity from kidney was markedly reduced by OCT knockout or pretreatment with cimetidine. Conclusions: [ 11 C]Rhodamine-123 was unpromising as a PET probe for P-gp function and appears to be a strong substrate of OCT in kidney. Cimetidine appears effective for blocking OCT in kidney in vivo.

  3. Newly Identified CYP2C93 Is a Functional Enzyme in Rhesus Monkey, but Not in Cynomolgus Monkey

    OpenAIRE

    Uno, Yasuhiro; Uehara, Shotaro; Kohara, Sakae; Iwasaki, Kazuhide; Nagata, Ryoichi; Fukuzaki, Koichiro; Utoh, Masahiro; Murayama, Norie; Yamazaki, Hiroshi

    2011-01-01

    Cynomolgus monkey and rhesus monkey are used in drug metabolism studies due to their evolutionary closeness and physiological resemblance to human. In cynomolgus monkey, we previously identified cytochrome P450 (P450 or CYP) 2C76 that does not have a human ortholog and is partly responsible for species differences in drug metabolism between cynomolgus monkey and human. In this study, we report characterization of CYP2C93 cDNA newly identified in cynomolgus monkey and rhesus monkey. The CYP2C9...

  4. Peripheral metabolism of (R)-[{sup 11}C]verapamil in epilepsy patients

    Energy Technology Data Exchange (ETDEWEB)

    Abrahim, Aiman; Langer, Oliver [Medical University of Vienna, Department of Clinical Pharmacology, Division of Clinical Pharmacokinetics, Vienna (Austria); Austrian Research Centers GmbH - ARC, Department of Radiopharmaceuticals, Seibersdorf (Austria); Luurtsema, Gert; Lubberink, Mark; Lammertsma, Adriaan A. [VU University Medical Centre, Department of Nuclear Medicine and PET Research, Amsterdam (Netherlands); Bauer, Martin; Joukhadar, Christian; Mueller, Markus [Medical University of Vienna, Department of Clinical Pharmacology, Division of Clinical Pharmacokinetics, Vienna (Austria); Karch, Rudolf [Medical University of Vienna, Department of Medical Computer Sciences, Vienna (Austria); Pataraia, Ekaterina; Baumgartner, Christoph [Medical University of Vienna, Department of Neurology, Vienna (Austria); Kletter, Kurt [Medical University of Vienna, Department of Nuclear Medicine, Vienna (Austria)

    2008-01-15

    (R)-[{sup 11}C]verapamil is a new PET tracer for P-glycoprotein-mediated transport at the blood-brain barrier. For kinetic analysis of (R)-[{sup 11}C]verapamil PET data the measurement of a metabolite-corrected arterial input function is required. The aim of this study was to assess peripheral (R)-[{sup 11}C]verapamil metabolism in patients with temporal lobe epilepsy and compare these data with previously reported data from healthy volunteers. Arterial blood samples were collected from eight patients undergoing (R)-[{sup 11}C]verapamil PET and selected samples were analysed for radiolabelled metabolites of (R)-[{sup 11}C]verapamil by using an assay that measures polar N-demethylation metabolites by solid-phase extraction and lipophilic N-dealkylation metabolites by HPLC. Peripheral metabolism of (R)-[{sup 11}C]verapamil was significantly faster in patients compared to healthy volunteers (AUC of (R)-[{sup 11}C]verapamil fraction in plasma: 29.4 {+-} 3.9 min for patients versus 40.8 {+-} 5.0 min for healthy volunteers; p < 0.0005, Student's t-test), which resulted in lower (R)-[{sup 11}C]verapamil plasma concentrations (AUC of (R)-[{sup 11}C]verapamil concentration, normalised to injected dose per body weight: 25.5 {+-} 2.1 min for patients and 30.5 {+-} 5.9 min for healthy volunteers; p = 0.038). Faster metabolism appeared to be mainly due to increased N-demethylation as the polar [{sup 11}C]metabolite fraction was up to two-fold greater in patients. Faster metabolism of (R)-[{sup 11}C]verapamil in epilepsy patients may be caused by hepatic cytochrome P450 enzyme induction by antiepileptic drugs. Based on these data caution is warranted when using an averaged arterial input function derived from healthy volunteers for the analysis of patient data. Moreover, our data illustrate how antiepileptic drugs may decrease serum levels of concomitant medication, which may eventually lead to a loss of therapeutic efficacy. (orig.)

  5. 11C-radioisotope study of methanol co-reaction with ethanol over Ni-MCM-41 silica-alumina and Ni-alumina

    International Nuclear Information System (INIS)

    Sarkadi-Priboczki, E.; Kovacs, Z.; Tsoncheva, T.; Kumar, N.; Murzin, D.Yu.

    2009-01-01

    Complete text of publication follows. The Ni modifies the properties of acidic alumina and light acidic MCM-41 silica-alumina supports. The radioisotopic method is a suitable tool for distinction of the 11 Cradioisotopic methanol and its co-derivates from derivates of non-radioactive ethanol on these catalysts. Experimental. The Ni/A l 2O 3 (5 wt % Ni) is commercially available while H-MCMN-41 (Si/Al=20) and Ni-ion-exchanged MCM-41 silica-alumina (5 wt % Ni) were prepared and characterized in previous works. Before catalysis the Ni/Al 2 O 3 and Ni-MCM-41 were pre-reduced. The 11 C-methanol was formed by a radiochemical process from 11 C-carbon dioxide produced at cyclotron (T 1/2 = 20.4 min). The mixture of equivalent volume of radioactive methanol and non-radioactive ethanol was introduced into glass tube micro-flow reactor at ambient temperature. After adsorption, the valves were closed and the catalyst was heated up to the required temperatures. The desorption rate of the remaining 11 C-derivatives on catalysts were continuously followed by radiodetectors and the derivatives of methanol with ethanol were analyzed by Radio/FID-gas chromatography (FID is coupled on-line with a radiodetector). The ethanol and its derivates were identified by FID while the 11 C-methanol and its co-derivates (with ethanol) were detected by both of FID and radiodetector. Results The 11 C-dimethyl ether was the common product of the single 11 C-methanol transformation on H-MCM-41, Ni-MCM-41 and Ni- Al 2 O 3 at low temperature (200-280 degC) due to middle strong acid sites. At higher temperature (280-350 degC), the dimethyl ether and hydrocarbons were the dominant products on H-MCM-41 while dimethyl ether selectivity decreased on Ni-alumina and Ni-MCM-41 in favor of methane. The selectivities of methanol to formaldehyde and methane were the highest on Ni-MCM-41. During co-reaction of 11 C-methanol with non-radioactive ethanol, the 11 C-labeled coethers, namely 11 C-methyl ethyl ether

  6. The emergence of shared leadership in newly-formed teams with an initial structure of vertical leadership: A longitudinal analysis

    OpenAIRE

    Fransen, Katrien; Delvaux, Ellen; Mesquita, Batja; Van Puyenbroeck, Stef

    2018-01-01

    The importance of high-quality leadership for team effectiveness is widely recognized, with recent viewpoints arguing shared leadership to be a more powerful predictor than vertical leadership. To identify changes in leadership structures over time, we longitudinally tracked the leadership structure of 27 newly-formed teams (N = 195), all having an initial structure of vertical leadership. Our findings demonstrated that the average team leadership strengthened over the course of the 24-week p...

  7. The study of methanol transformation over Cu-modified ZSM-5, Beta zeolite and MCM-41 mesoporous silica using 11C-radioisotope labeling

    International Nuclear Information System (INIS)

    Sarkadi-Priboczki, E.; Kovacs, Z.

    2004-01-01

    Complete text of publication follows. The copper-containing zeolites and mesoporous silica, among other metals, are suitable for dehydrogenation of methanol. The Cu transition metal determines the route of methanol conversion on supports of ZSM-5 and Beta zeolite as well as MCM-41 mesoporous silica. The catalysis mechanism and the catalytic property are concluded from the composition of methanol derivates over Cu-modified catalysts. The Cu ion-exchanged ZSM-5 and Beta zeolite and MCM-41 mesoporous silica were synthesized and characterized using X-ray power diffraction, scanning electron microscope, nitrogen and pyridine adsorption, X-ray fluorescency and FTIR spectroscopy. The 11 C-radioactive labeling method ( 11 C radioisotope, T 1/2 = 20 min, is a gamma emitter by annihilation of its positron) is suitable for following the process of 11 C-methanol con- version i.e. adsorption, desorption and catalytic transformation as well as for investigation of small amounts of molecules over catalysts by very sensitive radioactivity detectors.The 11 C radioisotope was produced at cyclotron and the 11 C-methanol was synthesized by a classical radiochemical method. After catalysis the 11 C-radioactive and non radioactive volatile products were identified by radiogas chromatography hereby radiolabeled compound and -derivates were distinguished from other participant natural, nonradioactive carbon compounds. Along radioactive products dimethyl ether and small hydrocarbons products were formed by Bronsted acid sites of catalysts while formaldehyde and small methyl formate were formed by Cu metal over bifunctional Cu-ZSM-5, Cu-Beta zeolite and mesoporous Cu-MCM-41 silica at 240 deg C. The detection of methoxy methanol and dimethoxy methane confirmed the simultaneous presence of acid and basic sites of catalysts. At higher temperature (400 deg C) the CO and CO 2 final products were dominated. In our previous works, methanol conversion to hydrocarbons was observed by dehydration

  8. Newly identified CYP2C93 is a functional enzyme in rhesus monkey, but not in cynomolgus monkey.

    Directory of Open Access Journals (Sweden)

    Yasuhiro Uno

    Full Text Available Cynomolgus monkey and rhesus monkey are used in drug metabolism studies due to their evolutionary closeness and physiological resemblance to human. In cynomolgus monkey, we previously identified cytochrome P450 (P450 or CYP 2C76 that does not have a human ortholog and is partly responsible for species differences in drug metabolism between cynomolgus monkey and human. In this study, we report characterization of CYP2C93 cDNA newly identified in cynomolgus monkey and rhesus monkey. The CYP2C93 cDNA contained an open reading frame of 490 amino acids approximately 84-86% identical to human CYP2Cs. CYP2C93 was located in the genomic region, which corresponded to the intergenic region in the human genome, indicating that CYP2C93 does not correspond to any human genes. CYP2C93 mRNA was expressed predominantly in the liver among 10 tissues analyzed. The CYP2C93 proteins heterologously expressed in Escherichia coli metabolized human CYP2C substrates, diclofenac, flurbiprofen, paclitaxel, S-mephenytoin, and tolbutamide. In addition to a normal transcript (SV1, an aberrantly spliced transcript (SV2 lacking exon 2 was identified, which did not give rise to a functional protein due to frameshift and a premature termination codon. Mini gene assay revealed that the genetic variant IVS2-1G>T at the splice site of intron 1, at least partly, accounted for the exon-2 skipping; therefore, this genotype would influence CYP2C93-mediated drug metabolism. SV1 was expressed in 6 of 11 rhesus monkeys and 1 of 8 cynomolgus monkeys, but the SV1 in the cynomolgus monkey was nonfunctional due to a rare null genotype (c.102T>del. These results suggest that CYP2C93 can play roles as a drug-metabolizing enzyme in rhesus monkeys (not in cynomolgus monkeys, although its relative contribution to drug metabolism has yet to be validated.

  9. Capturing [11C]CO2 for use in aqueous applications

    International Nuclear Information System (INIS)

    Vandehey, Nicholas T.; O’Neil, James P.

    2014-01-01

    We present a simple method for trapping [ 11 C]CO 2 gas and releasing it into a buffered solution using an ion-exchange cartridge. Sodium hydroxide cartridges captured >99% of [ 11 C]CO 2 following NaOH activation. A sodium bicarbonate solution eluted >99% of trapped radioactivity. Trapping [ 11 C]CO 2 directly in small volumes of several solutions was less effective than cartridge methods. The recommended methods allow for fast and simple production of highly concentrated carbon-11 containing aqueous solutions for use in filling phantoms, calibrating detectors, or (bio)geochemical experiments. - Highlights: • An ion exchange resin can trap [ 11 C]CO 2 gas and release it with saturated bicarbonate. • Elution from cartridge requires as little as 300 µL volume, with eluant at pH=10. • SPE trap-and-release provided better results than trapping in solution

  10. High-level production of C-11-carboxyl-labeled amino acids

    International Nuclear Information System (INIS)

    Washburn, L.C.; Sun, T.T.; Byrd, B.L.; Hayes, R.L.; Butler, T.A.; Callahan, A.P.

    1979-01-01

    Carbon-11-labeled amino acids have significant potential as agents for positron tomographic functional imaging. We have developed a rapid, high-temperature, high-pressure modification of the Buecherer--Strecker amino acid synthesis and found it to be quite general for the production of C-11-carboxyl-labeled neutral amino acids. Production of C-11-carboxyl-labeled DL-tryptophan requires certain modifications in the procedure. Twelve different amino acids have been produced to date by this technique. Synthesis and chromatographic purification require approximately 40 min, and C-11-carboxyl-labeled amino acids have been produced in yields of up to 425 mCi. Two C-11-carboxyl-labeled amino acids are being investigated clinically for tumor scanning and two others for pancreatic imaging. Over 120 batches of the various agents have been produced for clinical use over a three-year period

  11. Use of newly developed standardized form for interpretation of high-resolution CT in screening for pneumoconiosis

    International Nuclear Information System (INIS)

    Julien, P.J.; Sider, L.; Silverman, J.M.; Dahlgren, J.; Harber, P.; Bunn, W.

    1991-01-01

    This paper reports that although the International Labour Office (ILO) standard for interpretation of the posteroanterior chest radiograph has been available for 10 years, there has been no attempt to standardize the high-resolution CT (HRTC) readings for screening of pneumoconiosis. An integrated respirator surveillance program for 87 workers exposed to inorganic dust was conducted. This program consisted of a detailed occupational exposure history, physical symptoms and signs, spirometry, chest radiography, and HRCT. Two groups of workers with known exposure were studied with HRCT. Group 1 had normal spirometry results and chest radiographs, and group 2 had abnormalities at spirometry or on chest radiographs. The HRCT scans were read independently of the clinical findings and chest radiographs. The HRCT scans were interpreted by using an ILO-based standard form developed by the authors for this project. With the newly developed HRCT form, individual descriptive abnormality localized severity, and overall rating systems have been developed and compared for inter- and intraobserver consistency

  12. Plant uptake of bicarbonate as measured with the 11C isotope

    International Nuclear Information System (INIS)

    Wallace, A.; Mueller, R.T.; Wood, R.A.; Soufi, S.M.

    1979-01-01

    11 C which is cyclotron produced by 14 N(P, α) 11 C(half-life 20.1 M) was used as a tracer of bicarbonate to determine its movements from a nutrient solution through roots to stems and leaves of bush bean plants (Phaseolus vulgaris L. var Improved Tendergreen). The short time involved and the high solution pH minimized the need for use of the Henderson Hasselbach equation for activity correction. Quantities of 11 C did move into roots, stems and leaves with a sharp decreasing gradient (root/stem = 14.5, stems/leaves = 11.7) More 11 C moved into plants with KHCO 3 than with NaHCO 3 . The (NH 4 ) 2 SO 4 enhanced 11 C uptake and KNO 3 decreased it. This enhancement and competition indicated possibility of some uptake of HCO 3 - . In an experiment with Galenia pubescens (Eckl. and Zeyh.) Druce, the 11 C was more readily moved to stems and leaves than in bush bean indicating substantial uptake of HCO 3 - . (Auth.)

  13. Improvement of strength and toughness of SKD11 type cold work tool steel; SKD 11 gata reikan koguko no kyojinsei no kaizen

    Energy Technology Data Exchange (ETDEWEB)

    Fukaura, K.; Sunada, H.; Yokoyama, Y. [Himeji Inst. of Technology, Hyogo (Japan); Teramoto, K. [Himeji Inst. of Technology, Hyogo (Japan). Graduate School| Sanyo Special Steel Co. Ltd., Hyogo (Japan)

    1998-03-01

    Toughness and wear resistance are the factors which affect on the lifetime of cold work tool steels importantly. Generally, both properties show the contrary characteristics. The evaluation of tool steel materials has been carried out focusing on the strength and wear resistance mainly. However, owing to the rapid progress of recent plastic working techniques, usage environments are under the severe conditions more and more. Therefore, it is expected to develop the high reliable cold work tool steels which balanced with toughness including wear resistance. In this study, the strength and toughness of a newly developed 0.8C-8Cr cold work tool steel whose composition was controlled to suppress the precipitation of massive eutectic M7C3 carbides were investigated with reference to microstructure and were compared with conventional SKD11. The toughness was evaluated by the area under the stress-strain curve. As a result, it was clarified that the tensile strength of the newly developed steel designated as Mod. SKD 11 was about 400 MPa higher and the toughness was 1.8 times larger than that of SKD 11 throughout a wide range of tempering temperatures and so forth. 17 refs., 13 figs., 1 tab.

  14. 11C-acetate PET imaging in patients with multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Kazushiro Takata

    Full Text Available BACKGROUND: Activation of glial cells is a cardinal feature in multiple sclerosis (MS pathology, and acetate has been reported to be selectively uptaken by astrocytes in the CNS. The aim of this study was to investigate the efficacy of PET with (11C-acetate for MS diagnosis. MATERIALS AND METHODS: Six patients with relapsing-remitting MS and 6 healthy volunteers (HV were enrolled. The (11C-acetate brain uptake on PET was measured in patients with MS and HV. Volume-of-interest analysis of cerebral gray and white matter based on the segmentation technique for co-registered MRI and voxel-based statistical parametric analysis were performed. Correlation between 11C-acetate uptake and the lesion number in T1- and T2- weighted MR images were also assessed. RESULTS: The standardized uptake value (SUV of 11C-acetate was increased in both white and gray matter in MS patients compared to HV. Voxel-based statistical analysis revealed a significantly increased SUV relative to that in the bilateral thalami (SUVt in a broad area of white matter, particularly in the subcortical white matter of MS patients. The numbers of T2 lesions and T1 black holes were significantly correlated with SUV of (11C-acetate in white and gray matter. CONCLUSIONS: The 11C-acetate uptake significantly increased in MS patients and correlated to the number of MRI lesions. These preliminary data suggest that (11C-acetate PET can be a useful clinical examination for MS patients.

  15. Low temperature synthesis of no-carrier-added [{sup 11}C]formaldehyde with metal hydrides and preparation of [1-{sup 11}C]1,2,3,4-Tetrahydro-{beta}-Carboline Derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Nader, M.W.; Zeisler, S.K.; Theobald, A.; Oberdorfer, F

    1998-12-01

    A comparative study has been performed on the selective reduction of cyclotron-produced [{sup 11}C]carbon dioxide to [{sup 11}C]formaldehyde with solutions of various complex metal hydrides at temperatures between -52 and +25 deg. C. Under optimal reaction conditions, lithium tetrahydridoaluminate gave the highest yield of [{sup 11}C]formaldehyde (58%, decay-corrected), followed by lithium triethylhydridoborate (34%) and sodium tetrahydridoborate (22%). Radiochemically pure [{sup 11}C]formaldehyde could be obtained with lithium tetrahydridoaluminate and sodium tetrahydridoborate, but not with lithium triethyl hydridoborate. The produced [{sup 11}C]formaldehyde was used for the synthesis of [1-{sup 11}C]1,2,3,4-tetrahydro-{beta}-carboline derivatives by the Pictet-Spengler reaction.

  16. [11C]PR04.MZ, a promising DAT ligand for low concentration imaging: synthesis, efficient 11C-O-methylation and initial small animal PET studies

    International Nuclear Information System (INIS)

    Riss, P.J.; Hooker, J.; Alexoff, D.; Kim, Sung-Won; Fowler, J.S.; Roesch, F.

    2009-01-01

    PR04.MZ was designed as a highly selective dopamine transporter inhibitor, derived from natural cocaine. Its binding profile indicates that [ 11 C]PR04.MZ may be suited as a PET radioligand for the non-invasive exploration of striatal and extrastriatal DAT populations. As a key feature, its structural design facilitates both, labelling with fluorine-18 at its terminally fluorinated butynyl moiety and carbon-11 at its methyl ester function. The present report concerns the efficient [ 11 C]MeI mediated synthesis of [ 11 C]PR04.MZ from an O-desmethyl precursor trifluoroacetic acid salt with Rb 2 CO 3 in DMF in up to 95 ± 5% labelling yield. A preliminary μPET-experiment demonstrates the reversible, highly specific binding of [ 11 C]PR04.MZ in the brain of a male Sprague-Dawley rat.

  17. Synthesis of 'no-carrier-added' sup(11)C-labelled nitrosoureas

    International Nuclear Information System (INIS)

    Diksic, M.; Farrokhzad, S.; Yamamoto, Y.L.; Feindel, W.

    1985-01-01

    Syntheses for sup(11)C-labelled chemotherapeutic drugs CCNU, BFNU and CFNU (analogs of BCNU) as well as an improved synthesis for sup(11)C-BCNU are described. The procedures for the separation of dual isomers in the case of sup(11)C-labelled CCNU and CFNU are discussed. The specific activity of these 'no-carrier-added' radiopharmaceuticals was approximately 10sup(4) lower than expected for a carrier-free product. The syntheses were normally finished 20-25 min after the end of the collection of sup(11)C-COClsub(2). Chemical and radiochemical purity of the final products as determined by HPLC and TLRC, respectively, was at least 98%. The syntheses yielded 10-25 mCi of nitrosourea ready for use in PET studies. (author)

  18. Low background and high contrast PET imaging of amyloid-β with [11C]AZD2995 and [11C]AZD2184 in Alzheimer's disease patients

    International Nuclear Information System (INIS)

    Forsberg, Anton; Andersson, Jan; Varnaes, Katarina; Halldin, Christer; Jureus, Anders; Swahn, Britt-Marie; Sandell, Johan; Julin, Per; Svensson, Samuel; Cselenyi, Zsolt; Schou, Magnus; Johnstroem, Peter; Farde, Lars; Eriksdotter, Maria; Freund-Levi, Yvonne; Jeppsson, Fredrik

    2013-01-01

    The aim of this study was to evaluate AZD2995 side by side with AZD2184 as novel PET radioligands for imaging of amyloid-β in Alzheimer's disease (AD). In vitro binding of tritium-labelled AZD2995 and AZD2184 was studied and compared with that of the established amyloid-β PET radioligand PIB. Subsequently, a first-in-human in vivo PET study was performed using [ 11 C]AZD2995 and [ 11 C]AZD2184 in three healthy control subjects and seven AD patients. AZD2995, AZD2184 and PIB were found to share the same binding site to amyloid-β. [ 3 H]AZD2995 had the highest signal-to-background ratio in brain tissue from patients with AD as well as in transgenic mice. However, [ 11 C]AZD2184 had superior imaging properties in PET, as shown by larger effect sizes comparing binding potential values in cortical regions of AD patients and healthy controls. Nevertheless, probably due to a lower amount of nonspecific binding, the group separation of the distribution volume ratio values of [ 11 C]AZD2995 was greater in areas with lower amyloid-β load, e.g. the hippocampus. Both AZD2995 and AZD2184 detect amyloid-β with high affinity and specificity and also display a lower degree of nonspecific binding than that reported for PIB. Overall [ 11 C]AZD2184 seems to be an amyloid-β radioligand with higher uptake and better group separation when compared to [ 11 C]AZD2995. However, the very low nonspecific binding of [ 11 C]AZD2995 makes this radioligand potentially interesting as a tool to study minute levels of amyloid-β. This sensitivity may be important in investigating, for example, early prodromal stages of AD or in the longitudinal study of a disease modifying therapy. (orig.)

  19. A PET imaging agent with fast kinetics: synthesis and in vivo evaluation of the serotonin transporter ligand [{sup 11}C]2-[2-dimethylaminomethylphenylthio]-5-fluorophenylamine ([{sup 11}C]AFA)

    Energy Technology Data Exchange (ETDEWEB)

    Huang Yiyun E-mail: hh285@columbia.edu; Narendran, Raj; Bae, Sung-A; Erritzoe, David; Guo Ningning; Zhu Zhihong; Hwang, D.-R.; Laruelle, Marc

    2004-08-01

    A new serotonin transporter (SERT) ligand, [{sup 11}C]2-[2-(dimethylaminomethylphenylthio)]-5-fluorophenylamine (10, [{sup 11}C]AFA), was synthesized and evaluated as a candidate PET radioligand in pharmacological and pharmacokinetic studies. As a PET radioligand, AFA (8) can be labeled with either C-11 or F-18. In vitro, AFA displayed high affinity for SERT (K{sub i} 1.46{+-}0.15 nM) and lower affinity for norepinephrine transporter (NET, K{sub i} 141.7{+-}47.4 nM) or dopamine transporter (DAT, K{sub i} >10,000 nM). [{sup 11}C]AFA (10) was prepared from its monomethylamino precursor 9 by reaction with high specific activity [{sup 11}C]methyl iodide. Radiochemical yield was 43{+-}20% based on [{sup 11}C]methyl iodide at end of bombardment (EOB, n = 10) and specific activity was 2,129 {+-} 1,369 Ci/mmol at end of synthesis (EOS, n = 10). Biodistribution studies in rats indicated that [{sup 11}C]AFA accumulated in brain regions known to contain high concentrations of SERT. Binding in SERT-rich brain regions was reduced significantly by pretreatment with either the cold compound 8 or with the selective serotonin reuptake inhibitor (SSRI) citalopram, but not by the selective norepinephrine reuptake inhibitor nisoxetine, thus underlining its in vivo binding selectivity and specificity for SERT. Imaging experiments in baboons demonstrated that the uptake pattern of [{sup 11}C]AFA in the baboon brain is consistent with the known distribution of SERT, with highest activity levels in the midbrain and thalamus, followed by striatum, hippocampus, and cortical regions. Activity levels in the baboon brain peaked at 15-40 min after radioligand injection, indicating a fast uptake kinetics for [{sup 11}C]AFA. Pretreatment of the baboon with citalopram (4 mg/kg) significantly reduced the specific binding of [{sup 11}C]AFA in all SERT-containing brain regions. Kinetic analysis revealed that the regional equilibrium specific to non-specific partition coefficients (V{sub 3}&apos

  20. {sup 11}C-MET PET/MRI for detection of recurrent glioma

    Energy Technology Data Exchange (ETDEWEB)

    Deuschl, C. [University Hospital Essen, Institute of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); University of Duisburg-Essen, Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen (Germany); Kirchner, J.; Schaarschmidt, B. [University Duesseldorf, Department of Diagnostic and Interventional Radiology, Medical Faculty, Duesseldorf (Germany); Poeppel, T.D.; Herrmann, K. [University Hospital Essen, Clinic for Nuclear Medicine, Essen (Germany); Kebir, S.; Glas, M. [University Hospital Essen, Division of Clinical Neurooncology, Department of Neurology, Essen (Germany); El Hindy, N. [University Hospital Essen, Department of Neurosurgery, Essen (Germany); Hense, J. [University Hospital Essen, Department of Medical Oncology, West German Cancer Center, Essen (Germany); Quick, H.H. [University of Duisburg-Essen, Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen (Germany); University Hospital Essen, High Field and Hybrid MR Imaging, Essen (Germany); Umutlu, L.; Moenninghoff, C.; Radbruch, A.; Forsting, M. [University Hospital Essen, Institute of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); Schlamann, M. [University Hospital Essen, Institute of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); University Hospital Cologne, Department of Diagnostic and Interventional Radiology, Cologne (Germany)

    2018-04-15

    Radiological assessment of brain tumors is widely based on the Radiology Assessment of Neuro-Oncology (RANO) criteria that consider non-specific T1 and T2 weighted images. Limitation of the RANO criteria is that they do not include metabolic imaging techniques that have been reported to be helpful to differentiate treatment related changes from true tumor progression. In the current study, we assessed if the combined use of MRI and PET with hybrid {sup 11}C-MET PET/MRI can improve diagnostic accuracy and diagnostic confidence of the readers to differentiate treatment related changes from true progression in recurrent glioma. Fifty consecutive patients with histopathologically proven glioma were prospectively enrolled for a hybrid {sup 11}C-MET PET/MRI to differentiate recurrent glioma from treatment induced changes. Sole MRI data were analyzed based on RANO. Sole PET data and in a third evaluation hybrid {sup 11}C-MET-PET/MRI data were assessed for metabolic respectively metabolic and morphologic glioma recurrence. Diagnostic performance and diagnostic confidence of the reader were calculated for the different modalities, and the McNemar test and Mann-Whitney U Test were applied for statistical analysis. Hybrid {sup 11}C-MET PET/MRI was successfully performed in all 50 patients. Glioma recurrence was diagnosed in 35 of the 50 patients (70%). Sensitivity and specificity were calculated for MRI (86.11% and 71.43%), for {sup 11}C-MET PET (96.77% and 73.68%), and for hybrid {sup 11}C-MET-PET/MRI (97.14% and 93.33%). For diagnostic accuracy hybrid {sup 11}C-MET-PET/MRI (96%) showed significantly higher values than MRI alone (82%), whereas no significant difference was found for 11C-MET PET (88%). Furthermore, by rating on a five-point Likert scale significantly higher scores were found for diagnostic confidence when comparing {sup 11}C-MET PET/MRI (4.26 ± 0,777) to either PET alone (3.44 ± 0.705) or MRI alone (3.56 ± 0.733). This feasibility study showed that hybrid

  1. Towards the total synthesis of Stawamycin. Synthesis of C11-C21 fragment

    Directory of Open Access Journals (Sweden)

    Dias Luiz C.

    2001-01-01

    Full Text Available The carbocyclic (C11-C21 fragment of Stawamycin has been prepared by a sequence involving 11 steps (10% overall yield from methyl (R-(--3-hydroxy-2-methylpropionate. Key steps are Pd-catalyzed Stille coupling reaction between a vinyl iodide and a vinylstannane followed by an intramolecular Diels-Alder cycloaddition reaction to afford the desired adduct as the major isomer together with three other possible adducts in 78% overall yield.

  2. Follicular thyroid cancer avid on C-11 Methionine PET/CT

    OpenAIRE

    Jochumsen, Mads Ryø; Iversen, Peter; Arveschoug, Anne Kirstine

    2018-01-01

    Summary A case of follicular thyroid cancer with intense focal Methionine uptake on 11C-Methionine PET/CT is reported here. The use of 11C-Methionine PET in differentiated thyroid cancer is currently being investigated as a surrogate tracer compared to the more widely used 18F-FDG PET. This case illustrates the potential incremental value of this modality, not only in the localizing of parathyroid adenoma, but also indicating that 11C-Methionine PET might have a potential of increasing the pr...

  3. Newly diagnosed hepatocellular carcinoma in patients with advanced hepatitis C treated with DAAs: A prospective population study.

    Science.gov (United States)

    Romano, Antonietta; Angeli, Paolo; Piovesan, Sara; Noventa, Franco; Anastassopoulos, Georgios; Chemello, Liliana; Cavalletto, Luisa; Gambato, Martina; Russo, Francesco Paolo; Burra, Patrizia; Vincenzi, Valter; Scotton, Pier Giorgio; Panese, Sandro; Tempesta, Diego; Bertin, Tosca; Carrara, Maurizio; Carlotto, Antonio; Capra, Franco; Carolo, Giada; Scroccaro, Giovanna; Alberti, Alfredo

    2018-03-16

    Direct-acting antiviral agents (DAAs) are safe and effective in patients with hepatitis C. Conflicting data were reported on the risk of hepatocellular carcinoma (HCC) during/after therapy with DAAs. The aim of this study was to evaluate the incidence of newly diagnosed HCC and associated risk factors in patients with advanced hepatitis C treated with DAAs. The study is based on the NAVIGATORE platform, a prospectively recording database of all patients with hepatitis C receiving DAAs in the Veneto region of Italy. The inclusion criteria were: fibrosis stage ≥F3. The exclusion criteria were: Child-Turcotte-Pugh (CTP)-C, liver transplantation before DAAs, history or presence of HCC, follow-up hepatocarcinoma during the first year is not higher, and might be lower, than that of untreated patients. The risk further declines thereafter. Early hepatocarcinoma appearance may reflect pre-existing, microscopic, undetectable tumors. Hepatocellular carcinoma is one of the complications of hepatitis C related cirrhosis. Treating patients with advanced hepatitis C with the new interferon-free direct-acting antiviral agents has been associated with improvement in liver function and survival, while more conflicting data have been reported regarding the risk of hepatocellular carcinoma. We report the results of a prospective population study on the incidence of newly diagnosed hepatocellular carcinoma in patients with advanced hepatitis C treated with direct-acting antiviral agents, clearly indicating that the residual hepatocellular carcinoma risk is reduced and declines progressively with time after a sustained virological response. Development of a liver tumor during/after therapy was associated with known risk factors and with virological failure. Copyright © 2018. Published by Elsevier B.V.

  4. The effect of microstructural stability on long-term creep behaviour of 11 %Cr steels for steam power plants with operating steam temperatures up to 650 C

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Y.; Scholz, A.; Berger, C. [Technische Univ. Darmstadt (DE). Inst. fuer Werkstoffkunde (IFW); Kauffmann, F.; Maile, K. [Stuttgart Univ. (DE). Materialpruefungsanstalt (MPA); Mayer, K.H. [Alstom Power, Nuernberg (Germany)

    2010-07-01

    The investigations of advanced ferritic/martensitic steels for 650 C power plant components focus on the improvement of high-temperature creep properties with respect to chemical composition. This study deals with the development of new heat resistant 11-12%Cr ferritic-martensitic steels with sufficient creep and oxidation resistance up to 650 application by using basic principles and concepts of physical metallurgy. The highest creep strength could be achieved with a 0.04% Nb alloyed 11%CrWCoMoVB melt, which is in addition alloyed with a higher C and B content as well as with lower W and Co portions. The microstructure evolution during creep of this newly developed steel was investigated in comparison to a sister alloy which comprises 0.06% Ta instead of the Nb. (orig.)

  5. (S)- and (R)-[[sup 11]C]nicotine and the metabolite (R/S)-[[sup 11]C]cotinine. Preparation, metabolite studies and in vivo distribution in the human brain using PET

    Energy Technology Data Exchange (ETDEWEB)

    Halldin, C.; Swahn, C.-G.; Nybaeck, H. (Karolinska Hospital, Stockholm (Sweden)); Naagren, K. (Turku Univ. (Finland). Medical Cyclotron-PET Centre/Radiochemistry Lab.); Laangstroem, B. (Uppsala Univ. (Sweden). Dept. of Organic Chemistry)

    1992-11-01

    In order to investigate [[sup 11]C]nicotine binding and metabolism in the living human brain by PET, routine protocols were developed for the preparation and purification of (S)-and (R)-[[sup 11]C]nicotine and the metabolite (R/S)-[[sup 11]C]cotinine. (S)- and (R)-[[sup 11]C]nicotine were prepared by N-methylation with [[sup 11]C]methyl iodide of the appropriate secondary amine, which was liberated in situ by 2,2,6,6,-tetramethylpiperidine (TMP) from its corresponding biscamsylate-salt. (R/S)-[[sup 11]C]Cotinine was prepared by N-methylation of the amide precursor using tetrabutylammonium hydroxide as a phase transfer catalyst. Straight-phase semipreparative HPLC was in all purifications found to be superior to reversed-phase since the contamination by the norcompounds was eliminated. Reaction in acetonitrile for both (S)- and (R)-[[sup 11]C]nicotine and (R/S)-[[sup 11]C]cotinine with subsequent straight-phase HPLC purification resulted in 35-45% radiochemical yield with a total synthesis time of 30-35 min, a specific radioactivity of 1000-1500 Ci/mmol (37-55 GBq/[mu]mol, EOS) and a radiochemical purity >99%. The uptake and distribution of these tracers in the human brain was studied in healthy volunteers by PET. The metabolite (R/S)-[[sup 11]C]cotinine did not cross the blood-brain barrier to any significant degree. (author).

  6. The applications of 11C-MET PET in brain tumor

    International Nuclear Information System (INIS)

    Hua Fengchun

    2002-01-01

    11 C-methionine (MET), an amino acid, is the most widely used radio pharmaceutics which can reflect transport metabolism of amino acid in vivo, and synthesis of protein in tumor. 11 C-MET PET can be used for evaluation of brain tumor: detection of tumor, differential diagnosis between recurrence and radiation necrosis and early evaluation of response to treatment. Especially, for the definition of tumor margin and detection of low-grade tumors, PET with 11 C-MET is better than PET with 18 F-FDG or other modalities such as CT and MRI

  7. C-11-labeled octadecylamine, a potential agent for positron tomographic pulmonary metabolism studies

    International Nuclear Information System (INIS)

    Washburn, L.C.; Wallace, R.T.; Byrd, B.L.; Sun, T.T.; Coffey, J.L.; Hubner, K.F.

    1984-01-01

    C-11-Labeled straight-chain primary aliphatic amines are rapidly and selectively sequestered by lung endothelial cells, making these agents potentially useful for positron tomographic studies of the lung as a metabolic organ. However, because amines having straight chains containing 4 to 13 carbon atoms are rapidly catabolized in vivo with loss of radiolabel, quantitation of pulmonary concentration is difficult. The authors have studied the effect of structural changes on the uptake and retention of primary aliphatic amines in rat lung and found that the metabolic loss form the lung decreased with increasing length of the straight carbon chain. In fact, the lung concentration of octadecylamine, a straight-chain amine with 18 carbon atoms, was constant between 1 and 30 minutes after intravenous administration. This highly insoluble amine was solubilized using 3% aqueous human serum albumin. Unilateral, radiation-induced lung injury in the rat was used as a model to study the potential of C-11-labeled octadecylamine. Radiation-damaged (3000 and 5000 Rads) lungs had significantly lower 15-minute uptakes of the labeled amine than the corresponding nonirradiated lungs. However, at 8000 Rads the concentration in both lungs was greatly suppressed, indicating that the decrease in metabolism becomes systemic at high radiation doses. These results suggest that C-11-labeled octadecylamine is a potentially useful agent for quantitative evaluation of pulmonary metabolism by positron tomography

  8. Modified synthesis of 11-[{sup 14}C]-clozapine

    Energy Technology Data Exchange (ETDEWEB)

    Matloubi, Hojatollah E-mail: hmatloubi@seai.neda.net.ir; Ghandi, Mehdi; Zarrindast, M.-R.; Saemian, Nader

    2001-11-01

    The reported synthetic pathway of 8-chloro-11-(4-methyl-1-piperazinyl)-11-[{sup 14}C]-5H-dibenzo[b,e][1,4]diazapine (clozapine) was modified in several steps. The synthetic pathway was shortened by 60% and the total yield was increased from 6% to 23%.

  9. Synthesis of racemic, R- and S-[1-11C]-β-hydroxybutyric acid

    International Nuclear Information System (INIS)

    Thorell, J.-O.; Stone-Elander, S.; Karolinska Hospital and Inst., Stockholm; Koenig, W.A.; Halldin, C.; Widen, L.

    1991-01-01

    Racemic, R- and S-β-hydroxybutyric acid were labelled with 11 C in the carboxylic position by a two-step stereospecific synthesis starting with carrier-added [ 11 C]cyanide and R/S, R- or S-propylene oxide. Hydrolysis of the intermediate nitrile with hydrochloric acid gave racemic [1- 11 C]-β-hydroxybutyric acid and R- or S-[1- 11 C]-β-hydroxybutyric acid with an enantiomeric excess of 87-97%. The total synthesis time (including HPLC purification) was 45-50 min from end of trapping. The isolated decay-corrected radiochemical yield was 20-30% based on [ 11 C]cyanide. The radiochemical purity of the products was > 99%]. (author)

  10. The synthesis of 5-(1- sup 11 C)ethyl barbiturates from labelled malonic esters

    Energy Technology Data Exchange (ETDEWEB)

    Gee, A.; Laangstroem, B. (Uppsala Univ. (Sweden). Dept. of Organic Chemistry)

    1991-01-01

    The synthesis of ({sup 11}C)phenobarbital, ({sup 11}C)pentobarbital and({sup 11}C)amobarbital labelled in the 5-(1-{sup 11}C)ethyl position is reported. The malonic esters R- CH(CO{sub 2}Et){sub 2} R phenyl-, 1-methylbutyl-, and 3- methylbutyl- were alkylated with (1-{sup 11}C)ethyl iodide prepared from ({sup 11}C)carbon dioxide. Ring closure of the 2-(1-{sup 11}C)ethyl-labelled malonic esters with urea afforded 5-(1-{sup 11}C)ethyl-phenobarbital,-phenobarbital, -pentobarbital and -amobarbital synthesis times of 42-47 min, counted from ({sup 11}C) carbon dioxide. In typical syntheses starting with 3 GBq pentobarbitol and (81 mCi) ({sup 11}C)carbon dioxide, 150-215 MBq (4-6 mCi) were produced in 25-30% decay corrected -amobarbital radiochemical yields with radiochemical purities greater than 98%. (author).

  11. Patterns of 11C-PIB cerebral retention in mild cognitive impairment patients.

    Science.gov (United States)

    Banzo, I; Jiménez-Bonilla, J F; Martínez-Rodríguez, I; Quirce, R; de Arcocha-Torres, M; Bravo-Ferrer, Z; Lavado-Pérez, C; Sánchez-Juan, P; Rodríguez, E; Jiménez-Alonso, M; López-Defilló, J; Carril, J M

    2016-01-01

    To evaluate the patterns of cerebral cortical distribution of (11)C-PIB in patients with mild cognitive impairment (MCI). The study included 69 patients (37 male, age range 42-79 years) with MCI, sub-classified as 53 with amnestic-MCI (A-MCI), and 16 with non-amnestic-MCI (NA-MCI). Patients underwent (11)C-PIB PET/CT scan 60min after intravenous injection of the radiotracer. A visual analysis of the images was performed by 2 experienced physicians. (11)C-PIB-positive studies were considered when gray matter uptake was equal to or greater than white matter. According to the regions involved, (11)C-PIB-positive studies were classified into A-pattern (predominant retention in frontal, anterior cingulate, lateral temporal, and basal ganglia) and B-pattern (generalized retention). Thirty-nine of the 69 (56%) patients with MCI showed (11)C-PIB retention. Of the 53 A-MCI patients, 36 (68%) showed (11)C-PIB retention. Eleven out of 36 (30%) positive scans in A-MCI patients showed A-pattern, and 25 out of 36 (70%) patients had a B-pattern. Positive (11)C-PIB was observed in 3 out of 16 (19%) patients with NA-MCI. Regional distribution in these 3 patients showed A-pattern in 1, and B-pattern in 2 patients. Cortical retention of (11)C-PIB was more frequent in A-MCI than in NA-MCI patients, and also B-pattern than A-pattern in the (11)C-PIB positive group. The recognition of (11)C-PIB distribution patterns allows MCI patients to be classified, and the A-pattern may offer a therapeutic window for potential future treatments. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

  12. Automated radiosynthesis of [{sup 11}C]morphine for clinical investigation

    Energy Technology Data Exchange (ETDEWEB)

    Fan Jinda [Department of Radiology, Washington University School of Medicine, 510 South Kingshighway Blvd. St. Louis, MO 63110 (United States); Meissner, Konrad [Department of Anesthesiology, Washington University School of Medicine, 510 South Kingshighway Blvd. St. Louis, MO 63110 (United States); Gaehle, Gregory G.; Li Shihong [Department of Radiology, Washington University School of Medicine, 510 South Kingshighway Blvd. St. Louis, MO 63110 (United States); Kharasch, Evan D. [Department of Anesthesiology, Washington University School of Medicine, 510 South Kingshighway Blvd. St. Louis, MO 63110 (United States); Mach, Robert H. [Department of Radiology, Washington University School of Medicine, 510 South Kingshighway Blvd. St. Louis, MO 63110 (United States); Tu Zhude, E-mail: tuz@mir.wustl.ed [Department of Radiology, Washington University School of Medicine, 510 South Kingshighway Blvd. St. Louis, MO 63110 (United States)

    2011-02-15

    To meet a multiple-dose clinical evaluation of the P-gp modulation of [{sup 11}C]morphine delivery into the human brain, radiosynthesis of [{sup 11}C]morphine was accomplished on an automated system by N-methylation of normorphine with [{sup 11}C]CH{sub 3}I. A methodology employing optimized solid phase extraction of the HPLC eluent was developed. Radiosynthesis took 45 min with a radiochemical yield ranging from 45% to 50% and specific activity ranging from 20 to 26 Ci/{mu}mol (decay corrected to end-of-bombardment); radiochemical and chemical purities were >95% (n=28).

  13. Follicular thyroid cancer avid on C-11 Methionine PET/CT

    Directory of Open Access Journals (Sweden)

    Mads Ryø Jochumsen

    2018-01-01

    Full Text Available A case of follicular thyroid cancer with intense focal Methionine uptake on 11C-Methionine PET/CT is reported here. The use of 11C-Methionine PET in differentiated thyroid cancer is currently being investigated as a surrogate tracer compared to the more widely used 18F-FDG PET. This case illustrates the potential incremental value of this modality, not only in the localizing of parathyroid adenoma, but also indicating that 11C-Methionine PET might have a potential of increasing the pretest likelihood of thyroid malignancy in a cold nodule with highly increased Sestamibi uptake.

  14. Haemonchus contortus: Characterization of the baculovirus expressed form of aminopeptidase H11

    NARCIS (Netherlands)

    Reszka, N.; Rijsewijk, F.A.M.; Zelnik, V.; Moskwa, B.; Bienkowska-Szewczyk, K.

    2007-01-01

    Recombinant form of Haemonchus contortus aminopeptidase H11, an intestinal membrane glycoprotein considered to be in its native form the most promising vaccine candidate, was produced in insect cells, characterised and tested in pilot vaccination-challenge trial on sheep. The sequence of the cloned

  15. Establishment probability in newly founded populations

    Directory of Open Access Journals (Sweden)

    Gusset Markus

    2012-06-01

    Full Text Available Abstract Background Establishment success in newly founded populations relies on reaching the established phase, which is defined by characteristic fluctuations of the population’s state variables. Stochastic population models can be used to quantify the establishment probability of newly founded populations; however, so far no simple but robust method for doing so existed. To determine a critical initial number of individuals that need to be released to reach the established phase, we used a novel application of the “Wissel plot”, where –ln(1 – P0(t is plotted against time t. This plot is based on the equation P0t=1–c1e–ω1t, which relates the probability of extinction by time t, P0(t, to two constants: c1 describes the probability of a newly founded population to reach the established phase, whereas ω1 describes the population’s probability of extinction per short time interval once established. Results For illustration, we applied the method to a previously developed stochastic population model of the endangered African wild dog (Lycaon pictus. A newly founded population reaches the established phase if the intercept of the (extrapolated linear parts of the “Wissel plot” with the y-axis, which is –ln(c1, is negative. For wild dogs in our model, this is the case if a critical initial number of four packs, consisting of eight individuals each, are released. Conclusions The method we present to quantify the establishment probability of newly founded populations is generic and inferences thus are transferable to other systems across the field of conservation biology. In contrast to other methods, our approach disaggregates the components of a population’s viability by distinguishing establishment from persistence.

  16. Preclinical and the first clinical studies on [11C]ITMM for mapping metabotropic glutamate receptor subtype 1 by positron emission tomography

    International Nuclear Information System (INIS)

    Toyohara, Jun; Sakata, Muneyuki; Fujinaga, Masayuki; Yamasaki, Tomoteru; Oda, Keiichi; Ishii, Kenji; Zhang, Ming Rong; Moriguchi Jeckel, Cristina Maria; Ishiwata, Kiichi

    2013-01-01

    Introduction: Preclinical studies and first positron emission tomography (PET) imaging studies were performed using N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-4-[ 11 C] methoxy-N-methylbenzamide ([ 11 C]ITMM) to map metabotropic glutamate receptor type 1 (mGluR1) in the human brain. Methods: [ 11 C]ITMM was synthesized by O-methylation of the desmethyl precursor with [ 11 C]methyl triflate in the presence of NaOH at room temperature. In vitro selectivity and brain distributions of [ 11 C]ITMM in mice were characterized. Radiation absorbed-dose by [ 11 C]ITMM in humans was calculated from mouse distribution data. Acute toxicity of ITMM at 4.72 mg/kg body weight (> 74,000-fold clinical equivalent dose of [ 11 C]ITMM) was evaluated. Mutagenicity of ITMM was studied by the Ames test. Clinical PET imaging of mGluR1 with [ 11 C] ITMM was performed in a healthy volunteer. Results: ITMM had low activity for a 28-standard receptor binding profile. Regional brain uptake of [ 11 C]ITMM in mice was heterogeneous and consistent with known mGluR1 distributions. The radiation absorbed-dose by [ 11 C]ITMM in humans was sufficiently low for clinical use, and no acute toxicity or mutagenicity of ITMM occurred. A 90-min dynamic PET scan with [ 11 C]ITMM in a healthy volunteer showed a gradual increase of radioactivity in the cerebellum. Total distribution volume of [ 11 C]ITMM was highest in the cerebellum, followed by thalamus, cerebral cortex, and striatum; regional differences in brain radioactivity corresponded to the mGluR1 distribution in the brain. Peripherally, [ 11 C]ITMM was stable in humans: 60% of the plasma radioactivity remained in the unchanged form for 60 min. Conclusions: [ 11 C] ITMM is a suitable radioligand for imaging mGluR1 in the human brain providing acceptable dosimetry and pharmacological safety at the dose required for PET

  17. 18F- and 11C-labelling of quantum dots with n.c.a. [18F]fluoroethyltosylate and [11C]methyliodide. A feasibility study

    International Nuclear Information System (INIS)

    Patt, M.; Schildan, A.; Habermann, B.; Mishchenko, O.; Patt, J.T.; Sabri, O.

    2010-01-01

    Quantum dots functionalized on the outer surface with either amino- or carboxyl functions were labelled with [ 18 F]fluoroethyltosylate and [ 11 C]methyliodide in order to use the positron emitter-labelled fluorescence agents for multimodality imaging techniques, i.e. fluorescence imaging and positron emission tomography. 18 F-Labelling of both compounds was realized with yields up to 5% as determined by size exclusion chromatography, which is twice as much as reported in literature before [1]. 11 C-Labelling of amino- and carboxyl-QDs proceeded with good yields (up to 45 and 35%, respectively) under optimized reaction conditions. In general for both QD-types and both labelling agents the labelling yield increased with the amount of QDs used in the reaction as well as with reaction time and reaction temperature. (author)

  18. C1-2 vertebral anomalies in 22q11.2 microdeletion syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Konen, Osnat; Armstrong, Derek; Padfield, Nancy; Blaser, Susan [Hospital for Sick Children, Diagnostic Imaging, Toronto (Canada); Clarke, Howard [Hospital for Sick Children, Plastic Surgery, Toronto (Canada); Weksberg, Rosanna [Hospital for Sick Children, Clinical and Metabolic Genetics, Toronto (Canada)

    2008-07-15

    Chromosome 22q11.2 microdeletion syndrome (22q11DS) is characterized by cleft palate, cardiac anomalies, characteristic facies, high prevalence of skeletal anomalies and learning disability. To evaluate the prevalence of craniovertebral junction anomalies in children with 22q11DS and compare these findings to those in nonsyndromic children with velopharyngeal insufficiency (VPI). Sequential CT scans performed for presurgical carotid assessment in 76 children (45 children positive for chromosome 22q11.2 deletion and 31 negative for the deletion) with VPI were retrospectively evaluated for assessment of C1-2 anomalies. C1-2 vertebral anomalies, specifically midline C1 defects, uptilted or upswept posterior elements of C2 and fusions of C2-3, were nearly universal in our cohort of 22q11DS patients with VPI. They were strikingly absent in the majority of non-22q11DS patients with VPI. C1-2 vertebral anomalies, particularly those listed above, are important radiographic markers for 22q11DS. (orig.)

  19. C1-2 vertebral anomalies in 22q11.2 microdeletion syndrome

    International Nuclear Information System (INIS)

    Konen, Osnat; Armstrong, Derek; Padfield, Nancy; Blaser, Susan; Clarke, Howard; Weksberg, Rosanna

    2008-01-01

    Chromosome 22q11.2 microdeletion syndrome (22q11DS) is characterized by cleft palate, cardiac anomalies, characteristic facies, high prevalence of skeletal anomalies and learning disability. To evaluate the prevalence of craniovertebral junction anomalies in children with 22q11DS and compare these findings to those in nonsyndromic children with velopharyngeal insufficiency (VPI). Sequential CT scans performed for presurgical carotid assessment in 76 children (45 children positive for chromosome 22q11.2 deletion and 31 negative for the deletion) with VPI were retrospectively evaluated for assessment of C1-2 anomalies. C1-2 vertebral anomalies, specifically midline C1 defects, uptilted or upswept posterior elements of C2 and fusions of C2-3, were nearly universal in our cohort of 22q11DS patients with VPI. They were strikingly absent in the majority of non-22q11DS patients with VPI. C1-2 vertebral anomalies, particularly those listed above, are important radiographic markers for 22q11DS. (orig.)

  20. L-[4-11C]aspartic acid: enzymatic synthesis, myocardial uptake, and metabolism

    International Nuclear Information System (INIS)

    Barrio, J.R.; Egbert, J.E.; Henze, E.; Schelbert, H.R.; Baumgartner, F.J.

    1982-01-01

    Sterile, pyrogen-free L-[4- 11 C]aspartic acid was prepared from 11 CO 2 using phosphoenolpyruvate carboxylase and glutamic/oxaloacetic acid transaminase immobilized on Sepharose supports to determine if it is a useful indicator for in vivo, noninvasive determination of myocardial metabolism. An intracoronary bolus injection of L-[4- 11 C]aspartic acid into dog myocardium showed a triexponential clearance curve with maximal production of 11 CO 2 100 s after injection. Inactivation of myocardial transaminase activity modified the tracer clearance and inhibited the production of 11 CO 2 . Positron-computed tomography imaging showed that the 11 C activities retained in rhesus monkey myocardium are higher than those observed in dog heart after intravenous injection of L-[4- 11 C]aspartic acid. These findings demonstrated the rapid incorporation of the carbon skeleton of L-aspartic acid into the tricarboxylic acid cycle after enzymatic transamination in myocardium and suggested that L-[4- 11 C]aspartic acid could be of value for in vivo, noninvasive assessment of local myocardial metabolism

  1. Double-step processes in the 12C(p,d)11C reaction at 45 MeV

    International Nuclear Information System (INIS)

    Couvert, Pierre.

    1974-01-01

    12 C(p,d) 11 C pick-up reaction was performed with a 45 MeV proton beam. A 130keV energy resolution was obtained and angular distributions of nine of the ten first levels of 11 C have been extracted within a large angular range. Assuming only neutron direct transfert, the strong relative excitation of high spin levels cannot be reproduced by a DWBA analysis. The double-step process assumption seems to be verified by a systematical analysis of the (p,d) reaction mechanisms. This analysis is done in the coupled-channel formalism for the five first negative parity states of 11 C. The 3/2 - ground state is essentially populated by the direct transfer of a Psub(3/2) neutron. The contribution of a double-step process, via the 2 + inelastic excitation of 12 C, is important for the four other states. A mechanism which assumes a deuteron inelastic scattering on the 11 C final nucleus after the neutron transfer cannot be neglected and improves the fits when it is taken into account [fr

  2. L-11C-methionine remote controlled synthetic system

    International Nuclear Information System (INIS)

    Tomiyoshi, Katsumi; Watanabe, Naoyuki; Tateno, Madoka; Oriuchi, Noboru; Hirano, Tsuneo; Inoue, Tomio; Endo, Keigo

    1992-01-01

    L- 11 C-methionine have been used clinically in studies of brain tumors in combination with 18 F-fluorodeoxyglucose ( 18 FDG). In respect with synthesizing radiopharmaceuticals, high radioactivity and constant radiochemical yield have to be obtained in routine bases. Therefore automatic synthesis apparatus is inevitable to carry out following points. 1) Radiation Exposure Protection: Half life of 11 C having 20 minutes, starting high radioactivity give a lot of exposure dose to hands and body. 2) Constant radiochemical yield: Amount of radiochemical yield is likely to be varied in manual synthesis which could lead little activity or cancellation to inject. (author)

  3. 29 CFR 1977.5 - Persons protected by section 11(c).

    Science.gov (United States)

    2010-07-01

    ... OCCUPATIONAL SAFETY AND HEALTH ACT OF 1970 General § 1977.5 Persons protected by section 11(c). (a) All employees are afforded the full protection of section 11(c). For purposes of the Act, an employee is defined... Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION...

  4. (R)-[11C]Emopamil as a novel tracer for imaging enhanced P-glycoprotein function

    International Nuclear Information System (INIS)

    Toyohara, Jun; Okamoto, Mayumi; Aramaki, Hiroki; Zaitsu, Yuto; Shimizu, Isao; Ishiwata, Kiichi

    2016-01-01

    Introduction: 2-Isopropyl-5-[methyl-(2-phenylethyl)amino]-2-phenylpentanenitrile (emopamil; EMP) is a calcium channel blocker of the phenylalkylamine class, with weak substrate properties for P-glycoprotein (P-gp). A weak substrate for P-gp would be suitable for measuring enhanced P-gp function. This study was performed to synthesise (R)- and (S)-[ 11 C]EMP and characterise their properties as P-gp tracers. Methods: We synthesised (R)- and (S)-[ 11 C]EMP and compared their biodistribution, peripheral metabolism, and effects of the P-gp inhibitor cyclosporine A (CsA, 50 mg/kg). We compared the brain pharmacokinetics of (R)-[ 11 C]EMP and (R)-[ 11 C]verapamil [(R)-[ 11 C]VER] at baseline and CsA pretreatment with small animal positron emission tomography (PET). Results: (R)- and (S)-[ 11 C]EMP were synthesised from (R)- and (S)-noremopamil, respectively, by methylation with [ 11 C]methyl triflate in the presence of NaOH at room temperature. (R)- and (S)-[ 11 C]EMP yields were ~ 30%, with specific activity > 74 GBq/μmol and radiochemical purity > 99%. (R)-[ 11 C]EMP showed significantly greater uptake in the mouse brain than (S)-[ 11 C]EMP. Both showed homogeneous non-stereoselective regional brain distributions. (R)- and (S)-[ 11 C]EMP were rapidly metabolised to hydrophilic metabolites. Unchanged plasma (S)-[ 11 C]EMP level was significantly lower than that of (R)-[ 11 C]EMP 15 minutes post-injection, whilst > 88% of radioactivity in the brain was intact at 15 minutes post-injection and was non-stereoselective. CsA pretreatment increased brain activity ~ 3-fold in mice, but was non-stereoselective. The baseline area-under-the-curve (AUC) of brain radioactivity (0–60 minutes) of (R)-[ 11 C]EMP was 2-fold higher than that of (R)-[ 11 C]VER, but their AUCs after CsA pretreatment were comparable. Conclusions: (R)-[ 11 C]EMP is a novel tracer for imaging P-gp function with higher baseline uptake than (R)-[ 11 C]VER.

  5. [11C]NS8880, a promising PET radiotracer targeting the norepinephrine transporter

    DEFF Research Database (Denmark)

    Vase, Karina Højrup; Peters, Dan; Nielsen, Elsebeth Ø

    2014-01-01

    -azabicyclo[3.2.1]octane (NS8880), targeting NET. NS8880 has an in vitro binding profile comparable to desipramine and is structurally not related to reboxetine. METHODS: Labeling of NS8880 with [11C] was achieved by a non-conventional technique: substitution of pyridinyl fluorine with [11C]methanolate...... yields with high purity. The PET in vivo evaluation in pig and rat revealed a rapid brain uptake of [11C]NS8880 and fast obtaining of equilibrium. Highest binding was observed in thalamic and hypothalamic regions. Pretreatment with desipramine efficiently reduced binding of [11C]NS8880. CONCLUSION: Based...... on the pre-clinical results obtained so far [11C]NS8880 displays promising properties for PET imaging of NET....

  6. 32 CFR Appendix C to Part 45 - DD Form 215

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 1 2010-07-01 2010-07-01 false DD Form 215 C Appendix C to Part 45 National... CERTIFICATE OF RELEASE OR DISCHARGE FROM ACTIVE DUTY (DD FORM 214/5 SERIES) Pt. 45, App. C Appendix C to Part 45—DD Form 215 EC21OC91.050 ...

  7. Tracers development for the PET study of nicotinic receptors: [{sup 11}C]-mecamylamine and [{sup 11}C]-SIB 1553A. Tritium and carbon-11 radiolabelling of a serine proteinase inhibitor: the t-PA{sub stop}; Developpement de traceurs pour l'etude des recepteurs nicotiniques par TEP: la [{sup 11}C]-mecamylamine et le [{sup 11}C]SIB 1553A. Radiomarquages par le tritium et le carbone-11 d'un inhibiteur d'une serine protease: le t-PA{sub stop}

    Energy Technology Data Exchange (ETDEWEB)

    Sobrio, F.

    2002-12-15

    In order to develop radiotracers for the Positron Emission Tomography (PET), we labelled both the mecamylamine and SIB-1553A with carbon-11 to study the nicotinic cholinergic receptors (nAChRs). The radiosynthesis of [{sup 11}C]-t-PA{sub stop} and the labelling with tritium of one analogue were realized for cerebral ischemia PET studies. The [{sup 11}C]-mecamylamine, a non-competitive and non-selective nAChRs antagonist was synthesized in 45 min via a N-[{sup 11}C]-methylation reaction. In the rat brain, the ex vivo studies showed no radio-metabolite 45 min after the injection of [{sup 11}C]-mecamylamine. The uptake kinetics in the rat brain or in vivo by PET in the anesthetized baboon or in the conscious monkey, reached a plateau around 45-50 min after injection. However, the saturation or displacement experiments did not permit to exhibit nor a significant difference of labelling between the different cerebral regions nor a specific uptake. In consequence, the [{sup 11}C]-mecamylamine was not an appropriate radioligand for nAChRs PET study. The labelling of [{sup 11}C]-SIB 1553A, a selective agonist for the nicotinic {beta}4 subunit, required the synthesis in 5 steps (56% overall yield) of precursor for the incorporation of carbon-11. The radiosynthesis was performed in 36 min by a N-[{sup 11}C]-methylation reaction (yield: 75%). The [{sup 11}C]-t-PA{sub stop} was obtained from [{sup 11}C]-KCN with yields from 80 to 90%. For the first time with carbon-11, the formation of an amidine group was realized from a nitrile group. The labelling by isotopic exchange of hydrogen by tritium of the t-PA{sub stop} did not permit to obtain the [{sup 3}H]-t-PA{sub stop} but a tritiated analogue. This compound will be used to study its vectorization by micro-encapsulation. (author)

  8. Biodistribution and radiation dosimetry of {sup 11}C-labelled docetaxel in cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Veldt, Astrid A.M. van der; Mooijer, Martien P.J.; Rijnders, Anneloes Y.; Windhorst, Albert D.; Lammertsma, Adriaan A.; Lubberink, Mark [VU University Medical Center, Department of Nuclear Medicine and PET Research, P.O. Box 7057, Amsterdam (Netherlands); Hendrikse, N.H. [VU University Medical Center, Department of Nuclear Medicine and PET Research, P.O. Box 7057, Amsterdam (Netherlands); VU University Medical Center, Department of Clinical Pharmacology and Pharmacy, Amsterdam (Netherlands); Smit, Egbert F. [VU University Medical Center, Department of Pulmonology, Amsterdam (Netherlands); Gerritsen, Winald R. [VU University Medical Center, Department of Medical Oncology, Amsterdam (Netherlands); Hoeven, Jacobus J.M. van der [Medical Center Alkmaar, Department of Internal Medicine, Alkmaar (Netherlands)

    2010-10-15

    Docetaxel is an important chemotherapeutic agent used for the treatment of several cancer types. As radiolabelled anticancer agents provide a potential means for personalized treatment planning, docetaxel was labelled with the positron emitter {sup 11}C. Non-invasive measurements of [{sup 11}C]docetaxel uptake in organs and tumours may provide additional information on pharmacokinetics and pharmacodynamics of the drug docetaxel. The purpose of the present study was to determine the biodistribution and radiation absorbed dose of [{sup 11}C]docetaxel in humans. Biodistribution of [{sup 11}C]docetaxel was measured in seven patients (five men and two women) with solid tumours using PET/CT. Venous blood samples were collected to measure activity in blood and plasma. Regions of interest (ROI) for various source organs were defined on PET (high [{sup 11}C]docetaxel uptake) or CT (low [{sup 11}C]docetaxel uptake). ROI data were used to generate time-activity curves and to calculate percentage injected dose and residence times. Radiation absorbed doses were calculated according to the MIRD method using OLINDA/EXM 1.0 software. Gall bladder and liver demonstrated high [{sup 11}C]docetaxel uptake, whilst uptake in brain and normal lung was low. The percentage injected dose at 1 h in the liver was 47 {+-} 9%. [{sup 11}C]docetaxel was rapidly cleared from plasma and no radiolabelled metabolites were detected. [{sup 11}C]docetaxel uptake in tumours was moderate and highly variable between tumours. The effective dose of [{sup 11}C]docetaxel was 4.7 {mu}Sv/MBq. As uptake in normal lung is low, [{sup 11}C]docetaxel may be a promising tracer for tumours in the thoracic region. (orig.)

  9. 24 CFR 55.11 - Applicability of subpart C decision making process.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Applicability of subpart C decision making process. 55.11 Section 55.11 Housing and Urban Development Office of the Secretary, Department of Housing and Urban Development FLOODPLAIN MANAGEMENT Application of Executive Order on Floodplain Management § 55.11 Applicability of subpart C...

  10. Osseous associated cervical spondylomyelopathy at the C2-C3 articular facet joint in 11 dogs.

    Science.gov (United States)

    Cooper, C; Gutierrez-Quintana, R; Penderis, J; Gonçalves, R

    2015-11-21

    In dogs, vertebral canal stenosis at C2-C3 due to articular facet joint degeneration is only sporadically identified. The authors' aims were to review the clinical presentation, MRI characteristics, treatment and outcome of dogs presenting with this condition. Eleven cases were eligible for inclusion. Neurological examination revealed tetraparesis and proprioceptive ataxia in all 4 limbs in 3/11, proprioceptive tetra-ataxia only in 4/11, pelvic limb proprioceptive ataxia in 2/11 and no gait abnormalities in 2/11 dogs. Cervical hyperaesthesia was present in 7/11 dogs. MRI revealed bilateral articular facet joint degeneration in 10/11 cases and unilateral degeneration in one. Surgery was performed in six cases and medical management elected in five. Long-term follow-up information was available for 11 animals. Four of the surgical cases are alive and have no neurological deficits, one was euthanased for an unrelated condition and one lost to follow-up. Of the cases managed medically, three are alive showing no neurological deficits, one is alive still displaying neurological deficits and one euthanased for an unrelated condition whilst still ataxic. This study shows that both medical and surgical management can result in good outcomes in dogs with vertebral canal stenosis resulting from articular facet joint degeneration at the level of C2-C3. British Veterinary Association.

  11. Studies on the Total Synthesis of Amphidinolide O (II): A Stereoselective Synthesis of C1-C11 Fragment

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Mi Yeon; Kim, Jong Woo; Lee, Duck Hyung [Sogang University, Seoul (Korea, Republic of)

    2005-10-15

    Two ketones and, the C1-C11 fragment of Amphidinolide O, were prepared stereoselectively via 14 and 16 step sequences in 8.7% and 2.0% overall yield, respectively. The amphidinolides were isolated from the marine dinoflagellate Amphidinium sp., which produces a host of secondary metabolites endowed with potent cytotoxicity against various cancer cell lines. Amphidinolide O displayed potent in vitro cytotoxicity against L1210 marine leukemia cells and human epidermoid carcinoma KB cells with 1.7 and 3.6 μg/mL of IC50s, respectively. In addition to our recent reports regarding to the synthesis of C12-C17 and C3-C11 fragments of amphidinolide O, we describe herein a new route to diastereoselective synthesis of C1-C11 fragment of. The retrosynthetic analysis of led to the C1-C11 fragment and C12-C17 fragment. The hemiketal was expected from acyclic precursor 4 which, in turn, would be derived by diastereoselective aldol reaction between ketone and aldehyde.

  12. Potential of [11C]DASB for measuring endogenous serotonin with PET: binding studies

    International Nuclear Information System (INIS)

    Lundquist, Pinelopi; Wilking, Helena; Hoeglund, A. Urban; Sandell, Johan; Bergstroem, Mats; Hartvig, Per; Langstroem, Bengt

    2005-01-01

    The serotonin transporter radioligand [ 11 C]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile, or [ 11 C]DASB, was examined in order to assess its potential for measuring fluctuations in endogenous serotonin concentrations with positron emission tomography. Binding characteristics of [ 11 C]DASB and the propensity for serotonin to displace the tracer were explored in rat brain homogenates. Experiments showed that serotonin displaced [ 11 C]DASB in vitro. Ex vivo experiments performed after tranylcypromine injection (3 or 15 mg/kg) showed a dose-dependent trend in radioactivity uptake and suggested that serotonin may compete with [ 11 C]DASB for transporter binding

  13. Synthesis of electrophilic 11C-synthons: 11C-cyanogen bromide and some 11C-cyano reagents

    International Nuclear Information System (INIS)

    Westerberg, G.; Malmborg, P.; Langstroem, B.

    1990-01-01

    A fast, simple, and reliable method has been developed for the synthesis of carbon-11 labelled cyanogen bromide and several of its stabilized amine salts or cyanates. Preparation of cyanogen bromide is by bromination (bromine gas) of carbon-11 labelled hydrocyanic acid, followed by reaction with a tertiary amine or a phenol to yield the ammonium salts or cyanates

  14. The Buecherer-Strecker synthesis of D- and L-(1-11C)tyrosine and the in vivo study of 0100L-(1-11C)tyrosine in human brain using positron emission tomography

    International Nuclear Information System (INIS)

    Halldin, C.; Wiesel, F.A.

    1987-01-01

    The synthesis of D- and L-(1- 11 C)tyrosine, starting with 11 C-cyanide, is reported. DL-(1- 11 C)tyrosine was prepared by the Buecherer-Strecker reaction, from carrier added 11 C-cyanide with an incorporation of 80% in 20 min. The isolation of the pure D- and L-amino acid isomers from the enantiomeric mixture was accomplished within 15 min by preparative HPLC using a chiral stationary phase and a phosphate buffer as the mobile phase. Typically, the total synthesis time was 50 min (including purification) from end of trapping of 11 C-cyanide, with a radiochemical yield of D- and L-amino acid of 40%-60%. The D- and L-(1- 11 C)tyrosine were both obtained optically pure, with a carrier added specific activity of 0.3-0.5 Ci/mmol and a radiochemical purity better than 99%. The 11 C labelled L-tyrosine was used in an in vivo study in the human brain using positron emission tomography (PET). (orig.)

  15. Efficient and reproducible synthesis of [1-{sup 11}C]acetyl chloride using the loop method

    Energy Technology Data Exchange (ETDEWEB)

    Arai, Takuya [Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Zhang, Ming-Rong [Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan)], E-mail: zhang@nirs.go.jp; Ogawa, Masanao [Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); SHI Accelerator Service Co. Ltd., 1-17-6 Osaki, Shinagawa-ku, Tokyo 141-8686 (Japan); Fukumura, Toshimitsu; Kato, Koichi; Suzuki, Kazutoshi [Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan)

    2009-02-15

    [1-{sup 11}C]Acetyl chloride ([{sup 11}C]AcCl), an important [{sup 11}C]acylating agent, was synthesized by reacting [{sup 11}C]CO{sub 2} with methylmagnesium bromide coated on the inner surface of a polyethylene loop (loop method). By optimizing the reaction conditions and synthesis parameters, [1-{sup 11}C]phenylacetate and [1-{sup 11}C]benzylacetate were produced from [{sup 11}C]AcCl in high radiochemical yield and specific activity.

  16. Integrated MRI and [11 C]-PBR28 PET Imaging in Amyotrophic Lateral sclerosis.

    Science.gov (United States)

    Alshikho, Mohamad J; Zürcher, Nicole R; Loggia, Marco L; Cernasov, Paul; Reynolds, Beverly; Pijanowski, Olivia; Chonde, Daniel B; Izquierdo Garcia, David; Mainero, Caterina; Catana, Ciprian; Chan, James; Babu, Suma; Paganoni, Sabrina; Hooker, Jacob M; Atassi, Nazem

    2018-05-08

    To characterize [ 11 C]-PBR28 brain uptake using positron emission tomography (PET) in people with amyotrophic lateral sclerosis (ALS), and primary lateral sclerosis (PLS). We have previously shown increased [ 11 C]-PBR28 uptake in the precentral gyrus in a small group of ALS patients. Herein, we confirm our initial finding, study the longitudinal changes, and characterize the gray vs. white matter distribution of [ 11 C]-PBR28 uptake in a larger cohort of patients with ALS and PLS. Eighty-five participants including 53 ALS, 11 PLS and 21 healthy controls underwent integrated [ 11 C]-PBR28 PET-MR brain imaging. Patients were clinically assessed using the upper motor neuron burden (UMNB), and the revised ALS functional rating scale (ALSFRS-R). [ 11 C]-PBR28 uptake was quantified as standardized uptake value ratio (SUVR), and compared between groups. Cortical thickness, and fractional anisotropy were compared between groups and correlated with SUVR and the clinical data. [ 11 C]-PBR28 uptake and ALSFRS-R were compared longitudinally over six-month in ten ALS individuals. Whole brain voxel-wise, surface-based and region of interest analyses revealed increased [ 11 C]-PBR28 uptake in the precentral and paracentral gyri in ALS, and in the sub-cortical white matter for the same regions in PLS, compared to controls. The increase in [ 11 C]-PBR28 uptake co-localized and correlated with cortical thinning, reduced fractional anisotropy, increased mean diffusivity, and correlated with higher UMNB score. No significant changes were detected in [ 11 C]-PBR28 uptake over six-month despite clinical progression. Glial activation measured by in vivo [ 11 C]-PBR28 PET is increased in pathologically relevant regions in people with ALS and correlates with clinical measures. This article is protected by copyright. All rights reserved. © 2018 American Neurological Association.

  17. A spatially-supported forced-choice recognition test reveals children’s long-term memory for newly learned word forms

    Directory of Open Access Journals (Sweden)

    Katherine R. Gordon

    2014-03-01

    Full Text Available Children’s memories for the link between a newly trained word and its referent have been the focus of extensive past research. However, memory for the word form itself is rarely assessed among preschool-age children. When it is, children are typically asked to verbally recall the forms, and they generally perform at floor on such tests. To better measure children’s memory for word forms, we aimed to design a more sensitive test that required recognition rather than recall, provided spatial cues to off-set the phonological memory demands of the test, and allowed pointing rather than verbal responses. We taught 12 novel word-referent pairs via ostensive naming to sixteen 4-to-6-year-olds and measured their memory for the word forms after a week-long retention interval using the new spatially-supported form recognition test. We also measured their memory for the word-referent links and the generalization of the links to untrained referents with commonly used recognition tests. Children demonstrated memory for word forms at above chance levels; however, their memory for forms was poorer than their memory for trained or generalized word-referent links. When in error, children were no more likely to select a foil that was a close neighbor to the target form than a maximally different foil. Additionally, they more often selected correct forms that were among the first six than the last six to be trained. Overall, these findings suggest that children are able to remember word forms after a limited number of ostensive exposures and a long-term delay. However, word forms remain more difficult to learn than word-referent links and there is an upper limit on the number of forms that can be learned within a given period of time.

  18. Comparison of [(11)C]Choline ([(11)C]CHO) and [(18)F]Bombesin (BAY 86-4367) as Imaging Probes for Prostate Cancer in a PC-3 Prostate Cancer Xenograft Model.

    Science.gov (United States)

    Schwarzenböck, Sarah Marie; Schmeja, Philipp; Kurth, Jens; Souvatzoglou, Michael; Nawroth, Roman; Treiber, Uwe; Kundt, Guenther; Berndt, Sandra; Graham, Keith; Senekowitsch-Schmidtke, Reingard; Schwaiger, Markus; Ziegler, Sibylle I; Dinkelborg, Ludger; Wester, Hans-Jürgen; Krause, Bernd Joachim

    2016-06-01

    Carbon-11- and fluorine-18-labeled choline derivatives are commonly used in prostate cancer imaging in the clinical setting for staging and re-staging of prostate cancer. Due to a limited detection rate of established positron emission tomography (PET) tracers, there is a clinical need for innovative tumor-specific PET compounds addressing new imaging targets. The aim of this study was to compare the properties of [(18)F]Bombesin (BAY 86-4367) as an innovative biomarker for prostate cancer imaging targeting the gastrin-releasing peptide receptor and [(11)C]Choline ([(11)C]CHO) in a human prostate tumor mouse xenograft model by small animal PET/X-ray computed tomography (CT). We carried out a dual-tracer small animal PET/CT study comparing [(18)F]Bombesin and [(11)C]CHO. The androgen-independent human prostate tumor cell line PC-3 was implanted subcutaneously in the flanks of nu/nu NMRI mice (n = 10) (PET/CT measurements of two [(11)C]Choline mice could not be analyzed due to technical reasons). [(18)F]Bombesin and [(11)C]CHO PET/CT imaging was performed about 3-4 weeks after the implantation of PC-3 cells on two separate days. After the intravenous tail vein injection of 14 MBq [(18)F]Bombesin and 37 MBq [(11)C]CHO, respectively, a dynamic study over 60 min was acquired in list mode using an Inveon animal PET/CT scanner (Siemens Medical Solutions). The sequence of [(18)F]Bombesin and [(11)C]CHO was randomized. Image analysis was performed using summed images as well as dynamic data. To calculate static and dynamic tumor-to-muscle (T/M), tumor-to-blood (T/B), liver-to-blood (L/B), and kidney-to-blood (K/B) ratios, 4 × 4 × 4 mm(3) volumes of interest (VOIs) of tumor, muscle (thigh), liver, kidney, and blood derived from transversal slices were used. The mean T/M ratio of [(18)F]Bombesin and [(11)C]CHO was 6.54 ± 2.49 and 1.35 ± 0.30, respectively. The mean T/B ratio was 1.83 ± 0.79 for [(18)F]Bombesin and 0.55 ± 0.10 for [(11)C

  19. Synthesis of 1- and 3-11C-labelled L-lactic acid using multi-enzyme catalysis

    International Nuclear Information System (INIS)

    Bjurling, P.; Laangstroem, B.

    1990-01-01

    The synthesis of 1- and 3- 11 C-labelled L-lactic acid from the corresponding racemic 1- or 3- 11 C-labelled alanine using a multi-enzymatic reaction route, is presented. DL-[1- 11 C]Alanine was synthesised by reacting sodium 1-hydroxy-ethyl sulfite with hydrogen [ 11 C]cyanide, obtained from [ 11 C]carbon dioxide, and ammonia followed by acid hydrolysis. DL-[3- 11 C]-Alanine was synthesised by a methylation of a glycine derivative, N-(diphenylmethylene)-glycine tert-butyl ester, with [ 11 C]methyl iodide, obtained from [ 11 C]carbon dioxide, and subsequent hydrolysis. The racemic 1- or 3- 11 C-labelled alanine was then converted to pyruvic acid, by D-amino acid oxidase/catalase and glutamic-pyruvic transaminase, which was directly reduced to L-lactic acid by L-lactic dehydrogenase in a one-pot procedure. The total synthesis time was 40 minutes, counted from release of [ 11 C]carbon dioxide. The decay corrected radiochemical yields were ca. 80% for L-[1- 11 C]lactic acid, based on hydrogen cyanide, and ca. 60% for L-[3- 11 C]lactic acid, based on carbon dioxide. The radiochemical purities were higher than 99% analysed by HPLC. (author)

  20. Synthesis of a /sup 11/C-labelled neuroleptic drug: pimozide

    Energy Technology Data Exchange (ETDEWEB)

    Crouzel, C; Mestelan, G; Kraus, E; Lecomte, J M; Comar, D [CEA, 91 - Orsay (France). Service Hospitalier Frederic Joliot

    1980-09-01

    Pimozide, a neuroleptic drug which is one of the best ligands for brain dopaminergic receptors in mice in vivo, was labelled with /sup 11/C for eventual investigation in man. This synthesis was carried out in 30 min from phosgene as the /sup 11/C precursor. The synthesis, resulting specific activity and the tissue distribution kinetics in mice are presented and discussed.

  1. Radioisotope tracer study of co-reactions of methanol with ethanol using 11C-labelled methanol over alumina and H-ZSM-5

    International Nuclear Information System (INIS)

    Sarkadi-Priboczki, E.; Kovacs, Z.; Kumar, N.; Salmi, T.; Murzin, D.Yu

    2005-01-01

    Complete text of publication follows. The transformation of methanol has been investigated over alumina and H-ZSM-5 in our previous experiments by 11 C-radioisotope tracing. The main product in methanol conversion over alumina was dimethyl ether due to Lewis acid sites while over H-ZSM-5 mostly hydrocarbons were formed due to both Lewis and Brrnsted acid sites. With increasing temperature first the ethanol was dehydrated to diethyl ether followed by ethene formation over alumina and H-ZSM-5. In this work, 11 C-labelled methanol as radioisotope tracer was added to non-radioactive methanol for investigation of co-reaction with non-radioactive ethanol over alumina and H- ZSM-5. The 11 C-methanol tracer was used to distinguish the methanol derivates and co-reaction derivates of methanol with ethanol against non-radioactive ethanol derivates. The yield of methyl ethyl ether as mixed ether and the influence of ethanol for the yields of C 1 -C 5 hydrocarbons were studied as a function of reaction temperature and contact time. The 11 C-methanol was formed by a radiochemical process from 11 CO 2 produced at cyclotron. The mixture of methanol and ethanol was added to 11 C-methanol and injected to the catalyst. The catalysis was carried out in a glass tube fixed-bed reactor after its pretreatment. The derivates were analyzed by radio-gas chromatography (gas chromatograph with thermal conductivity detector coupled on-line with a radioactivity detector). The comparative analysis of yields of radioactive and non-radioactive products as a function of reaction temperature gives information about the reaction pathways. Over alumina the yields of dimethyl ether and methyl ethyl ether (co-product) as radioactive and diethyl ether with ethene as non-radioactive main products were monitored as a function of reaction temperature and reaction time in the range of 513-593 K. Alongside ethanol derivates the ethene turns into main product in contrast with methyl ethyl ether and diethyl

  2. Study of the excited levels of 11C and 12C by the analysis of protons induced reactions

    International Nuclear Information System (INIS)

    Rihet, Y.

    1984-07-01

    The present work is a study of 11 and 12 C excited states by reactions of non polarised protons on 10 B and 11 B. R-matrix analysis of the 10 B excitation curves in the range E p = 0 to 8 MeV was used to establish parameters of 41 levels in 11 C. Isobaric multiplets of T = 1/2 and T = 3/2 states in A = 11 nuclei are deduced. Analysis of 11 B excitation curves in the E p = 0.5 to 7.4 MeV range led to parameter values of 60 levels in 12 C. T = 1 states in A = 12 isobaric nuclei are discussed [fr

  3. Cocrystals of the antimalarial drug 11-azaartemisinin with three alkenoic acids of 1:1 or 2:1 stoichiometry.

    Science.gov (United States)

    Nisar, Madiha; Wong, Lawrence W Y; Sung, Herman H Y; Haynes, Richard K; Williams, Ian D

    2018-06-01

    The stoichiometry, X-ray structures and stability of four pharmaceutical cocrystals previously identified from liquid-assisted grinding (LAG) of 11-azaartemisinin (11-Aza; systematic name: 1,5,9-trimethyl-14,15,16-trioxa-11-azatetracyclo[10.3.1.0 4,13 .0 8,13 ]hexadecan-10-one) with trans-cinnamic (Cin), maleic (Mal) and fumaric (Fum) acids are herein reported. trans-Cinnamic acid, a mono acid, forms 1:1 cocrystal 11-Aza:Cin (1, C 15 H 23 NO 4 ·C 9 H 8 O 2 ). Maleic acid forms both 1:1 cocrystal 11-Aza:Mal (2, C 15 H 23 NO 4 ·C 4 H 4 O 4 ), in which one COOH group is involved in self-catenation, and 2:1 cocrystal 11-Aza 2 :Mal (3, 2C 15 H 23 NO 4 ·C 4 H 4 O 4 ). Its isomer, fumaric acid, only affords 2:1 cocrystal 11-Aza 2 :Fum (4). All cocrystal formation appears driven by acid-lactam R 2 2 (8) heterosynthons with short O-H...O=C hydrogen bonds [O...O = 2.56 (2) Å], augmented by weaker C=O...H-N contacts. Despite a better packing efficiency, cocrystal 3 is metastable with respect to 2, probably due to a higher conformational energy for the maleic acid molecule in its structure. In each case, the microcrystalline powders from LAG were useful in providing seeding for the single-crystal growth.

  4. Synthesis and distribution kinetics of 11C-chlorpromazine in animals

    International Nuclear Information System (INIS)

    Maziere, M.; Sainte-Laudy, J.L.; Crouzel, M.; Comar, D.

    1975-01-01

    A study on animals of the fast distribution kinetics of 11 C-chlorpromazine hydrochloride administered intravenously shows, in both rabbits and monkeys, a very early radioactivity build-up in the brain and lungs (immediately after injection). The lung and brain activities develop and decrease during the experimental period (about 60 min) whereas that of the liver increases. Quantitative results obtained on mice after removal of the organs and counting of the activity obtained by intravenous injection of 11 C-chlorpromazine hydrochloride prove that the radioactivity observed is indeed an accumulation and is not due to passage of the blood flow, the blood activity remaining low throughout. No tumor fixation of 11 C-chlorpromazine was observed in the mice under our experimental conditions. A quantitative kinetics study of 11 C-chlorpromazine in vivo is not easy to pursue in animals such as rabbits or monkeys, and even less so in mice, in view of the size of the animal and the resolution of the gamma camera collimator. But this, we think, is relatively unimportant as the aim of this work is to prepare for the application to humans of this new pharmacokinetics method

  5. Appearance of newly formed mRNA and rRNA as ribonucleoprotein-particles in the cytoplasmic subribosomal fraction of pea embryos

    International Nuclear Information System (INIS)

    Takahashi, Noribumi; Takaiwa, Fumio; Fukuei, Keisuke; Sakamaki, Tadashi; Tanifuji, Shigeyuki

    1977-01-01

    Incorporation studies with 3 H-uridine or 3 H-adenosine showed that germinating pea embryos synthesize all types of poly A(+) RNA, rRNA and 4-5S RNA at the early stage of germination. After the pulse labeling for 30 min, only heterodisperse RNA and 4-5S RNA appeared in the cytoplasm as labeled RNA species. At this time the radioactivity was associated with cytoplasmic structures heavier than 80S and RNP particles of 68-70S, 52-55S, 36-38S and 20-22S which are presumed to be free mRNP particles in plants. When the pulse-labeled embryos were incubated for a further 60 min in an isotope-free medium, the labeled 17S and 25S rRNA emerged in the cytoplasm, together with labeled heterodisperse and 4-5S RNAs. More radioactivity accumulated in the regions of the polysome, 62-65S and 38-42S particles. The results of analysis of RNAs extracted from the whole cytoplasm, polysome or subribosomal fractions indicated that small subunits of newly formed ribosomes appear more rapidly in the cytoplasm than new large subunits, which accumulate for a while as free particles in the cytoplasm than are incorporated into polysomes. The actinomycin treatment which caused preferential inhibition of rRNA synthesis reduced the accumulation of free, newly formed ribosome subunits and partially permitted detection of the presumed mRNP particles in the subribosomal region even after the chase treatment. (auth.)

  6. Captive solvent [11C]acetate synthesis in GMP conditions

    International Nuclear Information System (INIS)

    Soloviev, Dmitri; Tamburella, Claire

    2006-01-01

    Reliable procedure for the production of 1-[ 11 C]acetate in GMP conditions was developed based on a combination of the captive-solvent Grignard reaction conducted in the sterile catheter followed by the convenient solid-phase extraction purification on a series of ion-exchange cartridges. The described procedure proved to be reliable in more than 30 patient productions. The process provides stable radiochemical yields (65% EOB) of sodium acetate (1-[ 11 C]) of the Ph.Eur. quality (radiochemical purity better than 95%) in a short time (5 min)

  7. Biodistribution and radiation dosimetry of [11C]DASB in baboons

    International Nuclear Information System (INIS)

    Belanger, Marie-Jose; Simpson, Norman R.; Wang, Theodore

    2004-01-01

    Objective: The serotonin transporter has been implicated in a variety of conditions including mood disorders and suicidal behavior. In vivo human brain studies with positron emission tomography and the serotonin transporter antagonist [ 11 C]DASB ([ 11 C]-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile) are ongoing in several laboratories with the maximum administered activity based on dosimetry collected in rodents. We report on the biodistribution and dosimetry of [ 11 C]DASB in the baboon as this species may be a more reliable surrogate for human dosimetry. Methods: Four baboon studies (two studies in each of two baboons) were acquired in an ECAT ACCEL camera after the bolus injection of 183±5 MBq/2.3±1.0 nmol of [ 11 C]DASB. For each study, six whole-body emission scans were collected in 3D mode over 6/7 bed positions for 2 h. Regions of interest were drawn on brain, lungs, liver, gallbladder, spleen, kidneys, small intestine and bladder. Since no fluid was removed from the animal, total body radioactivity was calculated using the injected dose calibrated to the ACCEL image units. Results: Uptake was greatest in lungs, followed by the urinary bladder, gallbladder, brain and other organs. The ligand was eliminated via the hepato-billiary and renal systems. The largest absorbed dose was found in the lungs (3.6x10 -2 mSv/MBq). The absorbed radiation doses in lungs and gallbladder were four and nine times larger than that previously estimated from rat studies. Conclusion: Based on our baboon biodistribution and dose estimates, the lungs are the critical organs for administration of [ 11 C]DASB. In the United States, the absorbed dose to the lungs would limit [ 11 C]DASB administered with the approval of a Radioactive Drug Research Committee to 1400 MBq (37 mCi) in the adult male and 1100 MBq (30 mCi) in the adult female

  8. Sequence of a cloned cDNA encoding human ribosomal protein S11

    Energy Technology Data Exchange (ETDEWEB)

    Lott, J B; Mackie, G A

    1988-02-11

    The authors have isolated a cloned cDNA that encodes human ribosomal protein (rp) S11 by screening a human fibroblast cDNA library with a labelled 204 bp DNA fragment encompassing residues 212-416 of pRS11, a rat rp Sll cDNA clone. The human rp S11 cloned cDNA consists of 15 residues of the 5' leader, the entire coding sequence and all 51 residues of the 3' untranslated region. The predicted amino acid sequence of 158 residues is identical to rat rpS11. The nucleotide sequence in the coding region differs, however, from that in rat in the first position in two codons and in the third position in 44 codons.

  9. Synthesis of 11C-labelled haloalkanonitriles and examples of their use in some alkylation reactions

    International Nuclear Information System (INIS)

    Hoernfeldt, K.; Antoni, G.; Laangstroem, B.

    1992-01-01

    The synthesis of the 11 C-labelled bifunctional precursors 4-iodobutyro[ 11 C]nitrile (1), 4-tosyloxybutyro[ 11 C]nitrile (2), 5-iodovalero[ 11 C]nitrile (3), 5-toxyloxyvalero[ 11 C]nitrile (4) and 4-bromopentano[ 11 C]nitrile (5) are presented. The nucleophilic substitution reactions of [ 11 C]cyanide with dibromides, diiodides, ditosylates or mixed iodotosylates producing 1-5 have been carried out in different solvents and the labelled products were obtained in 62-98% radiochemical yields (not isolated), with a total synthesis time of 5 min counted from the end of the hydrogen [ 11 C]cyanide synthesis. The labelled haloalkanonitriles 1 and 3 have also been used in some alkylation reactions with various carbon and oxygen nucleophiles. (au)

  10. CD11c(hi) Dendritic Cells Regulate Ly-6C(hi) Monocyte Differentiation to Preserve Immune-privileged CNS in Lethal Neuroinflammation.

    Science.gov (United States)

    Kim, Jin Hyoung; Choi, Jin Young; Kim, Seong Bum; Uyangaa, Erdenebelig; Patil, Ajit Mahadev; Han, Young Woo; Park, Sang-Youel; Lee, John Hwa; Kim, Koanhoi; Eo, Seong Kug

    2015-12-02

    Although the roles of dendritic cells (DCs) in adaptive defense have been defined well, the contribution of DCs to T cell-independent innate defense and subsequent neuroimmunopathology in immune-privileged CNS upon infection with neurotropic viruses has not been completely defined. Notably, DC roles in regulating innate CD11b(+)Ly-6C(hi) monocyte functions during neuroinflammation have not yet been addressed. Using selective ablation of CD11c(hi)PDCA-1(int/lo) DCs without alteration in CD11c(int)PDCA-1(hi) plasmacytoid DC number, we found that CD11c(hi) DCs are essential to control neuroinflammation caused by infection with neurotropic Japanese encephalitis virus, through early and increased infiltration of CD11b(+)Ly-6C(hi) monocytes and higher expression of CC chemokines. More interestingly, selective CD11c(hi) DC ablation provided altered differentiation and function of infiltrated CD11b(+)Ly-6C(hi) monocytes in the CNS through Flt3-L and GM-CSF, which was closely associated with severely enhanced neuroinflammation. Furthermore, CD11b(+)Ly-6C(hi) monocytes generated in CD11c(hi) DC-ablated environment had a deleterious rather than protective role during neuroinflammation, and were more quickly recruited into inflamed CNS, depending on CCR2, thereby exacerbating neuroinflammation via enhanced supply of virus from the periphery. Therefore, our data demonstrate that CD11c(hi) DCs provide a critical and unexpected role to preserve the immune-privileged CNS in lethal neuroinflammation via regulating the differentiation, function, and trafficking of CD11b(+)Ly-6C(hi) monocytes.

  11. Beta adrenergic receptors in dog heart characterised in vivo by sup 11 C-CGP 12117 and positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Seto, Mikito [Kanazawa Univ. (Japan). School of Medicine

    1989-06-01

    Beta adrenergic receptors in the dog heart were demonstrated in vivo using a potent antagonist, {sup 11}C-CGP 12117 (Kd=0.2 nmol/kg, in vitro), and positron emission tomography (PET). {sup 11}C-CGP at a high specific radioactivity (approximately 500 Ci/mmol) was intravenously injectd in dogs. Axial transverse slices of the heart were obtained. The concentration of {sup 11}C-CGP 12177 in the myocardium rapidly increased and then remained nearly constant for about 30 minutes, before decreasing slowly. Designing a new method to distinguish specific receptor binding from the total ligand concentration in the heart measured by PET, beta adrenoceptor density in the dog myocardium (Bmax) was found to be 113 pmol/cm{sup 3}. Displacement and pre-saturation studies were performed to demonstrate the specifity of {sup 11}C-CGP 12177 binding for noradrenaline binding sites. The bolus injection of unlabeled CGP 12177 25 min following {sup 11}C-CGP 12177 injection led to a rapid decrease in the myocardial ligand concentration and a rapid fall in the heart rate. Both the pharmacological effect of CGP 12177 and the binding inhibition of radioligand were synchronous with the increasing amount of antagonist injected for displacement. In experiments of presaturation with an excessive dose of unlabeled antagonist injection 10 min before {sup 11}C-CGP 12177 injection, the heart/blood radioligand concentration ratio as a function of time was significantly lower than that in the control study. Thus, specific receptor binding of {sup 11}C-CGP 12177 for noradrenaline binding sites in the living heart was proved by PET, which might be the ideal method to study the physiologically active form of receptors in vivo. (author).

  12. Improved synthesis and application of [(11) C]benzyl iodide in positron emission tomography radiotracer production.

    Science.gov (United States)

    Pekošak, Aleksandra; Filp, Ulrike; Rotteveel, Lonneke; Poot, Alex J; Windhorst, Albert D

    2015-06-30

    Positron emission tomography has increased the demand for new carbon-11 radiolabeled tracers and building blocks. A promising radiolabeling synthon is [(11) C]benzyl iodide ([(11) C]BnI), because the benzyl group is a widely present functionality in biologically active compounds. Unfortunately, synthesis of [(11) C]BnI has received little attention, resulting in limited application. Therefore, we investigated the synthesis in order to significantly improve, automate, and apply it for labeling of the dopamine D2 antagonist [(11) C]clebopride as a proof of concept. [(11) C]BnI was synthesized from [(11) C]CO2 via a Grignard reaction and purified prior the reaction with desbenzyl clebopride. According to a one-pot procedure, [(11) C]BnI was synthesized in 11 min from [(11) C]CO2 with high yield, purity, and specific activity, 52 ± 3% (end of the cyclotron bombardment), 95 ± 3%, and 123 ± 17 GBq/µmol (end of the synthesis), respectively. Changes in the [(11) C]BnI synthesis are reduced amounts of reagents, a lower temperature in the Grignard reaction, and the introduction of a solid-phase intermediate purification. [(11) C]Clebopride was synthesized within 28 min from [(11) C]CO2 in an isolated decay-corrected yield of 11 ± 3% (end of the cyclotron bombardment) with a purity of >98% and specific activity (SA) of 54 ± 4 GBq/µmol (n = 3) at the end of the synthesis. Conversion of [(11) C]BnI to product was 82 ± 11%. The reliable synthesis of [(11) C]BnI allows the broad application of this synthon in positron emission tomography radiopharmaceutical development. Copyright © 2015 John Wiley & Sons, Ltd.

  13. Improving performance of AliRoot using C++11

    CERN Document Server

    Agarwal, Abhineet

    2014-01-01

    The aim of the project was to increase the performance and better the memory management which is currently used in AliRoot. For this, we want to look up to certain ROOT libraries and containers which could be replaced using C++ containers and standard libraries. Also, to better the memory management, we wanted to use the smart pointers used in C++11.

  14. A STUDY TO CORRELATE HBA1C LEVELS AND LEFT VENTRICULAR DIASTOLIC DYSFUNCTION IN NEWLY DIAGNOSED TYPE II DIABETES MELLITUS

    OpenAIRE

    Vasanthi; Namitha; Jayanthi; Elangumanan; Mohamed; Uma Maheshwari; Pravin Selvam; Santhi

    2016-01-01

    AIM To assess the correlation of HBA1C levels with left ventricular diastolic dysfunction in newly diagnosed Type 2 diabetic patient. This prospective study was done at Department of General Medicine, OPD, Medical Wards, Stanley Medical College and Hospital, Chennai. RESULT The mean HBA1C levels were meaningfully more in Left Ventricular Diastolic Dysfunction (LVDD) positive group compared to the LVDD negative group by 1.33%. This significant difference of 15% increase in...

  15. New large-Nc relations for the electromagnetic nucleon-to-Δ form factors

    International Nuclear Information System (INIS)

    Vladimir Pascalutsa; Marc Vanderhaeghen

    2006-01-01

    We establish relations which express the three N → Δ transition form factors in terms of the nucleon form factors. These relations are based on the known large-N c relation between the N → Δ electric quadrupole moment and the neutron charge radius, and a newly derived large-N c relation between the electric quadrupole (E2) and Coulomb quadrupole (C2) transitions. Namely, in the large-N c limit we find C2=E2. We show that these relations provide predictions for the N → Δ electromagnetic form factors which are found to be in very good agreement with experiment for moderate momentum transfers. They also provide constraints for the N → Δ GPDs

  16. A new synthesis of [3-11C]pyruvic acid using alanine racemase

    International Nuclear Information System (INIS)

    Ikemoto, M.; Okamoto, E.; Sasaki, M.; Haradahira, T.; Omura, H.; Furuya, Y.; Suzuki, K.; Watanabe, Y.

    1998-01-01

    The synthesis of [3- 11 C]pyruvic acid was attempted by two reaction systems (A: alanine racemase and D-amino acid oxidase, B: alanine racemase and L-alanine dehydrogenase) utilizing a new thermostable enzyme, alanine racemase. Conversion rates from D,L-[3- 11 C]alanine to [3- 11 C]pyruvic acid were almost 100% in both methods. Similar results were obtained with immobilized enzymes packed in a single column. Furthermore, the same column could be used repeatedly without a remarkable decrease of the [3- 11 C]pyruvic acid yield. Various matrices were tested for the immobilizing enzyme, and Aminopropyl-CPG was concluded to be the most suitable since the loss of the enzyme activity was the least in the studied matrices

  17. Synthesis of 'no-carrier-added' sup(11)C-labelled nitrosoureas

    Energy Technology Data Exchange (ETDEWEB)

    Diksic, M.; Farrokhzad, S.; Yamamoto, Y.L.; Feindel, W. (Montreal Neurological Inst., Quebec (Canada))

    1985-03-01

    Syntheses for sup(11)C-labelled chemotherapeutic drugs CCNU, BFNU and CFNU (analogs of BCNU) as well as an improved synthesis for sup(11)C-BCNU are described. The procedures for the separation of dual isomers in the case of sup(11)C-labelled CCNU and CFNU are discussed. The specific activity of these 'no-carrier-added' radiopharmaceuticals was approximately 10sup(4) lower than expected for a carrier-free product. The syntheses were normally finished 20-25 min after the end of the collection of sup(11)C-COClsub(2). Chemical and radiochemical purity of the final products as determined by HPLC and TLRC, respectively, was at least 98%. The syntheses yielded 10-25 mCi of nitrosourea ready for use in PET studies.

  18. [11C]-Acetoacetate PET imaging: a potential early marker for cardiac heart failure

    International Nuclear Information System (INIS)

    Croteau, Etienne; Tremblay, Sébastien; Gascon, Suzanne; Dumulon-Perreault, Véronique; Labbé, Sébastien M.; Rousseau, Jacques A.; Cunnane, Stephen C.; Carpentier, André C.; Bénard, François; Lecomte, Roger

    2014-01-01

    The ketone body acetoacetate could be used as an alternate nutrient for the heart, and it also has the potential to improve cardiac function in an ischemic–reperfusion model or reduce the mitochondrial production of oxidative stress involved in cardiotoxicity. In this study, [ 11 C]-acetoacetate was investigated as an early marker of intracellular damage in heart failure. Methods: A rat cardiotoxicity heart failure model was induced by doxorubicin, Dox(+). [ 14 C]-Acetoacetate, a non-positron (β −) emitting radiotracer, was used to characterize the arterial blood input function and myocardial mitochondrial uptake. Afterward, [ 11 C]-acetoacetate (β +) myocardial PET images were obtained for kinetic analysis and heart function assessment in control Dox(−) (n = 15) and treated Dox(+) (n = 6) rats. The uptake rate (K 1 ) and myocardial clearance rate (k 2 or k mono ) were extracted. Results: [ 14 C]-Acetoacetate in the blood was increased in Dox(+), from 2 min post-injection until the last withdrawal point when the heart was harvested, as well as the uptake in the heart and myocardial mitochondria (unpaired t-test, p < 0.05). PET kinetic analysis of [ 11 C]-acetoacetate showed that rate constants K 1 , k 2 and k mono were decreased in Dox(+) (p < 0.05) combined with a reduction of 24% of the left ventricular ejection fraction (p < 0.001). Conclusion: Radioactive acetoacetate ex vivo analysis [ 14 C], and in vivo kinetic [ 11 C] studies provided evidence that [ 11 C]-acetoacetate can assess heart failure Dox(+). Contrary to myocardial flow reserve (rest–stress protocol), [ 11 C]-acetoacetate can be used to assess reduced kinetic rate constants without requirement of hyperemic stress response. The proposed [ 11 C]-acetoacetate cardiac radiotracer in the investigation of heart disease is novel and paves the way to a potential role for [ 11 C]-acetoacetate in cardiac pathophysiology

  19. 27 CFR 28.122 - Application or notice, YYN Form 5100.11.

    Science.gov (United States)

    2010-04-01

    ... Form 5100.11 to withdraw wine without payment of tax for transportation to and deposit in such... TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS EXPORTATION OF ALCOHOL Withdrawal of Wine Without... Customs Bonded Warehouse, or Transportation to a Manufacturing Bonded Warehouse § 28.122 Application or...

  20. Low background and high contrast PET imaging of amyloid-{beta} with [{sup 11}C]AZD2995 and [{sup 11}C]AZD2184 in Alzheimer's disease patients

    Energy Technology Data Exchange (ETDEWEB)

    Forsberg, Anton; Andersson, Jan; Varnaes, Katarina; Halldin, Christer [Karolinska Institutet, Centre for Psychiatry Research, Department of Clinical Neuroscience, Stockholm (Sweden); Jureus, Anders; Swahn, Britt-Marie; Sandell, Johan; Julin, Per; Svensson, Samuel [AstraZeneca Research and Development, Neuroscience Research and Therapy Area, Soedertaelje (Sweden); Cselenyi, Zsolt; Schou, Magnus; Johnstroem, Peter; Farde, Lars [Karolinska Institutet, Centre for Psychiatry Research, Department of Clinical Neuroscience, Stockholm (Sweden); Karolinska Hospital, AstraZeneca Translational Sciences Centre, PET CoE, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm (Sweden); Eriksdotter, Maria; Freund-Levi, Yvonne [Karolinska Institutet, Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Stockholm (Sweden); Karolinska University Hospital, Department of Geriatric Medicine, Stockholm (Sweden); Jeppsson, Fredrik [AstraZeneca Research and Development, Neuroscience Research and Therapy Area, Soedertaelje (Sweden); Karolinska Institutet, Science for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Stockholm (Sweden)

    2013-04-15

    The aim of this study was to evaluate AZD2995 side by side with AZD2184 as novel PET radioligands for imaging of amyloid-{beta} in Alzheimer's disease (AD). In vitro binding of tritium-labelled AZD2995 and AZD2184 was studied and compared with that of the established amyloid-{beta} PET radioligand PIB. Subsequently, a first-in-human in vivo PET study was performed using [{sup 11}C]AZD2995 and [{sup 11}C]AZD2184 in three healthy control subjects and seven AD patients. AZD2995, AZD2184 and PIB were found to share the same binding site to amyloid-{beta}. [{sup 3}H]AZD2995 had the highest signal-to-background ratio in brain tissue from patients with AD as well as in transgenic mice. However, [{sup 11}C]AZD2184 had superior imaging properties in PET, as shown by larger effect sizes comparing binding potential values in cortical regions of AD patients and healthy controls. Nevertheless, probably due to a lower amount of nonspecific binding, the group separation of the distribution volume ratio values of [{sup 11}C]AZD2995 was greater in areas with lower amyloid-{beta} load, e.g. the hippocampus. Both AZD2995 and AZD2184 detect amyloid-{beta} with high affinity and specificity and also display a lower degree of nonspecific binding than that reported for PIB. Overall [{sup 11}C]AZD2184 seems to be an amyloid-{beta} radioligand with higher uptake and better group separation when compared to [{sup 11}C]AZD2995. However, the very low nonspecific binding of [{sup 11}C]AZD2995 makes this radioligand potentially interesting as a tool to study minute levels of amyloid-{beta}. This sensitivity may be important in investigating, for example, early prodromal stages of AD or in the longitudinal study of a disease modifying therapy. (orig.)

  1. Asymmetric synthesis of L-[3-11C]phenylalanine using chiral hydrogenation catalysts

    International Nuclear Information System (INIS)

    Halldin, C.; Langstroem, B.

    1984-01-01

    The seven-step synthesis of L-[3- 11 C]phenylalanine using chiral diphosphines as ligands in rhodium catalysts is reported. [ 11 C]Benzaldehyde, prepared in a three-step reaction from [ 11 C]carbon dioxide, as reported elsewhere, was reacted with 2-phenyl-5-oxazolone or 2-(4-chloro)phenyl-5-oxazolone in the presence of the tertiary amine diazabicyclooctane (DABCO). The resultant [α- 11 C]-4-arylene-2-atyl-5-oxazolones were hydrogenated after ring opening, using the chiral rhodium complex of (R)-1,2-bis(diphenylphosphino)propane [(R)-PROPHOS] or (+)-2,3-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino)butane [(+)-DIOP]. After removal of the amino protecting group, the labelled amino acid was obtained on purification by preparative LC in 10-15% radiochemical yield, and radiochemical purity higher than 95% from [ 11 C]carbon dioxide within 60 min. The optical purity of the products determined by the tRNA method and capillary GC, was 80 and 60% e.e., respectively (i.e. L/D=90/10 and 80/20). (author)

  2. Gas separation techniques with liquid Ar for production of 11C ions

    International Nuclear Information System (INIS)

    Hojo, Satoru; Honma, Toshihiro; Kanazawa, Mitsutaka; Muramatsu, Masayuki; Sakamoto, Yukio; Sugiura, Akinori; Suzuki, Naokata; Noda, Koji

    2009-01-01

    Heavy-ion cancer therapy with 12 C-beam has been carried out at HIMAC (Heavy Ion Medical Accelerator in Chiba) in NIRS (National Institute of Radiological Sciences) since 1994. One of the feasibility study in HIMAC is to use a positron emitter beam such as 11 C-beam for the cancer therapy. A nuclear reaction, 14 N (p,α) 11 C will be applied in the present study; it can be expected to obtain a considerably large number of 11 C-particles by utilizing the commonly used short-lives RI production techniques for PET (Positron Emission Tomography). The amount of 11 C gas is limited in this technique. The 11 CO 2 gas was produced from N 2 gas that is irradiated high-energy proton beam. Therefore, CO 2 gas separation from N 2 gas is very important. The gas-separation techniques with cryogenic system utilizing a liquid Ar were tested by dummy gas (N 2 + 12 CO 2 ). Details of the gas-separation techniques and measurement of CO 2 partial pressure are discussed. (author)

  3. Synthesis and characterization of [11C]PK11195 as a PET radiopharmaceutical

    International Nuclear Information System (INIS)

    Almeida, Fernanda A. F.; Silveira, Marina B.; Oliveira, Amanda P.; Nascimento, Leonardo T.C.; Silva, Juliana B.; Mamede, Marcelo

    2017-01-01

    The radiopharmaceutical [ 11 C]PK11195 has been used for Positron Emission Tomography (PET) imaging of neuroinflammatory diseases. PK11195 is a tracer that binds to the benzodiazepine peripheral receptor (PBR) currently known as membrane translocator protein (TSPO). [ 11 C]PK11195 is differentially accumulated in tissues which have high TSPO expression, typically microglia activation in brain tissue, which has normally low TSPO expression. The aim of this work was to synthesize and characterize [ 11 C]PK11195 at the Radiopharmaceutical Production Unit of CDTN to make it available for future studies and applications in major brain inflammatory diseases. The [ 11 C]PK11195 syntheses were performed using Tracerlab™ FXC PRO (GE) by [ 11 C]methylation of the precursor (R)-[N-desmethyl] PK11195. Optimizations of the reaction conditions for the synthesis of [ 11 C]PK11195 were: Anhydrous dimethylsulfoxide (DMSO) volume, mass of precursor, and potassium hydroxide (KOH), labelling reaction temperature and time. After comparison of the results obtained for each condition evaluated, the standard best reaction parameters were defined as: 1mg of the precursor dissolved in 300 μL of DMSO (anhydrous); 10-15mg of KOH; and labeling reaction temperature of 40°C during 2 minutes. The total synthesis time was 40 minutes and the mean non-decay-corrected radiochemical yield was 10.93 ± 3.44%. All quality control criteria were met according to previous specifications. (author)

  4. Significant decreases in frontal and temporal [11C]-raclopride binding after THC challenge.

    Science.gov (United States)

    Stokes, Paul R A; Egerton, Alice; Watson, Ben; Reid, Alistair; Breen, Gerome; Lingford-Hughes, Anne; Nutt, David J; Mehta, Mitul A

    2010-10-01

    Delta9-tetrahydrocannabinol (THC) increases prefrontal cortical dopamine release in animals, but this is yet to be examined in humans. In man, striatal dopamine release can be indexed using [11C]-raclopride positron emission tomography (PET), and recent reports suggest that cortical [11C]-raclopride binding may also be sensitive to dopaminergic challenges. Using an existing dataset we examined whether THC alters [11C]-raclopride binding potential (BP(ND)) in cortical regions. Thirteen healthy volunteers underwent two [11C]-raclopride PET scans following either oral 10 mg THC or placebo. Significant areas of decreased cortical [11C]-raclopride BP(ND) were identified using whole brain voxel-wise analysis and quantified using a region of interest (ROI) ratio analysis. Effect of blood flow on binding was estimated using a simplified reference tissue model analysis. Results were compared to [11C]-raclopride test-retest reliability in the ROIs identified using a separate cohort of volunteers. Voxel-wise analysis identified three significant clusters of decreased [11C]-raclopride BP(ND) after THC in the right middle frontal gyrus, left superior frontal gyrus and left superior temporal gyrus. Decreases in [11C]-raclopride BPND following THC were greater than test-retest variability in these ROIs. R1, an estimate of blood flow, significantly decreased in the left superior frontal gyrus in the THC condition but was unchanged in the other ROIs. Decreased frontal binding significantly correlated to catechol-o-methyl transferase (COMT) val108 status. We have demonstrated for the first time significant decreases in bilateral frontopolar cortical and left superior temporal gyrus [11C]-raclopride binding after THC. The interpretation of these findings in relation to prefrontal dopamine release is discussed. Copyright 2010 Elsevier Inc. All rights reserved.

  5. [11C]β-CIT, a cocaine analogue. Preparation, autoradiography and preliminary PET investigations

    International Nuclear Information System (INIS)

    Mueller, Lars; Halldin, Christer; Farde, Lars; Karlsson, Per; Hall, Haakan; Swahn, C.-G.

    1993-01-01

    β-CIT (2β-carbomethoxy-3β-(4-iodophenyl)tropane) is a cocaine analogue with a high affinity for the dopamine transporter. [ 11 C]β-CIT was prepared by N-methylation of nor-β-CIT with [ 11 C]methyl iodide. The total radiochemical yield of [ 11 C]β-CIT was 40-50% with an overall synthesis time of 35-40 min. The radiochemical purity was > 99% and the specific radioactivity at the time of injection was about 1000 Ci/mmol (37 GBq/μmol). Autoradiographic examination of [ 11 C]β-CIT binding in human brains post-mortem demonstrated a high level of specific binding in the striatum. PET examination of [ 11 C]β-CIT in a Cynomolgus monkey showed a marked accumulation of radioactivity in the striatum. The ratio of radioactivity in the striatum-to-cerebellum approached 5 after 87 min. In a displacement experiment, radioactivity in the striatum but not in the cerebellum, was markedly reduced after injection of unlabelled cocaine. [ 11 C]β-CIT has a potential as ligand for PET examination of cocaine effects in man. (author)

  6. Development of [11C]/[3H]THK-5351 – A potential novel carbon-11 tau imaging PET radioligand

    International Nuclear Information System (INIS)

    Stepanov, Vladimir; Svedberg, Marie; Jia, Zhisheng; Krasikova, Raisa; Lemoine, Laetitia; Okamura, Nobujuki; Furumoto, Shozo; Mitsios, Nicholas; Mulder, Jan; Långström, Bengt; Nordberg, Agneta; Halldin, Christer

    2017-01-01

    Introduction: Due to the rise in the number of patients with dementia the imperative for finding new diagnostic and treatment options becomes ever more pressing. While significant progress has been made in PET imaging of Aβ aggregates both in vitro and in vivo, options for imaging tau protein aggregates selectively are still limited. Based on the work previously published by researchers from the Tohoku University, Japan, that resulted in the development of [ 18 F]THK-5351, we have undertaken an effort to develop a carbon-11 version of the identical structure - [ 11 C]THK-5351. In parallel, THK-5351 was also labeled with tritium ([ 3 H]THK-5351) for use in in vitro autoradiography (ARG). Methods: The carbon-11 labeling was performed starting with di-protected enantiomeric pure precursor - tert-butyl 5-(6-((2S)-3-fluoro-2-(tetrahydro-2H-pyran-2-yloxy)propoxy)quinolin-2-yl) pyridin-2-yl carbamate, which was reacted with [ 11 C]MeI, using DMF as the solvent and NaH as base, followed by deprotection with trifluoroacetic acid/water mixture, resulting in enantiomerically pure carbon-11 radioligand, [ 11 C]THK-5351 - (S)-1-fluoro-3-(2-(6-([ 11 C]methylamino)pyridin-3-yl)quinolin-6-yloxy) propan-2-ol. Tritium labeling and purification of [ 3 H]THK-5351 were undertaken using similar approach, resulting in [ 3 H]THK-5351 with RCP >99.8% and specific radioactivity of 1.3 GBq/μmol. Results: [ 11 C]THK-5351 was produced in good yield (1900 ± 355 MBq), specific radioactivity (SRA) (361 ± 119 GBq/μmol at EOS + 20 min) and radiochemical purity (RCP) (>99.8%), with enantiomeric purity of 98.7%. [ 3 H]THK-5351 was evaluated for ARG of tau binding in post-mortem human brain tissue using cortical sections from one AD patient and one control subject. [ 3 H]THK-5351 binding density was higher in the AD patient compared to the control subject, the binding was displaced by unlabeled THK-5351 confirming specific [ 3 H]THK-5351 binding.

  7. Radiosynthesis of [11C]glyburide for in vivo imaging of BCRP function with PET

    International Nuclear Information System (INIS)

    Kuhnast, B.; Damont, A.L.; Tournier, N.; Saba, W.; Valette, H.; Bottlaender, M.; Dolle, F.

    2011-01-01

    Complete text of publication follows: Objectives: The human breast cancer resistance protein (BCRP/ABCG2) belongs to the ABC-transporter super-family in which P-gp (MDR1/ABCB1) is probably the most emblematic and best known member. BCRP, which was initially discovered in multidrug resistant breast cancer cell lines, is also highly expressed in numerous tissues e.g. the blood-brain barrier (BBB). BCRP confers upon these tissues resistance to chemotherapeutic agents but also transports drugs and xenobiotics thus participating to the ADME processes although the biochemical mechanisms remain largely unknown to date. The hypoglycaemic sulfonylurea glyburide (glibenclamide) has been described as a specific substrate of BCRP in vitro and in vivo. Its isotopic labelling with the positron emitter carbon-11 (20.4 min) would provide a valuable tool to study in vivo with PET the BCRP transport activity. Herein are reported the synthesis of desmethyl-glyburide (2), as precursor, as well as the preparation of [ 11 C]glyburide ([ 11 C]-1) using [ 11 C]methyl triflate as radio-methylation agent. Methods: Chemistry: Desmethyl-glyburide (2), as precursor for [ 11 C]labelling, was obtained in one chemical step by treating glyburide (1) with a 1 M solution of BBr 3 (4 eq.) in dichloromethane at low temperature (-90 C to - 20 C). Radiochemistry: Carbon-11 labeling of glyburide (1) was performed using a TRACERLab FX-C Pro synthesizer (GEMS) and comprised (1) trapping at -10 C of [ 11 C]MeOTf in acetone (0.3 mL) containing the precursor 2 (0.5-0.8 mg) and aq. 3N NaOH (5 μL); (2) heating at 110 C for 2 min; (3) dilution in 1.0 mL of the HPLC mobile phase and purification using semi-preparative reversed-phase HPLC (Waters Symmetry R C-18 - eluent: CH 3 CN / H 2 O / TFA: 45 / 55 / 0.1 (v:v:v) - flow rate: 5 mL/min - detection at 254 nm) and (4) SepPak R Plus C-18-based formulation for i.v. injection. The measurement of log P and log D 7.4 was performed using the shaked flask method

  8. Fast synthesis of 11C-Raclopride and its initial PET study on animal model

    International Nuclear Information System (INIS)

    Zhang Jinming; Tian Jiahe; Yao Shulin; Ding Weimin; Yin Dayi; Liu Boli

    2008-01-01

    Objective: 11 C-Raclopride is a type-2 dopamine receptor (D 2 R) binding agent used in the study of Parkinson's disease. This study introduced a fast and convenient method for preparation of 11 C- Raclopride and reported on the preclinical trial of this receptor tracer on animal studies. Methods: 11 C- Raclopride was synthesized via reaction of 11 C-CH 3 -Triflate with Nor-Raclopride. The mixture of primary product was water-diluted and loaded on Sep-Pak C18 column for separation. The final product, 11 C-Raclopride, was purified by column chromatography and then eluted from the C18 column with ethanol. The bio-distribution was studied in SD rats and the in vivo imaging pattern was studied in hem ipark insonjan mon- keys. Results: Within 16 min from beginning of processing with 11 CO 2 , the synthetic yield of 11 C-Raclopride was 60%, radiochemical purity (RCP) > 95% and specific activity 8 GBq/mmol. The uptake ratios of striatum to cerebellum and cerebral cortex were 4.67 and 6.20, respectively, at 30 min after 11 C-Raclopride administration. The striatal uptake in normal rat brain could be blocked by N-methylspiperone (NMSP) and raclopride, but not by Nor-raclopride. PET imaging showed higher striatal D 2 R uptake on the D 2 receptor up-regulated side of the experimental monkeys relative to the contralateral side. Conclusions: Column chromatography for purification of 11 C-Raclopride was fast, convenient and with a RCP similar to that of high performance liquid chromatography purification. Preliminary PET findings using animal model suggested that 11 C-Raclopride by column chromatogram purification might be considered for clinical use. (authors)

  9. Synthesis of [11C]citalopram and brain distribution studies in rats

    International Nuclear Information System (INIS)

    Ram, S.; Krishnan, K.R.R.; Bissette, G.; Knight, D.L.; Coleman, R.E.

    1990-01-01

    The study of serotonin uptake sites in the living human brain by PET with [ 11 C]citalopram may be valuable in investigating the anatomic locus and the therapeutic role of depression and prevention of suicide. For this purpose, the authors have synthesized [ 11 C]citalopram. In vivo biodistribution in rats has been determined

  10. High heat load properties of nanostructured, recrystallized W–1.1TiC

    Energy Technology Data Exchange (ETDEWEB)

    Tokunaga, K., E-mail: tokunaga@riam.kyushu-u.ac.jp [Research Institute for Applied Mechanics, Kyushu University, Kasuga, Fukuoka 816-8580 (Japan); Kurishita, H.; Arakawa, H.; Matsuo, S. [International Research Center for Nuclear Materials Science, IMR, Tohoku University, Oarai, Ibaraki 311-1313 (Japan); Hotta, T. [Interdisciplinary Graduate School of Engineering Sciences, Kyushu University, Kasuga, Fukuoka 816-8580 (Japan); Araki, K.; Miyamoto, Y.; Fujiwara, T.; Nakamura, K. [Research Institute for Applied Mechanics, Kyushu University, Kasuga, Fukuoka 816-8580 (Japan); Takida, T.; Kato, M.; Ikegaya, A. [A.L.M.T. Corp., Toyama 931-8543 (Japan)

    2013-11-15

    Steady state (1973 K, 180 s) and repeated (723 K–1524 K, 380 times) heat loading experiments of ITER grade W and toughened, fine-grained, recrystallized W–1.1TiC (TFGR W–1.1TiC) have been performed using an electron beam irradiation system. In ITER grade W, the irradiation around 1973 K causes recrystallization and grain growth up to the average diameters of 50–100 μm. Repeated irradiations cause significant surface roughening, cracking at grain boundaries and surface exfoliation. On the other hand, TFGR W–1.1TiC does not exhibit any surface roughening or cracking after repeated heat loading although grain boundaries on the surface of TFGR W–1.1TiC can be observed after irradiation at around 1973 K 180 s by steady state heat loading.

  11. Bipolaron formation in B/sub 12/ and (B/sub 11/C)/sup +/ icosahedra

    International Nuclear Information System (INIS)

    Howard, I.A.; Beckel, C.L.; Emin, D.

    1987-01-01

    Boron carbides, B/sub 1-x/C/sub x/ with 0.085 ≤ x ≤ 0.200, generally contain both B/sub 12/ and B/sub 11/C icosahedra. However, the electronic transport with 0.1 ≤ x ≤ 0.2 is believed to occur by means of bipolaron hopping between only B/sub 11/C icosahedra. The authors have calculated the changes in energy, atomic positions and charge distribution when a pair of electrons is added to the isoelectronic icosahedral clusters B/sub 12/ and (B/sub 11/C)/sup +/. They simulate an icosahedron in a neutral lattice by bonding the icosahedral atoms to hydrogenic atoms which the authors constrain to be neutral. The computations are performed with a self-consistent molecular-orbital method, PRDDO. They find a total energy reduction of -- 3.7 eV for two electrons added to a B/sub 12/ icosahedron. Of this, -- 2.7 eV arises from the electrons filling the icosahedron's bonding orbitals. The remaining -- 1.0 eV comes from the contraction of the icosahedron's radius by -- 0.09 A. For two electrons added to a (B/sub 11/C)/sup +/ icosahedron the authors find a total energy reduction of -- 18.2 eV. Of this, -- 16.5 eV arises from filling the icosahedron's bonding orbitals. The remainder arises from a -- 0.09 A contraction of the icosahedron's radius. Thus, the authors find (B/sub 11/C)/sup +/ icosahedra to be strongly energetically favored over B/sub 12/ icosahedra as bipolaron sites. The positive charge associated with a (B/sub 11/C)/sup +/ icosahedron is distributed over the eleven boron atoms. Concomitantly, they find the added two electrons of the bipolaron to be distributed over all twelve sites of the B/sub 11/C icosahedron. They find the energy difference between an electron pair added to B/sub 12/ and (B/sub 11/C)/sup +/ icosahedra to arise principally from the increased Coulombic attraction provided by the extra positive charge of the (B/sub 11/C)/sup +/ icosahedron

  12. Synthesis of [11C](-)-α,α-dideutero-phenylephrine for in vivo kinetic isotope studies

    International Nuclear Information System (INIS)

    Rosario, R.B. del; Wieland, D.M.

    1995-01-01

    (-)-[ 11 C]Phenylephrine and positron emission tomography could potentially be used to assess neuronal monoamine oxidase activity in the heart. Previous data for (-)-[ 11 C]phenylephrine indicate that, although its retention and neuronal selectivity parallel that of the neuronal mapping agent (-)-[ 11 C]hydroxyephedrine, its neuronal storage and clearance properties are quite different. In order to study the in vivo kinetics of (-)-[ 11 C]phenylephrine in greater detail, the dideutero analog [ 11 C]-(-)-α,α-dideutero-phenylephrine. 1, was synthesized by [ 11 C]methylation of the precursor (-)-α,α-dideutero-m-octopamine. The key step in the procedure was BD 3 reduction of the cyanohydrin derived from 3-hydroxybenzaldehyde. Deuterium incorporation at the alpha positions of m-octopamine was confirmed by NMR and mass spectroscopy of the deuterated product and by comparison of spectral data with undeuterated m-octopamine. (-)-α,α-Dideutero-m-octopamine was methylated with CF 3 SO 3 11 CH 3 to give 1 suitable for animal and clinical studies. (author)

  13. Synthesis of no-carrier-added alpha-[11C]methyl-L-tryptophan

    International Nuclear Information System (INIS)

    Chaly, T.; Diksic, M.

    1988-01-01

    Described here is a synthesis of no-carrier-added alpha-[ 11 C]methyl-L-tryptophan based on alkylation with 11 CH 3 I of an anion generated by reacting the Schiff base of L-tryptophan methyl ester with di-isopropylamine. The synthesis requires approximately 30 min after the end of 11 CO 2 collection and gives alpha-[ 11 C]methyl-L-tryptophan in a 20-25% radiochemical yield calculated at the end of the synthesis and without correction for radioactive decay. The specific activity of the final radiopharmaceutical, measured at the end of the synthesis, was around 2000 Ci/mmol. Data confirming the stereospecificity of the synthesis are also presented

  14. Thermodynamic and structural properties of the specific binding between Ag⁺ ion and C:C mismatched base pair in duplex DNA to form C-Ag-C metal-mediated base pair.

    Science.gov (United States)

    Torigoe, Hidetaka; Okamoto, Itaru; Dairaku, Takenori; Tanaka, Yoshiyuki; Ono, Akira; Kozasa, Tetsuo

    2012-11-01

    Metal ion-nucleic acid interactions have attracted considerable interest for their involvement in structure formation and catalytic activity of nucleic acids. Although interactions between metal ion and mismatched base pair duplex are important to understand mechanism of gene mutations related to heavy metal ions, they have not been well-characterized. We recently found that the Ag(+) ion stabilized a C:C mismatched base pair duplex DNA. A C-Ag-C metal-mediated base pair was supposed to be formed by the binding between the Ag(+) ion and the C:C mismatched base pair to stabilize the duplex. Here, we examined specificity, thermodynamics and structure of possible C-Ag-C metal-mediated base pair. UV melting indicated that only the duplex with the C:C mismatched base pair, and not of the duplexes with the perfectly matched and other mismatched base pairs, was specifically stabilized on adding the Ag(+) ion. Isothermal titration calorimetry demonstrated that the Ag(+) ion specifically bound with the C:C base pair at 1:1 molar ratio with a binding constant of 10(6) M(-1), which was significantly larger than those for nonspecific metal ion-DNA interactions. Electrospray ionization mass spectrometry also supported the specific 1:1 binding between the Ag(+) ion and the C:C base pair. Circular dichroism spectroscopy and NMR revealed that the Ag(+) ion may bind with the N3 positions of the C:C base pair without distorting the higher-order structure of the duplex. We conclude that the specific formation of C-Ag-C base pair with large binding affinity would provide a binding mode of metal ion-DNA interactions, similar to that of the previously reported T-Hg-T base pair. The C-Ag-C base pair may be useful not only for understanding of molecular mechanism of gene mutations related to heavy metal ions but also for wide variety of potential applications of metal-mediated base pairs in various fields, such as material, life and environmental sciences. Copyright © 2012 Elsevier

  15. Catalytic conversion of 11C-labeled methanol over Cs-ZSM-5 zeolite

    International Nuclear Information System (INIS)

    Sarkadi-Priboczki, E.; Kovacs, Z.; Kumar, N.; Salmi, T.; Murzin, D.Yu.

    2004-01-01

    Reaction mechanism of the conversion of 11 C labeled methanol over basic Cs-ZSM-5 zeolite catalyst was investigated and the reaction products obtained were compared with that of H-ZSM-5 acidic catalyst. The catalytic experiments were carried out by passing 11 C-labeled methanol with He as a carrier gas over Cs-ZSM-5 packed in a micro reactor. After adsorption of the radio methanol, the catalyst was heated up to 330 deg C. The products of the catalytic conversion of the 11 C-labeled methanol were analyzed by radio-gas chromatography (gas chromatograph with thermal conductivity detector on-line coupled with a radioactivity detector). (N.T.)

  16. The relationship between subcortical brain volume and striatal dopamine D2/3 receptor availability in healthy humans assessed with [11 C]-raclopride and [11 C]-(+)-PHNO PET.

    Science.gov (United States)

    Caravaggio, Fernando; Ku Chung, Jun; Plitman, Eric; Boileau, Isabelle; Gerretsen, Philip; Kim, Julia; Iwata, Yusuke; Patel, Raihaan; Chakravarty, M Mallar; Remington, Gary; Graff-Guerrero, Ariel

    2017-11-01

    Abnormalities in dopamine (DA) and brain morphology are observed in several neuropsychiatric disorders. However, it is not fully understood how these abnormalities may relate to one another. For such in vivo findings to be used as biomarkers for neuropsychiatric disease, it must be understood how variability in DA relates to brain structure under healthy conditions. We explored how the availability of striatal DA D 2/3 receptors (D 2/3 R) is related to the volume of subcortical brain structures in a sample of healthy humans. Differences in D 2/3 R availability measured with an antagonist radiotracer ([ 11 C]-raclopride) versus an agonist radiotracer ([ 11 C]-(+)-PHNO) were examined. Data from 62 subjects scanned with [ 11 C]-raclopride (mean age = 38.98 ± 14.45; 23 female) and 68 subjects scanned with [ 11 C]-(+)-PHNO (mean age = 38.54 ± 14.59; 25 female) were used. Subcortical volumes were extracted from T1-weighted images using the Multiple Automatically Generated Templates (MAGeT-Brain) algorithm. Partial correlations were used controlling for age, gender, and total brain volume. For [ 11 C]-(+)-PHNO, ventral caudate volumes were positively correlated with BP ND in the dorsal caudate and globus pallidus (GP). Ventral striatum (VS) volumes were positively correlated with BP ND in the VS. With [ 11 C]-raclopride, BP ND in the VS was negatively correlated with subiculum volume of the hippocampus. Moreover, BP ND in the GP was negatively correlated with the volume of the lateral posterior nucleus of the thalamus. Findings are purely exploratory and presented corrected and uncorrected for multiple comparisons. We hope they will help inform the interpretation of future PET studies where concurrent changes in D 2/3 R and brain morphology are observed. Hum Brain Mapp 38:5519-5534, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  17. 11C-L-methionine for evaluation of pancreatic exocrine function

    International Nuclear Information System (INIS)

    Syrota, A.; Dop-Ngassa, M.; Cerf, M.; Paraf, A.; Crouzel, M.; Ricard, S.

    1981-01-01

    Pancreatic uptake of 11 C labelled L-methionine, was measured in 58 patients using a scintillation camera. Time-activity-curves obtained in areas of interest selected over the pancreas in 25 normal subjects and in 14 alcoholic patients showed a plateau or slight increase of activity with time. In contrast, in 19 patients with chronic pancreatitis, an initial increase in radioactivity was followed by a decrease for 10 to 20 minutes and then by a plateau. The ratio of the height of the plateau at the 50th minute to the height of the peak was 0.74 +- 0.21 in these patients, whereas it was 0.96 +- 0.09 in the other subjects (p 11 C radioactivity and of amylase and bicarbonate in duodenal aspirate. The median amount of 11 C incorporated into protein at the 70th minute was 53% of total activity in the control group, 28% in alcoholic patients, and only 3% in chronic pancreatitis. The absence of a peak of radioactivity in the duodenal juice, and the existence of a correlation between total 11 C output and amylase output suggested that there was no release of protein in the duodenum in chronic pancreatitis, and that the peak observed by external detection could be due to amino acid back-diffusion from the pancreas into the blood. (author)

  18. Evaluation of interim and final waste forms for the newly generated liquid low-level waste flowsheet

    International Nuclear Information System (INIS)

    Abotsi, G.M.K.; Bostick, D.T.; Beck, D.E.

    1996-05-01

    The purpose of this review is to evaluate the final forms that have been proposed for radioactive-containing solid wastes and to determine their application to the solid wastes that will result from the treatment of newly generated liquid low-level waste (NGLLLW) and Melton Valley Storage Tank (MVST) supernate at the Oak Ridge National Laboratory (ORNL). Since cesium and strontium are the predominant radionuclides in NGLLLW and MVST supernate, this review is focused on the stabilization and solidification of solid wastes containing these radionuclides in cement, glass, and polymeric materials-the principal waste forms that have been tested with these types of wastes. Several studies have shown that both cesium and strontium are leached by distilled water from solidified cement, although the leachabilities of cesium are generally higher than those of strontium under similar conditions. The situation is exacerbated by the presence of sulfates in the solution, as manifested by cracking of the grout. Additives such as bentonite, blast-furnace slag, fly ash, montmorillonite, pottery clay, silica, and zeolites generally decrease the cesium and strontium release rates. Longer cement curing times (>28 d) and high ionic strengths of the leachates, such as those that occur in seawater, also decrease the leach rates of these radionuclides. Lower cesium leach rates are observed from vitrified wastes than from grout waste forms. However, significant quantities of cesium are volatilized due to the elevated temperatures required to vitrify the waste. Hence, vitrification will generally require the use of cleanup systems for the off-gases to prevent their release into the atmosphere

  19. Neighborhood Walkable Urban Form and C-Reactive Protein

    Science.gov (United States)

    Background: Walkable urban form predicts physical activity and lower body mass index, which lower C-reactive protein (CRP). However, urban form is also related to pollution, noise, social and health behavior, crowding, and other stressors, which may complement or contravene walka...

  20. Comparative Evaluation of the Translocator Protein Radioligands 11C-DPA-713, 18F-DPA- 714, and 11C-PK11195 in a Rat Model of Acute Neuro-inflammation

    International Nuclear Information System (INIS)

    Chauveau, F.; Van Camp, N.; Dolle, F.; Kuhnast, B.; Hinnen, F.; Damont, A.; Boutin, H.; Tavitian, B.; Chauveau, F.; Van Camp, N.; Boutin, H; Tavitian, B.; Chauveau, F.; Boutin, H.; James, M.; Kassiou, M.; Kassiou, M.

    2009-01-01

    Overexpression of the translocator protein, TSPO (18 kDa), formerly known as the peripheral benzodiazepine receptor, is a hallmark of activation of cells of monocytic lineage (micro-glia and macrophages) during neuro-inflammation. Radiolabeling of TSPO ligands enables the detection of neuro-inflammatory lesions by PET. Two new radioligands, 11 C-labeled N, N-diethyl-2-[2-(4- methoxy-phenyl)-5, 7-dimethylpyrazolo[1, 5-a]pyrimidin-3-yl] acetamide (DPA-713) and 18 F-labeled N, N-diethyl-2-(2-(4-(2- fluoroethoxy)phenyl)-5, 7-dimethylpyrazolo[1, 5-a]pyrimidin-3-yl) acetamide (DPA-714), both belonging to the pyrazolopyrimidine class, were compared in vivo and in vitro using a rodent model of neuro-inflammation. Methods: 11 C-DPA-713 and 18 F-DPA-714, as well as the classic radioligand 11 C-labeled (R)-N-methyl- N-(1-methylpropyl)-1-(2-chlorophenyl)isoquinoline-3-carboxamide (PK11195), were used in the same rat model, in which intra-striatal injection of (R, S)-a-amino-3-hydroxy-5-methyl-4-isoxazolopropionique gave rise to a strong neuro-inflammatory response. Comparative endpoints included in vitro autoradiography and in vivo imaging on a dedicated small-animal PET scanner under identical conditions. Results: 11 C-DPA-713 and 18 F-DPA-714 could specifically localize the neuro-inflammatory site with a similar signal-to-noise ratio in vitro. In vivo, 18 F-DPA-714 performed better than 11 C-DPA-713 and 11 C-PK11195, with the highest ratio of ipsilateral to contralateral uptake and the highest binding potential. Conclusion: 18 F-DPA-714 appears to be an attractive alternative to 11 C-PK11195 because of its increased bioavailability in brain tissue and its reduced nonspecific binding. Moreover, its labeling with 18 F, the preferred PET isotope for radiopharmaceutical chemistry, favors its dissemination and wide clinical use. 18 F-DPA-714 will be further evaluated in longitudinal studies of neuro-inflammatory conditions such as are encountered in stroke or neuro

  1. Activation of a remote (1-year old) emotional memory interferes with the retrieval of a newly formed hippocampus-dependent memory in rats.

    Science.gov (United States)

    Zoladz, Phillip R; Woodson, James C; Haynes, Vernon F; Diamond, David M

    2010-01-01

    The persistent intrusion of remote traumatic memories in people with post-traumatic stress disorder (PTSD) may contribute to the impairment of their ongoing hippocampal and prefrontal cortical functioning. In the current work, we have developed a rodent analogue of the intrusive memory phenomenon. We studied the influence of the activation of a remote traumatic memory in rats on their ability to retrieve a newly formed hippocampus-dependent memory. Adult male Sprague-Dawley rats were given inhibitory avoidance (IA) training, and then 24 h or 1, 6 or 12 months later, the same rats were trained to learn, and then remember across a 30-min delay period, the location of a hidden escape platform in the radial-arm water maze (RAWM). When IA-trained rats spent the 30-min delay period in the IA apparatus, they exhibited intact remote (1-year old) memory of the shock experience. More importantly, activation of the rats' memory of the shock experience profoundly impaired their ability to retrieve the newly formed spatial memory of the hidden platform location in the RAWM. Our finding that reactivation of a remote emotional memory exerted an intrusive effect on new spatial memory processing in rats provides a novel approach toward understanding how intrusive memories of traumatic experiences interfere with ongoing cognitive processing in people with PTSD.

  2. Radiosynthesis and ex vivo evaluation of (R)-(-)-2-chloro-N-[1-11C-propyl]n-propylnorapomorphine

    International Nuclear Information System (INIS)

    Palner, Mikael; McCormick, Patrick; Gillings, Nic; Begtrup, Mikael; Wilson, Alan A.; Knudsen, Gitte M.

    2010-01-01

    Introduction: Several dopamine D 2 agonist radioligands have been used with positron emission tomography (PET), including [ 11 C-]-(-)-MNPA, [ 11 C-]-(-)-NPA and [ 11 C]-(+)-PHNO. These radioligands are considered particularly powerful for detection of endogenous dopamine release, but they either provide PET brain images with limited contrast or have affinity for both D 2 and D 3 receptors. We here present the carbon-11 radiolabeling and ex vivo evaluation of 2-Cl-(-)-NPA, a novel PET-tracer candidate with high in vitro D 2 /D 3 selectivity. Methods: 2-Cl-[ 11 C]-(-)-NPA and [ 11 C]-(-)-NPA were synthesized by a two step N-acylation-reduction process using [ 11 C]-propionyl chloride. Awake rats were injected with either tracer, via the tail vein. The rats were decapitated at various times, the brains were removed and quickly dissected, and plasma metabolites were measured. Radioligand specificity, and P-glycoprotein involvement in brain uptake, was also assessed. Results: 2-Cl-[ 11 C]-(-)-NPA and [ 11 C]-(-)-NPA were produced in high specific activity and purity. 2-Cl-[ 11 C]-(-)-NPA accumulated slower in the striatum than [ 11 C]-(-)-NPA, reaching maximum concentrations after 30 min. The maximal striatal uptake of 2-Cl-[ 11 C]-(-)-NPA (standard uptake value 0.72±0.24) was approximately half that of [ 11 C]-(-)-NPA (standard uptake value 1.37±0.18). Nonspecific uptake was similar for the two compounds. 2-Cl-[ 11 C]-(-)-NPA was metabolized quickly, leaving only 17% of the parent compound in the plasma after 30 min. The specific binding of 2-Cl-[ 11 C]-(-)-NPA was completely blocked and inhibition of P-glycoprotein did not alter the brain uptake. Conclusion: Ex vivo experiments showed, despite a favorable D 2 /D 3 selectivity, that 2-Cl-[ 11 C]-(-)-NPA is inferior to [ 11 C]-(-)-NPA as a PET tracer in rat, because of slower brain uptake and lower specific to nonspecific binding ratio.

  3. Improved sensitivity of human brain MAO B measurement using deuterium substituted [{sup 11}C]L-deprenyl ([{sup 11}C]L-deprenyl-D2)

    Energy Technology Data Exchange (ETDEWEB)

    Fowler, J.S.; Volkow, N.D.; Wang, G.J. [Brookhaven National Laboratory, Upton, NY (United States)] [and others

    1995-05-01

    Post-mortem reports that human brain monoamine oxidase B (MAO B) increases in normal aging and neurodegenerative disorders due to the proliferation of MAO B-rich glial cells suggest that PET measures of MAO B may track gliosis. We have recently shown that the MAO B tracer [{sup 11}C]L-deprenyl has limited sensitivity in regions of high MAO B due to its rapid rate of trapping. This limits its utility for measuring MAO B in brain regions where MAO B is higher and/or where blood flow is low. We have recently demonstrated that [{sup 11}C]L-deprenyl-D2 has improved sensitivity in regions of high MAO B due to the deuterium isotope effect which reduces the rate of trapping. We report studies [{sup 11}C]L-deprenyl-D2 in normal human brain in 16 healthy men and women (age range 23-73) to assess tracer sensitivity, regional distribution, and reproducibility. Graphical analysis for irreversible systems was used to calculate Ki (influx constant) as an index of MAO B concentration in different brain regions. The uptake of carbon-11 in different brain regions was rapid, peaking at 5 minutes and plateauing from 30-60 minutes after an initial clearance. MAO B was highest in subcortical regions: thalamus{ge}basal ganglia>cingulate gyrus>frontal cortex=occipital cortex=cerebellum in agreement with post-mortem measurements. Ki values were highly correlated within an individual. Repeated measures at 1-4 week intervals were highly correlated (r=0.9; p=0.0001). In women (n=8: age range 23-73), Ki increased with increasing age for 8 brain regions (p < 0.04). Though men (N=8; age range 34-70) showed no correlation with age, a larger sample size is needed to adequately assess trends. In summary, the use of [{sup 11}C]L-deprenyl-D2 improves the measurement of MAO B in the human brain permitting its investigation as a positive tracer for glial cell proliferation in neurodegenerative disorders.

  4. Simple automated preparation of O-[{sup 11}C]methyl-L-tyrosine for routine clinical use

    Energy Technology Data Exchange (ETDEWEB)

    Ishikawa, Yoichi [CYRIC Tohoku University, Aramaki, Aoba-ku, Sendai 980-8578 (Japan); Iwata, Ren [CYRIC Tohoku University, Aramaki, Aoba-ku, Sendai 980-8578 (Japan)]. E-mail: rencyric@cyric.tohoku.ac.jp; Furumoto, Shozo [TUBERO, Tohoku University, Sendai 980-8575 (Japan); Pascali, Claudio [National Cancer Institute, 20133 Milan (Italy); Bogni, Anna [National Cancer Institute, 20133 Milan (Italy); Kubota, Kazuo [International Medical Center, Tokyo 162-8655 (Japan); Ishiwata, Kiichi [Tokyo Metropolitan Institute of Gerontology, Tokyo 173-0022 (Japan)

    2005-07-01

    The previously reported preparation of O-[{sup 11}C]methyl-L-tyrosine ([{sup 11}C]MT), a promising tumor imaging agent, has been now considerably simplified and automated. Main changes were the use of [{sup 11}C]methyl iodide ([{sup 11}C]MeI) in the reaction with L-tyrosine disodium and the use of solid phase extraction on commercially available cartridges instead of HPLC for the final purification. An injectable saline solution of [{sup 11}C]MT was obtained within 30 min after EOB with radiochemical yield of ca. 60% (decay-corrected, based on [{sup 11}C]MeI). Radiochemical purity was over 97%. The automated preparation was carried out using a miniature module employing manifold valves.

  5. Extraction of left ventricular myocardial mass from dynamic 11C-acetate PET

    DEFF Research Database (Denmark)

    Harms, Hans; Tolbod, Lars Poulsen; Hansson, Nils Henrik

    Background: Dynamic 11C-acetate PET is used to quantify oxygen metabolism, which is used to calculate left ventricular (LV) myocardial efficiency, an early marker of heart failure. This requires estimation of LV myocardial mass and is typically derived from a separate cardiovascular magnetic...... resonance (CMR) scan. The aim of this study was to explore the feasibility of estimating myocardial mass directly from a dynamic 11C-acetate PET scan. Methods: 21 subjects underwent a 27-min 11C-acetate PET scan on a Siemens Biograph TruePoint 64 PET/CT scanner. In addition, 10 subjects underwent a dynamic...... 11C-acetate 27-min PET scan on a GE Discovery ST PET/CT scanner. Parametric images of uptake rate K1 and both arterial (VA) and venous (VV) spillover fractions were generated using a basis function implementation of the standard single tissue compartment model using non-gated dynamic data. The LV...

  6. Imaging cAMP-specific phosphodiesterase-4 in human brain with R-[11C]rolipram and positron emission tomography

    International Nuclear Information System (INIS)

    DaSilva, Jean N.; Lourenco, Celia M.; Meyer, Jeffrey H.; Houle, Sylvain; Hussey, Douglas; Potter, William Z.

    2002-01-01

    Evidence of disruptions in cAMP-mediated signaling in several neuropsychiatric disorders has led to the development of R-[ 11 C]rolipram for imaging phosphodiesterase-4 (PDE4) enzymes with positron emission tomography (PET). The high-affinity PDE4 inhibitor rolipram was previously reported to have an antidepressant effect in humans. PDE4 is abundant in the brain, and it hydrolyzes cAMP produced following stimulation of various neurotransmitter systems. PDE4 is regulated by intracellular cAMP levels. This paper presents the first PET study of R-[ 11 C]rolipram in living human brain. Consistent with the wide distribution of PDE4, high radioactivity retention was observed in all regions representing the gray matter. Rapid metabolism was observed, and kinetic analysis demonstrated that the data fit in a two-tissue compartment model. R-[ 11 C]Rolipram is thus suitable for imaging PDE4 and possibly cAMP signal transduction in the living human brain with PET. (orig.)

  7. Newly elected IAEA Board of Governors

    International Nuclear Information System (INIS)

    2000-01-01

    The document gives information about the election of 11 Member States to the IAEA Board of Governors, the 35-member policy-making body, during the 44th regular session of the IAEA's General Conference (18 - 22 September 2000, Austria Center, Vienna). The newly elected Member States are: Argentina, Egypt, Ghana, Ireland, Libyan Arab Jamahiriya, Mexico, Pakistan, Peru, Switzerland, Thailand, Ukraine. The other 24 Member States of the Board are also given

  8. New developments of 11C post-accelerated beams for hadron therapy and imaging

    Science.gov (United States)

    Augusto, R. S.; Mendonca, T. M.; Wenander, F.; Penescu, L.; Orecchia, R.; Parodi, K.; Ferrari, A.; Stora, T.

    2016-06-01

    Hadron therapy was first proposed in 1946 and is by now widespread throughout the world, as witnessed with the design and construction of the CNAO, HIT, PROSCAN and MedAustron treatment centres, among others. The clinical interest in hadron therapy lies in the fact that it delivers precision treatment of tumours, exploiting the characteristic shape (the Bragg peak) of the energy deposition in the tissues for charged hadrons. In particular, carbon ion therapy is found to be biologically more effective, with respect to protons, on certain types of tumours. Following an approach tested at NIRS in Japan [1], carbon ion therapy treatments based on 12C could be combined or fully replaced with 11C PET radioactive ions post-accelerated to the same energy. This approach allows providing a beam for treatment and, at the same time, to collect information on the 3D distributions of the implanted ions by PET imaging. The production of 11C ion beams can be performed using two methods. A first one is based on the production using compact PET cyclotrons with 10-20 MeV protons via 14N(p,α)11C reactions following an approach developed at the Lawrence Berkeley National Laboratory [2]. A second route exploits spallation reactions 19F(p,X)11C and 23Na(p,X)11C on a molten fluoride salt target using the ISOL (isotope separation on-line) technique [3]. This approach can be seriously envisaged at CERN-ISOLDE following recent progresses made on 11C+ production [4] and proven post-acceleration of pure 10C3/6+ beams in the REX-ISOLDE linac [5]. Part of the required components is operational in radioactive ion beam facilities or commercial medical PET cyclotrons. The driver could be a 70 MeV, 1.2 mA proton commercial cyclotron, which would lead to 8.1 × 10711C6+ per spill. This intensity is appropriate using 11C ions alone for both imaging and treatment. Here we report on the ongoing feasibility studies of such approach, using the Monte Carlo particle transport code FLUKA [6,7] to simulate

  9. Automated chemoenzymatic synthesis of no-carrier-added [carbonyl-11C]propionyl L-carnitine for pharmacokinetic studies

    International Nuclear Information System (INIS)

    Davenport, R.J.; Pike, V.W.; Dowsett, K.; Turton, D.R.; Poole, K.

    1997-01-01

    Propionyl-L-carnitine (PLC) is under development as a therapeutic for the treatment of peripheral artery disease, coronary heart disease and chronic heart failure. Three methods were examined for labelling PLC in its propionyl group with positron-emitting carbon-11 (t 1/2 = 20.3 min), one chemical and two chemoenzymatic. The former was based on the preparation of [ 11 C]propionyl chloride as labelling agent via 11 C-carboxylation of ethylmagnesium bromide with cyclotron-produced [ 11 C]carbon dioxide and subsequent chlorination. Reaction of carrier-added [ 11 C]propionyl chloride with L-carnitine in trifluoroacetic acid gave [ 11 C]PLC in 12% radiochemical yield (decay-corrected) from cyclotron-produced [ 11 C]carbon dioxide. However, the radiosynthesis was unsuccessful at the no-carrier added (NCA) level of specific radioactivity. [ 11 C]Propionate, as a radioactive precursor for chemoenzymatic routes, was prepared via carboxylation of ethylmagnesium bromide with [ 11 C]carbon dioxide and hydrolysis. NCA [ 11 C]PLC was prepared in 68 min in 14% radiochemical yield (decay-corrected) from [ 11 C]propionate via sequential conversions catalysed by acetate kinase, phosphotransacetylase and carnitine acetyltransferase. A superior chemoenzymatic synthesis of NCA [ 11 C]PLC was developed, based on the use of a novel supported Grignard reagent for the synthesis of [ 11 C]propionate and conversions by S-acetyl-CoA synthetase and carnitine acetyltransferase. This gave an overall radiochemical yield of 30-48% (decay-corrected). This synthesis was automated for radiation safety and provides pure NCA [ 11 C]PLC in high radioactivities ready for intravenous administration within 25 min from radionuclide production. The [ 11 C]PLC is suitable for pharmacokinetic studies in human subjects with PET and the elucidation of the fate of the propionyl group of PLC in vivo. (Author)

  10. (11)C-labeling and preliminary evaluation of vortioxetine as a PET radioligand

    DEFF Research Database (Denmark)

    Andersen, Valdemar L; Hansen, Hanne D; Herth, Matthias M

    2014-01-01

    . Preliminary evaluation of [(11)C]vortioxetine in a Danish Landrace pig showed rapid brain uptake and brain distribution in accordance with the pharmacological profile, all though an unexpected high binding in cerebellum was also observed. [(11)C]vortioxetine displayed slow tracer kinetics with peak uptake...

  11. Quantification of (R)-[11C]PK11195 binding in rheumatoid arthritis

    International Nuclear Information System (INIS)

    Kropholler, M.A.; Boellaard, R.; Kloet, R.W.; Lammertsma, A.A.; Elzinga, E.H.; Voskuyl, A.E.; Laken, C.J. van der; Dijkmans, B.A.C.; Maruyama, K.

    2009-01-01

    Rheumatoid arthritis (RA) involves migration of macrophages into inflamed areas. (R)-[ 11 C]PK11195 binds to peripheral benzodiazepine receptors, expressed on macrophages, and may be used to quantify inflammation using positron emission tomography (PET). This study evaluated methods for the quantification of (R)-[ 11 C]PK11195 binding in the knee joints of RA patients. Data from six patients with RA were analysed. Dynamic PET scans were acquired in 3-D mode following (R)-[ 11 C]PK11195 injection. During scanning arterial radioactivity concentrations were measured to determine the plasma (R)-[ 11 C]PK11195 concentrations. Data were analysed using irreversible and reversible one-tissue and two-tissue compartment models and input functions with various types of metabolite correction. Model preferences according to the Akaike information criterion (AIC) and correlations between measures were evaluated. Correlations between distribution volume (V d ) and standardized uptake values (SUV) were evaluated. AIC indicated optimal performance for a one-tissue reversible compartment model including blood volume. High correlations were observed between V d obtained using different input functions (R 2 =0.80-1.00) and between V d obtained with one- and two-tissue reversible compartment models (R 2 =0.75-0.94). A high correlation was observed between optimal V d and SUV after injection (R 2 =0.73). (R)-[ 11 C]PK11195 kinetics in the knee were best described by a reversible single-tissue compartment model including blood volume. Applying metabolite corrections did not increase sensitivity. Due to the high correlation with V d , SUV is a practical alternative for clinical use. (orig.)

  12. Pharmacokinetics and biodistribution of 11C-HupA in the normal animal

    International Nuclear Information System (INIS)

    Yan Jin; Guan Yihui; Xue Fangping; Zhang Zhenwen; Liu Ping; Lin Yiangtong

    2009-01-01

    Objective: Hula is one of the potential drugs which can be used to treat Alzheimer's disease (Ad). The aim of this study was to explore the pharmacokinetics and biodistribution of Hula in vivo by using 11 C-Hula. Methods: A total of 25 Sd rats were studied. They were divided into 5 groups (5 rats in each group). All had intravenous injection of 22 MBq (in 0.2 ml) 11 C-Hula through tail vein. Dynamic imaging Was acquired from 5 to 90 minutes after injection. Venous blood and organ activities were collected at 5, 15, 30, 60. and 90 minutes after injection. Percentage activity of injected dose per gram of tissue (%ID/g) was calculated to characterize the biodistribution of tracer in different brain regions: frontal,apical, temporal, occipital, cerebellum, hippocampus, striatum, thalamencephalon, and brain stem, Variance analysis using SPSS 11.5 software was performed and compared among the study groups. Results: 11 C-HupA was characteristic for its quick clearance from blood, with half time T 1/2 of (14.61 ± 1.77) min, and clearance rate (CL) of (0.12 ± 0.01) ml · min -1 · kg -1 . Metabolism was through liver, and excretion through kidney. Pharmacokinetics of 11 C-HupA in rats corresponded to a one-compartment model. with an activity curve (area under curve, AUC) 0-8 integral of (167.57 ± 12.39) ml · min -1 · kg -1 . There was significant difference of 11 C-HupA distribution in different brain regions, being greater in cerebral cortex, hippocampus, hypothalamus and brain stem. Conclusions: Pharmacokinetic study of 11 C-HupA in brain was fast. convenient and showed high specificity and sensitivity. Its ability to quantitatively evaluate brain function and its characteristic distribution in mice provided some evidence for monitoring therapy in AD patients. (authors)

  13. Biodistribution and radiation dosimetry of [{sup 11}C]DASB in baboons

    Energy Technology Data Exchange (ETDEWEB)

    Belanger, Marie-Jose [Department of Psychiatry, Columbia University College of Physicians and Surgeons New York, NY 10032 (United States); Division of Brain Imaging, Department of Neuroscience, New York State Pyschiatric Institute, New York, NY 10032 (United States); Simpson, Norman R. [Department of Radiology, Columbia University College of Physicians and Surgeons and Division of Brain Imaging, Department of Neuroscience, New York State Psychiatric Institute, New York, NY 10032 (United States); Wang, Theodore [Department of Radiology, Columbia University College of Physicians and Surgeons and Division of Brain Imaging, Department of Neuroscience, New York State Psychiatric Institute, New York, NY 10032 (United States); Division of Brain Imaging, Department of Neuroscience, New York State Pyschiatric Institute, New York, NY 10032 (United States)] [and others

    2004-11-01

    Objective: The serotonin transporter has been implicated in a variety of conditions including mood disorders and suicidal behavior. In vivo human brain studies with positron emission tomography and the serotonin transporter antagonist [{sup 11}C]DASB ([{sup 11}C]-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile) are ongoing in several laboratories with the maximum administered activity based on dosimetry collected in rodents. We report on the biodistribution and dosimetry of [{sup 11}C]DASB in the baboon as this species may be a more reliable surrogate for human dosimetry. Methods: Four baboon studies (two studies in each of two baboons) were acquired in an ECAT ACCEL camera after the bolus injection of 183{+-}5 MBq/2.3{+-}1.0 nmol of [{sup 11}C]DASB. For each study, six whole-body emission scans were collected in 3D mode over 6/7 bed positions for 2 h. Regions of interest were drawn on brain, lungs, liver, gallbladder, spleen, kidneys, small intestine and bladder. Since no fluid was removed from the animal, total body radioactivity was calculated using the injected dose calibrated to the ACCEL image units. Results: Uptake was greatest in lungs, followed by the urinary bladder, gallbladder, brain and other organs. The ligand was eliminated via the hepato-billiary and renal systems. The largest absorbed dose was found in the lungs (3.6x10{sup -2} mSv/MBq). The absorbed radiation doses in lungs and gallbladder were four and nine times larger than that previously estimated from rat studies. Conclusion: Based on our baboon biodistribution and dose estimates, the lungs are the critical organs for administration of [{sup 11}C]DASB. In the United States, the absorbed dose to the lungs would limit [{sup 11}C]DASB administered with the approval of a Radioactive Drug Research Committee to 1400 MBq (37 mCi) in the adult male and 1100 MBq (30 mCi) in the adult female.

  14. Visualizing pancreatic β-cell mass with [11C]DTBZ

    International Nuclear Information System (INIS)

    Simpson, Norman Ray; Souza, Fabiola; Witkowski, Piotr; Maffei, Antonella; Raffo, Anthony; Herron, Alan; Kilbourn, Michael; Jurewicz, Agata; Herold, Kevan; Liu, Eric; Hardy, Mark Adam; Van Heertum, Ronald; Harris, Paul Emerson

    2006-01-01

    β-Cell mass (BCM) influences the total amount of insulin secreted, varies by individual and by the degree of insulin resistance, and is affected by physiologic and pathologic conditions. The islets of Langerhans, however, appear to have a reserve capacity of insulin secretion and, overall, assessments of insulin and blood glucose levels remain poor measures of BCM, β-cell function and progression of diabetes. Thus, novel noninvasive determinations of BCM are needed to provide a quantitative endpoint for novel therapies of diabetes, islet regeneration and transplantation. Built on previous gene expression studies, we tested the hypothesis that the targeting of vesicular monoamine transporter 2 (VMAT2), which is expressed by β cells, with [ 11 C]dihydrotetrabenazine ([ 11 C]DTBZ), a radioligand specific for VMAT2, and the use of positron emission tomography (PET) can provide a measure of BCM. In this report, we demonstrate decreased radioligand uptake within the pancreas of Lewis rats with streptozotocin-induced diabetes relative to their euglycemic historical controls. These studies suggest that quantitation of VMAT2 expression in β cells with the use of [ 11 C]DTBZ and PET represents a method for noninvasive longitudinal estimates of changes in BCM that may be useful in the study and treatment of diabetes

  15. 34 CFR 601.11 - Private education loan disclosures and self-certification form.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 3 2010-07-01 2010-07-01 false Private education loan disclosures and self...-Affiliated Organizations § 601.11 Private education loan disclosures and self-certification form. (a) A... education loan disclosures to the prospective borrower, regardless of whether the covered institution or...

  16. Synthesis and characterization of [{sup 11}C]PK11195 as a PET radiopharmaceutical

    Energy Technology Data Exchange (ETDEWEB)

    Almeida, Fernanda A. F.; Silveira, Marina B.; Oliveira, Amanda P.; Nascimento, Leonardo T.C.; Silva, Juliana B.; Mamede, Marcelo, E-mail: nanda10a@gmail.com, E-mail: mamede.mm@gmail.com [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizontge, MG (Brazil). Unidade de Pesquisa e Produção de Radiofármacos

    2017-07-01

    The radiopharmaceutical [{sup 11}C]PK11195 has been used for Positron Emission Tomography (PET) imaging of neuroinflammatory diseases. PK11195 is a tracer that binds to the benzodiazepine peripheral receptor (PBR) currently known as membrane translocator protein (TSPO). [{sup 11}C]PK11195 is differentially accumulated in tissues which have high TSPO expression, typically microglia activation in brain tissue, which has normally low TSPO expression. The aim of this work was to synthesize and characterize [{sup 11}C]PK11195 at the Radiopharmaceutical Production Unit of CDTN to make it available for future studies and applications in major brain inflammatory diseases. The [{sup 11}C]PK11195 syntheses were performed using Tracerlab™ FXC PRO (GE) by [{sup 11}C]methylation of the precursor (R)-[N-desmethyl] PK11195. Optimizations of the reaction conditions for the synthesis of [{sup 11}C]PK11195 were: Anhydrous dimethylsulfoxide (DMSO) volume, mass of precursor, and potassium hydroxide (KOH), labelling reaction temperature and time. After comparison of the results obtained for each condition evaluated, the standard best reaction parameters were defined as: 1mg of the precursor dissolved in 300 μL of DMSO (anhydrous); 10-15mg of KOH; and labeling reaction temperature of 40°C during 2 minutes. The total synthesis time was 40 minutes and the mean non-decay-corrected radiochemical yield was 10.93 ± 3.44%. All quality control criteria were met according to previous specifications. (author)

  17. Synthesis of 11C-methylated inulin as a radiopharmaceutical for imaging brain edema and pulmonary edema

    International Nuclear Information System (INIS)

    Hara, Toshihiko; Iio, Masaaki; Inagaki, Keizo

    1988-01-01

    11 C-methylated inulin, supposedly useful for imaging of brain edema and pulmonary edema, was prepared using cyclotron produced 11 CO 2 . The synthesis consists of the production of 11 C-methyl iodide and its coupling with inulin alkoxide sodium in dimethylsulfoxide as solvent. 11 C labeled inulin was purified by alcohol precipitation. The radiochemical yield of pure 11 C-inulin was 34% of 11 CO 2 30 min after the end of bombardment. The blood clearance and body distribution of 11 C was observed in rabbits after i.v. injection of 11 C-inulin. The blood clearance curve was composed of a sum of three exponential functions. The gamma camera image showed that the 11 C activity in blood moved quickly to kidneys and urine and a small dose of radioactivity remained persistently in edematous tissues, i.e. the edematous lung tissues produced by oleic acid treatment. (orig.)

  18. Form factors of ηc in light-front quark model

    International Nuclear Information System (INIS)

    Geng, Chao-Qiang; Lih, Chong-Chung

    2013-01-01

    We study the form factors of the η c meson in the light-front quark model. We explicitly show that the transition form factor of η c → γ * γ as a function of the momentum transfer is consistent with the experimental data by the BaBar collaboration, while the decay constant of η c is found to be f η c = 230.5 +52.2 -61.0 and 303.6 +115.2 -116.4 MeV for η cc anti c by using two η c → γγ decay widths of 5.3 ± 0.5 and 7.2 ± 2.1 keV, given by Particle Data Group and Lattice QCD calculation, respectively. (orig.)

  19. Characterization of a Gas-Purge Method to Access 11C-Carbon-Dioxide Radioactivity in Blood

    International Nuclear Information System (INIS)

    Ng, Y.; Green, M.A.

    2014-01-01

    Carbon-11 (t 1/2 : 20 minutes) labeled radiotracers, such as 11 C-acetate and 11 C-palmitate are widely used in positron emission tomography (PET) for noninvasive evaluation of myocardial metabolism under varied physiological conditions. These tracers are attractive probes of tissue physiology, because they are simply radiolabeled versions of the native biochemical substrates. One of the major metabolites generated by these tracers upon the administration is 11 CO 2 produced via the citric acid cycle. In quantitative modeling of 11 C-acetate and 11 C-palmitate PET data, the fraction of blood 11 C radioactivity present as 11 CO 2 needs to be measured to obtain a correct radiotracer arterial input function. Accordingly, the literature describes a method whereby the total blood 11 C-activity is counted in blood samples treated with base solution, while the fraction of 11 CO 2 is measured after the blood is treated with acid followed by a 10 minutes gas-purge. However, a detailed description of the experimental validation of this method was not provided. The goal of this study was to test the reliability of a 10-minute gas purging method used to assay 11 CO 2 radioactivity in blood. (author)

  20. Newly elected IAEA Board of Governors

    International Nuclear Information System (INIS)

    2001-01-01

    The document gives information about the election of 11 Member States to the IAEA Board of Governors, the 35-member policy-making body, during the 45th regular session of the IAEA's General Conference (17-21 September 2001, Austria Center, Vienna). The newly elected Member States are: Bulgaria, Burkina Faso, Chile, Colombia, Islamic Republic of Iran, Kuwait, Morocco, Philippines, Romania, Spain, and Turkey. The other 24 Member States of the Board are also given

  1. Cross sections for the production of 11C in C targets by 3.65 AGeV projectiles

    International Nuclear Information System (INIS)

    Kozma, P.; Tolstov, K.D.; Yanovskij, V.V.

    1989-01-01

    The absolute cross sections for the production of 11 C in C targets by 3.65 AGeV protons, deuterons, 4 He- and 12 C-ions were measured. Annihialtion radiation from 11 C was counted using a large volume NaI(Tl) and BaF 2 detectors. The flux measurement technique based on registration of charged particles by means of a thin nuclear emulsion layer rotating in a beam as well as fission chamber was used. The results are compared with earlier measurements of the cross sections in carbon targets using high-energy projectiles and Glauber theoretical prediction, as well. 10 refs.; 3 figs.; 1 tab

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

    Energy Technology Data Exchange (ETDEWEB)

    Maiti, Dilip K. [Department of Pediatrics, School of Medicine, PET Center, Children' s Hospital of Michigan, Wayne State University, 3901 Beaubien Blvd., Detroit, MI 48201 (United States); Chakraborty, Pulak K. [Department of Radiology, School of Medicine, PET Center, Children' s Hospital of Michigan, Wayne State University, 3901 Beaubien Blvd., Detroit, MI 48201 (United States)]. E-mail: pulak@pet.wayne.edu; Chugani, Diane C. [Department of Pediatrics, School of Medicine, PET Center, Children' s Hospital of Michigan, Wayne State University, 3901 Beaubien Blvd., Detroit, MI 48201 (United States); Department of Radiology, School of Medicine, PET Center, Children' s Hospital of Michigan, Wayne State University, 3901 Beaubien Blvd., Detroit, MI 48201 (United States); Muzik, Otto [Department of Pediatrics, School of Medicine, PET Center, Children' s Hospital of Michigan, Wayne State University, 3901 Beaubien Blvd., Detroit, MI 48201 (United States); Department of Radiology, School of Medicine, PET Center, Children' s Hospital of Michigan, Wayne State University, 3901 Beaubien Blvd., Detroit, MI 48201 (United States); Mangner, Thomas J. [Department of Radiology, School of Medicine, PET Center, Children' s Hospital of Michigan, Wayne State University, 3901 Beaubien Blvd., Detroit, MI 48201 (United States); Chugani, Harry T. [Department of Pediatrics, School of Medicine, PET Center, Children' s Hospital of Michigan, Wayne State University, 3901 Beaubien Blvd., Detroit, MI 48201 (United States); Department of Radiology, School of Medicine, PET Center, Children' s Hospital of Michigan, Wayne State University, 3901 Beaubien Blvd., Detroit, MI 48201 (United States); Department of Neurology, School of Medicine, PET Center, Children' s Hospital of Michigan, Wayne State University, 3901 Beaubien Blvd., Detroit, MI 48201 (United States)

    2005-05-01

    An improved one-pot synthesis procedure for routine production of [carbonyl-{sup 11}C]desmethyl-WAY-100635 ([{sup 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{sub 2}PO{sub 4} buffer (20mM, pH=6.5) as the eluent. The desired product fraction was collected in a 2.0-2.5mL volume and formulated with 11mL of 0.9% saline. The radioligand was ready for human use in 45min (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 133.2-185.0GBq/{mu}mol (3.6-5.0Ci/{mu}mol, EOS, n=2) when ca. 37.0GBq (ca. 1.0Ci) of starting [{sup 11}C]CO{sub 2} was used. Unlabeled mass of [{sup 11}C]DWAY was found to be 0.15-0.24{mu}g/mL and the precursor was present in less than 50ng/mL in final production solution.

  3. Synthesis of 2-iodo- and 2-phenyl-[11C]melatonin: potential PET tracers for melatonin binding sites

    International Nuclear Information System (INIS)

    Chen Jiajun; Fiehn-Schulze, Brita; Firnau, Guenter; Brough, Paul A.; Snieckus, Victor

    1998-01-01

    Two 11 C-labelled melatonin derivatives, 2-iodo-[ 11 C]melatonin (2-iodo-5-methoxy-N[ 11 C-acetyl]-tryptamine, an agonist) and 2-phenyl-[ 11 C]melatonin (2-phenyl-5-methoxy-N[ 11 C-acetyl]tryptamine, a putative antagonist) were synthesized from [ 11 C]carbon dioxide. The reaction sequence was common to both compounds and consisted of three steps: (i) carbonylation of methyl magnesium bromide with [ 11 C]carbon dioxide, (ii) conversion of the adduct to [ 11 C]acetyl chloride, (iii) acetylation of the amine precursors (2-iodo-5-methoxy-tryptamine or 2-phenyl-5-methoxy-tryptamine) with [ 11 C]acetyl chloride. The precursors were especially prepared. The radiochemical yield was 19% for 2-iodomelatonin and 32% for 2-phenymelatonin, based on [ 11 C]carbon dioxide; the specific activity ranged from 300 to 600 mCi/μmol. Both labelled 2-substituted-melatonins are intended to be used as radiotracers to study melatonin binding sites in man with positron emission tomography

  4. Regulation of adipocyte 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1 by CCAAT/enhancer-binding protein (C/EBP β isoforms, LIP and LAP.

    Directory of Open Access Journals (Sweden)

    Cristina L Esteves

    Full Text Available 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1 catalyses intracellular regeneration of active glucocorticoids, notably in liver and adipose tissue. 11β-HSD1 is increased selectively in adipose tissue in human obesity, a change implicated in the pathogenesis of metabolic syndrome. With high fat (HF-feeding, adipose tissue 11β-HSD1 is down-regulated in mice, plausibly to counteract metabolic disease. Transcription of 11β-HSD1 is directly regulated by members of the CCAAT/enhancer binding protein (C/EBP family. Here we show that while total C/EBPβ in adipose tissue is unaltered by HF diet, the ratio of the C/EBPβ isoforms liver-enriched inhibitor protein (LIP and liver-enriched activator protein (LAP (C/EBPβ-LIP:LAP is increased in subcutaneous adipose. This may cause changes in 11β-HSD1 expression since genetically modified C/EBPβ((+/L mice, with increased C/EBPβ-LIP:LAP ratio, have decreased subcutaneous adipose 11β-HSD1 mRNA levels, whereas C/EBPβ(ΔuORF mice, with decreased C/EBPβ-LIP:LAP ratio, show increased subcutaneous adipose 11β-HSD1. C/EBPβ-LIP:LAP ratio is regulated by endoplasmic reticulum (ER stress and mTOR signalling, both of which are altered in obesity. In 3T3-L1 adipocytes, 11β-HSD1 mRNA levels were down-regulated following induction of ER stress by tunicamycin but were up-regulated following inhibition of mTOR by rapamycin. These data point to a central role for C/EBPβ and its processing to LIP and LAP in transcriptional regulation of 11β-HSD1 in adipose tissue. Down-regulation of 11β-HSD1 by increased C/EBPβ-LIP:LAP in adipocytes may be part of a nutrient-sensing mechanism counteracting nutritional stress generated by HF diet.

  5. 17 CFR 9.11 - Form, contents and delivery of notice of disciplinary or access denial action.

    Science.gov (United States)

    2010-04-01

    ... notice of disciplinary or access denial action. 9.11 Section 9.11 Commodity and Securities Exchanges... OTHER ADVERSE ACTIONS Notice and Effective Date of Disciplinary Action or Access Denial Action § 9.11 Form, contents and delivery of notice of disciplinary or access denial action. (a) When required...

  6. 17 CFR 274.11 - Form N-1, registration statement of open-end management investment companies.

    Science.gov (United States)

    2010-04-01

    ... statement of open-end management investment companies. 274.11 Section 274.11 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) FORMS PRESCRIBED UNDER THE INVESTMENT COMPANY ACT...(b) of the Investment Company Act of 1940 by open-end management investment companies that are...

  7. Visual assessment of [11C]PIB PET in patients with cognitive impairment

    International Nuclear Information System (INIS)

    Suotunen, Timo; Hirvonen, Jussi; Arponen, Eveliina; Teraes, Mika; Seppaenen, Marko; Immonen-Raeihae, Pirjo; Aalto, Sargo; Lisinen, Irina; Koski, Kari; Sulkava, Raimo; Rinne, Juha O.

    2010-01-01

    The aim of this study was to evaluate the visual assessment of positron emission tomography images of N-[methyl-11C]2-(4 ' -methylaminophenyl)-6-hydroxybenzothiazole ([11C]PIB) in a patient population with mild to moderate memory impairment or dementia. We compared the visual ratings of two readers using kappa statistics and correlated the results of visual and quantitative region of interest (ROI) analyses. The one reader had good experience in evaluating PIB images and the other had little previous experience. The sensitivity and specificity of the visual assessment was determined using quantitative data from 18 healthy controls previously examined: [11C]PIB uptake was considered as abnormal if it was more than 2 SD above the mean of the healthy subjects. The evaluation of visual classification as ''normal'' or ''abnormal'' showed good interobserver agreement (κ = 0.90). There was a clear correlation between visual and quantitative analysis (r = 0.47-0.79, p 11 C]PIB images conforms with quantitative analyses also in a clinical patient population supporting the feasibility of visual evaluation in clinical settings. (orig.)

  8. D2 dopamine receptors in neuroleptic-naive schizophrenic patients. A positron emission tomography study with [11C]raclopride

    International Nuclear Information System (INIS)

    Farde, L.; Wiesel, F.A.; Stone-Elander, S.; Halldin, C.; Nordstroem, A.L.H.; Hall, H.; Sedvall, G.

    1990-01-01

    Several groups have reported increased densities of D2 dopamine receptors in the basal ganglia of schizophrenic brains postmortem. The significance of this finding has been questioned, since an upregulation of receptor number may be a neuronal response to neuroleptic drug treatment. We have used positron emission tomography and [ 11 C]raclopride to examine central D2 dopamine receptor binding in 20 healthy subjects and 18 newly admitted, young, neuroleptic-naive patients with schizophrenia. An in vivo saturation procedure was applied for quantitative determination of D2 dopamine receptor density (Bmax) and affinity (Kd). When the two groups were compared, no significant difference in Bmax or Kd values was found in the putamen or the caudate nucleus. The hypothesis of generally elevated central D2 dopamine receptor densities in schizophrenia was thus not supported by the present findings. In the patients but not in the healthy controls, significantly higher densities were found in the left than in the right putamen but not in the caudate nucleus

  9. [11C]palmitate kinetics across the splanchnic bed in arterial, portal and hepatic venous plasma during fasting and euglycemic hyperinsulinemia

    International Nuclear Information System (INIS)

    Guiducci, Letizia; Jaervisalo, Mikko; Kiss, Jan; Nagren, Kjell; Viljanen, Antti; Naum, Alexandru G.; Gastaldelli, Amalia; Savunen, Timo; Knuuti, Juhani; Salvadori, Piero A.; Ferrannini, Ele; Nuutila, Pirjo; Iozzo, Patricia

    2006-01-01

    Purpose: The liver is fundamental in regulating lipid metabolism, and it supplies fatty acids (FA) to the rest of the body in the form of triglycerides (TG); the time-related relevance of this process is incompletely defined. The aim of the study was to investigate the appearance of labeled TG in the hepatic vascular bed after [ 11 C]palmitate injection during fasting and insulin stimulation. Methods: Plasma [ 11 C]palmitate kinetics in arterial, portal and hepatic venous lipid fractions was studied in eight anesthetized pigs during fasting or euglycemic hyperinsulinemia. Plasma analyses were conducted at 10 and 40 min after tracer injection. Corresponding liver positron emission tomography (PET) images were acquired for the semiquantitative determination of hepatic FA uptake. Results: At 10 min, plasma levels of unchanged [ 11 C]palmitate were lower in hyperinsulinemic than in fasting experiments in the artery and in the portal vein (P≤.03), suggesting faster clearance. Levels of unmetabolized [ 11 C]palmitate did not differ between portal and arterial plasma. In the fasting state, a tendency to a positive arterial and portal vs. hepatic venous gradient was observed, indicative of net hepatic [ 11 C]palmitate extraction. Labeled TG were already detectable at 10 min (fasting vs. hyperinsulinemia, ns) and were higher in fasting than in hyperinsulinemic animals at 40 min (92±1% and 82±6% of arterial plasma radioactivity). Higher proportions of labeled TG were recovered in portal vein plasma, suggesting release by the gut. The portal and the arterial-portal vs. hepatic venous TG gradient tended to be positive. Accordingly, hepatic FA uptake was higher, but declined more rapidly during fasting than during hyperinsulinemia. Conclusion: The study indicates that the redistribution of [ 11 C]palmitate between different lipid pools occurs within the short time interval of most PET experiments and is strongly influenced by insulin. Labeled TG constitute an additional

  10. Validation of tomographic measurement of cerebral blood volume with C-11-labeled carboxyhemoglobin

    International Nuclear Information System (INIS)

    Phelps, M.E.; Huang, S.C.; Hoffman, E.J.; Kuhl, D.E.

    1979-01-01

    Red blood cells, tagged with C-11 administration of 11 CO gas, have been used to portray the distribution of blood in the brain. To date, however, the accuracy of this approach has not been validated. We have performed in vitro measurements of regional cerebral blood volume (CBV) with red blood cells labeled with C-11 and Cr-51 in four dogs and two rhesus monkeys. These studies yielded a ratio of CBV/sub C-1/ to CBV/sub Cr-11/ of 1.02 +- 0.03 (s.d.) from 92 samples. A least-squares fit to these data showed CBV/sub C-11/ = 1.01 CBV/sub Cr-51/ + 0.037; P much 11 CO-RBC gave coefficients of variation of +- 2.8% and +- 4.8% for cross-sectional CBV and regional (approx.4 cm 2 ) CBV over an 80-min period. The average human CBV was found to be 4.2 +- 0.4 cc blood per 100 g tissue. Clear tomographic delineation of the distribution of CBV in human subjects is achieved with ECT, which provides a ''live'' measurement of this parameter of cerebral hemodynamics. These data demonstrate that 11 CO administered by single-breath inhalation is a reliable and accurate blood tracer for measurement of CBV with ECT

  11. The synthesis of [O-methyl-{sup 11}C]venlafaxine: a non-classical, fast-acting antidepressant

    Energy Technology Data Exchange (ETDEWEB)

    Gee, A.D.; Gjedde, A. [Aarhus Univ. Hospital, PET Center, Aarhus (Denmark); Smith, D.F. [Aarhus Univ. Psychiatric Hospital, Inst. for Biological Psychiatry, Risskov (Denmark)

    1997-01-01

    As part of our program to develop PET tracers for the 5-HT reuptake site, venlafaxine, a non-classical, fast-acting antidepressant, was selected as a candidate for labelling with {sup 11}C for in vivo evaluation. [O-methyl-{sup 11}C]venlafaxine was produced by the alkylation of O-desmethyl venlafaxine with [{sup 11}C]methyl iodide followed by HPLC purification and formulation. Radiochemically pure [O-methyl-{sup 11}C]venlafaxine was obtained in a 30 {+-} 5% decay corrected radiochemical yield and a specific activity > 50 GBq/{mu}mol(1.4 Ci/{mu}mol) at the end of synthesis. For a typical production starting with 46 GBq (1.3 Ci) [{sup 11}C]CO{sub 2}, 5.2 GBq (140 mCi) [O-methyl-{sup 11}C]venlafaxine was obtained as a sterile, formulated solution in a synthesis time of 30 min (counted from EOB). (Author).

  12. Measurement of carbon fixation and allocation using 11C-labeled carbon dioxide

    International Nuclear Information System (INIS)

    Strain, B.R.; Goeschl, J.D.; Jaeger, C.H.; Fares, Y.; Magnuson, C.E.; Nelson, C.E.

    1983-01-01

    This paper describes the use of continuously produced and applied 11 C in measurements of carbon dioxide assimilation and C movement in plant research. This technique differs from the pulsing type 11 C research underway in other laboratories by being continuous and on-line with computer analysis making steady-state measurements of carbon fixation and movement possible. The studies to be described here make clear the advantages of using continuously produced and applied short half-lived isotopes

  13. Localization of viable, ischemic myocardium by positron-emission tomography with 11C-palmitate

    International Nuclear Information System (INIS)

    Lerch, R.A.; Ambos, H.D.; Bergmann, S.R.; Welch, M.J.; Ter-Pogossian, M.M.; Sobel, B.E.

    1981-01-01

    A study was performed to determine whether viable, but ischemic, tissue could be detected and localized in vivo based on external detection of impaired fatty acid metabolism. Accordingly, regional clearance of 11 C-palmitate was assessed by sequential PET in 15 anesthetized dogs. Clearance was consistently monoexponential from 5-15 minutes after administration of the tracer. In the absence of coronary stenosis (n = 7), clearance was homogeneous throughout the heart, with an average rate constant (k) of -0.060 +/- 0.005 min -1 (+/- SEM) and a coefficient of variation (CV) of 11.1 +/- 2.1% in each heart. Homogeneity persisted when the heart rate was increased from 84.4 +/- 6.0 to 202.7 +/- 11.5 beats/min with atropine (CV 13.2 +/- 3.5%). With left circumflex coronary stenosis (less than or equal to70% reduction in vessel diameter), homogeneity of 11 C-clearance under control conditions and with tachycardia did not differ from clearance in hearts without coronary stenosis. However, with stenosis >70% sufficient to induce ischemia without gross infarction, regional clearance of 11 C became markedly heterogeneous under control conditions (CV 28.1 +/- 5.5%, p 11 C in regions supplied by the stenotic vessel (k = -0.044 +/- 0.011 min -1 ) compared with clearance in well perfused regions (k = -0.064 +/- 0.011 min -1 , p 11 C-palmitate delineates zones of viable, ischemic myocardium that characteristically exhibit impaired oxidation of extracted fatty acid

  14. Radiosynthesis and ex vivo evaluation of (R)-(-)-2-chloro-N-[1-{sup 11}C-propyl]n-propylnorapomorphine

    Energy Technology Data Exchange (ETDEWEB)

    Palner, Mikael [Neurobiology Research Unit, Rigshospitalet, University of Copenhagen, DK-2300, Copenhagen (Denmark); Center for Integrated Molecular Brain Imaging, Copenhagen (Denmark)], E-mail: mikael.palner@nru.dk; McCormick, Patrick [PET Centre, Centre for Addiction and Mental Health, M5T 1RB, Toronto, ON (Canada); Gillings, Nic [Center for Integrated Molecular Brain Imaging, Copenhagen (Denmark); PET and Cyclotron Unit, Rigshospitalet, DK-2300, Copenhagen (Denmark); Begtrup, Mikael [Center for Integrated Molecular Brain Imaging, Copenhagen (Denmark); Institute for Medicinal Chemistry, Pharmaceutical Faculty, University of Copenhagen, DK-2300, Copenhagen (Denmark); Wilson, Alan A. [PET Centre, Centre for Addiction and Mental Health, M5T 1RB, Toronto, ON (Canada); Knudsen, Gitte M. [Neurobiology Research Unit, Rigshospitalet, University of Copenhagen, DK-2300, Copenhagen (Denmark); Center for Integrated Molecular Brain Imaging, Copenhagen (Denmark)

    2010-01-15

    Introduction: Several dopamine D{sub 2} agonist radioligands have been used with positron emission tomography (PET), including [{sup 11}C-]-(-)-MNPA, [{sup 11}C-]-(-)-NPA and [{sup 11}C]-(+)-PHNO. These radioligands are considered particularly powerful for detection of endogenous dopamine release, but they either provide PET brain images with limited contrast or have affinity for both D{sub 2} and D{sub 3} receptors. We here present the carbon-11 radiolabeling and ex vivo evaluation of 2-Cl-(-)-NPA, a novel PET-tracer candidate with high in vitro D{sub 2}/D{sub 3} selectivity. Methods: 2-Cl-[{sup 11}C]-(-)-NPA and [{sup 11}C]-(-)-NPA were synthesized by a two step N-acylation-reduction process using [{sup 11}C]-propionyl chloride. Awake rats were injected with either tracer, via the tail vein. The rats were decapitated at various times, the brains were removed and quickly dissected, and plasma metabolites were measured. Radioligand specificity, and P-glycoprotein involvement in brain uptake, was also assessed. Results: 2-Cl-[{sup 11}C]-(-)-NPA and [{sup 11}C]-(-)-NPA were produced in high specific activity and purity. 2-Cl-[{sup 11}C]-(-)-NPA accumulated slower in the striatum than [{sup 11}C]-(-)-NPA, reaching maximum concentrations after 30 min. The maximal striatal uptake of 2-Cl-[{sup 11}C]-(-)-NPA (standard uptake value 0.72{+-}0.24) was approximately half that of [{sup 11}C]-(-)-NPA (standard uptake value 1.37{+-}0.18). Nonspecific uptake was similar for the two compounds. 2-Cl-[{sup 11}C]-(-)-NPA was metabolized quickly, leaving only 17% of the parent compound in the plasma after 30 min. The specific binding of 2-Cl-[{sup 11}C]-(-)-NPA was completely blocked and inhibition of P-glycoprotein did not alter the brain uptake. Conclusion: Ex vivo experiments showed, despite a favorable D{sub 2}/D{sub 3} selectivity, that 2-Cl-[{sup 11}C]-(-)-NPA is inferior to [{sup 11}C]-(-)-NPA as a PET tracer in rat, because of slower brain uptake and lower specific to

  15. Estimating the impact of newly arrived foreign-born persons on tuberculosis in the United States.

    Directory of Open Access Journals (Sweden)

    Yecai Liu

    Full Text Available Among approximately 163.5 million foreign-born persons admitted to the United States annually, only 500,000 immigrants and refugees are required to undergo overseas tuberculosis (TB screening. It is unclear what extent of the unscreened nonimmigrant visitors contributes to the burden of foreign-born TB in the United States.We defined foreign-born persons within 1 year after arrival in the United States as "newly arrived", and utilized data from U.S. Department of Homeland Security, U.S. Centers for Disease Control and Prevention, and World Health Organization to estimate the incidence of TB among newly arrived foreign-born persons in the United States. During 2001 through 2008, 11,500 TB incident cases, including 291 multidrug-resistant TB incident cases, were estimated to occur among 20,989,738 person-years for the 1,479,542,654 newly arrived foreign-born persons in the United States. Of the 11,500 estimated TB incident cases, 41.6% (4,783 occurred among immigrants and refugees, 36.6% (4,211 among students/exchange visitors and temporary workers, 13.8% (1,589 among tourists and business travelers, and 7.3% (834 among Canadian and Mexican nonimmigrant visitors without an I-94 form (e.g., arrival-departure record. The top 3 newly arrived foreign-born populations with the largest estimated TB incident cases per 100,000 admissions were immigrants and refugees from high-incidence countries (e.g., 2008 WHO-estimated TB incidence rate of ≥100 cases/100,000 population/year; 235.8 cases/100,000 admissions, 95% confidence interval [CI], 228.3 to 243.3, students/exchange visitors and temporary workers from high-incidence countries (60.9 cases/100,000 admissions, 95% CI, 58.5 to 63.3, and immigrants and refugees from medium-incidence countries (e.g., 2008 WHO-estimated TB incidence rate of 15-99 cases/100,000 population/year; 55.2 cases/100,000 admissions, 95% CI, 51.6 to 58.8.Newly arrived nonimmigrant visitors contribute substantially to the burden of

  16. Estimating the impact of newly arrived foreign-born persons on tuberculosis in the United States.

    Science.gov (United States)

    Liu, Yecai; Painter, John A; Posey, Drew L; Cain, Kevin P; Weinberg, Michelle S; Maloney, Susan A; Ortega, Luis S; Cetron, Martin S

    2012-01-01

    Among approximately 163.5 million foreign-born persons admitted to the United States annually, only 500,000 immigrants and refugees are required to undergo overseas tuberculosis (TB) screening. It is unclear what extent of the unscreened nonimmigrant visitors contributes to the burden of foreign-born TB in the United States. We defined foreign-born persons within 1 year after arrival in the United States as "newly arrived", and utilized data from U.S. Department of Homeland Security, U.S. Centers for Disease Control and Prevention, and World Health Organization to estimate the incidence of TB among newly arrived foreign-born persons in the United States. During 2001 through 2008, 11,500 TB incident cases, including 291 multidrug-resistant TB incident cases, were estimated to occur among 20,989,738 person-years for the 1,479,542,654 newly arrived foreign-born persons in the United States. Of the 11,500 estimated TB incident cases, 41.6% (4,783) occurred among immigrants and refugees, 36.6% (4,211) among students/exchange visitors and temporary workers, 13.8% (1,589) among tourists and business travelers, and 7.3% (834) among Canadian and Mexican nonimmigrant visitors without an I-94 form (e.g., arrival-departure record). The top 3 newly arrived foreign-born populations with the largest estimated TB incident cases per 100,000 admissions were immigrants and refugees from high-incidence countries (e.g., 2008 WHO-estimated TB incidence rate of ≥100 cases/100,000 population/year; 235.8 cases/100,000 admissions, 95% confidence interval [CI], 228.3 to 243.3), students/exchange visitors and temporary workers from high-incidence countries (60.9 cases/100,000 admissions, 95% CI, 58.5 to 63.3), and immigrants and refugees from medium-incidence countries (e.g., 2008 WHO-estimated TB incidence rate of 15-99 cases/100,000 population/year; 55.2 cases/100,000 admissions, 95% CI, 51.6 to 58.8). Newly arrived nonimmigrant visitors contribute substantially to the burden of foreign

  17. Search for resonant states in 10C and 11C and their impact on the primordial 7Li abundance

    Science.gov (United States)

    Hammache, F.; Coc, A.; de Séréville, N.; Stefan, I.; Roussel, P.; Assié, M.; Audouin, L.; Beaumel, D.; Franchoo, S.; Fernandez-Dominguez, B.; Fox, S.; Hamadache, C.; Kiener, J.; Laird, A.; Le Crom, B.; Lefebvre-Schuhl, A.; Lefebvre, L.; Matea, I.; Matta, A.; Mavilla, G.; Mrazek, J.; Morfouace, P.; de Oliveira Santos, F.; Parikh, A.; Perrot, L.; Sanchez-Benitez, A. M.; Suzuki, D.; Tatischeff, V.; Ujic, P.; Vandebrouck, Marine

    2018-01-01

    The cosmological 7Li problem arises from the significant discrepancy of about a factor 3 between the predicted primordial 7Li abundance and the observed one. The main process for the production of 7Li during Big-Bang nucleosynthesis is the decay of 7Be. Many key nuclear reactions involved in the production and destruction of 7Be were investigated in attempt to explain the 7Li deficit but none of them led to successful conclusions. However, some authors suggested recently the possibility that the destruction of 7Be by 3He and 4He may reconcile the predictions and observations if missing resonant states in the compound nuclei 10C and 11C exist. Hence, a search of these missing resonant states in 10C and 11C was investigated at the Orsay Tandem-Alto facility through 10B(3He,t)10C and 11B(3He,t)11C charge-exchange reactions respectively. After a short overview of the cosmological 7Li problem from a nuclear physics point of view, a description of the Orsay experiment will be given as well as the obtained results and their impact on the 7Li problem.

  18. 12 CFR 563c.1 - Form and content of financial statements.

    Science.gov (United States)

    2010-01-01

    ... ACCOUNTING REQUIREMENTS Form and Content of Financial Statements § 563c.1 Form and content of financial... statements shall: (1) Be prepared and presented in accordance with generally accepted accounting principles... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Form and content of financial statements. 563c...

  19. Imaging of muscarinic acetylcholine receptors using (+)N-[11C]methyl-3-piperidyl benzilate (11C-3NMPB) in vascular dementia and Alzheimer's disease

    International Nuclear Information System (INIS)

    Saito, Hirohiko

    2006-01-01

    In order to clarify the integrity of muscarinic acetylcholine receptor (mAChR) in vascular dementia (VaD) and Alzheimer's disease (AD), PET imaging with (+) N-[ 11 C]methyl-3-piperidyl benzilate ( 11 C-3NMPB) was performed in 12 patients with VaD, 11 patients with AD, and 7 normal controls (NC group). The mAChR binding was compared by the ratios compared with the cerebellum which were calculated from the regions of interest (ROI), and by three-dimensional statistic analysis. Compared with the NC group, mAChR was not significantly reduced in any ROI in AD patients. In those with VaD due to cortical lesions, mAChR was reduced in the infarcted areas. On the other hand, mAChR was significantly reduced in the thalamus and anterior cingulated gyrus, but not in other cerebral cortices in patients with VaD due to subcortical lesions. Accordingly, it is suggested that the mAChR is preserved in the cerebral cortices in patients with VaD due to subcortical lesions as well as in AD patients. (author)

  20. Cluster Structure of 12C and 11Be

    International Nuclear Information System (INIS)

    Freer, M.; Fujita, H.; Buthelezi, Z.; Carter, J.; Fearick, R.W.; Foertsch, S.V.; Neveling, R.; Perez, S.M.; Papka, P.; Smit, F.D.; Swartz, J.A.; Usman, I.; Haigh, P.J.; Ashwood, N.I.; Bloxham, T.; Curtis, N.; McEwan, P.; Bohlen, H.G.; Dorsch, T.; Kokalova, Tz.

    2010-01-01

    The structure of the nucleus 12 C is discussed, in particular the spectrum of states above the α-decay threshold. A search for the 2 + excitation of the Hoyle-state is reported. The structural link between halo-like states and molecular states is explored in the case of 11 Be.

  1. Cerebral Blood Flow and A beta-Amyloid Estimates by WARM Analysis of [C-11]PiB Uptake Distinguish among and between Neurodegenerative Disorders and Aging

    DEFF Research Database (Denmark)

    Rodell, Anders B.; O'Keefe, Graeme; Rowe, Christopher C.

    2017-01-01

    groups as a whole, sCBF estimates revealed the greatest discrimination between the patient and HC groups. WARM resolves a major issue of amyloid load quantification with [11C]PiB in human brain by determining absolute sCBF and amyloid load measures from the same images. The two parameter approach......Background: We report results of the novel Washout Allometric Reference Method (WARM) that uses estimates of cerebral blood flow and amyloid load from the same [11C]Pittsburgh Compound B ([11C]PiB) retention maps in brain to distinguish between patients with different forms dementia, including...... with Lewy bodies (DLB), five patients with frontotemporal lobar degeneration (FTLD), five patients with mild cognitive impairment, and 29 age-matched healthy control subjects (HC)], underwent analysis of PiB delivery and retention by means of WARM for quantitation of [11C]PiB's binding potentials (BPND...

  2. [(11)C]5-HTP and microPET are not suitable for pharmacodynamic studies in the rodent brain

    NARCIS (Netherlands)

    Visser, Anniek K D; Ramakrishnan, Nisha K; Willemsen, Antoon T M; Di Gialleonardo, Valentina; de Vries, Erik F J; Kema, Ido P; Dierckx, Rudi A J O; van Waarde, Aren

    The PET tracer [C-11]5-hydroxytryptophan ([C-11]5-HTP), which is converted to [C-11]5-hydroxytryptamine ([C-11]5-HT) by aromatic amino acid decarboxylase (AADC), is thought to measure 5-HT synthesis rates. But can we measure these synthesis rates by kinetic modeling of [C-11]5-HTP in rat? Male rats

  3. Synthesis and positron emission tomography studies of C-11-labeled isotopomers and metabolites of GTS-21, a partial α7 nicotinic cholinergic agonist drug

    International Nuclear Information System (INIS)

    Kim, Sung Won; Ding Yushin; Alexoff, David; Patel, Vinal; Logan, Jean; Lin, K.-S.; Shea, Colleen; Muench, Lisa; Xu Youwen; Carter, Pauline; King, Payton; Constanzo, Jasmine R.; Ciaccio, James A.; Fowler, Joanna S.

    2007-01-01

    Introduction: (3E)-3-[(2,4-dimethoxyphenyl)methylene]-3,4,5,6-tetrahydro-2,3'-bipyridine (GTS-21), a partial α7 nicotinic acetylcholine receptor agonist drug, has recently been shown to improve cognition in schizophrenia and Alzheimer's disease. One of its two major demethylated metabolites, 4-OH-GTS-21, has been suggested to contribute to its therapeutic effects. Methods: We labeled GTS-21 in two different positions with carbon-11 ([2-methoxy- 11 C]GTS-21 and [4- 11 C]GTS-21) along with two corresponding demethylated metabolites ([2-methoxy- 11 C]4-OH-GTS-21 and [4-methoxy- 11 C]2-OH-GTS-21) for pharmacokinetic studies in baboons and mice with positron emission tomography (PET). Results: Both [2- 11 C]GTS-21 and [4-methoxy- 11 C]GTS-21 showed similar initial high rapid uptake in baboon brain, peaking from 1 to 3.5 min (0.027-0.038%ID/cc) followed by rapid clearance (t 1/2 11 C]GTS-21 continued to clear while [4-methoxy- 11 C]GTS-21 plateaued, suggesting the entry of a labeled metabolite into the brain. Comparison of the pharmacokinetics of the two labeled metabolites confirmed expected higher brain uptake and retention of [4-methoxy- 11 C]2-OH-GTS-21 (the labeled metabolite of [4-methoxy- 11 C]GTS-21) relative to [2-methoxy- 11 C]4-OH-GTS-21 (the labeled metabolite of [2-methoxy- 11 C]GTS-21), which had negligible brain uptake. Ex vivo studies in mice showed that GTS-21 is the major chemical form in the mouse brain. Whole-body dynamic PET imaging in baboon and mouse showed that the major route of excretion of C-11 is through the gallbladder. Conclusions: The major findings are as follows: (a) extremely rapid uptake and clearance of [2-methoxy- 11 C]GTS-21 from the brain, which may need to be considered in developing optimal dosing of GTS-21 for patients, and (b) significant brain uptake of 2-OH-GTS-21, suggesting that it might contribute to the therapeutic effects of GTS-21. This study illustrates the value of comparing different label positions and labeled

  4. FLO11 gene length and transcriptional level affect biofilm-forming ability of wild flor strains of Saccharomyces cerevisiae.

    Science.gov (United States)

    Zara, Giacomo; Zara, Severino; Pinna, Claudia; Marceddu, Salvatore; Budroni, Marilena

    2009-12-01

    In Saccharomyces cerevisiae, FLO11 encodes an adhesin that is associated with different phenotypes, such as adherence to solid surfaces, hydrophobicity, mat and air-liquid biofilm formation. In the present study, we analysed FLO11 allelic polymorphisms and FLO11-associated phenotypes of 20 flor strains. We identified 13 alleles of different lengths, varying from 3.0 to 6.1 kb, thus demonstrating that FLO11 is highly polymorphic. Two alleles of 3.1 and 5.0 kb were cloned into strain BY4742 to compare the FLO11-associated phenotypes in the same genetic background. We show that there is a significant correlation between biofilm-forming ability and FLO11 length both in different and in the same genetic backgrounds. Moreover, we propose a multiple regression model that allows prediction of air-liquid biofilm-forming ability on the basis of transcription levels and lengths of FLO11 alleles in a population of S. cerevisiae flor strains. Considering that transcriptional differences are only partially explained by the differences in the promoter sequences, our results are consistent with the hypothesis that FLO11 transcription levels are strongly influenced by genetic background and affect biofilm-forming ability.

  5. The synthesis of some 11C-labelled antiepileptic drugs with potential utility as radiopharmaceuticals: hydantoins and barbiturates

    International Nuclear Information System (INIS)

    Roeda, D.; Westera, G.

    1981-01-01

    11 C-labelled phenytoin and 5-ethyl-5-phenyl hydantoin were prepared using 11 COCl 2 as the starting material. 11 C-urea was used to produce 11 C-phenobarbital and 11 C-barbital. The methods developed are suitable for automation in a lead shielded cell. (author)

  6. Automated chemoenzymatic synthesis of no-carrier-added [carbonyl-{sup 11}C]propionyl L-carnitine for pharmacokinetic studies

    Energy Technology Data Exchange (ETDEWEB)

    Davenport, R.J.; Pike, V.W.; Dowsett, K.; Turton, D.R.; Poole, K. [Hammersmith Hospital, London (United Kingdom). MRC Cyclotron Unit

    1997-07-30

    Propionyl-L-carnitine (PLC) is under development as a therapeutic for the treatment of peripheral artery disease, coronary heart disease and chronic heart failure. Three methods were examined for labelling PLC in its propionyl group with positron-emitting carbon-11 (t{sub 1/2} = 20.3 min), one chemical and two chemoenzymatic. The former was based on the preparation of [{sup 11}C]propionyl chloride as labelling agent via {sup 11}C-carboxylation of ethylmagnesium bromide with cyclotron-produced [{sup 11}C]carbon dioxide and subsequent chlorination. Reaction of carrier-added [{sup 11}C]propionyl chloride with L-carnitine in trifluoroacetic acid gave [{sup 11}C]PLC in 12% radiochemical yield (decay-corrected) from cyclotron-produced [{sup 11}C]carbon dioxide. However, the radiosynthesis was unsuccessful at the no-carrier added (NCA) level of specific radioactivity. [{sup 11}C]Propionate, as a radioactive precursor for chemoenzymatic routes, was prepared via carboxylation of ethylmagnesium bromide with [{sup 11}C]carbon dioxide and hydrolysis. NCA [{sup 11}C]PLC was prepared in 68 min in 14% radiochemical yield (decay-corrected) from [{sup 11}C]propionate via sequential conversions catalysed by acetate kinase, phosphotransacetylase and carnitine acetyltransferase. A superior chemoenzymatic synthesis of NCA [{sup 11}C]PLC was developed, based on the use of a novel supported Grignard reagent for the synthesis of [{sup 11}C]propionate and conversions by S-acetyl-CoA synthetase and carnitine acetyltransferase. This gave an overall radiochemical yield of 30-48% (decay-corrected). This synthesis was automated for radiation safety and provides pure NCA [{sup 11}C]PLC in high radioactivities ready for intravenous administration within 25 min from radionuclide production. The [{sup 11}C]PLC is suitable for pharmacokinetic studies in human subjects with PET and the elucidation of the fate of the propionyl group of PLC in vivo. (Author).

  7. Four newly recorded species of Dryopteridaceae from Kashmir valley, India

    Directory of Open Access Journals (Sweden)

    SHAKOOR AHMAD MIR

    2014-04-01

    Full Text Available Mir SA, Mishra AK, Reshi ZA, Sharma MP. 2014. Four newly recorded species of Dryopteridaceae from Kashmir valley, India. Biodiversitas 15: 6-11. Habitat diversity, elevation, cloud cover, rainfall, seasonal and temperature variations have created many ideal sites for the luxuriant growth of pteridophytes in the Kashmir valley, yet all the regions of the valley have not been surveyed. In Kashmir valley the family Dryopteridaceae is represented by 31 species. During the recent extensive field surveys of Shopian district four more species viz., Dryopteris caroli-hopei Fraser-Jenkins, Dryopteris blanfordii subsp. nigrosquamosa (Ching Fraser-Jenkins, Dryopteris pulvinulifera (Bedd. Kuntze and Polystichum Nepalense (Spreng C. Chr. have been recorded for the first time from the valley. The taxonomic description, synonyms, distribution and photographs of each species are given in this article.

  8. Modeling of a cyclotron target for the production of 11C with Geant4.

    Science.gov (United States)

    Chiappiniello, Andrea; Zagni, Federico; Infantino, Angelo; Vichi, Sara; Cicoria, Gianfranco; Morigi, Maria Pia; Marengo, Mario

    2018-04-12

    In medical cyclotron facilities, 11C is produced according to the 14N(p,α)11C reaction and widely employed in studies of prostate and brain cancers by Positron Emission Tomography. It is known from literature [1] that the 11C-target assembly shows a reduction in efficiency during time, meaning a decrease of activity produced at the end of bombardment. This effect might depend on aspects still not completely known. Possible causes of the loss of performance of the 11C-target assembly were addressed by Monte Carlo simulations. Geant4 was used to model the 11C-target assembly of a GE PETtrace cyclotron. The physical and transport parameters to be used in the energy range of medical applications were extracted from literature data and 11C routine productions. The Monte Carlo assessment of 11C saturation yield was performed varying several parameters such as the proton energy and the angle of the target assembly with respect to the proton beam. The estimated 11C saturation yield is in agreement with IAEA data at the energy of interest, while is about the 35% greater than experimental value. A more comprehensive modeling of the target system, including thermodynamic effect, is required. The energy absorbed in the inner layer of the target chamber was up to 46.5 J/mm2 under typical irradiation conditions. This study shows that Geant4 is potentially a useful tool to design and optimize targetry for PET radionuclide productions. Tests to choose the Geant4 physics libraries should be performed before using this tool with different energies and materials. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. Uptake of inflammatory cell marker [{sup 11}C]PK11195 into mouse atherosclerotic plaques

    Energy Technology Data Exchange (ETDEWEB)

    Laitinen, Iina; Marjamaeki, Paeivi; Naagren, Kjell; Roivainen, Anne; Knuuti, Juhani [University of Turku, Turku PET Centre, Turku (Finland); Laine, V.J.O. [Turku University Hospital, Department of Pathology, Turku (Finland); Wilson, Ian [GE Healthcare Biosciences, Medical Diagnostics, London (United Kingdom); Leppaenen, Pia; Ylae-Herttuala, Seppo [University of Kuopio, A.I. Virtanen Institute, Kuopio (Finland)

    2009-01-15

    The ligand [{sup 11}C]PK11195 binds with high affinity and selectivity to peripheral benzodiazepine receptor, expressed in high amounts in macrophages. In humans, [{sup 11}C]PK11195 has been used successfully for the in vivo imaging of inflammatory processes of brain tissue. The purpose of this study was to explore the feasibility of [{sup 11}C]PK11195 in imaging inflammation in the atherosclerotic plaques. The presence of PK11195 binding sites in the atherosclerotic plaques was verified by examining the in vitro binding of [{sup 3}H]PK11195 onto mouse aortic sections. Uptake of intravenously administered [{sup 11}C]PK11195 was studied ex vivo in excised tissue samples and aortic sections of a LDLR/ApoB48 atherosclerotic mice. Accumulation of the tracer was compared between the atherosclerotic plaques and non-atherosclerotic arterial sites by autoradiography and histological analyses. The [{sup 3}H]PK11195 was found to bind to both the atherosclerotic plaques and the healthy wall. The autoradiography analysis revealed that the uptake of [{sup 11}C]PK11195 to inflamed regions in plaques was more prominent (p = 0.011) than to non-inflamed plaque regions, but overall it was not higher than the uptake to the healthy vessel wall. Also, the accumulation of {sup 11}C radioactivity into the aorta of the atherosclerotic mice was not increased compared to the healthy control mice. Our results indicate that the uptake of [{sup 11}C]PK11195 is higher in inflamed atherosclerotic plaques containing a large number of inflammatory cells than in the non-inflamed plaques. However, the tracer uptake to other structures of the artery wall was also prominent and may limit the use of [{sup 11}C]PK11195 in clinical imaging of atherosclerotic plaques. (orig.)

  10. Reproducibility of repeated measures of deuterium substituted [11C]L-deprenyl ([11C]L-deprenyl-D2) binding in the human brain

    International Nuclear Information System (INIS)

    Logan, Jean; Fowler, Joanna S.; Volkow, Nora D.; Wang, Gene-Jack; MacGregor, Robert R.; Shea, Colleen

    2000-01-01

    The purpose of this study was to assess the reproducibility of repeated positron emission tomography (PET) measures of brain monoamine oxidase B (MAO B) using deuterium-substituted [ 11 C]L-deprenyl ([ 11 C]L-deprenyl-D2) in normal subjects and to validate the method used for estimating the kinetic constants from the irreversible 3-compartment model applied to the tracer binding. Five normal healthy subjects (age range 23-73 years) each received two PET scans with [ 11 C]L-deprenyl-D2. The time interval between scans was 7-27 days. Time-activity data from eight regions of interest and an arterial plasma input function was used to calculate λk 3 , a model term proportional to MAO B, and K 1 , the plasma to brain transfer constant that is related to blood flow. Linear (LIN) and nonlinear least-squares (NLLSQ) estimation methods were used to calculate the optimum model constants. A comparison of time-activity curves for scan 1 and scan 2 showed that the percent of change for peak uptake varied from -18.5 to 15.0% and that increases and decreases in uptake on scan 2 were associated with increases and decreases in the value of the arterial input of the tracer. Calculation of λk 3 showed a difference between scan 1 and scan 2 in the global value ranging between -6.97 and 4.5% (average -2.1±4.7%). The average percent change for eight brain regions for the five subjects was -2.84±7.07%. Values of λk 3 for scan 1 and scan 2 were highly correlated (r 2 =0.98; p 1 showed a significant correlation between scan 1 and scan 2 (r 2 =0.61; p 11 C]L-deprenyl-D2 varied between scan 1 and scan 2, driven by the differences in arterial tracer input. Application of a 3-compartment model to regional time-activity data and arterial input function yielded λk 3 values for scan 1 and scan 2 with an average difference of -2.84 ± 7.07%. Linear regression applied to values of λk 3 from the LIN and NLLSQ methods validated the use of the linear method for calculating λk 3

  11. Tailoring of SiC nanoprecipitates formed in Si

    Energy Technology Data Exchange (ETDEWEB)

    Velisa, G., E-mail: gihan.velisa@cea.fr [CEA, DEN, Service de Recherches de Métallurgie Physique, Laboratoire JANNUS, F-91191 Gif-sur-Yvette (France); Horia Hulubei National Institute for Physics and Nuclear Engineering, P.O. Box MG-6, 077125 Magurele (Romania); Trocellier, P. [CEA, DEN, Service de Recherches de Métallurgie Physique, Laboratoire JANNUS, F-91191 Gif-sur-Yvette (France); Thomé, L. [Centre de Spectrométrie Nucléaire et de Spectrométrie de Masse, UMR8609, Bât. 108, 91405 Orsay (France); Vaubaillon, S. [CEA, INSTN, UEPTN, Laboratoire JANNUS, F-91191 Gif-sur-Yvette (France); Miro, S.; Serruys, Y.; Bordas, É. [CEA, DEN, Service de Recherches de Métallurgie Physique, Laboratoire JANNUS, F-91191 Gif-sur-Yvette (France); Meslin, E. [CEA, DEN, Service de Recherches de Métallurgie Physique, F-91191 Gif-sur-Yvette (France); Mylonas, S. [Centre de Spectrométrie Nucléaire et de Spectrométrie de Masse, UMR8609, Bât. 108, 91405 Orsay (France); Coulon, P.E. [Ecole Polytechnique, Laboratoire des Solides Irradiés, CEA/DSM/IRAMIS-CNRS, 91128 Palaiseau Cedex (France); Leprêtre, F.; Pilz, A.; Beck, L. [CEA, DEN, Service de Recherches de Métallurgie Physique, Laboratoire JANNUS, F-91191 Gif-sur-Yvette (France)

    2013-07-15

    The SiC synthesis through single-beam of C{sup +}, and simultaneous-dual-beam of C{sup +} and Si{sup +} ion implantations into a Si substrate heated at 550 °C has been studied by means of three complementary analytical techniques: nuclear reaction analysis (NRA), Raman, and transmission electron microscopy (TEM). It is shown that a broad distribution of SiC nanoprecipitates is directly formed after simultaneous-dual-beam (520-keV C{sup +} and 890-keV Si{sup +}) and single-beam (520-keV C{sup +}) ion implantations. Their shape appear as spherical (average size ∼4–5 nm) and they are in epitaxial relationship with the silicon matrix.

  12. 17 CFR 274.11b - Form N-3, registration statement of separate accounts organized as management investment companies.

    Science.gov (United States)

    2010-04-01

    ... statement of separate accounts organized as management investment companies. 274.11b Section 274.11b... accounts organized as management investment companies. Form N-3 shall be used as the registration statement... offer variable annuity contracts to register as management investment companies. This form shall also be...

  13. Five-year follow-up of 11C-PIB uptake in Alzheimer's disease and MCI

    International Nuclear Information System (INIS)

    Kemppainen, N.M.; Scheinin, N.M.; Koivunen, J.; Johansson, J.; Toivonen, J.T.; Naagren, K.; Rokka, J.; Rinne, J.O.; Karrasch, M.; Parkkola, R.

    2014-01-01

    The aim of this study was to evaluate the longitudinal changes in [ 11 C]PIB uptake in mild cognitive impairment (MCI) and Alzheimer's disease (AD) over a long-term follow-up. Six AD patients, ten MCI patients and eight healthy subjects underwent a [ 11 C]PIB PET scan at baseline and at 2 and 5 years. The clinical status of the MCI patients was evaluated every 6 months. The MCI group showed a significant increase in [ 11 C]PIB uptake over time (p 11 C]PIB scan at baseline but increased uptake later. There was an increase in [ 11 C]PIB uptake with time in the AD group (p = 0.02), but this did not significantly differ from the change in the control group. Our results revealed a significant increase in amyloid load even at the time of AD diagnosis in some of the MCI patients who converted. A positive [ 11 C]PIB scan at baseline in MCI patients strongly predicted future conversion to AD but a negative PIB scan in MCI patients did not exclude future conversion. The results suggest that there is wide individual variation in the brain amyloid load in MCI, and in the course of amyloid accumulation in relation to the clinical diagnosis of AD. (orig.)

  14. 12C(n , 2 n )11C cross section from threshold to 26.5 MeV

    Science.gov (United States)

    Yuly, M.; Eckert, T.; Hartshaw, G.; Padalino, S. J.; Polsin, D. N.; Russ, M.; Simone, A. T.; Brune, C. R.; Massey, T. N.; Parker, C. E.; Fitzgerald, R.; Sangster, T. C.; Regan, S. P.

    2018-02-01

    The 12C(n ,2 n )11C cross section was measured from just below threshold to 26.5 MeV using the Pelletron accelerator at Ohio University. Monoenergetic neutrons, produced via the 3H(d ,n )4He reaction, were allowed to strike targets of polyethylene and graphite. Activation of both targets was measured by counting positron annihilations resulting from the β+ decay of 11C. Annihilation gamma rays were detected, both in coincidence and singly, using back-to-back NaI detectors. The incident neutron flux was determined indirectly via 1H(n ,p ) protons elastically scattered from the polyethylene target. Previous measurements fall into upper and lower bands; the results of the present measurement are consistent with the upper band.

  15. Mutations in c10orf11, a melanocyte-differentiation gene, cause autosomal-recessive albinism.

    Science.gov (United States)

    Grønskov, Karen; Dooley, Christopher M; Østergaard, Elsebet; Kelsh, Robert N; Hansen, Lars; Levesque, Mitchell P; Vilhelmsen, Kaj; Møllgård, Kjeld; Stemple, Derek L; Rosenberg, Thomas

    2013-03-07

    Autosomal-recessive albinism is a hypopigmentation disorder with a broad phenotypic range. A substantial fraction of individuals with albinism remain genetically unresolved, and it has been hypothesized that more genes are to be identified. By using homozygosity mapping of an inbred Faroese family, we identified a 3.5 Mb homozygous region (10q22.2-q22.3) on chromosome 10. The region contains five protein-coding genes, and sequencing of one of these, C10orf11, revealed a nonsense mutation that segregated with the disease and showed a recessive inheritance pattern. Investigation of additional albinism-affected individuals from the Faroe Islands revealed that five out of eight unrelated affected persons had the nonsense mutation in C10orf11. Screening of a cohort of autosomal-recessive-albinism-affected individuals residing in Denmark showed a homozygous 1 bp duplication in C10orf11 in an individual originating from Lithuania. Immunohistochemistry showed localization of C10orf11 in melanoblasts and melanocytes in human fetal tissue, but no localization was seen in retinal pigment epithelial cells. Knockdown of the zebrafish (Danio rerio) homolog with the use of morpholinos resulted in substantially decreased pigmentation and a reduction of the apparent number of pigmented melanocytes. The morphant phenotype was rescued by wild-type C10orf11, but not by mutant C10orf11. In conclusion, we have identified a melanocyte-differentiation gene, C10orf11, which when mutated causes autosomal-recessive albinism in humans. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  16. Individual radiation response of parotid glands investigated by dynamic 11C-methionine PET

    International Nuclear Information System (INIS)

    Buus, Simon; Grau, Cai; Munk, Ole Lajord; Rodell, Anders; Jensen, Kenneth; Mouridsen, Kim; Keiding, Susanne

    2006-01-01

    Background and Purpose: Previously, we showed that the net metabolic clearance of 11 C-methionine of the parotid gland, K, calculated from dynamic 11 C-methionine PET, can be used as a measure of parotid gland function. The aim of this study was to investigate by dynamic 11 C-methionine PET the individual radiation dose response relationship of parotid glands in head and neck cancer patients. Patients and methods: Twelve head and neck cancer patients were examined by dynamic 11 C-methionine PET after radiotherapy. Parametric images of K were generated, co-registered and compared voxel-by-voxel with the 3D radiation dose plan within the parotid gland to assess the individual radiation dose-function relationship. Results: In each patient, voxel-values of K decreased with increasing radiation dose. Population based analysis showed a sigmoid dose response relationship of parotid gland, from which we estimated a threshold radiation dose of 16 Gy and a mean TD 5 of 30 Gy. TD 5 ranged from 7 to 50 Gy in the group of patients. Conclusions: Individual radiation dose response of parotid glands can be measured by dynamic 11 C-methionine PET. The dose response analysis revealed a sigmoid relationship, a threshold radiation dose of 16 Gy, and a mean TD 5 of 30 Gy

  17. Simplified PET measurement for evaluating histamine H1 receptors in human brains using [11C]doxepin

    International Nuclear Information System (INIS)

    Mochizuki, Hideki; Kimura, Yuichi; Ishii, Kenji; Oda, Keiichi; Sasaki, Toru; Tashiro, Manabu; Yanai, Kazuhiko; Ishiwata, Kiichi

    2004-01-01

    The aim of this study was to develop simplified positron emission tomography measurement using [ 11 C]doxepin ([ 11 C]DOX) to evaluate histamine H 1 receptors (H1Rs) in human brains. We evaluated the correlation between the distribution volume (DV) of [ 11 C]DOX, estimated quantitatively with a two-compartment model, and the [ 11 C]DOX uptake obtained at various time intervals and normalized using the metabolite-corrected plasma radioactivity. We found that the static 70- to 90-min images normalized using the plasma radioactivity at 10 min postinjection reflected the DV of [ 11 C]DOX-H1R binding

  18. Preliminary Ionization Efficiencies of 11C and 14O with the LBNL ECR Ion Sources

    International Nuclear Information System (INIS)

    Xie, Z.Q.; Cerny, J.; Guo, F.Q.; Joosten, R.; Larimer, R.M.; Lyneis, C.M.; McMahan, P.; Norman, E.B.; O'Neil, J.P.; Powell, J.; Rowe, M.W.; VanBrocklin, H.F.; Wutte, D.; Xu, X.J.; Haustein, P.

    1998-01-01

    High charge states, up to fully stripped 11 C and 14 O ion, beams have been produced with the electron cyclotron resonance ion sources (LBNL, ECR and AECR-U) at Lawrence Berkeley National Laboratory. The radioactive atoms of 11 C and 14 O were collected in batch mode with an LN 2 trap and then bled into the ECR ion sources. Ionization efficiency as high as 11% for 11 C 4+ was achieved

  19. 12C(3He,3He n)11C cross section at 910 MeV

    International Nuclear Information System (INIS)

    Aslanides, E.; Fassnacht, P.; Dellacasa, G.; Gallio, M.; Tuyn, J.W.N.

    1981-01-01

    The 12 C( 3 He, 3 He n) 11 C cross section at 910 MeV was measured by using a Ge(Li) gamma spectrometer to determine the disintegration rate and measuring the incident flux by means of a scintillator telescope. Cross sections for the production of 7 Be in C and Al and for the production of 24 Na in Al are then determined using the measured cross section as a monitor

  20. Effect of P addition on glass forming ability and soft magnetic properties of melt-spun FeSiBCuC alloy ribbons

    International Nuclear Information System (INIS)

    Xu, J.; Yang, Y.Z.; Li, W.; Chen, X.C.; Xie, Z.W.

    2016-01-01

    The dependency of phosphorous content on the glass forming ability, thermal stability and soft magnetic properties of Fe 83.4 Si 2 B 14−x P x Cu 0.5 C 0.1 (x=0,1,2,3,4) alloys was investigated. The experimental results showed that the substitution of B by P increased the glass forming ability in this alloy system. The Fe 83.4 Si 2 B 10 P 4 Cu 0.5 C 0.1 alloy shows a fully amorphous character. Thermal stability of melt-spun ribbons increases and temperature interval between the first and second crystallization peaks enlarges with the increase of P content. And the saturation magnetic flux density (Bs) shows a slight increase with the increase of P content. The Fe 83.4 Si 2 B 11 P 3 Cu 0.5 C 0.1 nanocrystalline alloy exhibits a high Bs about 200.6 emu/g. The Bs of fully amorphous alloy Fe 83.4 Si 2 B 10 P 4 Cu 0.5 C 0.1 drops dramatically to 172.1 emu/g, which is lower than that of other nanocrystallines. Low material cost and excellent soft magnetic properties make the FeSiBPCuC alloys promise soft magnetic materials for industrial applications. - Highlights: • Partial substituting B by P helps to improve the glass forming ability of the alloy. • The addition of P content reduces the thermal stability and improves heat treatment temperature region for these alloys. • The Fe 83.4 Si 2 B 11 P 3 Cu 0.5 C 0.1 nanocrystalline alloy exhibits a high saturation magnetic density of 200.6 emu/g.

  1. Radiosynthesis of [11C]SB-705498, a selective transient receptor potential Vanilloid 1 (TRPV1) receptor antagonist

    International Nuclear Information System (INIS)

    Dolle, F.; Bramoulle, Y.; Deverre, J.R.; Bottlaender, M.; Passchier, J.

    2011-01-01

    Complete text of publication follows: Objectives: The transient receptor potential vanilloid 1 (TRPV1) receptor, previously known as the vanilloid receptor 1 (VR1), is a non-selective cation channel activated by a range of noxious stimuli and highly expressed in nociceptive fibres. TRPV1 receptor is involved in pain and sensitisation associated with tissue injury and inflammation and therefore represents a pharmacological target of choice for the development of novel therapeutic agents for the treatment of chronic pain, migraine and gastrointestinal disorders. Among a novel series of pyrrolidinyl ureas recently discovered by GSK, SB-705498 (1, namely 1-(2-bromophenyl)-3-[(R)-1-(5- trifluoromethylpyridin-2-yl)pyrrolidin-3-yl]urea) has been identified as a potent, selective and orally bioavailable TRPV1 antagonist and considered for positron emission tomography studies. SB-705498 (1) has therefore been isotopically labelled with the short-lived positron-emitter carbon-11 (t1/2: 20.38 min) at its urea site using [ 11 C]phosgene in a one-pot two-step process, via the intermediate preparation of 2-bromophenyl [ 11 C]isocyanate. Methods: Carbon-11-labeling of SB-705498 comprises: (A) Trapping of [ 11 C]phosgene (radio-synthesized from cyclotron-produced [ 11 C]methane via [ 11 C]carbon tetrachloride using minor modifications of published processes) at room temperature for 1 to 2 minutes in 250 μL of acetonitrile containing 0.6 μmole of 2-bromoaniline (2) giving 2-bromophenyl [ 11 C]isocyanate ([ 11 C]-3), followed by (B) addition of an excess of chiral (R)-1-(5- trifluoromethylpyridin-2-yl)pyrrolidin-3-ylamine (4, 40 μmoles in 500 μL of acetonitrile) as the second amine and reaction at room temperature for an additional one minute giving the desired urea derivative ([ 11 C]SB-705498 ([ 11 C]-1)), (C) dilution of the crude reaction mixture with water (500 μL) containing 4% (v:v) of DEA, injection and purification on a semi-preparative Waters Symmetry R C18 HPLC

  2. A role for 11C-methionine PET imaging in ACTH-dependent Cushing's syndrome.

    Science.gov (United States)

    Koulouri, Olympia; Steuwe, Andrea; Gillett, Daniel; Hoole, Andrew C; Powlson, Andrew S; Donnelly, Neil A; Burnet, Neil G; Antoun, Nagui M; Cheow, Heok; Mannion, Richard J; Pickard, John D; Gurnell, Mark

    2015-10-01

    We report our experience of functional imaging with (11)C-methionine positron emission tomography-computed tomography (PET-CT) co-registered with 3D gradient echo (spoiled gradient recalled (SPGR)) magnetic resonance imaging (MRI) in the investigation of ACTH-dependent Cushing's syndrome. Twenty patients with i) de novo Cushing's disease (CD, n=10), ii) residual or recurrent hypercortisolism following first pituitary surgery (±radiotherapy; n=8) or iii) ectopic Cushing's syndrome (n=2) were referred to our centre for functional imaging studies between 2010 and 2015. Six of the patients with de novo CD and five of those with persistent/relapsed disease had a suspected abnormality on conventional MRI. All patients underwent (11)C-methionine PET-CT. For pituitary imaging, co-registration of PET-CT images with contemporaneous SPGR MRI (1 mm slice thickness) was performed, followed by detailed mapping of (11)C-methionine uptake across the sella in three planes (coronal, sagittal and axial). This allowed us to determine whether suspected adenomas seen on structural imaging exhibited focal tracer uptake on functional imaging. In seven of ten patients with de novo CD, asymmetric (11)C-methionine uptake was observed within the sella, which co-localized with the suspected site of a corticotroph microadenoma visualised on SPGR MRI (and which was subsequently confirmed histologically following successful transsphenoidal surgery (TSS)). Focal (11)C-methionine uptake that correlated with a suspected abnormality on pituitary MRI was seen in five of eight patients with residual or recurrent Cushing's syndrome following first TSS (and pituitary radiotherapy in two cases). Two patients elected to undergo repeat TSS with histology confirming a corticotroph tumour in each case. In two patients with the ectopic ACTH syndrome, (11)C-methionine was concentrated in sites of distant metastases, with minimal uptake in the sellar region. (11)C-methionine PET-CT can aid the detection of

  3. 48 CFR 1846.672 - Preparing DD Forms 250 and 250c.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Preparing DD Forms 250 and 250c. 1846.672 Section 1846.672 Federal Acquisition Regulations System NATIONAL AERONAUTICS AND SPACE... DD Forms 250 and 250c. ...

  4. Quantitation of cardiac sympathetic innervation in rabbits using 11C-hydroxyephedrine PET: relation to 123I-MIBG uptake

    International Nuclear Information System (INIS)

    Nomura, Yusuke; Kajinami, Kouji; Matsunari, Ichiro; Takamatsu, Hiroyuki; Murakami, Yoshihiro; Matsuya, Takahiro; Chen, Wei-Ping; Taki, Junichi; Nakajima, Kenichi; Nekolla, Stephan G.

    2006-01-01

    Although 11 C-hydroxyephedrine ( 11 C-HED) PET is used to map cardiac sympathetic innervation, no studies have shown the feasibility of quantitation of 11 C-HED PET in small- to medium-sized animals. Furthermore, its relation to 123 I-MIBG uptake, the most widely used sympathetic nervous tracer, is unknown. The aims of this study were to establish in vivo sympathetic nerve imaging in rabbits using 11 C-HED PET, and to compare the retention of 11 C-HED with that of 123 I-MIBG. Twelve rabbits were assigned to three groups; control (n=4), chemical denervation by 6-hydroxydopamine (6-OHDA) (n=4) and reserpine treated to inhibit vesicular uptake (n=4). After simultaneous injection of 11 C-HED and 123 I-MIBG, all animals underwent dynamic 11 C-HED PET for 40 min with arterial blood sampling. The 11 C-HED retention fraction and normalised 11 C-HED activity measured by tissue sampling were compared with those measured by PET. Both the 11 C-HED retention fraction and the normalised 11 C-HED activity measured by PET correlated closely with those measured by tissue sampling (R=0.96027, p 11 C-HED and 123 I-MIBG. Reserpine pretreatment reduced 11 C-HED retention by 50%, but did not reduce 123 I-MIBG retention at 40 min after injection. Non-invasive quantitation of cardiac sympathetic innervation using 11 C-HED PET is feasible and gives reliable estimates of cardiac sympathetic innervation in rabbits. Additionally, although both 11 C-HED and 123 I-MIBG are specific for sympathetic neurons, 11 C-HED may be more specific for intravesicular uptake than 123 I-MIBG in some situations, such as that seen in reserpine pretreatment. (orig.)

  5. Brain kinetics of L-[β-11C]DOPA in humans studied by positron emission tomography

    International Nuclear Information System (INIS)

    Hartvig, P.; Agren, H.; Reibring, L.; Tedroff, J.; Bjurling, P.; Kihlberg, T.; Langstroem, B.

    1991-01-01

    The in vivo dopamine precursor L-3,4-dihydroxyphenylalanine (L-DOPA) labelled with 11 C in the β position has been used for positron emission tomography studies of L-DOPA utilization in the brain. The brain uptake and kinetics of L-[ 11 C]DOPA-derived radioactivity were studied in healthy male volunteers, and the specific utilization, i.e. decarboxylation rate of L-[ 11 C]DOPA in different brain areas, was quantified using a brain region devoid of specific L-[ 11 C]DOPA utilization as reference. Total uptake of L-[ 11 C]DOPA-derived radioactivity measured in the brain varied two- to three-fold between subjects, with highest radioactivity in the striatal region. Specific utilization of L-[ 11 C]DOPA radioactivity in the striatal region and in the prefrontal cortex varied twofold between subjects. No specific utilization was observed in other regions of the brain. The uptake of radioactivity in the brain increased dose-dependently with the simultaneous administration of unlabelled L-DOPA up to 10 mg. On the other hand, a decrease in brain radioactivity uptake was measured after pretreatment with 1 mg/kg oral L-DOPA, indicating competition for transport across the blood-brain barrier. Benserazide 0.5mg/kg orally increased somewhat the radioactivity uptake to the brain. None of these pharmacological perturbations demonstrated any clearcut effect on specific utilization of L-[ 11 C]DOPA. Thus, 11 C-labelled L-DOPA is introduced as an alternative to the well-established L-6-[ 18 F]fluoro-DOPA methodology in clinical studies on brain L-DOPA uptake and dopamine synthesis. (authors)

  6. Comparison of {sup 68}Ga-labelled PSMA-11 and {sup 11}C-choline in the detection of prostate cancer metastases by PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Schwenck, Johannes [Eberhard Karls University, Department of Nuclear Medicine and Clinical Molecular Imaging, Tuebingen (Germany); Eberhard Karls University, Department of Preclinical Imaging and Radiopharmacy, Tuebingen (Germany); Rempp, Hansjoerg; Nikolaou, Konstantin; Pfannenberg, Christina [Eberhard Karls University, Department of Diagnostic and Interventional Radiology, Tuebingen (Germany); Reischl, Gerald [Eberhard Karls University, Department of Preclinical Imaging and Radiopharmacy, Tuebingen (Germany); Kruck, Stephan; Stenzl, Arnulf [Eberhard Karls University, Department of Urology, Tuebingen (Germany); La Fougere, Christian [Eberhard Karls University, Department of Nuclear Medicine and Clinical Molecular Imaging, Tuebingen (Germany); German Cancer Consortium, German Cancer Research Center Partner Site, Heidelberg (Germany)

    2017-01-15

    Prostate-specific membrane antigen (PSMA) is expressed ubiquitously on the membrane of most prostate tumors and its metastasis. While PET/CT using {sup 11}C-choline was considered as the gold standard in the staging of prostate cancer, PET with radiolabelled PSMA ligands was introduced into the clinic in recent years. Our aim was to compare the PSMA ligand {sup 68}Ga-PSMA-11 with {sup 11}C-choline in patients with primary and recurrent prostate cancer. 123 patients underwent a whole-body PET/CT examination using {sup 68}Ga-PSMA-11 and {sup 11}C-choline. Suspicious lesions were evaluated visually and semiquantitatively (SUVavg). Out of these, 103 suffered from a confirmed biochemical relapse after prostatectomy and/or radiotherapy (mean PSA level of 4.5 ng/ml), while 20 patients underwent primary staging. In 67 patients with biochemical relapse, we detected 458 lymph nodes suspicious for metastasis. PET using {sup 68}Ga-PSMA-11 showed a significantly higher uptake and detection rate than {sup 11}C-choline PET. Also {sup 68}Ga-PSMA-11 PET identified significantly more patients with suspicious lymph nodes as well as affected lymph nodes regions especially at low PSA levels. Bone lesions suspicious for prostate cancer metastasis were revealed in 36 patients' biochemical relapse. Significantly more bone lesions were detected by {sup 68}Ga-PSMA-11, but only 3 patients had only PSMA-positive bone lesions. Nevertheless, we detected also 29 suspicious lymph nodes and 8 bone lesions, which were only positive as per {sup 11}C-choline PET. These findings led to crucial differences in the TNM classification and the identification of oligometastatic patients. In the patients who underwent initial staging, all primary tumors showed uptake of both tracers. Although significantly more suspicious lymph nodes and bone lesions were identified, only 2 patients presented with bone lesions only detected by {sup 68}Ga-PSMA-11 PET. Thus, PET using {sup 68}Ga-PSMA-11 showed a higher

  7. Dicty_cDB: FC-BS11 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available FC (Link to library) FC-BS11 (Link to dictyBase) - - - Contig-U16517-1 FC-BS11Z (Li...nk to Original site) - - FC-BS11Z 683 - - - - Show FC-BS11 Library FC (Link to library) Clone ID FC-BS11 (Li.../dictycdb.biol.tsukuba.ac.jp/CSM/FC/FC-BS/FC-BS11Q.Seq.d/ Representative seq. ID FC-BS...11Z (Link to Original site) Representative DNA sequence >FC-BS11 (FC-BS11Q) /CSM/FC/FC-BS/FC-BS11Q.Seq....s producing significant alignments: (bits) Value FC-BS11 (FC-BS11Q) /CSM/FC/FC-BS/FC-BS

  8. [{sup 11}C]palmitate kinetics across the splanchnic bed in arterial, portal and hepatic venous plasma during fasting and euglycemic hyperinsulinemia

    Energy Technology Data Exchange (ETDEWEB)

    Guiducci, Letizia [SSSUP Medical Sciences Branch, Pisa 56100 (Italy); Turku PET Centre, University of Turku, Turku 20520 (Finland); PET Centre, Institute of Clinical Physiology, CNR National Research Council, 56100 Pisa (Italy); Jaervisalo, Mikko [Turku PET Centre, University of Turku, Turku 20520 (Finland); Kiss, Jan [Turku PET Centre, University of Turku, Turku 20520 (Finland); Department of Surgery, University of Turku, Turku 20520 (Finland); Nagren, Kjell [Turku PET Centre, University of Turku, Turku 20520 (Finland); Viljanen, Antti [Turku PET Centre, University of Turku, Turku 20520 (Finland); Naum, Alexandru G. [Turku PET Centre, University of Turku, Turku 20520 (Finland); Gastaldelli, Amalia [PET Centre, Institute of Clinical Physiology, CNR National Research Council, 56100 Pisa (Italy); Savunen, Timo [Department of Surgery, University of Turku, Turku 20520 (Finland); Knuuti, Juhani [Turku PET Centre, University of Turku, Turku 20520 (Finland); Salvadori, Piero A. [PET Centre, Institute of Clinical Physiology, CNR National Research Council, 56100 Pisa (Italy); Ferrannini, Ele [PET Centre, Institute of Clinical Physiology, CNR National Research Council, 56100 Pisa (Italy); Department of Internal Medicine, University of Pisa School of Medicine, Pisa 56100 (Italy); Nuutila, Pirjo [Turku PET Centre, University of Turku, Turku 20520 (Finland); Department of Medicine, University of Turku, Turku 20520 (Finland); Iozzo, Patricia [Turku PET Centre, University of Turku, Turku 20520 (Finland) and PET Centre, Institute of Clinical Physiology, CNR National Research Council, 56100 Pisa (Italy)]. E-mail: patricia.iozzo@ifc.cnr.it

    2006-05-15

    Purpose: The liver is fundamental in regulating lipid metabolism, and it supplies fatty acids (FA) to the rest of the body in the form of triglycerides (TG); the time-related relevance of this process is incompletely defined. The aim of the study was to investigate the appearance of labeled TG in the hepatic vascular bed after [{sup 11}C]palmitate injection during fasting and insulin stimulation. Methods: Plasma [{sup 11}C]palmitate kinetics in arterial, portal and hepatic venous lipid fractions was studied in eight anesthetized pigs during fasting or euglycemic hyperinsulinemia. Plasma analyses were conducted at 10 and 40 min after tracer injection. Corresponding liver positron emission tomography (PET) images were acquired for the semiquantitative determination of hepatic FA uptake. Results: At 10 min, plasma levels of unchanged [{sup 11}C]palmitate were lower in hyperinsulinemic than in fasting experiments in the artery and in the portal vein (P{<=}.03), suggesting faster clearance. Levels of unmetabolized [{sup 11}C]palmitate did not differ between portal and arterial plasma. In the fasting state, a tendency to a positive arterial and portal vs. hepatic venous gradient was observed, indicative of net hepatic [{sup 11}C]palmitate extraction. Labeled TG were already detectable at 10 min (fasting vs. hyperinsulinemia, ns) and were higher in fasting than in hyperinsulinemic animals at 40 min (92{+-}1% and 82{+-}6% of arterial plasma radioactivity). Higher proportions of labeled TG were recovered in portal vein plasma, suggesting release by the gut. The portal and the arterial-portal vs. hepatic venous TG gradient tended to be positive. Accordingly, hepatic FA uptake was higher, but declined more rapidly during fasting than during hyperinsulinemia. Conclusion: The study indicates that the redistribution of [{sup 11}C]palmitate between different lipid pools occurs within the short time interval of most PET experiments and is strongly influenced by insulin. Labeled TG

  9. The antibiotic thiostrepton inhibits a functional transition within protein L11 at the ribosomal GTPase centre

    DEFF Research Database (Denmark)

    Porse, B T; Leviev, I; Mankin, A S

    1998-01-01

    A newly identified class of highly thiostrepton-resistant mutants of the archaeon Halobacterium halobium carry a missense mutation at codon 18 within the gene encoding ribosomal protein L11. In the mutant proteins, a proline, conserved in archaea and bacteria, is converted to either serine...... technique, demonstrated that a general tightening of the C-terminal domain occurred on rRNA binding, while thiostrepton produced a footprint centred on tyrosine 62 at the junction of the N and C-terminal domains of protein L11 complexed to rRNA. The intensity of this protein footprint was strongly reduced...

  10. 48 CFR 1846.673 - Distribution of DD Forms 250 and 250c.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Distribution of DD Forms... Reports 1846.673 Distribution of DD Forms 250 and 250c. (a) DD Forms 250 and 250c shall be distributed in accordance with installation procedures. (b) The contractor is responsible for distributing DD Forms 250 and...

  11. New developments of {sup 11}C post-accelerated beams for hadron therapy and imaging

    Energy Technology Data Exchange (ETDEWEB)

    Augusto, R.S., E-mail: r.s.augusto@cern.ch [European Organization for Nuclear Research – CERN, 1211 Geneva 23 (Switzerland); Ludwig Maximilians – University of Munich, Munich (Germany); Mendonca, T.M.; Wenander, F. [European Organization for Nuclear Research – CERN, 1211 Geneva 23 (Switzerland); Penescu, L. [MedAustron GmbH, Wiener Neustadt (Austria); Orecchia, R. [CNAO – Centro Nazionale di Adroterapia Oncologica per il trattamento dei tumori, Pavia (Italy); Parodi, K. [Ludwig Maximilians – University of Munich, Munich (Germany); Ferrari, A.; Stora, T. [European Organization for Nuclear Research – CERN, 1211 Geneva 23 (Switzerland)

    2016-06-01

    Hadron therapy was first proposed in 1946 and is by now widespread throughout the world, as witnessed with the design and construction of the CNAO, HIT, PROSCAN and MedAustron treatment centres, among others. The clinical interest in hadron therapy lies in the fact that it delivers precision treatment of tumours, exploiting the characteristic shape (the Bragg peak) of the energy deposition in the tissues for charged hadrons. In particular, carbon ion therapy is found to be biologically more effective, with respect to protons, on certain types of tumours. Following an approach tested at NIRS in Japan [1], carbon ion therapy treatments based on {sup 12}C could be combined or fully replaced with {sup 11}C PET radioactive ions post-accelerated to the same energy. This approach allows providing a beam for treatment and, at the same time, to collect information on the 3D distributions of the implanted ions by PET imaging. The production of {sup 11}C ion beams can be performed using two methods. A first one is based on the production using compact PET cyclotrons with 10–20 MeV protons via {sup 14}N(p,α){sup 11}C reactions following an approach developed at the Lawrence Berkeley National Laboratory [2]. A second route exploits spallation reactions {sup 19}F(p,X){sup 11}C and {sup 23}Na(p,X){sup 11}C on a molten fluoride salt target using the ISOL (isotope separation on-line) technique [3]. This approach can be seriously envisaged at CERN-ISOLDE following recent progresses made on {sup 11}C{sup +} production [4] and proven post-acceleration of pure {sup 10}C{sup 3/6+} beams in the REX-ISOLDE linac [5]. Part of the required components is operational in radioactive ion beam facilities or commercial medical PET cyclotrons. The driver could be a 70 MeV, 1.2 mA proton commercial cyclotron, which would lead to 8.1 × 10{sup 711}C{sup 6+} per spill. This intensity is appropriate using {sup 11}C ions alone for both imaging and treatment. Here we report on the ongoing feasibility

  12. Positron emission tomography with [11C]-acetate for evaluation of myocardial oxidative metabolism. Clinical use

    International Nuclear Information System (INIS)

    Litvinova, I.S.; Litvinov, M.M.; Rozhkova, G.G.; Leont'eva, I.V.; Sebeleva, I.A.; Tumanyan, M.R.; Koledinskij, D.G.; Sukhorukov, V.S.

    2001-01-01

    The diagnostic potentials of positron emission tomography (PET) with [ 11 C]-acetate as applied to mitochondrial disorders in children with cardiomyopathies (CMP) are evaluated. PET examinations are performed in 17 patients of the mean age of 7.5 ± 3.1 years with CMP. A dynamic study with [ 11 C]-acetate is conducted to evaluate the Krebs cycle activity. The experiments have indicated to a fewer accumulation of [ 11 C]-acetate and to its slower clearance in the ischemic zone as compared with the normal myocardium. The Krebs cycle activity has been reduced. By means of PET with [ 11 C]-acetate the oxidation rate constant of the Krebs cycle and the [ 11 C]-acetate-activity clearance half-time can be quantified. This makes possible to assess the extent of oxidative metabolism malfunction, including the case of perfusion reduction [ru

  13. Synthesis and positron emission tomography studies of C-11-labeled isotopomers and metabolites of GTS-21, a partial {alpha}7 nicotinic cholinergic agonist drug

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sung Won [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States) and Department of Chemistry, State University of New York at Stony Brook, Stony Brook, NY 11794-3400 (United States)]. E-mail: swkim@bnl.gov; Ding Yushin [Department of Chemistry, State University of New York at Stony Brook, Stony Brook, NY 11794-3400 (United States); Department of Radiology, Yale University School of Medicine, New Haven, CT 06520-8048 (United States); Alexoff, David [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Patel, Vinal [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Logan, Jean [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Lin, K.-S. [Department of Radiology, University of Pittsburgh, Pittsburgh, PA 15213 (United States); Shea, Colleen [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Muench, Lisa [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Xu Youwen [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Carter, Pauline [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); King, Payton [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Constanzo, Jasmine R. [Department of Chemistry, Fordham University, Bronx, NY 10458 (United States); Ciaccio, James A. [Department of Chemistry, Fordham University, Bronx, NY 10458 (United States); Fowler, Joanna S. [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Department of Chemistry, State University of New York at Stony Brook, Stony Brook, NY 11794-3400 (United States); Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10029 (United States)

    2007-07-15

    Introduction: (3E)-3-[(2,4-dimethoxyphenyl)methylene]-3,4,5,6-tetrahydro-2,3'-bipyridine (GTS-21), a partial {alpha}7 nicotinic acetylcholine receptor agonist drug, has recently been shown to improve cognition in schizophrenia and Alzheimer's disease. One of its two major demethylated metabolites, 4-OH-GTS-21, has been suggested to contribute to its therapeutic effects. Methods: We labeled GTS-21 in two different positions with carbon-11 ([2-methoxy-{sup 11}C]GTS-21 and [4-{sup 11}C]GTS-21) along with two corresponding demethylated metabolites ([2-methoxy-{sup 11}C]4-OH-GTS-21 and [4-methoxy-{sup 11}C]2-OH-GTS-21) for pharmacokinetic studies in baboons and mice with positron emission tomography (PET). Results: Both [2-{sup 11}C]GTS-21 and [4-methoxy-{sup 11}C]GTS-21 showed similar initial high rapid uptake in baboon brain, peaking from 1 to 3.5 min (0.027-0.038%ID/cc) followed by rapid clearance (t {sub 1/2}<15 min), resulting in low brain retention by 30 min. However, after 30 min, [2-methoxy-{sup 11}C]GTS-21 continued to clear while [4-methoxy-{sup 11}C]GTS-21 plateaued, suggesting the entry of a labeled metabolite into the brain. Comparison of the pharmacokinetics of the two labeled metabolites confirmed expected higher brain uptake and retention of [4-methoxy-{sup 11}C]2-OH-GTS-21 (the labeled metabolite of [4-methoxy-{sup 11}C]GTS-21) relative to [2-methoxy-{sup 11}C]4-OH-GTS-21 (the labeled metabolite of [2-methoxy-{sup 11}C]GTS-21), which had negligible brain uptake. Ex vivo studies in mice showed that GTS-21 is the major chemical form in the mouse brain. Whole-body dynamic PET imaging in baboon and mouse showed that the major route of excretion of C-11 is through the gallbladder. Conclusions: The major findings are as follows: (a) extremely rapid uptake and clearance of [2-methoxy-{sup 11}C]GTS-21 from the brain, which may need to be considered in developing optimal dosing of GTS-21 for patients, and (b) significant brain uptake of 2-OH-GTS-21

  14. Pharmacological evaluation of [11c]donepezil as tracer for visualization of acetylcholinesterase by PET

    International Nuclear Information System (INIS)

    Vos, F. de; Santens, P.; Vermeirsch, H.; Dewolf, I.; Dumont, F.; Slegers, G.; Dierckx, R.A.; Reuck, J. de

    2000-01-01

    Donepezil is a highly potent and selective reversible acetylcholinesterase inhibitor. [ 11 C]Donepezil is prepared by methylation with [ 11 C]CH 3 I of the corresponding 6'-O-desmethylprecursor. Tissue distribution in mice revealed a high uptake in brain and rapid clearance from the blood. Metabolization studies in mice indicated the formation of one 11 C-labeled polar metabolite that didn't penetrate the blood-brain barrier. Regional brain distribution in rabbits didn't reflect the measured achetylcholinesterase distribution in rabbit brain

  15. Visualizing pancreatic {beta}-cell mass with [{sup 11}C]DTBZ

    Energy Technology Data Exchange (ETDEWEB)

    Simpson, Norman Ray [Department of Radiology, Columbia University Medical School, New York, NY 10032 (United States); Souza, Fabiola [Department of Surgery, Columbia University Medical School, New York, NY 10032 (United States); Witkowski, Piotr [Department of Medicine, Columbia University Medical School, New York, NY 10032 (United States); Maffei, Antonella [Institute of Genetics and Biophysics ' Adriano Buzzati-Traverso' , CNR, Naples 80131 (Italy); Raffo, Anthony [Department of Surgery, Columbia University Medical School, New York, NY 10032 (United States); Herron, Alan [Center for Comparative Medicine and The Department of Pathology, Baylor College of Medicine, Houston, TX 77030 (United States); Kilbourn, Michael [Department of Radiology, University of Michigan, Ann Arbor, MI 48109-0638 (United States); Jurewicz, Agata [Department of Radiology, Columbia University Medical School, New York, NY 10032 (United States); Herold, Kevan [Department of Surgery, Columbia University Medical School, New York, NY 10032 (United States); Liu, Eric [Diabetes Branch, NIDDK, National Institutes of Health, Bethesda, MD 20854 (United States); Hardy, Mark Adam [Department of Medicine, Columbia University Medical School, New York, NY 10032 (United States); Van Heertum, Ronald [Department of Radiology, Columbia University Medical School, New York, NY 10032 (United States); Harris, Paul Emerson [Department of Surgery, Columbia University Medical School, New York, NY 10032 (United States)]. E-mail: peh1@columbia.edu

    2006-10-15

    {beta}-Cell mass (BCM) influences the total amount of insulin secreted, varies by individual and by the degree of insulin resistance, and is affected by physiologic and pathologic conditions. The islets of Langerhans, however, appear to have a reserve capacity of insulin secretion and, overall, assessments of insulin and blood glucose levels remain poor measures of BCM, {beta}-cell function and progression of diabetes. Thus, novel noninvasive determinations of BCM are needed to provide a quantitative endpoint for novel therapies of diabetes, islet regeneration and transplantation. Built on previous gene expression studies, we tested the hypothesis that the targeting of vesicular monoamine transporter 2 (VMAT2), which is expressed by {beta} cells, with [{sup 11}C]dihydrotetrabenazine ([{sup 11}C]DTBZ), a radioligand specific for VMAT2, and the use of positron emission tomography (PET) can provide a measure of BCM. In this report, we demonstrate decreased radioligand uptake within the pancreas of Lewis rats with streptozotocin-induced diabetes relative to their euglycemic historical controls. These studies suggest that quantitation of VMAT2 expression in {beta} cells with the use of [{sup 11}C]DTBZ and PET represents a method for noninvasive longitudinal estimates of changes in BCM that may be useful in the study and treatment of diabetes.

  16. 40 CFR 721.10143 - Amines, bis (C11-14-branched and linear alkyl).

    Science.gov (United States)

    2010-07-01

    ... linear alkyl). 721.10143 Section 721.10143 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.10143 Amines, bis (C11-14-branched and linear alkyl). (a) Chemical..., bis (C11-14-branched and linear alkyl) (PMN P-06-733; CAS No. 900169-60-0) is subject to reporting...

  17. Effects of Processing Parameters on the Forming Quality of C-Shaped Thermosetting Composite Laminates in Hot Diaphragm Forming Process

    Science.gov (United States)

    Bian, X. X.; Gu, Y. Z.; Sun, J.; Li, M.; Liu, W. P.; Zhang, Z. G.

    2013-10-01

    In this study, the effects of processing temperature and vacuum applying rate on the forming quality of C-shaped carbon fiber reinforced epoxy resin matrix composite laminates during hot diaphragm forming process were investigated. C-shaped prepreg preforms were produced using a home-made hot diaphragm forming equipment. The thickness variations of the preforms and the manufacturing defects after diaphragm forming process, including fiber wrinkling and voids, were evaluated to understand the forming mechanism. Furthermore, both interlaminar slipping friction and compaction behavior of the prepreg stacks were experimentally analyzed for showing the importance of the processing parameters. In addition, autoclave processing was used to cure the C-shaped preforms to investigate the changes of the defects before and after cure process. The results show that the C-shaped prepreg preforms with good forming quality can be achieved through increasing processing temperature and reducing vacuum applying rate, which obviously promote prepreg interlaminar slipping process. The process temperature and forming rate in hot diaphragm forming process strongly influence prepreg interply frictional force, and the maximum interlaminar frictional force can be taken as a key parameter for processing parameter optimization. Autoclave process is effective in eliminating voids in the preforms and can alleviate fiber wrinkles to a certain extent.

  18. Effect of TiC addition on surface oxidation behavior of SKD11 tool steel composites

    Science.gov (United States)

    Cho, Seungchan; Jo, Ilguk; Kim, Heebong; Kwon, Hyuk-Tae; Lee, Sang-Kwan; Lee, Sang-Bok

    2017-09-01

    Titanium carbide (TiC) reinforced tool steel matrix composites were successfully fabricated by a liquid pressing infiltration process and research was subsequently conducted to investigate the composites' oxidation resistance. The mass gain of the tested TiC-SKD11 composite held at 700 °C for 50 h in an air environment decreased by about 60%, versus that of the SKD11, which indicates improved oxidation resistance. Improved oxidation resistance of the TiC-SKD11 composite originates from uniformly reinforced TiC, with a phase transition to thermodynamically stable, volume-expanded TiO2.

  19. Radiosynthesis and ex vivo evaluation of (R)-(-)-2-chloro-N-[1-11C-propyl]n-propylnorapomorphine

    DEFF Research Database (Denmark)

    Palner, Mikael; McCormick, Patrick; Gillings, Nicolas

    2010-01-01

    Several dopamine D(2) agonist radioligands have been used with positron emission tomography (PET), including [(11)C-]-(-)-MNPA, [(11)C-]-(-)-NPA and [(11)C]-(+)-PHNO. These radioligands are considered particularly powerful for detection of endogenous dopamine release, but they either provide PET ...

  20. Sympathetic nerve damage and restoration after ischemia-reperfusion injury as assessed by {sup 11}C-hydroxyephedrine

    Energy Technology Data Exchange (ETDEWEB)

    Werner, Rudolf A.; Higuchi, Takahiro [University of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); University of Wuerzburg, Comprehensive Heart Failure Center, Wuerzburg (Germany); Maya, Yoshifumi [University of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); Nihon Medi-Physics Co., Ltd., Research Centre, Chiba (Japan); Rischpler, Christoph [Technische Universitaet Muenchen, Department of Nuclear Medicine, Klinikum rechts der Isar, Muenchen (Germany); Javadi, Mehrbod S. [Johns Hopkins University, Division of Nuclear Medicine, Russell H. Morgan Department of Radiology, Baltimore, MD (United States); Fukushima, Kazuhito [Hyogo College of Medicine, Department of Radiology, Hyogo (Japan); Lapa, Constantin [University of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); Herrmann, Ken [University of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); David Geffen School of Medicine at UCLA, Department of Molecular and Medical Pharmacology, Los Angeles, CA (United States)

    2016-02-15

    An altered state of the cardiac sympathetic nerves is an important prognostic factor in patients with coronary artery disease. The aim of this study was to investigate regional sympathetic nerve damage and restoration utilizing a rat model of myocardial transient ischemia and a catecholamine analog PET tracer, {sup 11}C-hydroxyephedrine ({sup 11}C-HED). Transient myocardial ischemia was induced by coronary occlusion for 20 min and reperfusion in male Wistar rats. Dual-tracer autoradiography was performed subacutely (7 days) and chronically (2 months) after ischemia, and in control rats without ischemia using {sup 11}C-HED as a marker of sympathetic innervation and {sup 201}TI for perfusion. Additional serial in vivo cardiac {sup 11}C-HED and {sup 18}F-FDG PET scans were performed in the subacute and chronic phases after ischemia. After transient ischemia, the {sup 11}C-HED uptake defect areas in both the subacute and chronic phases were clearly larger than the perfusion defect areas in the midventricular wall. The subacute {sup 11}C-HED uptake defect showed a transmural pattern, whereas uptake recovered in the subepicardial portion in the chronic phase. Tyrosine hydroxylase antibody nerve staining confirmed regional denervation corresponding to areas of decreased {sup 11}C-HED uptake. Serial in vivo PET imaging visualized reductions in the area of the {sup 11}C-HED uptake defects in the chronic phase consistent with autoradiography and histology. Higher susceptibility of sympathetic neurons compared to myocytes was confirmed by a larger {sup 11}C-HED defect with a corresponding histologically identified region of denervation. Furthermore, partial reinnervation was observed in the chronic phase as shown by recovery of subepicardial {sup 11}C-HED uptake. (orig.)

  1. In vivo binding of [11C]nemonapride to sigma receptors in the cortex and cerebellum.

    Science.gov (United States)

    Ishiwata, K; Senda, M

    1999-08-01

    Radiolabeled nemonapride (NEM, YM-09151-2) is widely used as a representative dopamine D2-like receptor ligand in pharmacological and neurological studies, and 11C-labeled analog ([11C]NEM) has been developed for positron emission tomography (PET) studies. The aim of this study was to evaluate whether [11C]NEM binds in vivo to sigma receptors. [11C]NEM and one of six dopamine D2-like receptor ligands or seven sigma receptor ligands were co-injected into mice, and the regional brain uptake of [11C]NEM was measured by a tissue dissection method. The striatal uptake of [11C]NEM was reduced by D2-like receptor ligands, NEM, haloperidol, (+)-butaclamol, raclopride, and sulpiride, but not by a D4 receptor ligand clozapine. In the cortex and cerebellum the uptake was also reduced by D2-like receptor ligands with affinity for sigma receptors, but not by raclopride. Although none of seven sigma receptor ligands, SA6298, N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]ethylamine hydrochloride (NE-100), (+)-pentazocine, R(-)-N-(3-phenyl-1-propyl)-1-phenyl-2-aminopropane hydrochloride ([-]-PPAP), (-)-pentazocine, R(+)-3-(3-hydroxyphenyl)-N-propylpiperidine hydrochloride ([+]-3-PPP), and (+)-N-allylnormetazocine hydrochloride ([+]-SKF 10047), blocked the striatal uptake, five of them with relatively higher affinity significantly reduced the [11C]NEM uptake by the cortex, and four of them reduced that by the cerebellum. We concluded that [11C]NEM binds in vivo not only to dopamine D2-like receptors in the striatum but also to sigma receptors in other regions such as cortex and cerebellum.

  2. In vivo binding of [11C]nemonapride to sigma receptors in the cortex and cerebellum

    International Nuclear Information System (INIS)

    Ishiwata, Kiichi; Senda, Michio

    1999-01-01

    Radiolabeled nemonapride (NEM, YM-09151-2) is widely used as a representative dopamine D 2 -like receptor ligand in pharmacological and neurological studies, and 11 C-labeled analog ([ 11 C]NEM) has been developed for positron emission tomography (PET) studies. The aim of this study was to evaluate whether [ 11 C]NEM binds in vivo to sigma receptors. [ 11 C]NEM and one of six dopamine D 2 -like receptor ligands or seven sigma receptor ligands were co-injected into mice, and the regional brain uptake of [ 11 C]NEM was measured by a tissue dissection method. The striatal uptake of [ 11 C]NEM was reduced by D 2 -like receptor ligands, NEM, haloperidol, (+)-butaclamol, raclopride, and sulpiride, but not by a D 4 receptor ligand clozapine. In the cortex and cerebellum the uptake was also reduced by D 2 -like receptor ligands with affinity for sigma receptors, but not by raclopride. Although none of seven sigma receptor ligands, SA6298, N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]ethylamine hydrochloride (NE-100), (+)-pentazocine, R(-)-N-(3-phenyl-1-propyl)-1-phenyl-2-aminopropane hydrochloride ([-]-PPAP), (-)-pentazocine, R(+)-3-(3-hydroxyphenyl)-N-propylpiperidine hydrochloride ([+]-3-PPP), and (+)-N-allylnormetazocine hydrochloride ([+]-SKF 10047), blocked the striatal uptake, five of them with relatively higher affinity significantly reduced the [ 11 C]NEM uptake by the cortex, and four of them reduced that by the cerebellum. We concluded that [ 11 C]NEM binds in vivo not only to dopamine D 2 -like receptors in the striatum but also to sigma receptors in other regions such as cortex and cerebellum

  3. [{sup 14}C]Serotonin uptake and [O-methyl-{sup 11}C]venlafaxine kinetics in porcine brain

    Energy Technology Data Exchange (ETDEWEB)

    Smith, D.F. E-mail: dfsmith@inet.uni2.dk; Hansen, S.B.; Oestergaard, L.; Gee, A.D.; Danielsen, E.; Ishizu, K.; Bender, D.; Poulsen, P.H.; Gjedde, A

    2001-08-01

    As part of our program of developing PET tracers for neuroimaging of psychotropic compounds, venlafaxine, an antidepressant drug, was evaluated. First, we measured in vitro rates of serotonin uptake in synaptosomes prepared from selected regions of porcine brain. Then, we determined the pharmacokinetics of venlafaxine, [O-methyl-{sup 11}C]-labeled for PET. Synaptosomal studies showed that the active uptake of [{sup 14}C]5-HT differed markedly between brain regions, with highest rates in hypothalamus, raphe region, and thalamus, and lowest rates in cortex and cerebellum. PET studies showed that the unidirectional rate of uptake of [O-methyl-{sup 11}C]venlafaxine from blood to brain was highest in the hypothalamus, raphe region, thalamus and basal ganglia and lowest in the cortex and cerebellum. Under normal physiological conditions, the capillary permeability-surface area (PS) product for [O-methyl-{sup 11}C]venlafaxine could not be estimated, because of complete flow-limitation of the cerebral uptake. Nevertheless, a correlation occurred between the apparent partition volume of the radiotracer and the rate of active uptake of 5-HT in selected regions of the porcine brain. During hypercapnia, limitations of blood-brain transfer were observed, giving PS-products for water that were only ca. 50% higher than those of venlafaxine. Thus, under normal physiological conditions, the rate of uptake of venlafaxine from blood into brain is completely flow-limited.

  4. Kinetic Modelling of Infection Tracers [18F]FDG, [68Ga]Ga-Citrate, [11C]Methionine, and [11C]Donepezil in a Porcine Osteomyelitis Model

    DEFF Research Database (Denmark)

    Jødal, Lars; Jensen, Svend Borup; Nielsen, Ole Lerberg

    2017-01-01

    Introduction. Positron emission tomography (PET) is increasingly applied for infection imaging using [18F]FDG as tracer, but uptake is unspecific. The present study compares the kinetics of [18F]FDG and three other PET tracers with relevance for infection imaging. Methods. A juvenile porcine...... osteomyelitis model was used. Eleven pigs underwent PET/CT with 60-minute dynamic PET imaging of [18F]FDG, [68Ga]Ga-citrate, [11C]methionine, and/or [11C]donepezil, along with blood sampling. For infectious lesions, kinetic modelling with one- and two-tissue-compartment models was conducted for each tracer...... for the analysis. Conclusions. The kinetics of the four studied tracers in infection was characterized. For clinical applications, [18F]FDG remains the first-choice PET tracer. [11C]methionine may have a potential for detecting soft tissue infections. [68Ga]Ga-citrate and [11C]donepezil were not found useful...

  5. Synthesis of N-[methyl-11C]hydromorphone by using multivariate strategies for optimization of radiochemical yields

    International Nuclear Information System (INIS)

    Rimland, Annika; Bergson, Goeran; Obenius, Ulf; Sjoeberg, Stefan; Langstroem, Bengt

    1987-01-01

    The synthesis of N-[methyl- 11 C]hydromorphone has been performed by using [ 11 C]methyl iodide and desmethyl hydromorphone in a mixture of dimethylsulphoxide and dimethylformamide as solvent. Optimization of the radiochemical yield by varying the reaction conditions was performed by using multivariate strategies. The labelled hydromorphone was obtained in 72% radiochemical yield in the alkylation reaction with [ 11 C]-methyl iodide, counted from the end of the [ 11 C]methyl iodide synthesis. N-[Methyl- 11 C]hydromorphone was obtained as a ready injectable pharmaceutical solution with a total synthesis time of 40 min and in a 10% total radiochemical yield, with a radiochemical purity > 99.5%, according to HPLC analysis. (author)

  6. C-11 Acid and the Stereochemistry of Abietic Acid

    Indian Academy of Sciences (India)

    IAS Admin

    While many features, like the phenanthrene-type of fusion of the three ... thought to contain the original ring A of abietic acid, retaining the. 'nuclear methyl .... Thinking that the anhydride he had obtained by the action of heat on the C-11 acid ...

  7. The synthesis of 1-11C-labelled ethyl, propyl, butyl and isobutyl iodides and examples of alkylation reactions

    International Nuclear Information System (INIS)

    Laangstroem, B.; Antoni, G.; Gullberg, P.; Halldin, C.; Naagren, K.; Rimland, A.; Svaerd, H.

    1986-01-01

    New 11 C-labelled precursors [1- 11 C]ethyl,[1- 11 C]propyl, [1- 11 C]butyl, and [1- 11 C]isobutyl iodides have been prepared by a 3-step reaction route using a one-pot system. The labelled iodides were obtained in 20-55#percent# radiochemical yields and 65-95#percent# radiochemical purities, with a total time for synthesis of the order of 10-14 min. The labelled iodides have been used in alkylation reactions with nitrogen, oxygen and carbon nucleophiles. The nitrogen alkylation reactions are exemplified by the synthesis of the analgetics N-[1- 11 C-ethyl]iodocaine and N-[1- 11 C-butyl] bupivacaine. The synthesis of 3-nitrophenyl[1- 11 C]propyl ether is also presented in this paper as an example of an oxygen alkylation. (author)

  8. Comparison of dosimetry between PET/CT and PET alone using 11C-ITMM

    International Nuclear Information System (INIS)

    Ito, Kimiteru; Sakata, Muneyuki; Wagarsuma, Kei; Toyohara, Jun; Ishibashi, Kenji; Ishii, Kenji; Ishiwata, Kiichi; Oda, Keiichi

    2016-01-01

    We used a new tracer, N-[4-[6-(isopropylamino) pyrimidin-4-yl]-1,3-thiazol-2-yl]-4- 11 C-methoxy-N-methylbenzamide ( 11 C-ITMM), to compare radiation doses from positron emission tomography (PET)/computed tomography (CT) with previously published doses from PET alone. Twelve healthy volunteers [six males (mean age ± SD, 27.7 ± 6.7 years) and six females (31.8 ± 14.5 years)] in 12 examinations were recruited. Dose estimations from PET/CT were compared with those from PET alone. Regions of interest (ROIs) in PET/CT were delineated on the basis of low-dose CT (LD-CT) images acquired during PET/CT. Internal and external radiation doses were estimated using OLINDA/EXM 1.0 and CT-Expo software. The effective dose (ED) for 11 C-ITMM calculated from PET/CT was estimated to be 4.7 ± 0.5 μSv/MBq for the male subjects and 4.1 ± 0.7 μSv/MBq for the female subjects. The mean ED for 11 C-ITMM calculated from PET alone in a previous report was estimated to be 4.6 ± 0.3 μSv/MBq (males, n = 3). The ED values for 11 C-ITMM calculated from PET/CT in the male subjects were almost identical to those from PET alone. The absorbed doses (ADs) of the gallbladder, stomach, red bone marrow, and spleen calculated from PET/CT were significantly different from those calculated from PET alone. The EDs of 11 C-ITMM calculated from PET/CT were almost identical to those calculated from PET alone. The ADs in several organs calculated from PET/CT differed from those from PET alone. LD-CT images acquired during PET/CT may facilitate organ identification.

  9. [11C]diclofenac sodium: synthesis and PET assessment of transdermal penetration

    International Nuclear Information System (INIS)

    Petroni, Debora; Menichetti, Luca; Sorace, Oreste; Poli, Michela; Vanasia, Massimo; Salvadori, Piero A.

    2011-01-01

    The aim of this work was to study the feasibility of using Positron Emission Tomography (PET) imaging as a new tool to detect transdermal penetration of topical drugs in human subjects. The compound used in the study is sodium 2-[(2,6-dichlorophenyl)amino]phenyl]acetate, better known as diclofenac sodium. This molecule belongs to the family of non-steroidal anti-inflammatory drugs and is considered one of the first choices among non-steroidal anti-inflammatory drugs for the treatment of inflammatory diseases; it is widely used and commercially present in a large number of pharmaceutical forms and formulations. 11 C-labeled diclofenac has been synthesized and coformulated, as an internal indicator, with a proprietary preparation based on the use of a sprayer. The radiolabeled preparation was topically administered to healthy volunteers, and PET imaging was used to evaluate transdermal penetration. Results obtained have demonstrated the efficacy of PET and radiolabeled tracers for the evaluation of transdermal penetration of active pharmaceutical ingredients as topical formulations.

  10. Positron Emission Tomographic Imaging of the Cannabinoid Type 1 Receptor System with [11C]OMAR ([11C]JHU75528: Improvements in Image Quantification Using Wild-Type and Knockout Mice

    Directory of Open Access Journals (Sweden)

    Raúl Herance

    2011-11-01

    Full Text Available In this study, we assessed the feasibility of using positron emission tomography (PET and the tracer [11C]OMAR ([11C]JHU75528, an analogue of rimonabant, to study the brain cannabinoid type 1 (CB1 receptor system. Wild-type (WT andCB1 knockout (KO animals were imaged at baseline and after pretreatment with blocking doses of rimonabant. Brain uptake in WT animals was higher (50% than in KO animals in baseline conditions. After pretreatment with rimonabant, WT uptake lowered to the level of KO animals. The results of this study support the feasibility of using PET with the radiotracer [11C]JHU75528 to image the brain CB1 receptor system in mice. In addition, this methodology can be used to assess the effect of new drugs in preclinical studies using genetically manipulated animals.

  11. Normal Uptake of 11C-Acetate in Pancreas, Liver, Spleen, and Suprarenal Gland in PET

    Directory of Open Access Journals (Sweden)

    Bogdan Malkowski

    2017-01-01

    Full Text Available Purpose. C11-Acetate is radiotracer being considered an alternative to 18F-fluorodeoxyglucose. Evaluation of C11-acetate biodistribution in human parenchymal organs is described. Methods and Materials. 60 consecutive patients referred to C11-acetate PET CT suspected of renal or prostate cancer relapse with negative results (no recurrent tumor were included in the study. Acquisition from the base of skull to upper thigh was made 20 min after i.v. injection of 720 MBq of C11-acetate. The distribution was evaluated by measuring the uptake in pancreas (uncinate process and body separately, liver, spleen, and left suprarenal gland. Clinical data of included patients showed no abnormalities in these organs. Results. Biodistributions of C11-acetate radiotracer were compared in different organs. Standardized uptake values of 11C-acetate were significantly higher in pancreatic parenchyma (SUV mean 6,4 than in liver (SUV mean 3,3, spleen (SUV mean 4,5, or suprarenal gland (SUV mean 2,7 tissues. No significant difference was found between pancreatic head (SUV mean 6,4 and body (SUV mean 5,9 uptake. In case of all aforementioned organs, there were no differences either between both sexes or between formerly diagnosed tumors (renal and prostate. Conclusions. Evaluation of C11-acetate uptake differences in parenchymal organs will allow establishing normal patterns of distribution. High pancreatic uptake may be used in quantitative assessment of organ function in diffuse nonneoplastic pathology.

  12. The 11C-radioisotopic study of methanol conversion on V-MCM-41; the influence of methyl iodide on the transformation

    International Nuclear Information System (INIS)

    Sarkadi-Priboczki, E.; Szelecsenyi, F.; Kovacs, Z.; Solmaz, A.; Balci, S.; Dogu, T.

    2007-01-01

    Complete text of publication follows. The MCM-41 mesoporous material has Lewis and even Bronsted acid sites to produce dimethyl ether with some hydrocarbons, while over metal modified MCM-41 mostly formaldehyde and dimethoxy methane (i.e. methylal) or methyl formate are produced. In present experiments V incorporated basically mild acid sites of MCM-41 was prepared by low temperature direct synthesis. The V-MCM-41 has enough main active Lewis sites (by V-) to form formaldehyde and also light Bronsted acid sites to let the adsorbed formaldehyde eliminate and afterwards, with methanol, to form dimethoxy methane in nonoxidative environment. This V-MCM-41 has been tested by ethanol conversion in non-oxidative environments too and diethoxy methane as main product was detected. In present work the methanol conversion, as well as the methanol co-reaction with methyl iodide are studied from the same V-MCM-41 sample using 11 C-technique. The 11 C-labelled radioactive methanol has been already applied for determination of methanol conversion rates on Cu-modified MCM-41. The V-MCM-41 was prepared by direct hydrothermal synthesis method. The adsorption rate of 11 C-methanol and, after the reaction, the desorption rate of the remaining 11 C-derivatives on catalyst were continuously detected by gamma detectors. The derivatives were analyzed by radio-gas chromatography (gas chromatograph with FID coupled on-line with a radioactivity detector). Both dimethyl ether and hydrocarbon formation are also in slight degrees according to weak Lewis and Bronsted acidities. Since the conversion was carried out without added oxygen gas, only the frame oxygen can take part into catalysis. In presence of non-radioactive methyl iodide, the radioactive methanol is converted to radioactive methyl iodide on V-MCM-41. The radio-GC analysis confirmed that the iodide induced change of the reaction performance was reversible i.e. the radioactive methyl iodide was regenerated to non-radioactive methyl

  13. Synthesis of 1-/sup 11/C-labelled ethyl, propyl, butyl and isobutyl iodides and examples of alkylation reactions

    Energy Technology Data Exchange (ETDEWEB)

    Laangstroem, B.; Antoni, G.; Gullberg, P.; Halldin, C.; Naagren, K.; Rimland, A.; Svaerd, H.

    1986-01-01

    New /sup 11/C-labelled precursors (1-/sup 11/C)ethyl,(1-/sup 11/C)propyl, (1-/sup 11/C)butyl, and (1-/sup 11/C)isobutyl iodides have been prepared by a 3-step reaction route using a one-pot system. The labelled iodides were obtained in 20-55% radiochemical yields and 65-95% radiochemical purities, with a total time for synthesis of the order of 10-14 min. The labelled iodides have been used in alkylation reactions with nitrogen, oxygen and carbon nucleophiles. The nitrogen alkylation reactions are exemplified by the synthesis of the analgetics N-(1-/sup 11/C-ethyl)iodocaine and N-(1-/sup 11/C-butyl) bupivacaine. The synthesis of 3-nitrophenyl(1-/sup 11/C)propyl ether is also presented in this paper as an example of an oxygen alkylation.

  14. Cholinergic PET imaging in infections and inflammation using 11C-donepezil and 18F-FEOBV

    DEFF Research Database (Denmark)

    Jørgensen, Nis Pedersen; Alstrup, Aage Kristian Olsen; Mortensen, Frank Viborg

    2017-01-01

    with Staphylococcus aureus, and PET scanned at 24, 72, 120, and 144 h post-inoculation. Four pigs with post-operative abscesses were also imaged. Finally, we present initial data from human patients with infections, inflammation, and renal and lung cancer. Results In mice, the FDG uptake in abscesses peaked at 24 h...... and remained stable. The 11C-donepezil and 18F-FEOBV uptake displayed progressive increase, and at 120–144 h was nearly at the FDG level. Moderate 11C-donepezil and slightly lower 18F-FEOBV uptake were seen in pig abscesses. PCR analyses suggested that the 11C-donepezil signal in inflammatory cells is derived...... from both acetylcholinesterase and sigma-1 receptors. In humans, very high 11C-donepezil uptake was seen in a lobar pneumonia and in peri-tumoral inflammation surrounding a non-small cell lung carcinoma, markedly superseding the 18F-FDG uptake in the inflammation. In a renal clear cell carcinoma no 11C...

  15. Serotonin 2A receptor agonist binding in the human brain with [11C]Cimbi-36

    DEFF Research Database (Denmark)

    Ettrup, Anders; Svarer, Claus; McMahon, Brenda

    2016-01-01

    INTRODUCTION: [(11)C]Cimbi-36 is a recently developed serotonin 2A (5-HT2A) receptor agonist positron emission tomography (PET) radioligand that has been successfully applied for human neuroimaging. Here, we investigate the test-retest variability of cerebral [(11)C]Cimbi-36 PET and compare [(11)C...... test-retest variability in [(11)C]Cimbi-36 binding measures, and another eight were scanned after a bolus plus constant infusion with [(18)F]altanserin. Regional differences in the brain distribution of [(11)C]Cimbi-36 and [(18)F]altanserin were assessed with a correlation of regional binding measures...... and with voxel-based analysis. RESULTS: Test-retest variability of [(11)C]Cimbi-36 non-displaceable binding potential (BPND) was consistently correlation between regional...

  16. Phytoremediation of carbamazepine and its metabolite 10,11-epoxycarbamazepine by C3 and C4 plants.

    Science.gov (United States)

    Ryšlavá, Helena; Pomeislová, Alice; Pšondrová, Šárka; Hýsková, Veronika; Smrček, Stanislav

    2015-12-01

    The anticonvulsant drug carbamazepine is considered as an indicator of sewage water pollution: however, its uptake by plants and effect on metabolism have not been sufficiently documented, let alone its metabolite (10,11-epoxycarbamazepine). In a model system of sterile, hydroponically cultivated Zea mays (as C4 plant) and Helianthus annuus (as C3 plant), the uptake and effect of carbamazepine and 10,11-epoxycarbamazepine were studied in comparison with those of acetaminophen and ibuprofen. Ibuprofen and acetaminophen were effectively extracted from drug-supplemented media by both plants, while the uptake of more hydrophobic carbamazepine was much lower. On the other hand, the carbamazepine metabolite, 10,11-epoxycarbamazepine, was, unlike sunflower, willingly taken up by maize plants (after 96 h 88 % of the initial concentration) and effectively stored in maize tissues. In addition, the effect of the studied pharmaceuticals on the plant metabolism (enzymes of Hatch-Slack cycle, peroxidases) was followed. The activity of bound peroxidases, which could cause xylem vessel lignification and reduction of xenobiotic uptake, was at the level of control plants in maize leaves contrary to sunflower. Therefore, our results indicate that maize has the potential to remove 10,11-epoxycarbamazepine from contaminated soils.

  17. First-principle calculations on the structural and electronic properties of hard C11N4

    International Nuclear Information System (INIS)

    Li, Dongxu; Shi, Jiancheng; Lai, Mengling; Li, Rongkai; Yu, Dongli

    2014-01-01

    A graphite-like C 11 N 4 model was built by stacking graphene and a C 3 N 4 triazine layer and simulated by first principle calculations, which transfers to a diamond-like structure under high pressure. The structural, mechanical, and electronic properties of both materials were calculated. The elastic constants of both materials satisfy the Born-criterion. Furthermore, no imaginary frequencies were observed in phonon calculations. The diamond-like C 11 N 4 is semiconducting and consists of polyhedral and hollow C–N cages. The Vickers hardness of diamond-like C 11 N 4 was calculated to be 58 GPa. The phase transformation from graphite-like to diamond-like C 11 N 4 is proposed to occur at approximately 27.2 GPa based on the pressure-dependent enthalpy

  18. The 12C(n, 2n)11C cross section from threshold to 26.5 MeV.

    Science.gov (United States)

    Yuly, M; Eckert, T; Hartshaw, G; Padalino, S J; Polsin, D N; Russ, M; Simone, A T; Brune, C R; Massey, T N; Parker, C E; Fitzgerald, R; Sangster, T C; Regan, S P

    2018-02-01

    The 12 C(n, 2n) 11 C cross section was measured from just below threshold to 26.5 MeV using the Pelletron accelerator at Ohio University. Monoenergetic neutrons, produced via the 3 H(d,n) 4 He reaction, were allowed to strike targets of polyethylene and graphite. Activation of both targets was measured by counting positron annihilations resulting from the β + decay of 11 C. Annihilation gamma rays were detected, both in coincidence and singly, using back-to-back NaI detectors. The incident neutron flux was determined indirectly via 1 H(n,p) protons elastically scattered from the polyethylene target. Previous measurements fall into upper and lower bands; the results of the present measurement are consistent with the upper band.

  19. CD11c controls herpes simplex virus 1 responses to limit virus replication during primary infection.

    Science.gov (United States)

    Allen, Sariah J; Mott, Kevin R; Chentoufi, Aziz A; BenMohamed, Lbachir; Wechsler, Steven L; Ballantyne, Christie M; Ghiasi, Homayon

    2011-10-01

    CD11c is expressed on the surface of dendritic cells (DCs) and is one of the main markers for identification of DCs. DCs are the effectors of central innate immune responses, but they also affect acquired immune responses to infection. However, how DCs influence the efficacy of adaptive immunity is poorly understood. Here, we show that CD11c(+) DCs negatively orchestrate both adaptive and innate immunity against herpes simplex virus type 1 (HSV-1) ocular infection. The effectiveness and quantity of virus-specific CD8(+) T cell responses are increased in CD11c-deficient animals. In addition, the levels of CD83, CD11b, alpha interferon (IFN-α), and IFN-β, but not IFN-γ, were significantly increased in CD11c-deficient animals. Higher levels of IFN-α, IFN-β, and CD8(+) T cells in the CD11c-deficient mice may have contributed to lower virus replication in the eye and trigeminal ganglia (TG) during the early period of infection than in wild-type mice. However, the absence of CD11c did not influence survival, severity of eye disease, or latency. Our studies provide for the first time evidence that CD11c expression may abrogate the ability to reduce primary virus replication in the eye and TG via higher activities of type 1 interferon and CD8(+) T cell responses.

  20. Shrinkage of Newly Formed Particles in an Urban Environment

    Czech Academy of Sciences Publication Activity Database

    Škrabalová, Lenka; Zíková, Naděžda; Ždímal, Vladimír

    2015-01-01

    Roč. 15, č. 4 (2015), s. 1313-1324 ISSN 1680-8584 R&D Projects: GA ČR GAP209/11/1342 Institutional support: RVO:67985858 Keywords : aerosol dynamics * ultrafine particles * particle shrinkage Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 2.393, year: 2015

  1. Pharmacokinetics of superselective intra-arterial and intravenous [11C]BCNU evaluated by PET

    International Nuclear Information System (INIS)

    Tyler, J.L.; Yamamoto, Y.L.; Diksic, M.; Theron, J.; Villemure, J.G.; Worthington, C.; Evans, A.C.; Feindel, W.

    1986-01-01

    The pharmacokinetics of i.v. and superselective intra-arterial carbon-11 1,3-bis-(2-chloroethyl)-1-nitrosourea ([ 11 C]BCNU) were directly compared for the first time in ten patients with recurrent gliomas using positron emission tomography (PET). Intra-arterial administration of [ 11 C]BCNU achieved concentrations of the drug in the tumor that averaged 50 times higher than with a comparable i.v. dose. These preliminary results suggest that the degree of early metabolic trapping of BCNU in tumor correlates with the clinical response to this chemotherapy

  2. [Principles of nutrition in patients with newly appointed stoma].

    Science.gov (United States)

    Pachocka, Lucyna Małgorzata; Urbanik, Anna

    2016-01-01

    The treatment of intestinal stoma is often a difficult experience for patients and results in numerous problems in the physical, psychological and social aspects. Therefore, post-operative care of the patient with the newly appointed stoma should be taken by therapeutic team consisting of doctors, nurses, physiotherapists, dieticians, psychologists and social workers. Appropriate nutritional education of patients aims to improve their quality of life and to prevent from unpleasant ailments formed after the operation. The specific type of stoma may decide about certain dietary recommendations. The presented work provides a practical dietary recommendations for patients with newly appointed stoma.

  3. Regional brain [(11)C]carfentanil binding following tobacco smoking.

    Science.gov (United States)

    Domino, Edward F; Hirasawa-Fujita, Mika; Ni, Lisong; Guthrie, Sally K; Zubieta, Jon Kar

    2015-06-03

    To determine if overnight tobacco abstinent carriers of the AG or GG (*G) vs. the AA variant of the human mu opioid receptor (OPRM1) A118G polymorphism (rs1799971) differ in [(11)C]carfentanil binding after tobacco smoking. Twenty healthy American male smokers who abstained from tobacco overnight were genotyped and completed positron emission tomography (PET) scans with the mu opioid receptor agonist, [(11)C]carfentanil. They smoked deniconized (denic) and average nicotine (avnic) cigarettes during the PET scans. Smoking avnic cigarette decreased the binding potential (BPND) of [(11)C]carfentanil in the right medial prefrontal cortex (mPfc; 6, 56, 18), left anterior medial prefrontal cortex (amPfc; -2, 46, 44), right ventral striatum (vStr; 16, 3, -10), left insula (Ins; -42, 10, -12), right hippocampus (Hippo; 18, -6, -14) and left cerebellum (Cbl; -10, -88, -34), and increased the BPND in left amygdala (Amy; -20, 0, -22), left putamen (Put; -22, 10, -6) and left nucleus accumbens (NAcc; -10, 12, -8). In the AA allele carriers, avnic cigarette smoking significantly changed the BPND compared to after denic smoking in most brain areas listed above. However in the *G carriers the significant BPND changes were confirmed in only amPfc and vStr. Free mu opioid receptor availability was significantly less in the *G than the AA carriers in the Amy and NAcc. The present study demonstrates that BPND changes induced by avnic smoking in OPRM1 *G carriers were blunted compared to the AA carriers. Also *G smokers had less free mu opioid receptor availability in Amy and NAcc. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Form factors of {eta}{sub c} in light-front quark model

    Energy Technology Data Exchange (ETDEWEB)

    Geng, Chao-Qiang [Chongqing University of Posts and Telecommunications, College of Mathematics and Physics, Chongqing (China); National Center for Theoretical Sciences, Physics Division, Hsinchu (China); National Tsing Hua University, Department of Physics, Hsinchu (China); Lih, Chong-Chung [Shu-Zen College of Medicine and Management, Department of Optometry, Kaohsiung Hsien (China); National Center for Theoretical Sciences, Physics Division, Hsinchu (China); National Tsing Hua University, Department of Physics, Hsinchu (China)

    2013-08-15

    We study the form factors of the {eta}{sub c} meson in the light-front quark model. We explicitly show that the transition form factor of {eta}{sub c} {yields} {gamma}{sup *}{gamma} as a function of the momentum transfer is consistent with the experimental data by the BaBar collaboration, while the decay constant of {eta}{sub c} is found to be f{sub {eta}{sub c}} = 230.5{sup +52.2}{sub -61.0} and 303.6{sup +115.2}{sub -116.4} MeV for {eta}{sub c} {proportional_to} c anti c by using two {eta}{sub c} {yields} {gamma}{gamma} decay widths of 5.3 {+-} 0.5 and 7.2 {+-} 2.1 keV, given by Particle Data Group and Lattice QCD calculation, respectively. (orig.)

  5. Simple automated system for simultaneous production of 11C-labeled tracers by solid supported methylation

    International Nuclear Information System (INIS)

    Quincoces, Gemma; Penuelas, Ivan; Valero, Marta; Serra, Patricia; Collantes, Maria; Marti-Climent, Josep; Arbizu, Javier; Jose Garcia-Velloso, Maria; Angel Richter, Jose

    2006-01-01

    We herein describe a simple setup for the automated simultaneous synthesis of L-[methyl- 11 C]methionine and N-[methyl- 11 C]choline by solid-supported methylation . The setup is extremely simple and easy to adapt to other automated systems and due to its versatility, the method can be utilized for the production of other radiopharmaceuticals requiring a simple [ 11 C]methylation step. Furthermore, it can be used for multiple simultaneous synthesis

  6. [11C]UCB-A, a novel PET tracer for synaptic vesicle protein 2 A

    International Nuclear Information System (INIS)

    Estrada, Sergio; Lubberink, Mark; Thibblin, Alf; Sprycha, Margareta; Buchanan, Tim; Mestdagh, Nathalie; Kenda, Benoit; Mercier, Joel; Provins, Laurent; Gillard, Michel; Tytgat, Dominique; Antoni, Gunnar

    2016-01-01

    Introduction: Development of a selective and specific high affinity PET tracer, [ 11 C]UCB-A, for the in vivo study of SV2A expression in humans. Radiochemistry and preclinical studies in rats and pigs including development of a tracer kinetic model to determine V T . A method for the measurement of percent intact tracer in plasma was developed and the radiation dosimetry was determined in rats. Results: 3–5 GBq of [ 11 C]UCB-A could be produced with radiochemical purity exceeding 98% with a specific radioactivity of around 65 GBq/μmol. In vitro binding showed high selective binding towards SV2A. [ 11 C]UCB-A displayed a dose-dependent and reversible binding to SV2A as measured with PET in rats and pigs and the V T could be determined by Logan analysis. The dosimetry was favorable and low enough to allow multiple administrations of [ 11 C]UCB-A to healthy volunteers, and the metabolite analysis showed no sign of labeled metabolites in brain. Conclusions: We have developed the novel PET tracer, [ 11 C]UCB-A, that can be used to measure SV2A expression in vivo. The dosimetry allows up to 5 administrations of 400 MBq of [ 11 C]UCB-A in humans. Apart from measuring drug occupancy, as we have shown, the tracer can potentially be used to compare SV2A expression between individuals because of the rather narrow range of baseline V T values. This will have to be further validated in human studies.

  7. In vivo detection of central dopaminergic processes: studies with 1-C-11-dopa and C-11-labelled N-alkylated ADTN derivatives

    International Nuclear Information System (INIS)

    Werf, J.F. van der; Molen, H.D. Beerling-Van der; Paans, A.M.J.; Wiegman, T.; Korf, J.; Vaalburg, W.

    1982-01-01

    N-alkyl derivatives of 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydro-naphthalene were labelled with 11 C by methylation with methyl iodide. They are dopamine agonists and have been found to bind, with high affinity, to dopamine receptors, in vitro and in vivo, after intracerebral administration. These compounds can pass the blood-brain barrier while the non-alkyl compound (ADTN) cannot. (U.K.)

  8. Characterization of A-11, a newly discovered X-chromosomal gene that is under both single-active-X control and tissue-specific control

    International Nuclear Information System (INIS)

    Nadon, N.L.

    1987-01-01

    The A-11 transcript is present in fibroblasts, but is not normally expressed in B- or T-lymphoblastoid cells. The regulation of the A-11 loci on both the active and inactive X chromosomes is very easily perturbed. The A-11 locus on the fibroblast-derived inactive X in a hybrid cell is reactivated at a very high rate by 5-azacytidine, an inhibitor of DNA methylation, while the A-11 locus on the active X in B-lymphoblastoid cells is derepressed at a very high rate after gamma irradiation. The A-11 gene codes for a mature transcript of about 1.9 kb. The A-11 cDNA clone is incomplete, and contains 753 bases from the 3' end of the gene. A genomic clone that contains about 17 kb of human DNA and hybridizes to the A-11 cDNA was isolated. This clone contains at least the last exon of the A-11 gene, as determined by Northern blotting, nuclease protection experiments, and DNA sequencing. When the genomic clone is transferred into mouse cells. A-11 transcripts of both normal and abnormal sizes are produced, indicating that it is possible that the genomic clone contains the entire locus. However, at this time, the 5' end of the gene has not been located

  9. Comparison of plasma input and reference tissue models for analysing [(11)C]flumazenil studies

    NARCIS (Netherlands)

    Klumpers, Ursula M. H.; Veltman, Dick J.; Boellaard, Ronald; Comans, Emile F.; Zuketto, Cassandra; Yaqub, Maqsood; Mourik, Jurgen E. M.; Lubberink, Mark; Hoogendijk, Witte J. G.; Lammertsma, Adriaan A.

    2008-01-01

    A single-tissue compartment model with plasma input is the established method for analysing [(11)C]flumazenil ([(11)C]FMZ) studies. However, arterial cannulation and measurement of metabolites are time-consuming. Therefore, a reference tissue approach is appealing, but this approach has not been

  10. Study of the (d,α) reactions on the nuclei 10B, 11B, 12C, and 13C and the reaction 13C(p,α)10B and their microscopic and semicroscopic analysis

    International Nuclear Information System (INIS)

    Abd el-Kariem, S.E.S.

    1984-01-01

    In the framework of a systematic analysis of many-particle transfer reactions on light nuclei in the present thesis the two-particle transfer reactions of the type (d,α) on the nucleus 10 B at Esub(d) = 16 MeV and on the nuclei 11 B, 12 C and 13 C at Esub(d) = 24 MeV as well as the three-particle transfer reaction 13 C(p,α) 10 B at eight incident energies between 16 and 45 MeV have been studied. In the case of the residual nuclei 10 B and 11 B transitions up to an excitation energy Esub(x) approx.= 7.5 respectively approx.= 9,0 MeV, in the case of the residual nuclei 8 Be and 9 Be transitions up to Esub(x) approx.= 17 respectively 2.5 MeV were evaluated. Under the assumption that the studied reactions behave as direct one-stage transfer processes the measurement results were analyzed in the framework of the DWBA theory in zero-range approximation. The parameters for the optical potentials used in the DWBA calculations were taken from literature and partly modified by fitting to the angular distributions of the reactions studied here. Microscopic and semimicroscopic calculations were performed. In the semimicroscopic calculations the spectroscopic amplitudes calculated microscopically or in SU(3) approximation were used together with a cluster form factor, in the other case with a microscopically calculated form factor. For the residual nucleus for some higher excited states results on spin, parity, and isospin could be partly obtained, partly confirmed. (orig./HSI) [de

  11. Retention and clearance of C-11 palmitic acid in ischemic and reperfused canine myocardium

    International Nuclear Information System (INIS)

    Schwaiger, M.; Schelbert, H.R.; Keen, R.; Vinten-Johansen, J.; Hansen, H.; Selin, C.; Barrio, J.; Huang, S.C.; Phelps, M.E.

    1985-01-01

    Free fatty acids are the major energy source for cardiac muscle. Oxidation of fatty acid decreases or even ceases during ischemia. Its recovery after transient ischemia remains largely unexplored. Using intracoronary carbon-11 palmitic acid as a tracer of myocardial fatty acid metabolism in an open chest dog model, retention and clearance of tracer in myocardium were evaluated at control, during ischemia and after reperfusion following a 20 minute occlusion of the left anterior descending coronary artery. Myocardial C-11 time-activity curves were analyzed with biexponential curve-fitting routines yielding fractional distribution and clearance half-times of C-11 palmitic acid in myocardial tissue. In animals with permanent occlusion and intracoronary injection of C-11 palmitic acid distal to the occlusion site, the relative size and half-time of the early clearance curve component differed markedly from control values and did not change with ongoing ischemia. Conversely, in animals with only 20 minutes of coronary occlusion, the relative size of the early C-11 clearance phase was still significantly depressed at 20 and 90 minutes of reperfusion but returned to control level at 180 minutes. Tissue C-11 clearance half-times remained significantly prolonged throughout the reperfusion period. Regional function in reperfused myocardium monitored with ultrasonic crystals recovered slowly and was still less than control after 3 hours of reperfusion. The data indicate that after transient ischemia, myocardial fatty acid metabolism fails to recover immediately. Because the metabolic recovery occurs in parallel with recovery of regional function, C-11 palmitic acid in conjunction with positron tomography may be useful for studying regional fatty acid metabolism noninvasively after an ischemic injury, and may be helpful in identifying reversible tissue injury

  12. Towards the PET radiotracer for p75 neurotrophin receptor: [(11)C]LM11A-24 shows biological activity in vitro, but unfavorable ex vivo and in vivo profile.

    Science.gov (United States)

    Gibon, Julien; Kang, Min Su; Aliaga, Arturo; Sharif, Behrang; Rosa-Neto, Pedro; Séguéla, Philippe; Barker, Philip A; Kostikov, Alexey

    2016-10-01

    Mature neurotrophins as well as their pro forms are critically involved in the regulation of neuronal functions. They are signaling through three distinct types of receptors: tropomyosin receptor kinase family (TrkA/B/C), p75 neurotrophin receptor (p75(NTR)) and sortilin. Aberrant expression of p75(NTR) in the CNS is implicated in a variety of neurodegenerative diseases, including Alzheimer's disease. The goal of this work was to evaluate one of the very few reported p75(NTR) small molecule ligands as a lead compound for development of novel PET radiotracers for in vivo p75(NTR) imaging. Here we report that previously described ligand LM11A-24 shows significant inhibition of carbachol-induced persistent firing (PF) of entorhinal cortex (EC) pyramidal neurons in wild-type mice via selective interaction with p75(NTR). Based on this electrophysiological assay, the compound has very high potency with an EC50<10nM. We optimized the radiosynthesis of [(11)C]LM11A-24 as the first attempt to develop PET radioligand for in vivo imaging of p75(NTR). Despite some weak interaction with CNS tissues, the radiolabeled compound showed unfavorable in vivo profile presumably due to high hydrophilicity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. [11C]-MeJDTic: a novel radioligand for κ-opioid receptor positron emission tomography imaging

    International Nuclear Information System (INIS)

    Poisnel, Geraldine; Oueslati, Farhana; Dhilly, Martine; Delamare, Jerome; Perrio, Cecile; Debruyne, Daniele; Barre, Louisa

    2008-01-01

    Introduction: Radiopharmaceuticals that can bind selectively the κ-opioid receptor may present opportunities for staging clinical brain disorders and evaluating the efficiency of new therapies related to stroke, neurodegenerative diseases or opiate addiction. The N-methylated derivative of JDTic (named MeJDTic), which has been recently described as a potent and selective antagonist of κ-opioid receptor in vitro, was labeled with carbon-11 and evaluated for in vivo imaging the κ-opioid receptor in mice. Methods: [ 11 C]-MeJDTic was prepared by methylation of JDTic with [ 11 C]-methyl triflate. The binding of [ 11 C]-MeJDTic to κ-opioid receptor was investigated ex vivo by biodistribution and competition studies using nonfasted male CD1 mice. Results: [ 11 C]-MeJDTic exhibited a high and rapid distribution in peripheral organs. The uptake was maximal in lung where the κ receptor is largely expressed. [ 11 C]-MeJDTic rapidly crossed the blood-brain barrier and accumulated in the brain regions of interest (hypothalamus). The parent ligand remained the major radioactive compound in brain during the experiment. Chase studies with U50,488 (a κ referring agonist), morphine (a μ agonist) and naltrindole (a δ antagonist) demonstrated that this uptake was the result of specific binding to the κ-opioid receptor. Conclusion: These findings suggested that [ 11 C]-MeJDTic appeared to be a promising selective 'lead' radioligand for κ-opioid receptor PET imaging

  14. Mapping a2 Adrenoceptors of the Human Brain with 11C-Yohimbine

    DEFF Research Database (Denmark)

    Nahimi, Adjmal; Jakobsen, Steen; Munk, Ole

    2015-01-01

    A previous study from this laboratory suggested that 11C-yohimbine, a selective α2-adrenoceptor antagonist, is an appropriate ligand for PET of α2 adrenoceptors that passes readily from blood to brain tissue in pigs but not in rodents. To test usefulness in humans, we determined blood–brain...... values of VT ranged from 0.82 mL cm−3 in the right frontal cortex to 0.46 mL cm−3 in the corpus callosum, with intermediate VT values in subcortical structures. Binding potentials averaged 0.6–0.8 in the cortex and 0.2–0.5 in subcortical regions. Conclusion: The maps of 11C-yohimbine binding to α2...... adrenoceptors in human brain had the highest values in cortical areas and hippocampus, with moderate values in subcortical structures, as found also in vitro. The results confirm the usefulness of the tracer 11C-yohimbine for mapping α2 adrenoceptors in human brain in vivo....

  15. Synthetic techniques of radiopharmaceuticals production labeled with C-11 for PET in cardiology

    Science.gov (United States)

    Dyubkov, V. S.; Ekaeva, I. V.; Katunina, T. A.; Rumyantsev, A. S.; Silchenkov, A. V.; Tuflina, T. V.

    2017-01-01

    Positron emission tomography (PET) and PET-Computerised Tomography (CT) are unique, non-invasive diagnostic techniques, in which the local, temporal and quantitative distributions of radioactive labelled substances are measured to investigate physiological processes. It is well known that PET centre of Bakulev Scientific Centre for Cardiovascular Surgery is the oldest one in Moscow. During more than fifteen years a large number of patients have received PET scans. Due to main stream of Scientific Centre, emphasis is placed on examining the heart functioning. For the diagnosis innervation of the heart muscle a number of radiopharmaceuticals are used, including PET radiopharmaceuticals such as 11C-CGP 12177, 11C-meta-hydroxyephedrine as well as its synthetic analogues labelled with other PET radionuclides (18F, 68Ga). 11C-meta-hydroxyephedrine is one of the most perspective radiopharmaceutical for an investigation of cardiac receptors function due to required materials availability for a radio synthesis in Russia. The main advantage of proposed 11C-meta-hydroxyephedrine synthesis technique is the use of a catalyst which allows one decrease reaction time from 5 minutes to 30 seconds. Obtained results allow one decrease reaction time of methylation and increase radiochemical and technological yields.

  16. Possible association of 3' UTR +357 A>G, IVS11-nt 93 T>C, c.1311 C>T polymorphism with G6PD deficiency.

    Science.gov (United States)

    Sirdah, Mahmoud M; Shubair, Mohammad E; Al-Kahlout, Mustafa S; Al-Tayeb, Jamal M; Prchal, Josef T; Reading, N Scott

    2017-07-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common X-linked inherited enzymopathic disorder affecting more than 500 million people worldwide. It has so far been linked to 217 distinct genetic variants in the exons and exon-intron boundaries of the G6PD gene, giving rise to a wide range of biochemical heterogeneity and clinical manifestations. Reports from different settings suggested the association of intronic and other mutations outside the reading frame of the G6PD gene with reduced enzyme activity and presenting clinical symptoms. The present study aimed to investigate any association of other variations apart of the exonic or exonic intronic boundaries in the development of G6PD deficiency. Sixty-seven unrelated Palestinian children admitted to the pediatric hospital with hemolytic crises due to G6PD deficiency were studied. In our Palestinian cohort of 67 [59 males (M) and 8 females (F)] G6PD-deficient children, previously hospitalized for acute hemolytic anemia due to favism, molecular sequencing of the G6PD gene revealed four cases (3M and 1F) that did not have any of the variants known to cause G6PD deficiency, but the 3' UTR c.*+357A>G (rs1050757) polymorphism in association with IVS 11 (c.1365-13T>C; rs2071429), and c.1311C>T (rs2230037). We now provide an additional evidence form Palestinian G6PD-deficient subjects for a possible role of 3' UTR c.*+357 A>G, c.1365-13T>C, and/or c.1311C>T polymorphism for G6PD deficiency, suggesting that not only a single variation in the exonic or exonic intronic boundaries, but also a haplotype of G6PD should considered as a cause for G6PD deficiency.

  17. Visual assessment of [{sup 11}C]PIB PET in patients with cognitive impairment

    Energy Technology Data Exchange (ETDEWEB)

    Suotunen, Timo; Hirvonen, Jussi; Arponen, Eveliina; Teraes, Mika; Seppaenen, Marko [Turku PET Centre, P.O. Box 52, Turku (Finland); Immonen-Raeihae, Pirjo [Turku University Hospital, Turku (Finland); Aalto, Sargo [Turku PET Centre, P.O. Box 52, Turku (Finland); Aabo Academy University, Department of Psychology, Turku (Finland); Lisinen, Irina [University of Turku, Research Centre of Applied and Preventive Cardiovascular Medicine, Turku (Finland); Koski, Kari [Salo Regional Hospital, Neurologic Outpatient Department, Salo (Finland); Sulkava, Raimo [Kuopio University Hospital, Kuopio (Finland); University of Kuopio, Geriatric Unit, School of Public Health and Clinical Nutrition, Kuopio (Finland); Rinne, Juha O. [Turku PET Centre, P.O. Box 52, Turku (Finland); Turku University Hospital, Turku (Finland)

    2010-06-15

    The aim of this study was to evaluate the visual assessment of positron emission tomography images of N-[methyl-11C]2-(4{sup '}-methylaminophenyl)-6-hydroxybenzothiazole ([11C]PIB) in a patient population with mild to moderate memory impairment or dementia. We compared the visual ratings of two readers using kappa statistics and correlated the results of visual and quantitative region of interest (ROI) analyses. The one reader had good experience in evaluating PIB images and the other had little previous experience. The sensitivity and specificity of the visual assessment was determined using quantitative data from 18 healthy controls previously examined: [11C]PIB uptake was considered as abnormal if it was more than 2 SD above the mean of the healthy subjects. The evaluation of visual classification as ''normal'' or ''abnormal'' showed good interobserver agreement ({kappa} = 0.90). There was a clear correlation between visual and quantitative analysis (r = 0.47-0.79, p < 0.001). The most difficult visually assessed brain area was the putamen ({kappa} = 0.11; correlation with quantitative analysis: reader A r = 0.22; reader B r = 0.60). Our study shows that visual evaluation of [{sup 11}C]PIB images conforms with quantitative analyses also in a clinical patient population supporting the feasibility of visual evaluation in clinical settings. (orig.)

  18. 11C-MCG: Synthesis, Uptake Selectivity, and Primate PET of a Probe for Glutamate Carboxypeptidase II (NAALADase

    Directory of Open Access Journals (Sweden)

    Martin G. Pomper

    2002-04-01

    Full Text Available Imaging of glutamate carboxypeptidase II (GCP II, also known as N-acetylated α-linked l-amino dipeptidase (NAALADase, may enable study of glutamatergic transmission, prostate cancer, and tumor neovasculature in vivo. Our goal was to develop a probe for GCP II for use with positron emission tomography (PET. Radiosynthesis of 11C–MeCys–C(O–Glu or 11C-(S-2-[3-((R-1-carboxy-2-methylsulfanyl-ethyl-ureido]-pentanedioic acid (11C-MCG, an asymmetric urea and potent (Ki = 1.9 nM inhibitor of GCP II, was performed by C-11 methylation of the free thiol. Biodistribution of 11C-MCG was assayed in mice, and quantitative PET was performed in a baboon. 11C-MCG was obtained in 16% radiochemical yield at the end of synthesis with specific radioactivities over 167 GBq/mmol (4000 Ci/mmol within 30 min after the end of bombardment. At 30 min postinjection, 11C-MCG showed 33.0 ± 5.1%, 0.4 ± 0.1%, and 1.1 ± 0.2% ID/g in mouse kidney (target tissue, muscle, and blood, respectively. Little radioactivity gained access to the brain. Blockade with unlabeled MCG or 2-(phosphonomethylpentanedioic acid (PMPA, another potent inhibitor of GCP II, provided sevenfold and threefold reductions, respectively, in binding to target tissue. For PET, distribution volumes (DVs were 1.38 then 0.87 pre- and postblocker (PMPA. Little metabolism of 11C-MCG occurred in the mouse or baboon. These results suggest that 11C-MCG may be useful for imaging GCP II in the periphery.

  19. Exploring C++ 11

    CERN Document Server

    Lischner, Ray

    2014-01-01

    Exploring C++ divides C++ up into bite-sized chunks that will help you learn the language one step at a time. Assuming no familiarity with C++, or any other C-based language, you'll be taught everything you need to know in a logical progression of small lessons that you can work through as quickly or as slowly as you need.C++ can be a complicated language. Writing even the most straight-forward of programs requires you to understand many disparate aspects of the language and how they interact with one another. C++ doesn't lend itself to neat compartmentalization the way other languages do. Rat

  20. Clinical impact of {sup 11}C-methionine PET on expected management of patients with brain neoplasm

    Energy Technology Data Exchange (ETDEWEB)

    Yamane, Tomohiko; Senda, Michio [Institution of Biomedical Research and Innovation, Division of Molecular imaging, Kobe (Japan); Sakamoto, Setsu [Kobe University Graduate School of Medicine, Department of Radiology, Kobe (Japan)

    2010-04-15

    We retrospectively examined the clinical efficacy of {sup 11}C-methionine positron emission tomography ({sup 11}C-MET PET) in patients with brain neoplasm, especially whether the {sup 11}C-MET PET changed the clinical management and whether the change was beneficial or detrimental. This study reviewed 89 {sup 11}C-MET PET scans for 80 patients (20 scans for initial diagnosis of brain tumor and 69 scans for differentiating tumor recurrence from radiation necrosis). Final diagnosis and the effect on the intended management were obtained from the questionnaire to the referring physicians or directly from the medical records. The diagnostic sensitivity, specificity, and accuracy for the {sup 11}C-MET PET were evaluated. Regarding the management impact, the rate of scans that caused changes in intended management was also evaluated. Moreover, the occurrence of scans having detrimental diagnostic impact (DDI) and beneficial diagnostic impact (BDI) were evaluated. Sensitivity, specificity, and accuracy of {sup 11}C-MET PET was 87.8, 80.0, and 85.9%. The intended management was changed in 50.0% of the scans. DDI and BDI were observed in 4.3 and 36.2% of the total relevant scans, respectively. {sup 11}C-MET PET can provide useful information in initial diagnosis and differentiating tumor recurrence from radiation necrosis. The intended management was changed in half of the scans. Since a few cases did not receive the requisite treatment due to false-negative results of {sup 11}C-MET PET, management decision should be made carefully, especially in the case of a negative scan. (orig.)

  1. Fully automated synthesis of 11C-acetate as tumor PET tracer by simple modified solid-phase extraction purification

    International Nuclear Information System (INIS)

    Tang, Xiaolan; Tang, Ganghua; Nie, Dahong

    2013-01-01

    Introduction: Automated synthesis of 11 C-acetate ( 11 C-AC) as the most commonly used radioactive fatty acid tracer is performed by a simple, rapid, and modified solid-phase extraction (SPE) purification. Methods: Automated synthesis of 11 C-AC was implemented by carboxylation reaction of MeMgBr on a polyethylene Teflon loop ring with 11 C-CO 2 , followed by acidic hydrolysis with acid and SCX cartridge, and purification on SCX, AG11A8 and C18 SPE cartridges using a commercially available 11 C-tracer synthesizer. Quality control test and animals positron emission tomography (PET) imaging were also carried out. Results: A high and reproducible decay-uncorrected radiochemical yield of (41.0±4.6)% (n=10) was obtained from 11 C-CO 2 within the whole synthesis time about 8 min. The radiochemical purity of 11 C-AC was over 95% by high-performance liquid chromatography (HPLC) analysis. Quality control test and PET imaging showed that 11 C-AC injection produced by the simple SPE procedure was safe and efficient, and was in agreement with the current Chinese radiopharmaceutical quality control guidelines. Conclusion: The novel, simple, and rapid method is readily adapted to the fully automated synthesis of 11 C-AC on several existing commercial synthesis module. The method can be used routinely to produce 11 C-AC for preclinical and clinical studies with PET imaging. - Highlights: • A fully automated synthesis of 11 C-acetate by simple modified solid-phase extraction purification has been developed. • Typical non-decay-corrected yields were (41.0±4.6)% (n=10) • Radiochemical purity was determined by radio-HPLC analysis on a C18 column using the gradient program, instead of expensive organic acid column or anion column. • QC testing (RCP>99%)

  2. Isothermal steam oxidation of the ferritic 11% Cr steel (DIN No. 1.4914) at 900 to 13000C

    International Nuclear Information System (INIS)

    Zurek, Z.

    1982-11-01

    The steam oxidation of ferritic 11% Cr steel tube and sheet samples at 900 to 1300 0 C has been studied gravimetrically, metallographically, by X-ray diffraction and in detail by electron probe microanalysis. The reaction rate could be described by parabolic kinetics of mass increase. During the oxidation a three-layer scale was formed on the surface. The inner layer was composed of iron-chromium spinel, the intermediate layer consisted of a mixture wustite and magnetite, the very thin outer layer was composed of magnetite. Within the inner scale layer small metallic particles enriched of nickel could be observed. The scale cohesion was generally poor for tube as well as for sheet material and was improving with oxidation time and temperature. After oxidation Pt-markers indicated the growth of inner and outer layer in relation to the initial metal surface. The sheet material specimens exposed at 1000-1100 0 C had blisters on their surfaces. A swelling of about 12-15% was measured for the oxidized tubing. Isotherme Dampf-Oxidation des ferritischen 11% Cr-Stahls (Werkstoff Nr. 1.4914) bei 900 - 1300 0 C. (orig.) [de

  3. 26 CFR 31.3306(c)(1)-1 - Agricultural labor.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 15 2010-04-01 2010-04-01 false Agricultural labor. 31.3306(c)(1)-1 Section 31... Agricultural labor. Services performed by an employee for the person employing him which constitute “agricultural labor” as defined in section 3306(k) are excepted from employment. For provisions relating to the...

  4. Reactions of newly formed fission products in the gas phase

    International Nuclear Information System (INIS)

    Strickert, R.G.

    1976-01-01

    A dynamic gas-flow system was constructed which stopped fission products in the gas phase and rapidly separated (in less than 2 sec) volatile compounds from non-volatile ones. The filter assembly designed and used was shown to stop essentially all non-volatile fission products. Between 5 percent and 20 percent of tellurium fission-product isotopes reacted with several hydrocarbon gases to form volatile compounds, which passed through the filter. With carbon monoxide gas, volatile tellurium compound(s) (probably TeCO) were also formed with similar efficiencies. The upper limits for the yields of volatile compounds formed between CO and tin and antimony fission products were shown to be less than 0.3 percent, so tellurium nuclides, not their precursors, reacted with CO. It was found that CO reacted preferentially with independently produced tellurium atoms; the reaction efficiency of beta-produced atoms was only 27 +- 3 percent of that of the independently formed atoms. The selectivity, which was independent of the over-all reaction efficiency, was shown to be due to reaction of independently formed atoms in the gas phase. The gas phase reactions are believed to occur mainly at thermal energies because of the independence of the yield upon argon moderator mole-fraction (up to 80 percent). It was shown in some experiments that about one-half of the TeCO decomposed in passing through a filter and that an appreciable fraction (approximately 20 percent) of the tellurium atoms deposited on the filter reacted agin with CO. Other tellurium atoms on the filter surface (those formed by beta decay and those formed independently but not reacting in the gas phase) also reacted with CO, but probably somewhat less efficiently than atoms formed by TeCO decomposition. No evidence was found for formation of TeCO as a direct result of beta-decay

  5. Imaging of sigma receptors in tumors by PET with [C-11]SA4503

    International Nuclear Information System (INIS)

    Kawamura, K.; Kobayashi, T.; Oda, K.; Ishiwata, K.; Kubota, K.

    2002-01-01

    Aim: Sigma receptors are implicated in some diseases in the central nervous system (CNS), such as schizophrenia, depression, dementia and ischemia, and are also expressed in a variety of human tumors, such as melanoma, carcinoma of the breast, lung and prostate, and the brain tumor. Therefore, several radioligands have been proposed for imaging of sigma receptors by positron emission tomography (PET) and by single photon emission computed tomography. Recently, we have applied [C-11]labeled 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine ([C-11]SA4503) to mapping sigma1 receptors in the brain of monkeys and human. In the present study, we evaluated the potential of the [C-11]SA4503 PET for imaging of sigma receptors using the AH109A bearing rats, and the VX-2 carcinoma bearing rabbits. Materials and Methods: [C-11]SA4503 was injected i.v. into AH109A bearing rats, and the tissue distribution was measured by tissue dissection. To determine the receptor-specific uptake, cold SA4503 or haloperidol was co-injected into the other group of rats. The PET scanning were performed in the rats in the baseline condition and after pretreatment with haloperidol. In the VX-2 carcinoma bearing rabbits, PET scanning was also performed in the baseline and blockade conditions. The sigma receptors in the AH109A and VX-2 were measured in vitro by the standard membrane binding assays. Results: The sigma receptors were found in AH109A and VX-2. The density was much higher in VX-2 than in AH109A. In the tissue dissection study, the AH109A uptake of [C-11]SA4503 increased for 60 min after injection. By the co-injection of SA4503 or haloperidol, the AH109A uptake was enhanced. The PET study also confirmed that the radioactivity level in the AH109A was enhanced by the pretreatment with haloperidol. On the other hand, In the VX-2 carcinoma bearing rabbits, the radioactivity level of in VX-2 remained constant after initial uptake in the baseline PET measurement, but the VX-2 uptake was

  6. Efficacy of acarbose and metformin in newly diagnosed type 2 diabetes patients stratified by HbA1c levels.

    Science.gov (United States)

    Zhang, Jin-Ping; Wang, Na; Xing, Xiao-Yan; Yang, Zhao-Jun; Wang, Xin; Yang, Wen-Ying

    2016-07-01

    The aim of the present study was to investigate whether the therapeutic efficacy of acarbose and metformin is correlated with baseline HbA1c levels in Chinese patients with newly diagnosed type 2 diabetes mellitus (T2DM). Data for 711 subjects were retrieved from the MARCH (Metformin and AcaRbose in Chinese as initial Hypoglycemic treatment) trial database and reviewed retrospectively. Patients were grouped according to baseline HbA1c levels (8%) and the results for these three groups were compared between acarbose and metformin treatments. Acarbose and metformin treatment significantly improved T2DM-associated parameters (weight, fasting plasma glucose [FPG], postprandial glucose [PPG], glucagon-like peptide-1 [GLP-1], HOMA-IR, and total cholesterol) across all HbA1c levels. Acarbose decreased PPG and HOMA-β significantly more than metformin, but only in subjects with lower baseline HbA1c (PPG in the HbA1c levels (P HbA1c groups (all P HbA1c levels, whereas metformin induced greater reductions in FPG. These results may help guide selection of initial therapy based on baseline HbA1c. © 2015 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

  7. High-level waste-form-product performance evaluation

    International Nuclear Information System (INIS)

    Bernadzikowski, T.A.; Allender, J.S.; Stone, J.A.; Gordon, D.E.; Gould, T.H. Jr.; Westberry, C.F. III.

    1982-01-01

    Seven candidate waste forms were evaluated for immobilization and geologic disposal of high-level radioactive wastes. The waste forms were compared on the basis of leach resistance, mechanical stability, and waste loading. All forms performed well at leaching temperatures of 40, 90, and 150 0 C. Ceramic forms ranked highest, followed by glasses, a metal matrix form, and concrete. 11 tables

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

    Science.gov (United States)

    Kil, Kun-Eek; Biegon, Anat; Ding, Yu-Shin; Fischer, Andre; Ferrieri, Richard A; Kim, Sung Won; Pareto, Deborah; Schueller, Michael J; Fowler, Joanna S

    2009-02-01

    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

  9. Profiling adrenal 11β-hydroxyandrostenedione metabolites in prostate cancer cells, tissue and plasma: UPC2-MS/MS quantification of 11β-hydroxytestosterone, 11keto-testosterone and 11keto-dihydrotestosterone.

    Science.gov (United States)

    du Toit, Therina; Bloem, Liezl M; Quanson, Jonathan L; Ehlers, Riaan; Serafin, Antonio M; Swart, Amanda C

    2017-02-01

    Adrenal C 19 steroids serve as precursors to active androgens in the prostate. Androstenedione (A4), 11β-hydroxyandrostenedione (11OHA4) and 11β-hydroxytestosterone (11OHT) are metabolised to potent androgen receptor (AR) agonists, dihydrotestosterone (DHT), 11-ketotestosterone (11KT) and 11-ketodihydrotestosterone (11KDHT). The identification of 11OHA4 metabolites, 11KT and 11KDHT, as active androgens has placed a new perspective on adrenal C11-oxy C 19 steroids and their contribution to prostate cancer (PCa). We investigated adrenal androgen metabolism in normal epithelial prostate (PNT2) cells and in androgen-dependent prostate cancer (LNCaP) cells. We also analysed steroid profiles in PCa tissue and plasma, determining the presence of the C 19 steroids and their derivatives using ultra-performance liquid chromatography (UHPLC)- and ultra-performance convergence chromatography tandem mass spectrometry (UPC 2 -MS/MS). In PNT2 cells, sixty percent A4 (60%) was primarily metabolised to 5α-androstanedione (5αDIONE) (40%), testosterone (T) (10%), and androsterone (AST) (10%). T (30%) was primarily metabolised to DHT (10%) while low levels of A4, 5αDIONE and 3αADIOL (≈20%) were detected. Conjugated steroids were not detected and downstream products were present at <0.05μM. Only 20% of 11OHA4 and 11OHT were metabolised with the former yielding 11keto-androstenedione (11KA4), 11KDHT and 11β-hydroxy-5α-androstanedione (11OH-5αDIONE) and the latter yielding 11OHA4, 11KT and 11KDHT with downstream products <0.03μM. In LNCaP cells, A4 (90%) was metabolised to AST-glucuronide via the alternative pathway while T was detected as T-glucuronide with negligible conversion to downstream products. 11OHA4 (80%) and 11OHT (60%) were predominantly metabolised to 11KA4 and 11KT and in both assays more than 50% of 11KT was detected in the unconjugated form. In tissue, we detected C11-oxy C 19 metabolites at significantly higher levels than the C 19 steroids, with

  10. The synthesis of a new cardiac sympathetic nerve imaging agent N-[11C]CH3-dopamine and biodistribution study

    International Nuclear Information System (INIS)

    Yulin He; Weina Zhou; Xiangcheng Wang; Baoliang Bao; Guojian Zhang; Cheng Wang; Chunmei Wang; Xuemei Wang; Wei Fang

    2014-01-01

    In this study, we synthesized and characterized N-[ 11 C]methyl-dopamine ([ 11 C]MDA) for cardiac sympathetic nerve imaging. [ 11 C]MDA was synthesized by direct N-methylation of dopamine with [ 11 C]methyl iodide and purified by semi-preparation reverse high pressure liquid chromatography (HPLC). The total synthesis time was 45 min including HPLC purification. The radiochemical yields of [ 11 C]MDA was 20 ± 3 %, without decay correction. The radiochemical purity was >98 % and the specific activity was about 50 GBq/mmol. The biological properties of [ 11 C]MDA were evaluated by biodistribution study in normal mice. PET imaging was performed in healthy Chinese mini-swines. Biodistribution study showed that [ 11 C]MDA had high myocardium uptake. PET/CT imaging showed [ 11 C]MDA had clear and symmetrical myocardium uptake, which was blocked obviously by injecting imipramine hydrochloride. [ 11 C]MDA would be a promising candidate of radiotracer for cardiac sympathetic nervous system imaging. (author)

  11. Study of two-step mechanisms in the 12C(p,d)11C reaction at 45 MeV

    International Nuclear Information System (INIS)

    Couvert, Pierre.

    1974-01-01

    An attempt was made to find the nuclear reaction mechanisms explaining the intensity and behavior of the cross sections in the 12 C(p,d) 11 C reaction at 45 MeV. First, the conventional interpretation of the experimental data leads to two closely related conclusions. The behavior of the cross-sections measured cannot be explained without including the intermediate stage of collective 2 + 12 C excitation or accounting for its possible interference with the direct capture of a neutron. The relative intensity of the different mechanisms is directly bound up with the value of the nuclear structure parameters of the wave function adopted. As a result this study is found to be an excellent wave function test and the results obtained seem to prove that the wave function calculated by Clegg for 11 B is also suitable for 11 C. Next a two-stage process was introduced, using inelastic deuteron scattering on 11 C as the intermediate stage. The problem which then arises is to determine the deformation parameters of the final nucleus in its different excitation states. The model adopted is in fact very crude and only gives quantitative information on the physical reality of such a process. Some improvement is shown to be obtained by finite range and non-local potential corrections. It is observed that track-transitions, which correspond in fact to new processes interfering with those already introduced play an important part. The most realistic way to treat the problem is thus to make an exact calculation within the coupled equation system, keeping strictly to physically justified hypotheses [fr

  12. Mapping adenosine A1 receptors in the cat brain by positron emission tomography with [11C]MPDX

    International Nuclear Information System (INIS)

    Shimada, Yuhei; Ishiwata, Kiichi; Kiyosawa, Motohiro; Nariai, Tadashi; Oda, Keiichi; Toyama, Hinako; Suzuki, Fumio; Ono, Kenichirou; Senda, Michio

    2002-01-01

    We evaluated the potential of [ 11 C]MPDX as a radioligand for mapping adenosine A 1 receptors in comparison with previously proposed [ 11 C]KF15372 in cat brain by PET. Two tracers showed the same brain distribution. Brain uptake of [ 11 C]MPDX (Ki=4.2 nM) was much higher and washed out faster than that of [ 11 C]KF15372 (Ki=3.0 nM), and was blocked by carrier-loading or displaced with an A 1 antagonist. The regional A 1 receptor distribution evaluated with kinetic analysis is consistent with that previously measured in vitro. [ 11 C]MPDX PET has a potential for mapping adenosine A 1 receptors in brain

  13. Accumulation of operational history through emulation test to meet proven technology requirement for newly developed I and C technology

    International Nuclear Information System (INIS)

    Yeong Cheol, Shin; Sung Kon, Kang; Han Seong, Son

    2006-01-01

    As new advanced digital I and C technology with potential benefits of higher functionality and better cost effectiveness is available in the market, NPP (Nuclear Power Plant) operators are inclined to use the new technology for the construction of new plant and the upgrade of existing plants. However, this new technology poses risks to the NPP operators at the same time. These risks are mainly due to the poor reliability of newly developed technology. KHNP's past experiences with the new equipment shows many cases of reliability problems. And their consequences include unintended plant trips, lowered acceptance of the new digital technology by the plant I and C maintenance crew, and increased licensing burden in answering for questions from the nuclear regulatory body. Considering the fact that the risk of these failures in the nuclear plant operation is far greater than those in other industry, nuclear power plant operators want proven technology for I and C systems. This paper presents an approach for the emulation of operational history through which a newly developed technology becomes a proven technology. One of the essential elements of this approach is the feedback scheme of running the new equipment in emulated environment, gathering equipment failure, and correcting the design(and test bed). The emulation of environment includes normal and abnormal events of the new equipment such as reconfiguration of control system due to power failure, plant operation including full spectrum of credible scenarios in an NPP. Emulation of I and C equipment execution mode includes normal operation, initialization and termination, abnormal operation, hardware maintenance and maintenance of algorithm/software. Plant specific simulator is used to create complete profile of plant operational conditions that I and C equipment is to experience in the real plant. Virtual operating crew technology is developed to run the simulator scenarios without involvement of actual operators

  14. 48 CFR 1852.227-11 - Patent Rights-Retention by the Contractor (Short Form).

    Science.gov (United States)

    2010-10-01

    ... subparagraph (c)(1). NASA prefers that the contractor use either the electronic or paper version of NASA Form.... Both the electronic and paper versions of NASA Form 1679 may be accessed at the electronic New... copies of the patent application file, by the Government, when a Federal Government employee is a...

  15. Automated no-carrier-added synthesis of [1-11C]-labeled D- and L-enantiomers of lactic acid

    International Nuclear Information System (INIS)

    Drandarov, Konstantin; Schubiger, P. August; Westera, Gerrit

    2006-01-01

    The first purely chemical method for automated no-carrier-added synthesis of [1- 11 C]-labeled D(R)- and L(S)-2-hydroxypropanoic acid (lactic acid) was developed for experimental neurophysiology studies and position emission tomography (PET) diagnosis. Starting from sodium 1-hydroxyethanesulfonate and [ 11 C]HCN (trapped as [ 11 C]KCN) the intermediate DL-(R,S)-[1- 11 C]-2-hydroxypropanenitrile was prepared. Its rapid acid hydrolysis gave DL-(R,S)-[1- 11 C]lactic acid, which was isolated by preparative reversed phase HPLC and automatically injected on a second preparative C 18 HPLC column coated with a chiral selector, where both [1- 11 C]lactic acid enantiomers were separated by chiral ligand-exchange chromatography. Two novel chiral selectors for HPLC enantiomeric separation of α-hydroxy acids, namely D(R)- or L(S)-2-amino-3-methyl-3-(5-phenylpentylsulfanyl)-butanoic acid were utilized for the preparative HPLC separation of the [1- 11 C]lactic acid enantiomers. The preparation of the selectors and the coating procedure for the manufacturing of the preparative chiral HPLC columns are described. A highly efficient trap for [ 11 C]HCN is presented. The whole radiosynthesis is automated, takes about 45 min and leads to more than 80% decay corrected overall radiochemical yield of each enantiomer (up to 2.5 GBq) with over 99% radiochemical, chemical and enantiomeric purity. The specific activity at the end of the synthesis is about 400 GBq/μmol

  16. Radiosynthesis and in vitro evaluation of 2-(N-alkyl-N-1'-11C-propyl)amino-5-hydroxytetralin analogs as high affinity agonists for dopamine D-2 receptors

    International Nuclear Information System (INIS)

    Shi Bingzhi; Narayanan, Tanjore K.; Yang, Z.-Y.; Christian, Bradley T.; Mukherjee, Jogeshwar

    1999-01-01

    We have developed radiotracers based on agonists that may potentially allow the in vivo assessment of the high affinity (HA) state of the dopamine D-2 receptors. The population of HA state, which is likely the functional state of the receptor, may be altered in certain diseases. We carried out radiosyntheses and evaluated the binding affinities, lipophilicity, and in vitro autoradiographic binding characteristics of three dopamine D-2 receptor agonists: (±)-2-(N,N-dipropyl)amino-5-hydroxytetralin (5-OH-DPAT), (±)-2-(N-phenethyl-N-propyl)amino-5-hydroxytetralin (PPHT), and (±)-2-(N-cyclohexylethyl-N-propyl)amino-5-hydroxytetralin (ZYY-339). In 3 H-spiperone assays using rat striata, ZYY-339 exhibited subnanomolar affinity for D-2 receptor sites ( IC 50 =0.010 nM), PPHT was somewhat weaker ( IC 50 =0.65 nM), and 5-OH-DPAT exhibited the weakest affinity ( IC 50 =2.5 nM) of the three compounds. Radiosynthesis of these derivatives, 2-(N-propyl-N-1'- 11 C-propyl)amino-5-hydroxytetralin ( 11 C-5-OH-DPAT), 2-(N-phenethyl-N-1'- 11 C-propyl)amino-5-hydroxytetralin ( 11 C-PPHT), and 2-(N-cyclohexylethyl-N-1'- 11 C-propyl)amino-5-hydroxytetralin ( 11 C-ZYY-339) was achieved by first synthesizing 11 C-1-propionyl chloride and subsequent coupling with the appropriate secondary amine precursor to form the respective amide, which was then reduced to provide the desired tertiary amine products. The final products were obtained by reverse-phase high performance liquid chromatography (HPLC) purification in radiochemical yields of 5-10% after 60-75 min from the end of 11 CO 2 trapping and with specific activities in the range of 250-1,000 Ci/mmol. In vitro autoradiographs in rat brain slices with 11 C-5-OH-DPAT, 11 C-PPHT, and 11 C-ZYY-339 revealed selective binding of the three radiotracers to the dopamine D-2 receptors in the striata

  17. Discrimination between Newly Formed and Aged Thrombi Using Empirical Mode Decomposition of Ultrasound B-Scan Image

    Directory of Open Access Journals (Sweden)

    Jui Fang

    2015-01-01

    Full Text Available Ultrasound imaging is a first-line diagnostic method for screening the thrombus. During thrombus aging, the proportion of red blood cells (RBCs in the thrombus decreases and therefore the signal intensity of B-scan can be used to detect the thrombus age. To avoid the effect of system gain on the measurements, this study proposed using the empirical mode decomposition (EMD of ultrasound image as a strategy to classify newly formed and aged thrombi. Porcine blood samples were used for the in vitro induction of fresh and aged thrombi (at hematocrits of 40%. Each thrombus was imaged using an ultrasound scanner at different gains (15, 20, and 30 dB. Then, EMD of ultrasound signals was performed to obtain the first and second intrinsic mode functions (IMFs, which were further used to calculate the IMF-based echogenicity ratio (IER. The results showed that the performance of using signal amplitude of B-scan to reflect the thrombus age depends on gain. However, the IER is less affected by the gain in discriminating between fresh and aged thrombi. In the future, ultrasound B-scan combined with the EMD may be used to identify the thrombus age for the establishment of thrombolytic treatment planning.

  18. Synthesis of [11C]PBR170, a novel imidazopyridine, for imaging the translocator protein with PET

    International Nuclear Information System (INIS)

    Bourdier, Thomas; Henderson, David; Fookes, Christopher J.R.; Lam, Peter; Mattner, Filomena; Fulham, Michael; Katsifis, Andrew

    2014-01-01

    The translocator protein (TSPO) ligand 2-(6,8-dichloro-2-(4-ethoxyphenyl)imidazo[1,2-a]pyridin-3-yl) –N-(2-fluoropyridin-3-yl)–N-methylacetamide (PBR170), is a novel imidazopyridineacetamide with high affinity (2.6 nm) and selectivity for the TSPO. The synthesis of [ 11 C]PBR170 was accomplished by N-methylation of the corresponding desmethyl precursor with [ 11 C]methyl iodide in the presence of sodium hydroxide in dimethylformamide. [ 11 C]PBR170 was produced in 30–45% radiochemical yield (decay-corrected, based on [ 11 C]methyl iodide) with a radiochemical purity >98% and a specific activity of 90–190 GBq/μmol after 35 min of synthesis time. - Highlights: • Radiosynthesis of a novel ligand PBR170 with carbon-11. • 30–45% radiochemical yield (decay-corrected, based on [ 11 C]methyl iodide). • Radiosynthesis and formulation achieved in 35 min. • High radiochemical purity (>98%) and specific activity (90–190 GBq/µmol). • High affinity and selectivity for the translocator protein (TSPO)

  19. 11C-ORM-13070, a novel PET ligand for brain α2C-adrenoceptors: radiometabolism, plasma pharmacokinetics, whole-body distribution and radiation dosimetry in healthy men

    International Nuclear Information System (INIS)

    Luoto, Pauliina; Oikonen, Vesa; Arponen, Eveliina; Helin, Semi; Virta, Jere; Virtanen, Kirsi; Roivainen, Anne; Suilamo, Sami; Herttuainen, Jukka; Hietamaeki, Johanna; Holopainen, Aila; Rouru, Juha; Sallinen, Jukka; Kailajaervi, Marita; Peltonen, Juha M.; Scheinin, Mika; Volanen, Iina; Rinne, Juha O.

    2014-01-01

    11 C-labelled 1-[(S)-1-(2,3-dihydrobenzo[1,2]dioxin-2-yl)methyl] -4-(3-methoxy-methylpyridin-2- yl)-piperazine ( 11 C-ORM-13070) is a novel PET tracer for imaging of α 2C -adrenoceptors in the human brain. Brain α 2C -adrenoceptors may be therapeutic targets in several neuropsychiatric disorders, including depression, schizophrenia and Alzheimer's disease. To validate the use of 11 C-ORM-13070 in humans, we investigated its radiometabolism, pharmacokinetics, whole-body distribution and radiation dose. Radiometabolism was studied in a test-retest setting in six healthy men. After intravenous injection of 11 C-ORM-13070, blood samples were drawn over 60 min. Plasma samples were analysed by radio-HPLC for intact tracer and its radioactive metabolites. Metabolite-corrected plasma time-activity curves were used for calculation of pharmacokinetics. In a separate group of 12 healthy men, the whole-body distribution of 11 C-ORM-13070 and radiation exposure were investigated by dynamic PET/CT imaging without blood sampling. Two radioactive metabolites of 11 C-ORM-13070 were detected in human arterial plasma. The proportion of unchanged 11 C-ORM-13070 decreased from 81 ± 4 % of total radioactivity at 4 min after tracer injection to 23 ± 4 % at 60 min. At least one of the radioactive metabolites penetrated into red blood cells, while the parent tracer remained in plasma. The apparent elimination rate constant and corresponding half-life of unchanged 11 C-ORM-13070 in arterial plasma were 0.0117 ± 0.0056 min -1 and 73.6 ± 35.8 min, respectively. The organs with the highest absorbed doses were the liver (12 μSv/MBq), gallbladder wall (12 μSv/MBq) and pancreas (9.1 μSv/MBq). The mean effective dose was 3.9 μSv/MBq, with a range of 3.6 - 4.2 μSv/MBq. 11 C-ORM-13070 was rapidly metabolized in human subjects after intravenous injection. The effective radiation dose of 11 C-ORM-13070 was in the same range as that of other 11 C-labelled brain receptor tracers. An injection

  20. Comparative Genetic Analyses of Human Rhinovirus C (HRV-C) Complete Genome from Malaysia

    Science.gov (United States)

    Khaw, Yam Sim; Chan, Yoke Fun; Jafar, Faizatul Lela; Othman, Norlijah; Chee, Hui Yee

    2016-01-01

    Human rhinovirus-C (HRV-C) has been implicated in more severe illnesses than HRV-A and HRV-B, however, the limited number of HRV-C complete genomes (complete 5′ and 3′ non-coding region and open reading frame sequences) has hindered the in-depth genetic study of this virus. This study aimed to sequence seven complete HRV-C genomes from Malaysia and compare their genetic characteristics with the 18 published HRV-Cs. Seven Malaysian HRV-C complete genomes were obtained with newly redesigned primers. The seven genomes were classified as HRV-C6, C12, C22, C23, C26, C42, and pat16 based on the VP4/VP2 and VP1 pairwise distance threshold classification. Five of the seven Malaysian isolates, namely, 3430-MY-10/C22, 8713-MY-10/C23, 8097-MY-11/C26, 1570-MY-10/C42, and 7383-MY-10/pat16 are the first newly sequenced complete HRV-C genomes. All seven Malaysian isolates genomes displayed nucleotide similarity of 63–81% among themselves and 63–96% with other HRV-Cs. Malaysian HRV-Cs had similar putative immunogenic sites, putative receptor utilization and potential antiviral sites as other HRV-Cs. The genomic features of Malaysian isolates were similar to those of other HRV-Cs. Negative selections were frequently detected in HRV-Cs complete coding sequences indicating that these sequences were under functional constraint. The present study showed that HRV-Cs from Malaysia have diverse genetic sequences but share conserved genomic features with other HRV-Cs. This genetic information could provide further aid in the understanding of HRV-C infection. PMID:27199901

  1. A fast chemoenzymatic synthesis of [11C]-N5,N10-methylenetetrahydrofolate as a potential PET tracer for proliferating cells

    International Nuclear Information System (INIS)

    Saeed, Muhammad; Tewson, Timothy J.; Erdahl, Colbin E.; Kohen, Amnon

    2012-01-01

    Introduction: Thymidylate synthase and folate receptors are well-developed targets of cancer therapy. Discovery of a simple and fast method for the conversion of 11 CH 3 Ito[ 11 C]-formaldehyde ( 11 CH 2 O) encouraged us to label the co-factor of this enzyme. Preliminary studies conducted on cell lines have demonstrated a preferential uptake of [11- 14 C]-(R)-N 5 ,N 10 -methylene-5,6,7,8-tetrahydrofolate ( 14 CH 2 H 4 folate) by cancerous cell vs. normal cells from the same organ (Saeed M., Sheff D. and Kohen A. Novel positron emission tomography tracer distinguishes normal from cancerous cells. J Biol Chem 2011;286:33872–33878), pointing out 11 CH 2 H 4 folate as a positron emission tomography (PET) tracer for cancer imaging. Herein we report the synthesis of 11 CH 2 H 4 folate, which may serve as a potential PET tracer. Methods: In a remotely controlled module, methyl iodide ( 11 CH 3 I) was bubbled into a reaction vial containing trimethylamine N-oxide in N,N-Dimethylformamide (DMF) and heated to 70°C for 2 min. Formaldehyde ( 11 CH 2 O) formed after the completion of reaction was then mixed with a solution of freshly prepared tetrahydrofolate (H 4 folate) by using a fast chemoenzymatic approach to accomplish synthesis of 11 CH 2 H 4 folate. Purification of the product was carried out by loading the crude reaction mixture on a SAX cartridge, washing with water to remove unbound impurities and finally eluting with a saline solution. Results: The synthesis and purification of 11 CH 2 H 4 folate were completed within 5 min. High-performance liquid chromatography analysis of the product after SAX purification indicates that more than 90% of the radioactivity that was retained on the SAX cartridge was in 11 CH 2 H 4 folate, with minor ( 11 CH 2 O. Conclusion: We present a fast (∼5 min) synthesis and purification of 11 CH 2 H 4 folate as a potential PET tracer. The final product is received in physiologically compatible buffer (100 mM sodium phosphate, pH 7

  2. Comparison of the binding of the irreversible monoamine oxidase tracers, [11C]clorgyline and [11C]l-deprenyl in brain and peripheral organs in humans

    International Nuclear Information System (INIS)

    Fowler, Joanna S.; Logan, Jean; Wang, Gene-Jack; Volkow, Nora D.; Telang, Frank; Ding Yushin; Shea, Colleen; Garza, Victor; Xu Youwen; Li Zizhong; Alexoff, David; Vaska, Paul; Ferrieri, Richard; Schlyer, David; Zhu Wei; John Gatley, S.

    2004-01-01

    The monoamine oxidase A and B (MAO A and B) radiotracers [ 11 C]clorgyline (CLG) and [ 11 C]L-deprenyl (DEP) and their deuterium labeled counterparts (CLG-D and DEP-D) were compared to determine whether their distribution and kinetics in humans are consistent with their physical, chemical and pharmacological properties and the reported ratios of MAO A:MAO B in post-mortem human tissues. Irreversible binding was consistently higher for DEP in brain, heart, kidneys and spleen but not lung where CLG >DEP and not in thyroid where there is no DEP binding. The generally higher DEP binding is consistent with its higher enzyme affinity and larger free fraction in plasma while differences in regional distribution for CLG and DEP in brain, heart, thyroid and lungs are consistent with different relative ratios of MAO A and B in humans

  3. SPO11-C631T Gene Polymorphism: Association With Male Infertility and an in Silico-Analysis

    Directory of Open Access Journals (Sweden)

    Mohammad Karimian

    2016-04-01

    Full Text Available Objective: To investigate the association of C631T single nucleotide polymorphisms in SPO11 gene with male infertilityfollowed by an in silico approach. SPO11 is a gene involved in meiosis and spermatogenesis process, which in humans, this gene is located on chromosome 20 (20q13.2-13.3 with 13 exons.Materials and methods: In a case-control study, 200 blood samples were collected from the IVF center (Kashan, Iran including; 100 infertile and 100 healthy control men. SPO11-C631T were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP method.The effects of C631T transition on the structure of mRNA and protein of SPO11 was evaluated by bioinformatics tools.Results: Our data revealed that all subjects were wild-type homozygous inC631T positionsand just a sample from fertile group was heterozygousin C631T (OR: 0.3300, 95% CI: 0.0133 to 8.1992, p = 0.4988.Our in silico-analysis revealed that C631T transition could make fundamental changes in the structure of the mRNA (Score: 0.1983 and protein (PROVEAN Score: -3.371; Reliability Index: 4; Expected Accuracy: 82% of SPO11. Also, C631T substitution could change the aggregation prone regions of the SPO11 protein (dTANGO = 209.99.Conclusion: So even though the SPO11-C631T don’t increase the risk of male infertility, it could be deleterious for themRNA and protein.

  4. Dosimetry of D- and L-enantiomers of 11C-labeled tryptophan and valine

    International Nuclear Information System (INIS)

    Washburn, L.C.; Byrd, B.L.; Sun, T.T.; Crook, J.E.; Hubner, K.F.; Coffey, J.L.; Watson, E.E.

    1985-01-01

    We have previously reported the radiation dosimetry of 11 C-labeled DL-tryptophan and DL-valine, as well as clinical pancreatic imaging studies with these agents. Because of significant uptake in both normal pancreas and in pancreatic tumors (thought to be due to the presence of the D-enantiomer), differential diagnosis of pancreatic carcinoma was not feasible. High-performance liquid chromatographic (HPLC) methods were developed for rapid resolution of 11 C-labeled DL-tryptophan and DL-valine. Radiation dose estimates to the various organs in man were calculated for the D- and L-enantiomers of 11 C-labeled tryptophan and valine, based on tissue distribution data in rats. The dose estimates were sufficiently low that 20-mCi doses of each of the enantiomeric amino acids were approved by the FDA for intravenous administration to humans. 21 refs., 3 tabs

  5. Dosimetry of D- and L-enantiomers of 11C-labeled tryptophan and valine

    International Nuclear Information System (INIS)

    Washburn, L.C.; Byrd, B.L.; Sun, T.T.; Crook, J.E.; Hubner, K.F.; Coffey, J.L.; Watson, E.E.

    1986-01-01

    The authors have previously reported the radiation dosimetry of 11 C-labeled DL-tryptophan and DL-valine, as well as clinical pancreatic imaging studies with these agents. Because of significant uptake in both normal pancreas and in pancreatic tumors (thought to be due to the presence of the D-enantiomer), differential diagnosis of pancreatic carcinoma was not feasible. High-performance liquid chromatographic (HPLC) methods were developed for rapid resolution of 11 C-labeled DL-tryptophan and DL-valine. Radiation dose estimates to the various organs in man were calculated for the D- and L-enantiomers of 11 C-labeled tryptophan and valine, based on tissue distribution data in rats. The dose estimates were sufficiently low that 20-mCi doses of each of the enantiomeric amino acids were approved by the FDA for intravenous administration to humans. 21 references, 3 tables

  6. Lifestyle and clinical factors associated with elevated C-reactive protein among newly diagnosed Type 2 diabetes mellitus patients

    DEFF Research Database (Denmark)

    Svensson, Elisabeth; Mor, Anil; Rungby, Jørgen

    2014-01-01

    BACKGROUND: We aimed to examine the prevalence of and modifiable factors associated with elevated C-reactive Protein (CRP), a marker of inflammation, in men and women with newly diagnosed Type 2 Diabetes mellitus (DM) in a population-based setting. METHODS: CRP was measured in 1,037 patients (57...... was primarily elevated among patients with no regular physical activity (aRR 1.5 (95% CI 1.1-1.9)), previous cardiovascular disease (aRR1.5 (95% CI 1.2-1.9) and other comorbidity. For both genders, elevated CRP was 1.4-fold increased in those with weight gain >30 kg since age 20 years. Sensitivity analyses...

  7. Positron emission tomography studies with 11C-ethanol in intratumoral therapy for cell carcinoma

    International Nuclear Information System (INIS)

    Dimitrakopoulou-Strauss, A.; Gutzler, F.; Strauss, L.G.; Irngartinger, G.; Oberdorfer, F.; Doll, J.; Stremmel, W.; Kaick, G. van

    1996-01-01

    Positron emission tomography (PET) is a noninvasive functional method for the study of solid tumor perfusion, metabolism and interaction with different therapeutic agents. The aim of the study was the investigation of the metabolism of hepatocellular carcinomas (HCC) and the kinetics during a treatment with intratumoral ethanol by PET. The ongoing study includes seven patients with child A cirrhosis and HCC (UICC stage III-IVA; tumor size 3-6 cm). Dynamic PET studies (60 min) with 18 F-fluordeoxyglucose (FDG) were performed prior to therapy to assess tumor viability. The evaluation of the FDG data demonstrated a liver-equivalent uptake in six of the tumors (well and moderately differentiated HCC), which were poorly delinated against the normal liver parenchyma. One moderately differentiated HCC showed an increased FDG metabolism, indicating no correlation between histology and metabolism. A dose of 37-80 MBq 11 C-ethanol was applied together with a nonlabelled therapeutic dose of the drug via a puncture needle positioned under sonography. Five out of seven tumors demonstrated a high 11 C uptake shortly after the end of the ethanol injection followed by constant 11 C-ethanol concentration during the whole study period of 45 min. The PET data demonstrated no significant elimination of the 11 C-ethanol from the tumor and no accumulation in the surrounding liver tissue. One case showed a decrease of the intratumoral 11 C -ethanol concentration due to a punkture of a tumor vein, and in another case the surrounding liver parenchyma demonstrated significant 11 C uptake in the early phase following paratumoral injection of the drug. In conclusion, PET is a useful tool for the study of the mechanism and the kinetics of percutaneous intratumoral ethanol injection of HCC. (orig.) [de

  8. Automated calculation of myocardial external efficiency from a single 11C-acetate PET/CT scan

    DEFF Research Database (Denmark)

    Harms, Hans; Tolbod, Lars Poulsen; Hansson, Nils Henrik

    of this study was to develop and validate an automated method of calculating MEE from a single dynamic 11C-acetate PETscan. Methods: 21 subjects underwent a dynamic 27 min 11C-acetate PETscan on a Siemens Biograph TruePoint 64 PET/CTscanner. Using cluster analysis, the LV-aortic time-activity curve (TACLV......). Conclusion: Myocardial efficiencycanbe derived directly andautomatically froma single dynamic 11C-acetate PET scan. This eliminates the need for a separate CMR scan and eliminates any potential errors due to different loading conditions between CMR and PETscans.......Background: Dynamic PETwith 11C-acetate can be used to assess myocardial oxygen use which in turn is usedto calculate myocardial external efficiency (MEE), anearly marker of heart failure. MEE is defined as the ratio of total work (TW) and total energy use (TE). Calculation of TW and TE requires...

  9. Being a team leader: newly registered nurses relate their experiences.

    Science.gov (United States)

    Ekström, Louise; Idvall, Ewa

    2015-01-01

    This paper presents a study that explores how newly qualified registered nurses experience their leadership role in the ward-based nursing care team. A nurse's clinical leadership affects the quality of care provided. Newly qualified nurses experience difficulties during the transition period from student to qualified professional and find it challenging to lead nursing care. Twelve nurses were interviewed and the transcribed texts analysed using qualitative content analysis to assess both manifest and latent content. Five themes were identified: feeling stranded; forming well-functioning teams; learning to lead; having the courage, strength, and desire to lead; and ensuring appropriate care. The findings indicate that many factors limit nurses' leadership but some circumstances are supportive. The leadership prerequisites for newly registered nurses need to improve, emphasizing different ways to create a supportive atmosphere that promotes professional development and job satisfaction. To increase nurse retention and promote quality of care, nurse managers need to clarify expectations and guide and support newly qualified nurses in a planned way. © 2013 John Wiley & Sons Ltd.

  10. Newly Generated Liquid Waste Processing Alternatives Study, Volume 1

    Energy Technology Data Exchange (ETDEWEB)

    Landman, William Henry; Bates, Steven Odum; Bonnema, Bruce Edward; Palmer, Stanley Leland; Podgorney, Anna Kristine; Walsh, Stephanie

    2002-09-01

    This report identifies and evaluates three options for treating newly generated liquid waste at the Idaho Nuclear Technology and Engineering Center of the Idaho National Engineering and Environmental Laboratory. The three options are: (a) treat the waste using processing facilities designed for treating sodium-bearing waste, (b) treat the waste using subcontractor-supplied mobile systems, or (c) treat the waste using a special facility designed and constructed for that purpose. In studying these options, engineers concluded that the best approach is to store the newly generated liquid waste until a sodium-bearing waste treatment facility is available and then to co-process the stored inventory of the newly generated waste with the sodium-bearing waste. After the sodium-bearing waste facility completes its mission, two paths are available. The newly generated liquid waste could be treated using the subcontractor-supplied system or the sodium-bearing waste facility or a portion of it. The final decision depends on the design of the sodium-bearing waste treatment facility, which will be completed in coming years.

  11. In vivo binding of [{sup 11}C]nemonapride to sigma receptors in the cortex and cerebellum

    Energy Technology Data Exchange (ETDEWEB)

    Ishiwata, Kiichi E-mail: ishiwata@pet.tmig.or.jp; Senda, Michio

    1999-08-01

    Radiolabeled nemonapride (NEM, YM-09151-2) is widely used as a representative dopamine D{sub 2}-like receptor ligand in pharmacological and neurological studies, and {sup 11}C-labeled analog ([{sup 11}C]NEM) has been developed for positron emission tomography (PET) studies. The aim of this study was to evaluate whether [{sup 11}C]NEM binds in vivo to sigma receptors. [{sup 11}C]NEM and one of six dopamine D{sub 2}-like receptor ligands or seven sigma receptor ligands were co-injected into mice, and the regional brain uptake of [{sup 11}C]NEM was measured by a tissue dissection method. The striatal uptake of [{sup 11}C]NEM was reduced by D{sub 2}-like receptor ligands, NEM, haloperidol, (+)-butaclamol, raclopride, and sulpiride, but not by a D{sub 4} receptor ligand clozapine. In the cortex and cerebellum the uptake was also reduced by D{sub 2}-like receptor ligands with affinity for sigma receptors, but not by raclopride. Although none of seven sigma receptor ligands, SA6298, N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]ethylamine hydrochloride (NE-100), (+)-pentazocine, R(-)-N-(3-phenyl-1-propyl)-1-phenyl-2-aminopropane hydrochloride ([-]-PPAP), (-)-pentazocine, R(+)-3-(3-hydroxyphenyl)-N-propylpiperidine hydrochloride ([+]-3-PPP), and (+)-N-allylnormetazocine hydrochloride ([+]-SKF 10047), blocked the striatal uptake, five of them with relatively higher affinity significantly reduced the [{sup 11}C]NEM uptake by the cortex, and four of them reduced that by the cerebellum. We concluded that [{sup 11}C]NEM binds in vivo not only to dopamine D{sub 2}-like receptors in the striatum but also to sigma receptors in other regions such as cortex and cerebellum.

  12. Comparison of autologous 111In-leukocytes, 18F-FDG, 11C-methionine, 11C-PK11195 and 68Ga-citrate for diagnostic nuclear imaging in a juvenile porcine haematogenous Staphylococcus aureus osteomyelitis model

    DEFF Research Database (Denmark)

    Nielsen, Ole L.; Afzelius, Pia; Bender, Dirk

    characterized as abscesses/cellulitis, arthritis in three joints and five enlarged lymph nodes. None of the tracers accumulated in joints with arthritis. By comparing the 10 infectious lesions, 18F-FDG accumulated in nine, 111In-leukocytes in eight, 11C-methionine in six, 68Ga-citrate in four and 11C-PK11195...

  13. Frequency of Ketoacidosis in Newly Diagnosed Type 1 Diabetic Children

    Science.gov (United States)

    Razavi, Zahra

    2010-01-01

    Objectives Diabetic ketoacidosis (DKA) is the leading cause of morbidity and mortality in children with type 1 diabetes mellitus (TIDM). Many patients with newly diagnosed type 1 diabetes present with DKA. The aim of this study is to determine the frequency and the clinical presentation of diabetic ketoacidosis at the diagnosis of type 1 diabetes mellitus in youths in hamadan, Western Province of Iran. Methods The Clinical and laboratory data of a total of 200 patients under 19 years of age with newly diagnosed type 1 diabetes mellitus between 1995-2005 were retrospectively reviewed. Statistical analysis was performed using SPSS 11. Results 48 (24%)of the children were presented in a state of ketoacidosis. Sever form of DKA (pH≤7.2) was observed in 54.5% of patients. The mean age at diagnosis was 7.3±5.15 years in DKA group and 8.59±3.07 in non-DKA group (p=0.22). 60.4% of patient with DKA were female whereas in the non-DKA group, 53.3% of patients were female, the difference was not significant (p=0.38). The duration of symptoms before diagnosis was 14.84±8.19 days in patients with DKA and 22.39±2.27 in the non-DKA group, (p=0.11). No significant difference was found between the age, sex and duration of the symptoms and occurance of DKA. Polydipsia (85.4) polyuria (83.3%), weakness (68.8%) and abdominal pain (52.1%) were the most frequently notified symptoms among the patients. In two cases, diagnosis of DKA was preceded by as appendicitis and the patient underwent appendectomy. Conclusion Frequency of DKA at onset of type 1 diabetes mellitus was significant in the studied region. However, it was lower than other regions in Asia. Polydipsia, polyuria, fatigue and abdominal pain were the most common symptoms on presentation. PMID:22125712

  14. Frequency of Ketoacidosis in Newly Diagnosed Type 1 Diabetic Children

    Directory of Open Access Journals (Sweden)

    Zahra Razavi

    2010-04-01

    Full Text Available ABSTRACTObjectives: Diabetic ketoacidosis (DKA is the leading cause of morbidity and mortality in children with type 1 diabetes mellitus (TIDM. Many patients with newly diagnosed type 1 diabetes present with DKA. The aim of this study is to determine the frequency and the clinical presentation of diabetic ketoacidosis at the diagnosis of type 1 diabetes mellitus in youths in hamadan, Western Province of Iran.Methods: The Clinical and laboratory data of a total of 200 patients under 19 years of age with newly diagnosed type 1 diabetes mellitus between 1995-2005 were retrospectively reviewed. Statistical analysis was performed using SPSS 11.Results: 48 (24%of the children were presented in a state of ketoacidosis. Sever form of DKA (pH≤7.2 was observed in 54.5% of patients. The mean age at diagnosis was 7.3±5.15 years in DKA group and 8.59±3.07 in non-DKA group (p=0.22. 60.4% of patient with DKA were female whereas in the non-DKA group, 53.3% of patients were female, the difference was not significant (p=0.38. The duration of symptoms before diagnosis was 14.84±8.19 days in patients with DKA and 22.39±2.27 in the non-DKA group, (p=0.11. No significant difference was found between the age, sex and duration of the symptoms and occurance of DKA. Polydipsia (85.4 polyuria (83.3%, weakness (68.8% and abdominal pain (52.1% were the most frequently notified symptoms among the patients. In two cases, diagnosis of DKA was preceded by as appendicitis and the patient underwent appendectomy.Conclusion: Frequency of DKA at onset of type 1 diabetes mellitus was significant in the studied region. However, it was lower than other regions in Asia. Polydipsia, polyuria, fatigue and abdominal pain were the most common symptoms on presentation.

  15. [{sup 11}C]diclofenac sodium: synthesis and PET assessment of transdermal penetration

    Energy Technology Data Exchange (ETDEWEB)

    Petroni, Debora, E-mail: debora.petroni@ifc.cnr.i [CNR Institute of Clinical Physiology, Via Moruzzi 1, 56124 Pisa (Italy); Menichetti, Luca; Sorace, Oreste; Poli, Michela [CNR Institute of Clinical Physiology, Via Moruzzi 1, 56124 Pisa (Italy); Vanasia, Massimo [Gienne Pharma, Via Lorenteggio 270/A, 20152 Milan (Italy); Salvadori, Piero A. [CNR Institute of Clinical Physiology, Via Moruzzi 1, 56124 Pisa (Italy)

    2011-02-15

    The aim of this work was to study the feasibility of using Positron Emission Tomography (PET) imaging as a new tool to detect transdermal penetration of topical drugs in human subjects. The compound used in the study is sodium 2-[(2,6-dichlorophenyl)amino]phenyl]acetate, better known as diclofenac sodium. This molecule belongs to the family of non-steroidal anti-inflammatory drugs and is considered one of the first choices among non-steroidal anti-inflammatory drugs for the treatment of inflammatory diseases; it is widely used and commercially present in a large number of pharmaceutical forms and formulations. {sup 11}C-labeled diclofenac has been synthesized and coformulated, as an internal indicator, with a proprietary preparation based on the use of a sprayer. The radiolabeled preparation was topically administered to healthy volunteers, and PET imaging was used to evaluate transdermal penetration. Results obtained have demonstrated the efficacy of PET and radiolabeled tracers for the evaluation of transdermal penetration of active pharmaceutical ingredients as topical formulations.

  16. Evaluation of the kappa-opioid receptor-selective tracer [11C]GR103545 in awake rhesus macaques

    International Nuclear Information System (INIS)

    Schoultz, Bent W.; Hjornevik, Trine; Willoch, Frode; Marton, Janos; Noda, Akihiro; Murakami, Yoshihiro; Miyoshi, Sosuke; Nishimura, Shintaro; Aarstad, Erik; Drzezga, Alexander; Matsunari, Ichiro; Henriksen, Gjermund

    2010-01-01

    The recent development in radiosynthesis of the 11 C-carbamate function increases the potential of [ 11 C]GR103545, which for the last decade has been regarded as promising for imaging the kappa-opioid receptor (κ-OR) with PET. In the present study, [ 11 C]GR103545 was evaluated in awake rhesus macaques. Separate investigations were performed to clarify the OR subtype selectivity of this compound. Regional brain uptake kinetics of [ 11 C]GR103545 was studied 0-120 min after injection. The binding affinity and opioid subtype selectivity of [ 11 C]GR103545 was determined in cells transfected with cloned human opioid receptors. In vitro binding assays demonstrated a high affinity of GR103545 for κ-OR (K i = 0.02 ±0.01 nM) with excellent selectivity over μ-OR (6 x 10 2 -fold) and δ-OR (2 x 10 4 -fold). PET imaging revealed a volume of distribution (V T ) pattern consistent with the known distribution of κ-OR, with striatum = temporal cortex > cingulate cortex > frontal cortex > parietal cortex > thalamus > cerebellum. [ 11 C]GR103545 is selective for κ-OR and holds promise for use to selectively depict and quantify this receptor in humans by means of PET. (orig.)

  17. [Preparation and characterization of Forms A and B of benazepril hydrochloride].

    Science.gov (United States)

    Fang, Hong; Hu, Xiu-rong; Gu, Jian-ming; Chen, Guan-xi; Feng, Jian-yue; Tang, Gu-ping

    2012-11-01

    To prepare Form A and Form B of benazepril hydrochloride and to compare the differences in spectrums, thermodynamics and crystal structure between two polymorphic forms. Form A and Form B of benazepril hydrochloride were characterized by Fourier transform infrared spectroscopy (IR), thermal gravimetric analysis (TG), differential scanning calorimetry (DSC), powder x-ray diffraction (PXRD) and single crystal x-ray diffraction (SCXRD). Preparation method, crystal structure and polymorphic stability of Form A and Form B of benazepril hydrochloride were obtained. Based on the analysis of crystal structure of both polymorphs, Form A belonged to monoclone space group P2(1) with a=7.8655(4)Å, b= 11.7700(6)Å, c= 13.5560(7)Å, β= 102.9470(10)°, V=1223.07 (11)Å(3) and Z=2, while Form B belonged to orthorhombic space group P212121, with a=7.9353(8)Å, b=11.6654(11)Å, c=26.6453(16)Å, V=2466.5(4)Å(3) and Z=4. From the DSC and XRD results, Form B of benazepril hydrochloride could be transformed into Form A after heating treatment. Form A and Form B of benazepril hydrochloride are both anhydrous and displayed different polymorphs due to different molecular configuration. Furthermore, Form A exhibits more stable than Form B at high temperatures.

  18. Imaging of amyloid using [11C]-PIB PET in patients with Alzheimer's disease

    International Nuclear Information System (INIS)

    Hatashita, Shizuo; Yamasaki, Hidetomo

    2010-01-01

    We investigated whether [N-methyl- 11 C]2-(4'-metylaminophenyl)-6-hydroxybenzothiazole ([11C]-PIB) positron emission tomography (PET) detects underlying amyloid deposition at clinically different stages of Alzheimer's disease (AD). Post-mortem study of typical AD brain has recently demonstrated that the in vivo retention of PIB is related directly to the amount of insoluble amyloid B peptides, including amyloid plaques. Fifty-six patients who met criteria for AD and 74 age-matched healthy controls (HC) were included. All subjects underwent cognitive testing and 60-min dynamic [11C]-PIB PET. [11C]-PIB data were acquired from 35-60 min after injection. Regions of interest were defined on co-registered MRI and applied to dynamic images. Distribution volume ratios (DVR) of PIB retention were determined using Logan graphical analysis (cerebellar gray as reference region). All 56 patients with AD showed robust increases in PIB retention in cingulate, precuneus, frontal, parietal, and lateral temporal cortical regions (typical PIB AD-pattern). In contrast, there was no PIB retention in cortical regions in all HC subjects. Mean DVR values in 11 patients with moderate AD (clinical dementia rating (CDR): 2.1±0.4) showed significantly higher PIB retention (2.38±0.42, P<0.01) than in HC