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Sample records for 11c 13n 15o

  1. Characteristics of the chemical forms of 11C, 13N, and 15O induced in air by the operation of a 100 MeV electron linear accelerator.

    PubMed

    Endo, A; Kikuchi, M; Izawa, S; Ikezawa, Y

    1995-01-01

    To characterize airborne radioactivity induced by the operation of high-energy accelerators, the fractions of aerosol and gaseous components, and the chemical forms of 11C, 13N, and 15O produced in the air of a target room of a 100 MeV electron linear accelerator were studied. Measurements of radioactivity using a particulate air sampling filter and a gas flow-through ionization chamber showed that more than 98% of 11C, 13N, and 15O were present as gaseous forms. Their chemical forms, detected by means of radio-gas chromatography, were 11C as CO2; 13N as N2 and NO; and 15O as O2 and NO. Machine operating conditions, which affect the compositions of the induced radionuclides and of their chemical forms, and the resulting effect on the estimation of internal doses are discussed. PMID:7989199

  2. Study of the production yields of 18F, 11C, 13N and 15O positron emitters from plasma-laser proton sources at ELI-Beamlines for labeling of PET radiopharmaceuticals

    NASA Astrophysics Data System (ADS)

    Amato, Ernesto; Italiano, Antonio; Margarone, Daniele; Pagano, Benedetta; Baldari, Sergio; Korn, Georg

    2016-03-01

    The development of novel compact PET radionuclide production systems is of great interest to promote the diffusion of PET diagnostics, especially in view of the continuous development of microfluidics labeling approaches. We studied the feasibility to produce clinically-relevant amounts of PET isotopes by means of laser-accelerated proton sources such that expected at the ELI-Beamlines facility. 18F, 11C, 13N and 15O production yields were calculated through the TALYS software, by taking into account the broad proton spectra expected. With the hypothesized proton fluencies, clinically-relevant amounts of radionuclides can be obtained, suitable to prepare single doses of 18F-, 11C- and 13N-labeled radiopharmaceuticals exploiting fast and efficient microfluidic labeling systems.

  3. Study of Nuclear Reactions with 11C and 15O Radioactive Ion Beams

    SciTech Connect

    Lee, Dongwon

    2007-05-14

    Nuclear reaction study with radioactive ion beams is one of the most exciting research topics in modern nuclear physics. The development of radioactive ion beams has allowed nuclear scientists and engineers to explore many unknown exotic nuclei far from the valley of nuclear stability, and to further our understanding of the evolution of the universe. The recently developed radioactive ion beam facility at the Lawrence Berkeley National Laboratory's 88-inch cyclotron is denoted as BEARS and provides {sup 11}C, {sup 14}O and {sup 15}O radioactive ion beams of high quality. These moderate to high intensity, proton-rich radioactive ion beams have been used to explore the properties of unstable nuclei such as {sup 12}N and {sup 15}F. In this work, the proton capture reaction on {sup 11}C has been evaluated via the indirect d({sup 11}C, {sup 12}N)n transfer reaction using the inverse kinematics method coupled with the Asymptotic Normalization Coefficient (ANC) theoretical approach. The total effective {sup 12}N {yields} {sup 11}C+p ANC is found to be (C{sub eff}{sup 12{sub N}}){sup 2} = 1.83 {+-} 0.27 fm{sup -1}. With the high {sup 11}C beam intensity available, our experiment showed excellent agreement with theoretical predictions and previous experimental studies. This study also indirectly confirmed that the {sup 11}C(p,{gamma}) reaction is a key step in producing CNO nuclei in supermassive low-metallicity stars, bypassing the slow triple alpha process. The newly developed {sup 15}O radioactive ion beam at BEARS was used to study the poorly known level widths of {sup 16}F via the p({sup 15}O,{sup 15}O)p reaction. Among the nuclei in the A=16, T=1 isobaric triad, many states in {sup 16}N and {sup 16}O have been well established, but less has been reported on {sup 16}F. Four states of {sup 16}F below 1 MeV have been identified experimentally: 0{sup -}, 1{sup -}, 2{sup -}, and 3{sup -} (E{sub x} = 0.0, 0.19, 0.42, and 0.72 MeV, respectively). Our study utilized R

  4. Evaluation of myocardial metabolism, with /sup 13/N- and /sup 11/C-labeled amino acids and positron computed tomography

    SciTech Connect

    Henze, E.; Schelbert, H.R.; Barrio, J.R.; Egbert, J.E.; Hansen, H.W.; MacDonald, N.S.; Phelps, M.E.

    1982-08-01

    To evaluate the utility of labeled L-amino acids (AA) for imaging regional myocardial AA metabolism by positron computed tomography (PCT), the myocardial uptake and clearance of Ala,* Glu, Gln, Asp, Leu tagged with /sup 13/N, and of /sup 11/C-tagged Asp, and oxaloacetate (Oxal), were examined in 44 experiments at control, during ischemia, and after transaminase inhibition. The myocardial time-activity curves recorded after intracoronary tracer injection had two clearance phases (an early and a late) for all /sup 13/N AA, and three (early, intermediate, late) for the two /sup 11/C compounds, with significantly different clearance half-times of 18.7 +/- 8.0 (s.d.) sec for the early phase, 141.7 +/- 56.5 sec for the intermediate, and 61.2 +/- 43.5 min for the late phase. The residual fractions ranged from 0.07 to 0.23 in normal myocardium, and consistently increased with ischemia by 0.01-0.07 for /sup 13/N-labeled Ala, Glu, Asp, and Leu, but not for /sup 13/N Gln and /sup 11/C compounds. Transaminase inhibition shortened the half-times of the late phases of /sup 13/N-labeled Ala, Glu, Asp, and Leu; had no effect on t1/2 of /sup 13/N Gln and /sup 11/C Oxal; and resulted in a loss of /sup 11/C CO/sub 2/ production and of the intermediate phase for /sup 11/C Asp. On the PCT images, /sup 13/N activity from labeled Ala and Glu was not decreased in an ischemic segment despite a significant flow reduction, as demonstrated by /sup 13/N NH/sub 3/ imaging and labeled microspheres. From the results, a three-compartment tracer kinetic model is proposed for the noninvasive quantification of Krebscycle activity, protein synthesis, and metabolic derangements related to ischemia.

  5. Time-dependent chemical compositions of 13N and 15O induced in air by the operation of a high energy electron accelerator.

    PubMed

    Endo, A; Henshaw, J; Mignanelli, M A

    1998-04-01

    Time-dependent chemical compositions for 13N and 15O induced in the air atmosphere of a high energy electron accelerator room have been studied using a computer simulation method. A radiation chemistry model was developed to describe the chemical reactions of 13N and 15O species with the air molecules and their radiolytic products. By assuming several chemical forms of 13N and 15O generated by the (gamma, n) reaction, the variations of the concentrations of 13N and 15O species were simulated under a radiation field. From the comparison between the simulations and experiment in a 100 MeV electron linear accelerator (linac) facility, the following conclusions were obtained: (1) Just after the (gamma, n) reaction, 25-50% of 13N and 15O are present as atoms (13N, 15O) and/or their ions (13N+, 15O+) and the remainder as nitrogen and oxygen molecules (13NN, 15OO) and/or their ions (13NN+, 15OO+); (2) Neutralization of 13N+ and 15O+ ions into 13N and 15O atoms occurs instantaneously and the same is the case with the neutralization of 13NN+ and 15OO+ ions to 13NN and 15OO molecules; (3) The neutralized 13N and 15O atoms react with the air molecules and the radiolytic products to form nitrogen oxide compounds and ozone, while 13NN and 15OO remain as these molecules. Factors that control the chemical reactions of 13N and 15O are discussed. PMID:9525420

  6. N-11C-Methyl-Dopamine PET Imaging of Sympathetic Nerve Injury in a Swine Model of Acute Myocardial Ischemia: A Comparison with 13N-Ammonia PET

    PubMed Central

    Zhou, Weina; Wang, Xiangcheng; He, Yulin; Nie, Yongzhen; Zhang, Guojian; Wang, Cheng; Wang, Chunmei; Wang, Xuemei

    2016-01-01

    Objective. Using a swine model of acute myocardial ischemia, we sought to validate N-11C-methyl-dopamine (11C-MDA) as an agent capable of imaging cardiac sympathetic nerve injury. Methods. Acute myocardial ischemia was surgically generated in Chinese minipigs. ECG and serum enzyme levels were used to detect the presence of myocardial ischemia. Paired 11C-MDA PET and 13N-ammonia PET scans were performed at baseline, 1 day, and 1, 3, and 6 months after surgery to relate cardiac sympathetic nerve injury to blood perfusion. Results. Seven survived the surgical procedure. The ECG-ST segment was depressed, and levels of the serum enzymes increased. Cardiac uptake of tracer was quantified as the defect volume. Both before and immediately after surgery, the images obtained with 11C-MDA and 13N-ammonia were similar. At 1 to 6 months after surgery, however, 11C-MDA postsurgical left ventricular myocardial defect volume was significantly greater compared to 13N-ammonia. Conclusions. In the Chinese minipig model of acute myocardial ischemia, the extent of the myocardial defect as visualized by 11C-MDA is much greater than would be suggested by blood perfusion images, and the recovery from myocardial sympathetic nerve injury is much slower than the restoration of blood perfusion. 11C-MDA PET may provide additional biological information during recovery from ischemic heart disease. PMID:27034950

  7. Positron emission tomographic measurement of cerebral blood flow and permeability-surface area product of water using (/sup 15/O)water and (/sup 11/C)butanol

    SciTech Connect

    Herscovitch, P.; Raichle, M.E.; Kilbourn, M.R.; Welch, M.J.

    1987-10-01

    We have previously adapted Kety's tissue autoradiographic method for measuring regional CBF in laboratory animals to the measurement of CBF in humans with positron emission tomography (PET) and H/sub 2/(/sup 15/)O. Because this model assumes diffusion equilibrium between tissue and venous blood, the use of a diffusion-limited tracer, such as H/sub 2/(/sup 15/)O, may lead to an underestimation of CBF. We therefore validated the use of (/sup 11/C)butanol as an alternative freely diffusible tracer for PET. We then used it in humans to determine the underestimation of CBF that occurs with H/sub 2/(/sup 15/)O, and thereby were able to calculate the extraction Ew and permeability-surface area product PSw of H/sub 2/(/sup 15/)O. Measurements of the permeability of rhesus monkey brain to (/sup 11/C)butanol, obtained by means of an intracarotid injection, external detection technique, demonstrated that this tracer is freely diffusible up to a CBF of at least 170 ml/min-100 g. CBF measured in baboons with the PET autoradiographic method and (/sup 11/C)butanol was then compared with CBF measured in the same animals with a standard residue detection method. An excellent correspondence was obtained between both of these measurements. Finally, paired PET measurements of CBF were made with both H/sub 2/(/sup 15/)O and (/sup 11/C)butanol in 17 normal human subjects. Average global CBF was significantly greater when measured with (/sup 11/C)butanol (53.1 ml/min-100 g) than with H/sub 2/(/sup 15/)O (44.4 ml/min-100 g). Average global Ew was 0.84 and global PSw was 104 ml/min-100 g. Regional measurements showed a linear relationship between local PSw and CBF, while Ew was relatively uniform throughout the brain. Simulations were used to determine the potential error associated with the use of an incorrect value for the brain-blood partition coefficient for (/sup 11/C)butanol and to calculate the effect of tissue heterogeneity and errors in flow measurement on the calculation of PSw.

  8. The complete set of spin observables for the (13)C(polarized proton, polarized neutron)(13)N and (15)N(polarized proton, polarized neutron)(15)O reactions

    NASA Astrophysics Data System (ADS)

    Du, Qun Qun

    1998-12-01

    The 13C(p,n)13N and 15N(p,n)15O reactions have been a puzzle for more than ten years. The ground state transitions are Jπ=1/2- to Jπ=1/2-. These are 'mixed' transitions because they can involve quantum number changes either (/Delta T=1,/ /Delta J=0,/ /Delta/pi=0,/ /Delta S=0), or (/Delta T=1,/ /Delta J=1,/ /Delta/pi=0,/ /Delta S=1); these quantum number changes are refered to as 'Fermi' and 'Gamow-Teller' respectively. Because the quantum number changes are the same as for Fermi and Gamow-Teller beta decay. From the systematics of (p,n) and (n,p) reactions on pure Fermi transitions (e.g. 0 + to 0+) and pure Gamow-Teller transitions (e.g. 0+ to 1+), calibrations have been established of cross section per unit B(F) or unit B(GT), where 'B' refers to doubly reduced matrix elements extracted from beta decay. However, cross sections for the 13C(p,n)13N(g.s.) and 15N(p,n)15O(g.s.) reactions are substantially larger than one would then predict from the known B(F)s and B(GT)s for these transitions. To explore this anomaly, spin observables were used to extract separately the Fermi and Gamow-Teller cross sections for these reactions. To acquire the complete sets of polarization- transfer observables, a new neutron polarimeter was designed, built, commissioned and calibrated. This polarimeter, call the '2π polarimeter' because of its complete azimuthal coverage for scattered neutrons, has very good position and timing resolution (354 ps). The complete sets of spin-transfer coefficients Dij for 13C(p,n)13N (at 0o , 5.5o , and 11o ) and 15N(p,n)15O (at 0o ) at 135 MeV were measured. Following the formalism of Ichimura and Kawahigashi, we extracted the spin-longitudinal, and spin-transverse and spin-independent responses D0,/ Dq,/ Dn and Dp from the measured Dijs. The F and GT fractions of the (p,n) cross sections are then extracted as f F=D0 and fGT=Dn+Dp+Dq=1- d0. Values of Dk for both the 13C(p,n)13N(g.s) and 15N(p,n)15O(g.s.) were extracted. From these responses, we

  9. Production of radiohalogens and [11C]-methane at high specific activity

    NASA Astrophysics Data System (ADS)

    Nye, Jonathon Andrew

    2005-07-01

    The halogens, occupying Group VII of the periodic table, play an important role in the biochemical processes underlying health and disease. A variety of positron emitters covering a broad range of half-lives permit the imaging of the body's physiochemical behavior using PET. Neutron deficient isotopes of the halogen group can be produced by (p,n) reactions from enriched targets with low energy (<13MeV) biomedical cyclotrons. These cyclotrons are distributed relatively evenly throughout the United States at research institutions and commercial distribution sites (i.e., 100+ CTI RDS 11MeV proton cyclotrons). However, these sites concentrate on the core group of positron emitters: 15O, 13N, 11C, and primarily 18F-fluoride. The simplicity of the production process insures their role in the clinical/research environment, labeling H215 O, 13NH3, CH3-compounds and 18F-FDG. Halogens with half-lives longer than 18F have been avoided due to a combination of several factors, such as complexity of the target systems, expense of the enriched substrate, low reaction yields, and extensive post-processing to reclaim the target material. PET research over the last decade has forced a match between drug development and emerging small animal instrumentation, shifting focus to agents labeled with high specific activity 11CH3I and the long-lived radiohalogens, 76Br and 124I. A steady local supply of 18F-fluoride, 11C-methane, 76B-bromide, and 124I-iodide is essential to seize today's research opportunities or for limited distribution outside of our local area. To keep pace, new targetry developments are implemented to reliably produce these isotopes on a batch basis. The research presented details improvements on existing production methods for 18F-fluoride intended for nucleophilic substitution and high specific activity 11C-methane (→CH3I) for the N-methylation of a half-dozen neuroligands. A significant effort is placed on the novel use of low energy cyclotrons for the production

  10. Production of {sup 17}F, {sup 15}O and other radioisotopes for PET using a 3 MV electrostatic tandem accelerator

    SciTech Connect

    Roberts, A. D.; Davidson, R. J.; Nickles, R. J.

    1999-06-10

    Target systems for the production of positron emitting radioisotopes used for medical research with positron emission tomography (PET) are under development for a 3 MV electrostatic tandem accelerator (NEC 9SDH-2). This machine is intended primarily for the continuous production of short lived tracers labeled with {sup 15}O (t{sub 1/2}=122 s) or {sup 17}F (t{sub 1/2}=65 s) for determining regional cerebral blood flow in humans. Simple gas, liquid, and solid target systems are presented for the production of [{sup 15}O]H{sub 2}O (yield at saturation 13 mCi/{mu}A), [{sup 17}F]F{sub 2} (22 mCi/{mu}A), [{sup 17}F] fluoride (aq.) (12 mCi/{mu}A), [{sup 18}F]fluoride (aq.) (21 mCi/{mu}A), [{sup 13}N] in graphite (25 mCi/{mu}A), and [{sup 11}C]CO{sub 2} (2.3 mCi/{mu}A). Current limitations on single window targets for each production are discussed.

  11. Measurement of excitation functions in the reactions 197Au(11C, xn)208-xAt using a radioactive 11C beam

    PubMed

    Joosten; Powell; Guo; Haustein; Larimer; McMahan; Norman; O'Neil; Rowe; VanBrocklin; Wutte; Xu; Cerny

    2000-05-29

    A light-element radioactive ion-beam capability has been developed at the LBNL 88-Inch Cyclotron. The system is based on the coupled-cyclotrons method and utilizes short-lived species, e.g., 11C, 14O, 13N produced by (p,n) and (p,alpha) reactions at the LBNL Biomedical Isotope Facility Cyclotron. In a first experiment, 197Au(11C,xn)208-xAt excitation functions have been measured for energies ranging from the Coulomb barrier up to 110 MeV using a beam of 11C with intensities up to (1-2)x10(8) ions/sec on target. The results of this experiment are compared to measurements of 197Au(12C, xn)209-xAt excitation functions. PMID:10990868

  12. Design and automated production of 11C-alpha-methyl-l-tryptophan (11C-AMT).

    PubMed

    Huang, Xuan; Xiao, Xia; Gillies, Robert J; Tian, Haibin

    2016-05-01

    (11)C-alpha-methyl-l-tryptophan ([(11)C]AMT), a tryptophan metabolism PET tracer, has successfully been employed for brain serotonin pathway and indoleamine 2,3-dioxygenase (IDO) pathway related tumor imaging. We here report a reliable, automated procedure for routine synthesis of [(11)C]AMT based on an Eckert and Ziegler Modular-Lab system. The semi-preparative HPLC was incorporated into the system to improve chemical purity and specific activity. The 6-step radiosynthesis followed by HPLC-purification provided [(11)C]AMT in 5.3±1.2% (n=6, non-decay-corrected) overall radiochemical yield with radiochemical purity >99% and specific activity of 35-116GBq/μmol. Usually, 2.95±0.65GBq (n=6, EOS) patient ready dose was produced from about 55.5GBq [(11)C]CO2 in 50min. PMID:27150033

  13. Assessment of glutamine synthetase activity by [13N]ammonia uptake in living rat brain.

    PubMed

    Momosaki, Sotaro; Ito, Miwa; Tonomura, Misato; Abe, Kohji

    2015-01-01

    Glutamine synthetase (GS) plays an important role in glutamate neurotransmission or neurological disorder in the brain. [(13) N]Ammonia blood flow tracer has been reported to be metabolically trapped in the brain via the glutamate-glutamine pathway. The present study investigated the effect of an inhibitor of GS on [(13) N]ammonia uptake in order to clarify the feasibility of measuring GS activity in the living brain. l-Methionine sulfoximine (MSO), a selective GS inhibitor was microinjected into the ipsilateral striatum in rats. [(13) N]Ammonia uptake was quantified by autoradiography method as well as small animal positron emission tomography (PET) scans. The GS activity of the brain homogenate was assayed from the γ-glutamyl transferase reaction. Autoradiograms showed a decrease of [(13) N]ammonia radioactivity on the MSO-injected side compared with the saline-injected side of the striatum. This reduction could be detected with a small animal PET scanner. MSO had no effect on cerebral blood flow measured by uptake of [(15) O]H2 O. The reduction of [(13) N]ammonia uptake was closely related to the results of GS activity assay. These results indicated that [(13) N]ammonia may enable measurement of GS activity in the living brain. PMID:25196365

  14. 1-/sup 11/C-D-glucose and related compounds

    SciTech Connect

    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.

  15. 1-.sup.11 C-D-Glucose and related compounds

    DOEpatents

    Shiue, Chyng-Yann; Wolf, Alfred P.

    1984-03-27

    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.

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

    PubMed Central

    2012-01-01

    11C-labeled methylbenzoates [11C]4a–d were synthesized using Pd(0)-mediated rapid cross-coupling reactions employing [11C]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 [11C]O). The reaction conditions were highly favorable for the synthesis of [11C]Am80 ([11C]2) and [11C]methyl 4-((5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)carbamoyl)benzoate ([11C]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 [11C]4a, [11C]2-Me, and [11C]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%. PMID:24900383

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

    PubMed

    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%. PMID:24900383

  18. Optimization of [11C]HCN production and no-carrier-added [1-11C]amino acid synthesis.

    PubMed

    Iwata, R; Ido, T; Takahashi, T; Nakanishi, H; Iida, S

    1987-01-01

    The optimal conditions for the catalytic production of [11C]HCN from [11C]CO2 were investigated. [11C]CO2 was reduced to [11C]CH4 with H2 on Ni and then converted to [11C]HCN by reaction with NH3 on Pt in a radiochemical yield of more than 95% under the optimized conditions of an NH3 concentration of 5 vol%, a Pt furnace temperature of 920 degrees C, and a reaction gas flow rate of over 200 mL/min. Absorbers were used to remove O2 and H2O from the reaction gas. The synthesis of no-carrier-added [1-11C]amino acids from [11C]HCN via [11C]aminonitriles was successfully carried out. This method is suitable for automation of [1-11C]amino acid production. PMID:3032866

  19. Photonuclear target systems for producing clinically useful quantities of 11C using an electron linear accelerator.

    PubMed

    Piltingsrud, H V; Robbins, P J

    1985-01-01

    Described in this paper are what we believe to be the first practical photonuclear target systems for production of 11C containing CO and CO2 using bremsstrahlung produced from an electron linear accelerator similar to certain radiotherapy accelerators. This is a continuation of work reported earlier concerning a similar target system presently being used for production of 15O-O2. The 11C producing systems utilized liquid carbon dioxide, liquid cyclohexane, and liquid glacial acetic acid target materials. The carbon dioxide and glacial acetic acid target materials produced principally a 11C-CO product material. The cyclohexane target material produced a 11C-hydrocarbon product which was then oxidized to CO2. Target activity yields for these systems, normalized to a 20-cm-long by 10-cm-diam target chamber irradiated in a bremsstrahlung field produced by a 26-MeV, 100-microA electron beam, were 1.9 X 10(8) Bq (5 mCi) at 7.4 X 10(8) Bq g-1 (20 mCi g-1) for carbon dioxide, 1.4 X 10(8) Bq (3.8 mCi) at 3.7 X 10(10) Bq g-1 (1 Ci g-1) for cyclohexane, and 7.4 X 10(8) Bq (20 mCi) at 3.7 X 10(10) Bq g-1 (1 Ci g-1) for glacial acetic acid. PMID:3930932

  20. High molar activity of [11C]TCH346 via [11C]methyl triflate using the "wet" [11C]CO2 reduction method.

    PubMed

    Ermert, Johannes; Stüsgen, Stefan; Lang, Markus; Roden, Werner; Coenen, Heinz H

    2008-05-01

    [(11)C]TCH346, a compound acting on the glycolytic enzyme, glycerol-aldehyde-3-phosphate dehydrogenase, was produced under optimised conditions by methylation of the desmethyl compound with no-carrier added (n.c.a.) [(11)C]methyl triflate. An i.v. injectable solution of n.c.a. [(11)C]TCH346 containing 4040+/-1550 MBq (n=6) containing a molar activity between 40 and 5700 GBq/micromol and a radiochemical purity of >99% was obtained within 30 min (after EOB) by irradiation of nitrogen gas containing 0.5% oxygen with 16.5 MeV protons at 45 microA for 30 min. The alkylation reagent [(11)C]methyl triflate was prepared via on-line conversion of [(11)C]methyl iodide. For the formation of [(11)C]methyl iodide, [(11)C]carbon dioxide from the target chamber was reduced by a lithium aluminium hydride solution, and the methanol obtained on-line was converted using triphenylphosphine diiodide. The molar activity of [(11)C]TCH346 could be improved from 40 up to nearly 5700GB q/micromol during the optimisation of the synthesis using the same stock solution of lithium aluminium hydride solution in tetrahydrofuran. PMID:17827025

  1. Synthesis of (11)C-labeled retinoic acid, [(11)C]ATRA, via an alkenylboron precursor by Pd(0)-mediated rapid C-[(11)C]methylation.

    PubMed

    Suzuki, Masaaki; Takashima-Hirano, Misato; Ishii, Hideki; Watanabe, Chika; Sumi, Kengo; Koyama, Hiroko; Doi, Hisashi

    2014-08-01

    Retinoids are a class of chemical compounds which include both natural dietary vitamin A (retinol) metabolites and active synthetic analogs. Both experimental and clinical studies have revealed that retinoids regulate a wide variety of essential biological processes. In this study, we synthesized (11)C-labeled all-trans-retinoic acid (ATRA), the most potent biologically active metabolite of retinol and used in the treatment of acute promyelocytic leukemia. The synthesis of (11)C-labeled ATRA was accomplished by a combination of rapid Pd(0)-mediated C-[(11)C]methylation of the corresponding pinacol borate precursor prepared by 8 steps and hydrolysis. [(11)C]ATRA will prove useful as a PET imaging agent, particularly for elucidating the improved therapeutic activity of ATRA (natural retinoid) for acute promyelocytic leukemia by comparing with the corresponding PET probe [(11)C]Tamibarotene (artificial retinoid). PMID:24930828

  2. Synthesis of Diverse (11)C-Labeled PET Radiotracers via Direct Incorporation of [(11)C]CO2.

    PubMed

    Mossine, Andrew V; Brooks, Allen F; Jackson, Isaac M; Quesada, Carole A; Sherman, Phillip; Cole, Erin L; Donnelly, David J; Scott, Peter J H; Shao, Xia

    2016-05-18

    Three new positron emission tomography (PET) radiotracers of interest to our functional neuroimaging and translational oncology programs have been prepared through new developments in [(11)C]CO2 fixation chemistry. [(11)C]QZ (glutaminyl cyclase) was prepared via a tandem trapping of [(11)C]CO2/intramolecular cyclization; [(11)C]tideglusib (glycogen synthase kinase-3) was synthesized through a tandem trapping of [(11)C]CO2 followed by an intermolecular cycloaddition between a [(11)C]isocyanate and an isothiocyanate to form the 1,2,4-thiadiazolidine-3,5-dione core; [(11)C]ibrutinib (Bruton's tyrosine kinase) was synthesized through a HATU peptide coupling of an amino precursor with [(11)C]acrylic acid (generated from [(11)C]CO2 fixation with vinylmagnesium bromide). All radiochemical syntheses are fully automated on commercial radiochemical synthesis modules and provide radiotracers in 1-5% radiochemical yield (noncorrected, based upon [(11)C]CO2). All three radiotracers have advanced to rodent imaging studies and preliminary PET imaging results are also reported. PMID:27043721

  3. An efficient and practical radiosynthesis of [11C]temozolomide

    PubMed Central

    Moseley, Christian K.; Carlin, Stephen M.; Neelamegam, Ramesh

    2014-01-01

    Temozolomide (TMZ) is a prodrug for an alkylating agent used for the treatment of malignant brain tumors. A positron emitting version, [11C]TMZ, has been utilized to help elucidate the mechanism and biodistribution of TMZ. Challenges in [11C]TMZ synthesis and reformulation make it difficult for routine production. Herein we report a highly reproducible one-pot radiosynthesis of [11C]TMZ with a radiochemical yield of 17±5% and >97% radiochemical purity. PMID:23151019

  4. No-carrier-added [1.sup.11 c]putrescine

    DOEpatents

    McPherson, Daniel W.; Fowler, Joanna S.; Wolf, Alfred P.

    1989-01-01

    The invention relates to a new radiolabeled imaging agent, no-carrier-added [1-.sup.11 C]putrescine, and to the use of this very pure material as a radiotracer with positron emission tomography for imaging brain tumors. The invention further relates to the synthesis of no-carrier-added [1-.sup.11 C]putrescine based on the Michael addition of potassium .sup.11 C-labeled cyanide to acrylonitrile followed by reduction of the .sup.11 C-labeled dinitrile. The new method is rapid and efficient and provides radiotracer with a specific activity greater than 1.4 curies per millimol and in a purity greater than 95%.

  5. The clinical use of PET with 11C-acetate

    PubMed Central

    Grassi, Ilaria; Nanni, Cristina; Allegri, Vincenzo; Morigi, Joshua James; Montini, Gian Carlo; Castellucci, Paolo; Fanti, Stefano

    2012-01-01

    The aim of this review is to evaluate clinical applications of 11C-acetate positron emission tomography (PET). Acetate is quickly metabolized into acetyl-CoA in human cells. In this form it can either enter into the tricarboxylic acid cycle, thus producing energy, as happens in the myocardium, or participate in cell membrane lipid synthesis, as happens in tumor cells. 11C-acetate PET was originally employed in cardiology, to study myocardial oxygen metabolism. More recently it has also been used to evaluate myocardial perfusion, as well as in oncology. The first studies of 11C-acetate focused on its use in prostate cancer. Subsequently, 11C-acetate was studied in other urological malignancies, as well as renal cell carcinoma and bladder cancer. Well differentiated hepatocellular carcinoma represents an 18F-fluoro-deoxyglucose (18F-FDG) PET pitfall, so many authors have proposed to use 11C-acetate in addition to 18F-FDG in studying this tumor. 11C-acetate PET has also been used in other malignancies, such as brain tumors and lung carcinoma. Some authors reported a few cases in which 11C-acetate PET incidentally found multiple myeloma or rare tumors, such as thymoma, multicentric angiomyolipoma of the kidney and cerebellopontine angle schwannoma. Lastly, 11C-acetate PET was also employed in a differential diagnosis case between glioma and encephalitis. The numerous studies on 11C-acetate have demonstrated that it can be used in cardiology and oncology with no contraindications apart from pregnancy and the necessity of a rapid scan. Despite its limited availability, this tracer can surely be considered to be a promising one, because of its versatility and capacity to even detect non 18F-FDG-avid neoplasm, such as differentiated lung cancer or hepatocellular carcinoma. PMID:23133801

  6. Positron annihilation spectroscopy of biological tissue in 11C irradiation

    NASA Astrophysics Data System (ADS)

    Sakurai, Hiroshi; Itoh, Fumitake; Hirano, Yoshiyuki; Nitta, Munetaka; Suzuki, Kosuke; Kato, Daisuke; Yoshida, Eiji; Nishikido, Fumihiko; Wakizaka, Hidekatsu; Kanai, Tatsuaki; Yamaya, Taiga

    2014-11-01

    Positron annihilation spectroscopy (PAS) spectra of biological tissue in 11C irradiation are reported and spatial resolution coefficient of positron emission tomography (PET) obtained from the PAS spectrum is discussed for 11C irradiation. A PAS spectrum of the biological tissue with water is the same as that of the water pool phantom in 11C irradiation. However, a PAS spectrum of the biological tissue with less water differs from that of the water pool phantom. The PET spatial resolution coefficient depends on the kind of biological tissue. However, the PET spatial resolution coefficient, 0.00243  ±  0.00014, can be used as a common value of maximum limit.

  7. Synthesis of [11C]Bexarotene by Cu-Mediated [11C]Carbon Dioxide Fixation and Preliminary PET Imaging

    PubMed Central

    2014-01-01

    Bexarotene (Targretin) is a retinoid X receptor (RXR) agonist that has applications for treatment of T cell lymphoma and proposed mechanisms of action in Alzheimer’s disease that have been the subject of recent controversy. Carbon-11 labeled bexarotene ([11C-carbonyl]4-[1-(3,5,5,8,8-pentamethyltetralin-2-yl)ethenyl]benzoic acid) was synthesized using a Cu-mediated cross-coupling reaction employing an arylboronate precursor 1 and [11C]carbon dioxide under atmospheric pressure in 15 ± 2% uncorrected radiochemical yield (n = 3), based on [11C]CO2. Judicious choice of solvents, catalysts, and additives, as well as precursor concentration and purity of [11C]CO2, enabled the preparation of this 11C-labeled carboxylic acid. Formulated [11C]bexarotene was isolated (>37 mCi) with >99% radiochemical purity in 32 min. Preliminary positron emission tomography–magnetic resonance imaging revealed rapid brain uptake in nonhuman primate in the first 75 s following intravenous administration of the radiotracer (specific activity >0.3 Ci/μmol at time of injection), followed by slow clearance (Δ = −43%) over 60 min. Modest uptake (SUVmax = 0.8) was observed in whole brain and regions with high RXR expression. PMID:24944741

  8. Improved Automated Radiosynthesis of [11C]PBR28

    PubMed Central

    Solingapuram Sai, Kiran Kumar; Gage, Don; Nader, Mike; Mach, Robert H.; Mintz, Akiva

    2015-01-01

    Microglial activation is commonly identified by elevated levels of the 18 kDa translocator protein (TSPO) in response to several inflammatory processes. [11C]PBR28 is one of the most promising PET tracers to image TSPO in both human and non-human primates. In this study, we optimized the radiolabeling procedure of [11C]PBR28 for higher radiochemical yield, radiochemical purity, and specific activity, which can be easily translated to any automated module for clinical trials. Time-activity curves (TACs) derived from the dynamic PET imaging of male rhesus monkey brains demonstrated that [11C]PBR28 had suitable kinetics with radiotracer accumulation observed in the caudate, putamen, cerebellum, and frontal cortex region. PMID:26839827

  9. Preclinical PET Neuroimaging of [11C]Bexarotene.

    PubMed

    Rotstein, Benjamin H; Placzek, Michael S; Krishnan, Hema S; Pekošak, Aleksandra; Collier, Thomas Lee; Wang, Changning; Liang, Steven H; Burstein, Ethan S; Hooker, Jacob M; Vasdev, Neil

    2016-01-01

    Activation of retinoid X receptors (RXRs) has been proposed as a therapeutic mechanism for the treatment of neurodegeneration, including Alzheimer's and Parkinson's diseases. We previously reported radiolabeling of a Food and Drug Administration-approved RXR agonist, bexarotene, by copper-mediated [(11)C]CO2 fixation and preliminary positron emission tomography (PET) neuroimaging that demonstrated brain permeability in nonhuman primate with regional binding distribution consistent with RXRs. In this study, the brain uptake and saturability of [(11)C]bexarotene were studied in rats and nonhuman primates by PET imaging under baseline and greater target occupancy conditions. [(11)C]Bexarotene displays a high proportion of nonsaturable uptake in the brain and is unsuitable for RXR occupancy measurements in the central nervous system. PMID:27553293

  10. Myocradial extraction of 1-[{sup 11}C] betamethylheptadecanoic acid

    SciTech Connect

    Elmaleh, D.R.; Livni, E.; Alpert, N.M.

    1994-03-01

    Betamethylheptadecanoic acid (BMHA) is a branched chain fatty acid analog that is transported into myocardial cells by the same long chain fatty acid carrier protein mechanism as natural fatty acids, but cannot be completely catabolzied and accumulates in the tissue. Thus, {sup 11}C-labeled BMHA is a useful tracer for the noninvasive evaluation of myocardial fatty acid utilization by positron emission tomography (PET). As a prelude to PET studies, the metabolism of BMHA was studied by classical techniques. The authors measured the net extraction fraction (E{sub n}) of 1-[{sup 11}C]-beta-R,S-methylheptadecanoic acid (1-[{sup 11}C]BMHA) and compared it to that of natural fatty acids in dogs, using arterial/venous measurements and a mathematical model. Two groups of conditioned dogs were studied. In the first group, measurements were made under fasting (normal control) conditions and in the second group, measurements were made during glucose and insulin infusion. Myocardial blood flow, and the extraction/utilization of other substrates (glucose, oxygen and lactate) were also measured. For natural fatty acids in the basal state, E{sub n}(FA) was 0.335. After glucose/insulin infusion, this value decreased to 0.195. The 1-[{sup 11}C]BMHA showed a similar decrease in E{sub n}(BMHA) from 0.220 in the control group to 0.100 in the group treated with glucose/insulin infusion. Preliminary PET studies with 1-[{sup 11}C]BMHA verified the validity of performing these measurements noninvasively. The results of these studies indicate that rates of fatty acid metabolism in the myocardium can be determined from steady-state concentrations of 1-[{sup 11}C]BMHA. 36 refs., 6 figs., 4 tabs.

  11. Radiosynthesis and preliminary PET evaluation of glycogen synthase kinase 3β (GSK-3β) inhibitors containing [(11)C]methylsulfanyl, [(11)C]methylsulfinyl or [(11)C]methylsulfonyl groups.

    PubMed

    Kumata, Katsushi; Yui, Joji; Xie, Lin; Zhang, Yiding; Nengaki, Nobuki; Fujinaga, Masayuki; Yamasaki, Tomoteru; Shimoda, Yoko; Zhang, Ming-Rong

    2015-08-15

    Three compounds 1-3 containing methyl-sufanyl, sufinyl, or sulfonyl groups are strong inhibitors of glycogen synthase kinase 3β (GSK-3β), an enzyme associated with Alzheimer's disease. We labeled 1-3 with (11)C for a positron emission tomography (PET) brain imaging study. A novel thiophenol precursor 4 for radiosynthesis was prepared by reacting sulfoxide 2 with trifluoroacetic anhydride. [(11)C]1 was synthesized by reacting 4 with [(11)C]methyl iodide in 52 ± 5% radiochemical yield (n = 5, based on [(11)C]CO2, corrected for decay). Oxidation of [(11)C]1 with Oxone® produced [(11)C]2 and [(11)C]3, respectively. PET with [(11)C]1 and [(11)C]3 showed 2 fold higher brain uptake of radioactivity in a mouse model of cold water stress in which GSK-3β expression was increased, than in the controls. PMID:26067173

  12. (11)C-Methionine uptake in secondary brain epilepsy.

    PubMed

    Lopci, E; Bello, L; Chiti, A

    2014-01-01

    Carbon-11 methionine ((11)C-Methionine) is a radio-labeled amino acid currently utilized in Positron Emission Tomography (PET) for imaging primary and metastatic brain tumors. Its clinical use relies mostly on oncologic applications, but the tracer has the potential to investigate other non-malignant conditions. So far, very limited evidence concerns the use of (11)C-Methionine in patients suffering from seizure; however, the tracer can find a proper utilization in this setting especially as a diagnostic complement to (18)F-Fluorodeoxyglucose ((18)F-FDG). Herein we report the case of a 57-year-old patient presenting with epileptic crises secondary to a brain metastasis from bladder carcinoma, who was investigated in our institution with (11)C-Methionine PET. The scan documented the disease recurrence in the left parietal lobe associated with a diffused tracer uptake in the surrounding cerebral circumvolutions, derived from the comitial status. After surgical removal of the metastatic lesion, the patient experienced a complete recovery of symptoms and no further onset of secondary seizure. PMID:24630372

  13. Study of the 11C(p,gamma) reaction via the indirect d(11C,12N)ntransfer reaction

    SciTech Connect

    Lee, Dongwon; Powell, James; Perajarvi, Kari; Guo, Fanqing; Moltz, Dennis; Cerny, Joseph

    2008-01-07

    The {sup 11}C(p,{gamma}){sup 12}N reaction is expected to be an important branch point in supermassive low-metallicity stars because it could produce CNO seed nuclei before the traditional triple-alpha process turns on. In the present work, the d({sup 11}C, {sup 12}N)n transfer reaction was employed to evaluate this reaction using a radioactive ion beam of 150 MeV {sup 11}C with 6 x 10{sup 5} ions/s on target from the BEARS project at the 88-inch cyclotron at Lawrence Berkeley National Laboratory. Excellent agreement was obtained between the experimental cross sections ({theta}{sub c.m.} = 10.9{sup o} to 71.5{sup o}) and DWBA calculations. The asymptotic normalization coefficient was deduced to be (C{sub eff}{sup 12N}){sup 2} = (C{sub p1/2}{sup 12N}){sup 2} + (C{sub p3/2}{sup 12N}){sup 2} = 1.83 {+-} 0.27 fm{sup -1}.

  14. Mapping {sup 15}O Production Rate for Proton Therapy Verification

    SciTech Connect

    Grogg, Kira; Alpert, Nathaniel M.; Zhu, Xuping; Min, Chul Hee; Testa, Mauro; Winey, Brian; Normandin, Marc D.; Shih, Helen A.; Paganetti, Harald; Bortfeld, Thomas; El Fakhri, Georges

    2015-06-01

    Purpose: This work was a proof-of-principle study for the evaluation of oxygen-15 ({sup 15}O) production as an imaging target through the use of positron emission tomography (PET), to improve verification of proton treatment plans and to study the effects of perfusion. Methods and Materials: Dynamic PET measurements of irradiation-produced isotopes were made for a phantom and rabbit thigh muscles. The rabbit muscle was irradiated and imaged under both live and dead conditions. A differential equation was fitted to phantom and in vivo data, yielding estimates of {sup 15}O production and clearance rates, which were compared to live versus dead rates for the rabbit and to Monte Carlo predictions. Results: PET clearance rates agreed with decay constants of the dominant radionuclide species in 3 different phantom materials. In 2 oxygen-rich materials, the ratio of {sup 15}O production rates agreed with the expected ratio. In the dead rabbit thighs, the dynamic PET concentration histories were accurately described using {sup 15}O decay constant, whereas the live thigh activity decayed faster. Most importantly, the {sup 15}O production rates agreed within 2% (P>.5) between conditions. Conclusions: We developed a new method for quantitative measurement of {sup 15}O production and clearance rates in the period immediately following proton therapy. Measurements in the phantom and rabbits were well described in terms of {sup 15}O production and clearance rates, plus a correction for other isotopes. These proof-of-principle results support the feasibility of detailed verification of proton therapy treatment delivery. In addition, {sup 15}O clearance rates may be useful in monitoring permeability changes due to therapy.

  15. Mapping 15O production rate for proton therapy verification

    PubMed Central

    Grogg, Kira; Alpert, Nathaniel M.; Zhu, Xuping; Min, Chul Hee; Testa, Mauro; Winey, Brian; Normandin, Marc D.; Shih, Helen A.; Paganetti, Harald; Bortfeld, Thomas; El Fakhri, Georges

    2015-01-01

    Purpose This is a proof-of-principle study for the evaluation of 15O production as an imaging target, through the use of positron emission tomography (PET), to improve verification of proton treatment plans and study the effects of perfusion. Methods and Materials Dynamic PET measurements of irradiation-produced isotopes were taken for a phantom and rabbit thigh muscles. The rabbit muscle was irradiated and imaged in both live and dead conditions. A differential equation was fitted to the phantom and the in vivo data, yielding estimates of the 15O production and clearance rates, which was compared for live versus dead for the rabbit, and to Monte Carlo (MC) predictions. Results PET clearance rates agreed with the decay constants of the dominant radionuclide species in three different phantom materials. In two oxygen-rich materials, the ratio of 15O production rates agreed with the MC prediction. In the dead rabbit thighs, the dynamic PET concentration histories were accurately described using the 15O decay constant, while the live thigh activity decayed faster. Most importantly, the 15O production rates agreed within 2% (p> 0.5) between conditions. Conclusion We developed a new method for quantitative measurement of 15O production and clearance rates in the period immediately following proton therapy. Measurements in the phantom and rabbits were well described in terms of 15O production and clearance rates, plus a correction for other isotopes. These proof-of-principle results support the feasibility of detailed verification of proton therapy treatment delivery. In addition, 15O clearance rates may be useful in monitoring permeability changes due to therapy. PMID:25817530

  16. Regional Brain [11C]carfentanil Binding Following Tobacco Smoking

    PubMed Central

    Domino, Edward F; Hirasawa-Fujita, Mika; Ni, Lisong; Guthrie, Sally K; Zubieta, Jon Kar

    2015-01-01

    Objective 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 [11C]carfentanil binding after tobacco smoking. Methods 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, [11C]carfentanil. They smoked deniconized (denic) and average nicotine (avnic) cigarettes during the PET scans. Results Smoking avnic cigarette decreased the binding potential (BPND) of [11C]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. Conclusion The present study demonstrates 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. PMID:25598501

  17. Production of {sup 13}N Via Inertial Electrostatic Confinement Fusion

    SciTech Connect

    Weidner, J.W.; Kulcinski, G.L.; Santarius, J.F.; Ashley, R.P.; Piefer, G.; Cipiti, B.; Radel, R.; Murali, S. Krupakar

    2003-09-15

    This paper describes a proof of principle experiment to produce {sup 13}N using an inertial electrostatic confinement (IEC) fusion device. This radioisotope is often used in positron emission tomography scans to image the heart. The 10-minute half-life of {sup 13}N limits its use to those areas and clinics that possess an accelerator. A portable IEC device could be brought to remote locations, however, and produce short-lived PET isotopes on-site. Using the 14.7 MeV protons produced from the D-{sup 3}He fuel cycle, University of Wisconsin IEC device was used to produce approximately 4 - 8 Bq of {sup 13}N during two separate experiments.

  18. Cryogenic molecular separation system for radioactive 11C ion acceleration

    NASA Astrophysics Data System (ADS)

    Katagiri, K.; Noda, A.; Suzuki, K.; Nagatsu, K.; Boytsov, A. Yu.; Donets, D. E.; Donets, E. D.; Donets, E. E.; Ramzdorf, A. Yu.; Nakao, M.; Hojo, S.; Wakui, T.; Noda, K.

    2015-12-01

    A 11C molecular production/separation system (CMPS) has been developed as part of an isotope separation on line system for simultaneous positron emission tomography imaging and heavy-ion cancer therapy using radioactive 11C ion beams. In the ISOL system, 11CH4 molecules will be produced by proton irradiation and separated from residual air impurities and impurities produced during the irradiation. The CMPS includes two cryogenic traps to separate specific molecules selectively from impurities by using vapor pressure differences among the molecular species. To investigate the fundamental performance of the CMPS, we performed separation experiments with non-radioactive 12CH4 gases, which can simulate the chemical characteristics of 11CH4 gases. We investigated the separation of CH4 molecules from impurities, which will be present as residual gases and are expected to be difficult to separate because the vapor pressure of air molecules is close to that of CH4. We determined the collection/separation efficiencies of the CMPS for various amounts of air impurities and found desirable operating conditions for the CMPS to be used as a molecular separation device in our ISOL system.

  19. [11C]phenytoin revisited: synthesis by [11C]CO carbonylation and first evaluation as a P-gp tracer in rats

    PubMed Central

    2012-01-01

    Background At present, several positron emission tomography (PET) tracers are in use for imaging P-glycoprotein (P-gp) function in man. At baseline, substrate tracers such as R-[11C]verapamil display low brain concentrations with a distribution volume of around 1. [11C]phenytoin is supposed to be a weaker P-gp substrate, which may lead to higher brain concentrations at baseline. This could facilitate assessment of P-gp function when P-gp is upregulated. The purpose of this study was to synthesize [11C]phenytoin and to characterize its properties as a P-gp tracer. Methods [11C]CO was used to synthesize [11C]phenytoin by rhodium-mediated carbonylation. Metabolism and, using PET, brain pharmacokinetics of [11C]phenytoin were studied in rats. Effects of P-gp function on [11C]phenytoin uptake were assessed using predosing with tariquidar. Results [11C]phenytoin was synthesized via [11C]CO in an overall decay-corrected yield of 22 ± 4%. At 45 min after administration, 19% and 83% of radioactivity represented intact [11C]phenytoin in the plasma and brain, respectively. Compared with baseline, tariquidar predosing resulted in a 45% increase in the cerebral distribution volume of [11C]phenytoin. Conclusions Using [11C]CO, the radiosynthesis of [11C]phenytoin could be improved. [11C]phenytoin appeared to be a rather weak P-gp substrate. PMID:22747744

  20. The use of tetrabutylammonium fluoride to promote N- and O-(11) C-methylation reactions with iodo[(11) C]methane in dimethyl sulfoxide.

    PubMed

    Kikuchi, Tatsuya; Minegishi, Katsuyuki; Hashimoto, Hiroki; Zhang, Ming-Rong; Kato, Koichi

    2013-11-01

    The N- or O-methylation reactions of compounds bearing amide, aniline, or phenol moieties using iodo[(11) C]methane (1) with the aid of a base are frequently applied to the preparation of (11) C-labeled radiopharmaceuticals. Although sodium hydride and alkaline metal hydroxides are commonly employed as bases in these reactions, their poor solubility properties in organic solvents and hydrolytic activities have sometimes limited their application and made the associated (11) C-methylation reactions difficult. In contrast to these bases, tetrabutylammonium fluoride (TBAF) is moderately basic, highly soluble in organic solvents, and weakly nucleophilic. Although it was envisaged that TBAF could be used as the preferred base for (11) C-methylation reactions using 1, studies concerning the use of TBAF to promote (11) C-methylation reactions are scarce. Herein, we have evaluated the efficiency of the (11) C-methylation reactions of 13 model compounds using TBAF and 1. In most cases, the N-(11) C-methylations were efficiently promoted by TBAF in dimethyl sulfoxide at ambient temperature, whereas the O-(11) C-methylations required heating in some cases. Comparison studies revealed that the efficiencies of the (11) C-methylation reactions with TBAF were comparable or sometimes greater than those conducted with sodium hydride. Based on these results, TBAF should be considered as the preferred base for (11) C-methylation reactions using 1. PMID:25196029

  1. Development of a modular system for the synthesis of PET [(11)C]labelled radiopharmaceuticals.

    PubMed

    Boschi, Stefano; Lodi, Filippo; Cicoria, Gianfranco; Raul Ledesma, Jorge; Knopp, Roger; Rizzello, Anna; Di Pierro, Donato; Trespidi, Silvia; Marengo, Mario

    2009-10-01

    [((11))C]labelled radiopharmaceuticals as N-[(11)C]methyl-choline ([(11)C]choline), l-(S-methyl-[(11)C])methionine ([(11)C]methionine) and [(11)C]acetate have gained increasing importance in clinical PET and for the routine production of these radiopharmaceuticals, simple and reliable modules are needed to produce clinically relevant radioactivity. On the other hand, flexible devices are needed not only for the routine synthesis but also for more complex applications as the development of new tracers. The aim of this work was the adaptation of an Eckert Ziegler modular system for easy routine synthesis of [(11)C]choline, [(11)C]methionine and [(11)C]acetate using components that account for straightforward scaling up and upgrades. PMID:19535255

  2. Pharmacokinetic Analysis of 11C-PBR28 in the Rat Model of Herpes Encephalitis: Comparison with (R)-11C-PK11195.

    PubMed

    Parente, Andrea; Feltes, Paula Kopschina; Vállez García, David; Sijbesma, Jurgen W A; Moriguchi Jeckel, Cristina M; Dierckx, Rudi A J O; de Vries, Erik F J; Doorduin, Janine

    2016-05-01

    (11)C-PBR28 is a second-generation translocator protein (TSPO) tracer with characteristics supposedly superior to the most commonly used tracer for neuroinflammation, (R)-(11)C-PK11195. Despite its use in clinical research, no studies on the imaging properties and pharmacokinetic analysis of (11)C-PBR28 in rodent models of neuroinflammation have been published yet. Therefore, this study aimed to evaluate (11)C-PBR28 as a tool for detection and quantification of neuroinflammation in preclinical research and to compare its imaging properties with (R)-(11)C-PK11195. The herpes simplex encephalitis (HSE) model was used for induction of neuroinflammation in male Wistar rats. Six or 7 d after virus inoculation, a dynamic (11)C-PBR28 or (R)-(11)C-PK11195 PET scan with arterial blood sampling was obtained. Pharmacokinetic modeling was performed on the PET data and analyzed using volumes of interest and a voxel-based approach. Volume-of-interest- and voxel-based analysis of (11)C-PBR28 images showed overexpression of TSPO in brain regions known to be affected in the HSE rat model. (11)C-PBR28 was metabolized faster than (R)-(11)C-PK11195, with a metabolic half-life in plasma of 5 and 21 min, respectively. Overall, (11)C-PBR28 was more sensitive than (R)-(11)C-PK11195 in detecting neuroinflammation. The binding potential (BPND) of (11)C-PBR28 was significantly higher (P < 0.05) in the medulla (176%), pons (146%), midbrain (101%), hippocampus (85%), thalamus (73%), cerebellum (54%), and hypothalamus (49%) in HSE rats than in control rats, whereas (R)-(11)C-PK11195 showed a higher BPND only in the medulla (32%). The BPND in control animals was not significantly different between tracers, suggesting that the nonspecific binding of both tracers is similar. (11)C-PBR28 was more sensitive than (R)-(11)C-PK11195 in the detection of TSPO overexpression in the HSE rat model, because more brain regions with significantly increased tracer uptake could be found, irrespective of the data

  3. Compartmental analysis of washout effect in rat brain: in-beam OpenPET measurement using a 11C beam

    NASA Astrophysics Data System (ADS)

    Hirano, Yoshiyuki; Kinouchi, Shoko; Ikoma, Yoko; Yoshida, Eiji; Wakizaka, Hidekazu; Ito, Hiroshi; Yamaya, Taiga

    2013-12-01

    In-beam positron emission tomography (PET) is expected to enable visualization of a dose verification using positron emitters (β+ decay). For accurate dose verification, correction of the washout of the positron emitters should be made. In addition, the quantitative washout rate has a potential usefulness as a diagnostic index, but modeling for this has not been studied yet. In this paper, therefore, we applied compartment analyses to in-beam PET data acquired by our small OpenPET prototype, which has a physically opened field-of-view (FOV) between two detector rings. A rat brain was located at the FOV and was irradiated by a 11C beam. Time activity curves of the irradiated field were measured immediately after the irradiations, and the washout rate was obtained based on two models: the two-washout model (medium decay, k2m; slow decay, k2s) developed in a study of rabbit irradiation; and the two-compartment model used in nuclear medicine, where efflux from tissue to blood (k2), influx (k3) and efflux (k4) from the first to second compartments in tissue were evaluated. The observed k2m and k2s were 0.34 and 0.005 min-1, respectively, which was consistent with the rabbit study. Also k2m was close to the washout rate in cerebral blood flow (CBF) measurements by dynamic PET with 15O-water, while, k2, k3, and k4 were 0.16, 0.15 and 0.007 min-1. Our present work suggested the dynamics of 11C might be relevant to CBF or permeability of a molecule containing 11C atoms might be regulated by a transporter because the k2 was relatively low compared with a simple diffusion tracer.

  4. Synthesis and 11C-Radiolabelling of 2-Carboranyl Benzothiazoles.

    PubMed

    Gona, Kiran B; Thota, Jaya Lakshmi V N P; Baz, Zuriñe; Gómez-Vallejo, Vanessa; Llop, Jordi

    2015-01-01

    Dicarba-closo-dodecaboranes, commonly known as carboranes, possess unique physico-chemical properties and can be used as hydrophobic moieties during the design of new drugs or radiotracers. In this work, we report the synthesis of two analogues of 2-(4-aminophenyl)benzothiazole (a compound that was found to elicit pronounced inhibitory effects against certain breast cancer cell lines in vitro) in which the phenyl ring has been substituted by a m-carborane cage. Two different synthetic strategies have been used. For the preparation of 1-(9-amino-1,7-dicarba-closo-dodecaboran-1-yl)-benzo-thiazole, the benzothiazole group was first introduced on one of the cluster carbon atoms of m-carborane and the amine group was further attached in three steps. For the synthesis of 1-(9-amino-1,7-dicarba-closo-dodecaboran-1-yl)-6-hydroxybenzothiazole, iodination was performed before introducing the benzothiazole group, and the amino group was subsequently introduced in six steps. Both compounds were radiolabelled with carbon-11 using [11C]CH3OTf as the labelling agent. Radiolabelling yields and radiochemical purities achieved should enable subsequent in vitro and in vivo investigations. PMID:25915463

  5. Serial PET studies of human cerebral malignancy with (1-/sup 11/C)putrescine and (1-/sup 11/C)2-deoxy-D-glucose

    SciTech Connect

    Hiesiger, E.; Fowler, J.S.; Wolf, A.P.; Logan, J.; Brodie, J.D.; McPherson, D.; MacGregor, R.R.; Christman, D.R.; Volkow, N.D.; Flamm, E.

    1987-08-01

    Serial PET measurements of (1-/sup 11/C)putrescine ((/sup 11/C)PUT) uptake and glucose metabolic rate (GMR) using (1-/sup 11/C)2-deoxy-D-glucose ((/sup 11/C)2DG) were made on eight human subjects with a radiological and, in most cases, pathological diagnosis of primary or metastatic brain tumor. Blood-to-brain influx constants (Ki) were calculated for (/sup 11/C)PUT. Tumor uptake of /sup 11/C after (/sup 11/C)PUT injection was unidirectional peaking at 15 min. The mean +/- s.d. Kis for (/sup 11/C)PUT for tumor and normal brain tissue were 0.78 +/- 0.045 and 0.024 +/- 0.007 ml cc-1 min-1, respectively (average of ratio, 3.11 whereas the ratio of GMR for tumor and normal brain tissue was 1.2 +/- 0.5. The mean Ki for four active, high grade astrocytomas was 0.098 +/- 0.030 in contrast to 0.027 +/- 0.008 ml cc-1 min-1 for two patients with low grade astrocytoma. Active high grade astrocytomas also showed marked CT contrast enhancement and regional glucose hypermetabolism. In one subject with brain metastases, both (/sup 11/C)PUT and GMR correlated with a declining clinical picture in repeated studies over a 4-mo period. PET studies with (/sup 11/C)PUT provide a better signal:noise ratio than GMR measurements, are useful for locating small glycolytically hypometabolic tumors and, when used in longitudinal studies in a single subject, appear to provide an index of degree of malignancy.

  6. Target design considerations for high specific activity [{sup 11}C]O{sub 2}

    SciTech Connect

    Ferrieri, R.A.; Alexoff, D.L.; Schlyer, D.J.; McDonald, K.; Wolf, A.P.

    1993-12-31

    In the routine preparation of {sup 11}C-labeled compounds through N-[{sup 11}C]-methylation using [{sup 11}C]H{sub 3}I, total masses are always higher than synthesis mass contribution, suggesting that the target system contributes carrier carbon to the final product mass. This conclusion prompted this evaluation of target materials and target design for [{sup 11}C]O{sub 2} production. Ultimately, one is faced with the sprospect of compromising between [{sup 11}C]O{sub 2} specific activity and the amount that can be extracted from the target after a reasonable irradiation time.

  7. Optimization of [11C]DASB-synthesis: vessel-based and flow-through microreactor methods.

    PubMed

    Ungersboeck, Johanna; Philippe, Cecile; Haeusler, Daniela; Mitterhauser, Markus; Lanzenberger, Rupert; Dudczak, Robert; Wadsak, Wolfgang

    2012-11-01

    The intention for the present study was to implement a microfluidic set-up for N-(11)C-methylations in a flow-through microreactor device with [(11)C]DASB as model-compound and [(11)C]CH(3)I and [(11)C]CH(3)OTf, respectively, as (11)C-methylation agents. Due to an observed "aging" effect of the (11)C-methylation agents' solution, this goal was not achieved. Nevertheless, based on these observations, the time consumption for the vessel-based routine production of [(11)C]DASB was reduced (34±1 min) and RCY was increased to 45.1±4.6% (EOB; 5.2±0.95 GBq EOS). PMID:22940416

  8. Modeling [15O] oxygen tracer data for estimating oxygen consumption

    PubMed Central

    Deussen, Andreas; Bassingthwaighte, James B.

    2010-01-01

    The most direct measure of oxidative tissue metabolism is the conversion rate of oxygen to water via mitochondrial respiration. To calculate oxygen consumption from the analysis of tissue residue curves or outflow dilution curves after injection of labeled oxygen one needs realistic mathematical models that account for convection, diffusion, and transformation in the tissue. A linear, three-region, axially distributed model accounts for intravascular convection, penetration of capillary and parenchymal cell barriers (with the use of appropriate binding spaces to account for oxygen binding to hemoglobin and myoglobin), the metabolism to [15O]water in parenchymal cells, and [15O]water transport into the venous effluent. Model solutions fit residue and outflow dilution data obtained in an isolated, red blood cell-perfused rabbit heart preparation and give estimates of the rate of oxygen consumption similar to those obtained experimentally from the flow times the arteriovenous differences in oxygen contents. The proposed application is for the assessment of regional oxidative metabolism in vivo from tissue 15O-residue curves obtained by positron emission tomography. PMID:8780210

  9. An efficient and practical synthesis of [2-11C]indole via superfast nucleophilic [11C]cyanation and RANEY® Nickel catalyzed reductive cyclization

    DOE PAGESBeta

    So Jeong Lee; Fowler, Joanna S.; Alexoff, David; Schueller, Michael; Kim, Dohyun; Nauth, Alexander; Weber, Carina; Kim, Sung Won; Hooker, Jacob M.; Ma, Ling; et al

    2015-09-21

    We developed a rapid method for the synthesis of carbon-11 radiolabeled indole using a sub-nanomolar quantity of no-carrier-added [11C]cyanide as radio-precursor. Based upon a reported synthesis of 2-(2-nitrophenyl)acetonitrile (2), a highly reactive substrate 2-nitrobenzyl bromide (1) was evaluated for nucleophilic [11C]cyanation. Additionally, related reaction conditions were explored with the goal of obtaining of highly reactive 2-(2-nitrophenyl)-[1-11C]acetonitrile ([11C]-2) while inhibiting its rapid conversion to 2,3-bis(2-nitrophenyl)-[1-11C]propanenitrile ([11C]-3). Next, a Raney Nickel catalyzed reductive cyclization method was utilized for synthesizing the desired [2-11C]indole with hydrazinium monoformate as the active reducing agent. Extensive and iterative screening of basicity, temperature and stoichiometry was required tomore » overcome the large stoichiometry bias that favored 2-nitrobenzylbromide (1) over [11C]cyanide, which both caused further alkylation of the desired nitrile and poisoned the Raney Nickel catalyst. The result is an efficient two-step, streamlined method to reliably synthesize [2-11C]indole with an entire radiochemical yield of 21 ± 2.2% (n = 5, ranging from 18 – 24%). The radiochemical purity of the final product was > 98% and specific activity was 176 ± 24.8 GBq/μmol (n = 5, ranging from 141 – 204 GBq/μmol). The total radiosynthesis time including product purification by semi-preparative HPLC was 50 – 55 min from end of cyclotron bombardment.« less

  10. Comparison of (+)-11C-McN5652 and 11C-DASB as Serotonin Transporter Radioligands Under Various Experimental Conditions

    PubMed Central

    Szabo, Zsolt; McCann, Una D.; Wilson, Alan A.; Scheffel, Ursula; Owonikoko, Taofeek; Mathews, William B.; Ravert, Hayden T.; Hilton, John; Dannals, Robert F.; Ricaurte, George A.

    2007-01-01

    There has been considerable interest in the development of a PET radioligand selective for the serotonin (5-hydroxytryptamine [5-HT]) transporter (SERT) that can be used to image 5-HT neurons in the living human brain. The most widely used SERT radiotracer to date, trans-1,2,3,5,6,10-β-hexahydro-6-[4-(methylthio)phenyl[pyrrolo-[2,1-a]isoquinoline ((+)-11C-McN5652), has been successful in this regard but may have some limitations. Recently, another promising SERT radiotracer, 3-11C-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile (11C-DASB), has been described. The purpose of this study was to compare and contrast (+)-11C-McN5652 and 11C-DASB under various experimental conditions. Methods: Radioligand comparisons were performed in a control baboon, a baboon with reduced SERT density ((±)-3,4-methylenedioxymethamphetamine [MDMA] lesion), and a baboon with reduced SERT availability (paroxetine pretreatment). Under each of these experimental conditions, repeated (triplicate) PET studies were performed with each ligand. Results: Both radiotracers bound preferentially in brain regions known to contain high SERT density. For both ligands, there was a high correlation between the amount of regional brain ligand binding and the known regional brain concentration of SERT. Binding of both ligands was decreased after MDMA neurotoxicity (reduced SERT density), and (+)-11C-McN5652 and 11C-DASB were comparably effective in detecting reduced SERT density after MDMA-induced 5-HT neurotoxicity. Pretreatment with paroxetine dramatically altered the metabolism and kinetics of both tracers and appeared to displace both ligands primarily from regions with high SERT density. Compared with (+)-11C-McN5652, 11C-DASB had higher brain activity and a faster washout rate and provided greater contrast between subcortical and cortical brain regions. Conclusion: 11C-DASB and (+)-11C-McN5652 are suitable as PET ligands of the SERT and for detecting MDMA-induced 5-HT neurotoxicity. 11C

  11. [11C]PR04.MZ, a promising DAT ligand for low concentration imaging: synthesis, efficient 11C-0-methylation and initial small animal PET studies

    SciTech Connect

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

    2009-05-01

    PR04.MZ was designed as a highly selective dopamine transporter inhibitor, derived from natural cocaine. Its binding profile indicates that [{sup 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 [{sup 11}C]MeI mediated synthesis of [{sup 11}C]PR04.MZ from an O-desmethyl precursor trifluoroacetic acid salt with Rb{sub 2}CO{sub 3} in DMF in up to 95 {+-} 5% labelling yield. A preliminary {mu}PET-experiment demonstrates the reversible, highly specific binding of [{sup 11}C]PR04.MZ in the brain of a male Sprague-Dawley rat.

  12. Synthesis of radiotracers for studying muscarinic cholinergic receptors in the living human brain using positron emission tomography: [11C]dexetimide and [11C]levetimide.

    PubMed

    Dannals, R F; Långström, B; Ravert, H T; Wilson, A A; Wagner, H N

    1988-01-01

    Dexetimide (Fig. 1a), a potent muscarinic cholinergic receptor antagonist, and levetimide (Fig. 1b), its pharmacologically inactive enantiomer, were labeled with 11C for non-invasive in vivo studies of muscarinic cholinergic receptors in the human brain using positron emission tomography. The syntheses were completed in approximately 32 min using [alpha-11C]benzyl iodide as the precursor. The synthesis, purification, characterization and determination of specific activity are presented and discussed. PMID:2838435

  13. Neutron spectra due (13)N production in a PET cyclotron.

    PubMed

    Benavente, J A; Vega-Carrillo, H R; Lacerda, M A S; Fonseca, T C F; Faria, F P; da Silva, T A

    2015-05-01

    Monte Carlo and experimental methods have been used to characterize the neutron radiation field around PET (Positron Emission Tomography) cyclotrons. In this work, the Monte Carlo code MCNPX was used to estimate the neutron spectra, the neutron fluence rates and the ambient dose equivalent (H*(10)) in seven locations around a PET cyclotron during (13)N production. In order to validate these calculations, H*(10) was measured in three sites and were compared with the calculated doses. All the spectra have two peaks, one above 0.1MeV due to the evaporation neutrons and another in the thermal region due to the room-return effects. Despite the relatively large difference between the measured and calculated H*(10) for one point, the agreement was considered good, compared with that obtained for (18)F production in a previous work. PMID:25699664

  14. Assessment of Myocardial Triglyceride Oxidation with PET and 11C-Palmitate

    PubMed Central

    Kisrieva-Ware, Zulfia; Coggan, Andrew R.; Sharp, Terry L.; Dence, Carmen S.; Gropler, Robert J.; Herrero, Pilar

    2010-01-01

    Background The goal of this study was to test whether myocardial triglyceride (TG) turnover including oxidation of TG-derived fatty acids could be assessed with PET and 11C-palmitate. Methods and Results 26 dogs were studied fasted (FAST), during Intralipid infusion (IL), during a hyperinsulinemic-euglycemic clamp without (HIEG) or with Intralipid infusion (HIEG+IL). 11C-palmitate was injected, and 45 min were allowed for labeling of myocardial TG pool. 3-D PET data were then acquired for 60 min, with first 15 min at baseline followed by 45 min during cardiac work stimulated with constant infusion of either phenylephrine (FAST, n=6; IL, n=6; HIEG+IL, n=6) or dobutamine (FAST, n=4; HIEG, n=4). Myocardial 11C washout during adrenergic stimulation (AS) was fitted to a mono-exponential function (Km(PET)). To determine the source of this 11C clearance, Km(PET) was compared to direct coronary sinus-arterial measurements of total 11C activity, 11C-palmitate, and 11CO2. Before AS, PET curves in all groups were flat indicating absence of net clearance of 11C activity from heart. In both FAST groups, AS resulted in negligible net 11C activity and 11CO2 production higher than net 11C-palmitate uptake. AS with phenylephrine resulted in net myocardial uptake of total 11C activity and 11C-palmitate in IL and HIEG+IL, and 11CO2 production lower than 11C-palmitate uptake. In contrast, AS with dobutamine in HIEG resulted in net clearance of all 11C metabolites (total 11C activity, 11C-palmitate and 11CO2) with 11CO2 contributing 66% to endogenous FA oxidation. AS resulted in significant Km(PET) in all groups, except HIEG+IL. However, positive correlation between Km(PET) and 11CO2 was observed only in HIEG (R2=0.83, P=0.09). Conclusions This is the first study to demonstrate that using PET and pre-labeling of intracardiac TG pool with 11C-palmitate, noninvasive assessment of myocardial TG use is feasible under metabolic conditions that favor endogenous TG use such as increased

  15. Development of additive [11C]CO2 target system in the KOTRON-13 cyclotron and its application for [11C]radiopharmaceutical production

    NASA Astrophysics Data System (ADS)

    Moon, Byung Seok; Lee, Hong Jin; Lee, Won Kyung; Hur, Min Goo; Yang, Seung Dae; Lee, Byung Chul; Kim, Sang Eun

    2015-08-01

    The KOTRON-13 cyclotron, which was developed in South Korea for the production of medical radioisotopes, has the structural limitation of only one beam-output port, restricting the production of the carbon-11 isotope. In the present study, we investigate the design of a switchable target system and develop an effective carbon-11 target in the KOTRON-13 cyclotron, for combination with the fluorine-18 target. The target system was designed by introducing a sliding-type element between the fluorine-18 and carbon-11 targets, a tailor-made C-11 target and its cooling system. For the efficient production of [11C]CO2, the desirable target shape and internal volume were determined by a Stopping and Range of Ions in Matter (SRIM) simulation program, and the target grid was modified to resist the cavity pressure during beam irradiation. We evaluated the [11C]CO2 production while varying the material and thickness of the target foil, oxygen content of the nitrogen gas, and target loading pressure. Using sliding-type equipment including an additional gate valve and a high vacuum in a beam line, the bi-directional conversion between the fluorine-18 and carbon-11 targets was efficient regarding the accurate beam irradiation on both targets. The optimal [11C]CO2 production for 30 min irradiation at 60 μA (86.6 ± 1.7 GBq in the target at EOB) was observed at a thickness of 19 μm with HAVAR® material as a target foil and a target loading pressure of 24 bar with nitrogen plus 300 ppb of oxygen gas. Additionally, the coolant cavity system in the target grid and target chamber is useful to remove the heat transferred to the target body by the internal convection of water and thereby ensure the stability of the [11C]CO2 production under a high beam current. In the application of C-11 labeled radiopharmaceuticals such as [11C]PIB, [11C]DASB, [11C]PBR28, [11C]Methionine and [11C]Clozapine, the radiochemical yields were shown to be 25-38% (decay corrected) with over 166 GBq/μmol of

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

    SciTech Connect

    Ding, Y.S.; Fowler, J.S.; Volkow, N.D.

    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.

  17. 1-/sup 11/C-2-deoxy-D-glucose and process for the preparation thereof

    DOEpatents

    MacGregor, R.R.; Wolf, A.P.; Shiue, C.Y.; Wan, C.N.

    1980-02-08

    The novel labelled compound 1-/sup 11/C-2-deoxy-D-glucose, and a process for its preparation from 2,3:4,5-di-O-isopropylidene-D-arabinitol derivatives of relatively high reactivity are disclosed. 1-/sup 11/C-2-deoxy-D-glucose is useful for measuring regional brain glucose metabolism in vivo.

  18. Adequacy of a compartment model for CMRO2 quantitation using 15O-labeled oxygen and PET: a clearance measurement of 15O-radioactivity following intracarotid bolus injection of 15O-labeled oxyhemoglobin on Macaca fascicularis

    PubMed Central

    Iida, Hidehiro; Iguchi, Satoshi; Teramoto, Noboru; Koshino, Kazuhiro; Zeniya, Tsutomu; Yamamoto, Akihide; Kudomi, Nobuyuki; Moriguchi, Tetsuaki; Hori, Yuki; Enmi, Junichiro; Kawashima, Hidekazu; Joni Shah, Nadim; Nakagawara, Jyoji

    2014-01-01

    We aimed at evaluating the adequacy of the commonly employed compartmental model for quantitation of cerebral metabolic rate of oxygen (CMRO2) using 15O-labeled oxygen (15O2) and positron emission tomography (PET). Sequential PET imaging was carried out on monkeys following slow bolus injection of blood samples containing 15O2–oxyhemoglobin (15O2–Hb), 15O-labeled water (H215O), and C15O-labeled hemoglobin (C15O–Hb) into the internal carotid artery (ICA). Clearance slopes were assessed in the middle cerebral artery territory of the injected hemisphere. The time–activity curves were bi-exponential for both 15O2–Hb and H215O. Single exponential fitting to the early (5 to 40 seconds) and late (80 to 240 seconds) periods after the peak was performed and the 15O2–Hb and H215O results were compared. It was found that a significant difference between the clearance rates of the 15O2–Hb and H215O injections is unlikely, which supports the mathematical model that is widely used to describe the kinetics of 15O2–Hb and H215O in cerebral tissues and is the basis of recent approaches to simultaneously assess CMRO2 and cerebral blood flow in a single PET session. However, it should be noted that more data are necessary to unequivocally confirm the result. PMID:25005879

  19. PET Imaging of CRF1 with [11C]R121920 and [11C]DMP696: Is the Target of Sufficient Density?

    PubMed Central

    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 [11C]R121920 and [11C]DMP696 in the non‐human 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 [11C]R121920 and [11C]DMP696 distributed rapidly and uniformly throughout 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 [125I]Tyr0‐sauvagine and specific CRF1 antagonists CP154,526 and SN003 in human occipital cortex yielded maximal binding (Bmax) of 63.3 and 147.3 fmol/mg protein, respectively, and in human cerebellar cortex yielded Bmax of 103.6 and 64.6 fmol/mg protein, respectively. Dissociation constants (KD) were subnanomolar. In baboon, specific binding was not detectable in the same regions; therefore Bmax and KD were not measurable. Autoradiographic results were consistent except there was also detectable CRF1‐specific binding in baboon cerebellum. Conclusion Neither [11C]R121920 nor [11C]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. PMID:17499724

  20. In-house development of an optimized synthetic module for routine [11C]acetate production

    PubMed Central

    Jang, Hwa Youn; Kwon, Seong Young; Pyo, Ayoung; Hur, Min Goo; Kim, Sang Wook; Park, Jeong-Hoon; Kim, Hee-Jung; Yang, Seung Dae; Lee, Sunwoo; Kim, Dong-Yeon

    2015-01-01

    [11C]Acetate, a radiotracer for PET imaging, is a promising radiopharmaceutical for overcoming the limitation of 2-deoxy-2-[18F]fluoro-d-glucose in a number of cancers. Here, the optimized automatic synthesis of [11C]acetate using an in-house-developed module under different conditions has been reported for routine production. [11C]CO2 was produced in a 16.4 MeV PETtrace cyclotron, and methyl magnesium chloride was used for synthesis. For product purification, ion-exchange solid-phase extraction cartridges were used, connected in series. High-performance liquid chromatography and gas chromatography were used to measure radiochemical and chemical purity. The Limulus amebocyte lysate test and the fluid thioglycollate medium test were performed for quality control of [11C]acetate. The total reaction time of [11C]acetate was within 15 min, and the overall decay-corrected radiochemical yield was 84.33±8.85%. Radiochemical purity was greater than 98% when evaluated on an analytical high-performance liquid chromatography system. No endotoxins or anaerobic bacteria were seen on quality control checks. Optimized production of [11C]acetate was achieved by the in-house module. Radiochemical and biological properties of the [11C]acetate produced were appropriate for clinical PET study. PMID:25244351

  1. Incidental finding of parathyroid adenoma with 11C-choline PET/CT.

    PubMed

    Mapelli, Paola; Busnardo, Elena; Magnani, Patrizia; Freschi, Massimo; Picchio, Maria; Gianolli, Luigi; Messa, Cristina

    2012-06-01

    Positron emission tomography/computed tomography (PET/CT) with 11C-choline is an established diagnostic tool for restaging prostate cancer patients with biochemical failure after primary treatment. In the present case, 11C-choline PET/CT was performed in a prostate cancer patient with skeletal metastases, treated with hormonal therapy. In addition to the detection of pathologic uptake at prostate and vertebra, 11C-choline uptake occurred in the neck. The finding was suggestive for a parathyroid adenoma on subsequent ultrasound, then finally confirmed by parathyroid scintigraphy and histopathological analysis performed after hemithyroidectomy. PMID:22614195

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

    PubMed

    Andersen, Valdemar L; Hansen, Hanne D; Herth, Matthias M; Knudsen, Gitte M; Kristensen, Jesper L

    2014-06-01

    Vortioxetine is a new multi-modal drug against major depressive disorder with high affinity for a range of different serotonergic targets in the CNS. We report the (11)C-labeling of vortioxetine with [(11)C]MeI using a Suzuki-protocol that allows for the presence of an unprotected amine. 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 after 60 min and with limited wash-out from the brain. Further studies are needed but this radioligand may prove to be a valuable tool in unraveling the clinical effects of vortioxetine. PMID:24786133

  3. 11C-Choline and FDG PET/CT Imaging of Primary Cholangiocarcinoma: A Comparative Analysis

    PubMed Central

    Chotipanich, Chanisa; Promteangtrong, Chetsadaporn; Kunawudhi, Anchisa; Chanwat, Rawisak; Sricharunrat, Thaniya; Suratako, Savitree; Wongsa, Paramest

    2015-01-01

    Objective(s): This study aimed to compare the diagnostic values of 11C-choline and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in patients with cholangiocarcinoma (CCA). Methods: This prospective study was conducted on 10 patients (6 males and 4 females), aged 42-69 years, suspected of having CCA based on CT or magnetic resonance imaging (MRI) results. 11C-choline and 18F-FDG PET/CT studies were performed in all patients over 1 week. PET/CT results were visually analyzed by 2 independent nuclear medicine physicians and quantitatively by calculating the tumor-to-background ratio (T/B). Results: No 11C-choline PET/CT uptake was observed in primary extrahepatic or intrahepatic CCA cases. Intense 18F-FDG avidity was detected in the tumors of 8 patients (%80). Two patients, who were 18F-FDG negative, had primary extrahepatic CCA. Ki-67 measurements were positive in all patients (range; 14.2%-39.9%). The average T/B values of 11C-choline and 18F-FDG were 0.4±0.2 and 2.0±1.0 in all cases of primary CCA, respectively; these values were significantly lower for 11C-choline (P<0.005). Both FDG and 11C-choline PET/CT detected metastatic CCA foci in all 8 patients (two patients had no metastases). Conclusion: As the results suggested, primary CCA lesions showed a poor avidity for 11C-choline, whereas 18F-FDG PET/CT was of value for the detection of most primary CCA cases. In contrast to primary lesions, metastatic CCA lesions showed 11C-choline avidity.

  4. Production and suppression of {sup 11}C in the solar neutrino experiment Borexino

    SciTech Connect

    Meindl, Quirin; Bellini, G.; Benziger, J.; Bonetti, S.; Avanzini, M. Buizza; Caccianiga, B.; Cadonati, L.; Calaprice, F.; Carraro, C.; Chavarria, A.; Chepurnov, A.; Dalnoki-Veress, F.; D'Angelo, D.; Davini, S.; Kerret, H. de; Derbin, A.; Etenko, A.; Feilitzsch, F. von; Fomenko, K.; Franco, D.

    2011-04-27

    Cosmogenic {sup 11}C is produced in-situ by atmospheric muons and forms the main background for the measurement of solar pep- and CNO-neutrinos. However, FLUKA simulations show that the majority of {sup 11}C is accompanied by a free neutron in the final state, thus allowing for an efficient tagging method, the so-called Three-Fold Coincidence technique. The technique and its first applications on Borexino data are presented.

  5. 11C-radiolabeling study of methanol decomposition on copper oxide modified mesoporous SBA-15 silica

    NASA Astrophysics Data System (ADS)

    Tsoncheva, Tanya; Sarkadi-Priboczki, Eva

    2011-05-01

    11C-radiolabeling technique is applied to investigate methanol decomposition on copper oxide modified SBA-15. Nitrogen physisorption, XRD, FTIR, UV-vis and TPR techniques are used for catalyst characterization. Selective adsorption coverage of the catalytic active sites with 11C- and 12C-methanol molecules is carried out and the products of their conversion are followed. The mechanism of methyl formate, methylal and CO 2 formation from methanol is discussed.

  6. Serotonin 2A receptor agonist binding in the human brain with [11C]Cimbi-36

    PubMed Central

    Ettrup, Anders; da Cunha-Bang, Sophie; McMahon, Brenda; Lehel, Szabolcs; Dyssegaard, Agnete; Skibsted, Anine W; Jørgensen, Louise M; Hansen, Martin; Baandrup, Anders O; Bache, Søren; Svarer, Claus; Kristensen, Jesper L; Gillings, Nic; Madsen, Jacob; Knudsen, Gitte M

    2014-01-01

    [11C]Cimbi-36 was recently developed as a selective serotonin 2A (5-HT2A) receptor agonist radioligand for positron emission tomography (PET) brain imaging. Such an agonist PET radioligand may provide a novel, and more functional, measure of the serotonergic system and agonist binding is more likely than antagonist binding to reflect 5-HT levels in vivo. Here, we show data from a first-in-human clinical trial with [11C]Cimbi-36. In 29 healthy volunteers, we found high brain uptake and distribution according to 5-HT2A receptors with [11C]Cimbi-36 PET. The two-tissue compartment model using arterial input measurements provided the most optimal quantification of cerebral [11C]Cimbi-36 binding. Reference tissue modeling was feasible as it induced a negative but predictable bias in [11C]Cimbi-36 PET outcome measures. In five subjects, pretreatment with the 5-HT2A receptor antagonist ketanserin before a second PET scan significantly decreased [11C]Cimbi-36 binding in all cortical regions with no effects in cerebellum. These results confirm that [11C]Cimbi-36 binding is selective for 5-HT2A receptors in the cerebral cortex and that cerebellum is an appropriate reference tissue for quantification of 5-HT2A receptors in the human brain. Thus, we here describe [11C]Cimbi-36 as the first agonist PET radioligand to successfully image and quantify 5-HT2A receptors in the human brain. PMID:24780897

  7. Reference region modeling approaches for amphetamine challenge studies with [11C]FLB 457 and PET.

    PubMed

    Sandiego, Christine M; Gallezot, Jean-Dominique; Lim, Keunpoong; Ropchan, Jim; Lin, Shu-fei; Gao, Hong; Morris, Evan D; Cosgrove, Kelly P

    2015-04-01

    Detecting fluctuations in synaptic dopamine levels in extrastriatal brain regions with [(11)C]FLB 457 and positron emission tomography (PET) is a valuable tool for studying dopaminergic dysfunction in psychiatric disorders. The evaluation of reference region modeling approaches would eliminate the need to obtain arterial input function data. Our goal was to explore the use of reference region models to estimate amphetamine-induced changes in [(11)C]FLB 457 dopamine D2/D3 binding. Six healthy tobacco smokers were imaged with [(11)C]FLB 457 at baseline and at 3 hours after amphetamine (0.4 to 0.5 mg/kg, per os) administration. Simplified reference tissue models, SRTM and SRTM2, were evaluated against the 2-tissue compartmental model (2TC) to estimate [(11)C]FLB 457 binding in extrastriatal regions of interest (ROIs), using the cerebellum as a reference region. No changes in distribution volume were observed in the cerebellum between scan conditions. SRTM and SRTM2 underestimated binding, compared with 2TC, in ROIs by 26% and 9%, respectively, with consistent bias between the baseline and postamphetamine scans. Postamphetamine, [(11)C]FLB 457 binding significantly decreased across several brain regions as measured with SRTM and SRTM2; no significant change was detected with 2TC. These data support the sensitivity of [(11)C]FLB 457 for measuring amphetamine-induced dopamine release in extrastriatal regions with SRTM and SRTM2. PMID:25564239

  8. In vivo depletion of CD11c+ cells impairs scrapie agent neuroinvasion from the intestine.

    PubMed

    Raymond, Claudine R; Aucouturier, Pierre; Mabbott, Neil A

    2007-12-01

    Following oral exposure, some transmissible spongiform encephalopathy (TSE) agents accumulate first upon follicular dendritic cells (DCs) in the GALT. Studies in mice have shown that TSE agent accumulation in the GALT, in particular the Peyer's patches, is obligatory for the efficient transmission of disease to the brain. However, the mechanism through which TSE agents are initially conveyed from the gut lumen to the GALT is not known. Studies have implicated migratory hemopoietic DCs in this process, but direct demonstration of their involvement in vivo is lacking. In this study, we have investigated the contribution of CD11c(+) DCs in scrapie agent neuroinvasion through use of CD11c-diptheria toxin receptor-transgenic mice in which CD11c(+) DCs can be specifically and transiently depleted. Using two distinct scrapie agent strains (ME7 and 139A scrapie agents), we show that when CD11c(+) DCs were transiently depleted in the GALT and spleen before oral exposure, early agent accumulation in these tissues was blocked. In addition, CD11c(+) cell depletion reduced susceptibility to oral scrapie challenge indicating that TSE agent neuroinvasion from the GALT was impaired. In conclusion, these data demonstrate that migratory CD11c(+) DCs play a key role in the translocation of the scrapie agent from the gut lumen to the GALT from which neuroinvasion subsequently occurs. PMID:18025222

  9. Intersubject variability and reproducibility of 15O PET studies.

    PubMed

    Coles, Jonathan P; Fryer, Tim D; Bradley, Peter G; Nortje, Jurgens; Smielewski, Peter; Rice, Kenneth; Clark, John C; Pickard, John D; Menon, David K

    2006-01-01

    Oxygen-15 positron emission tomography (15O PET) can provide important data regarding patients with head injury. We provide reference data on intersubject variability and reproducibility of cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral metabolism (CMRO2) and oxygen extraction fraction (OEF) in patients and healthy controls, and explored alternative ways of assessing reproducibility within the context of a single PET study. In addition, we used independent measurements of CBF and CMRO2 to investigate the effect of mathematical correlation on the relationship between flow and metabolism. In patients, intersubject coefficients of variation (CoV) for CBF, CMRO2 and OEF were larger than in controls (32.9%+/-2.2%, 23.2%+/-2.0% and 22.5%+/-3.4% versus 13.5%+/-1.4%, 12.8%+/-1.1% and 7.3%+/-1.2%), while CoV for CBV were lower (15.2%+/-2.1% versus 22.5%+/-2.8%) (P<0.001). The CoV for the test-retest reproducibility of CBF, CBV, CMRO2 and OEF in patients were 2.1%+/-1.5%, 3.8%+/-3.0%, 3.7%+/-3.0% and 4.6%+/-3.5%, respectively. These were much lower than the intersubject CoV figures, and were similar to alternative measures of reproducibility obtained by fractionating data from a single study. The physiological relationship between flow and metabolism was preserved even when mathematically independent measures were used for analysis. These data provide a context for the design and interpretation of interventional PET studies. While ideally each centre should develop its own bank of such data, the figures provided will allow initial generic approximations of sample size for such studies. PMID:15988475

  10. Comparison of L-(1-/sup 11/C)methionine and L-methyl-(/sup 11/C)methionine for measuring in vivo protein synthesis rates with PET

    SciTech Connect

    Ishiwata, K.; Vaalburg, W.; Elsinga, P.H.; Paans, A.M.; Woldring, M.G.

    1988-08-01

    To evaluate the feasibility of using either L-(1-11C)-methionine or L-(methyl-11C)methionine for measuring protein synthesis rates by positron emission tomography (PET) in normal and neoplastic tissues, distribution and metabolic studies with 14C- and 11C-labeled methionines were carried out in rats bearing Walker 256 carcinosarcoma. The tissue distributions of the two 14C-labeled methionines were similar except for liver tissue. Similar distribution patterns were observed in vivo by PET using 11C-labeled methionines. The highest 14C incorporation rate into the protein-bound fraction was found in the liver followed by tumor, brain, and pancreas. The incorporation rates in liver and pancreas were different for the two methionines. By chloroform-methanol fractionation of these four tissues, in liver significantly different amounts of 14C were observed in macromolecules. Also in brain tissue slight differences were found. By HPLC analyses of the protein-free fractions of plasma, tumor, and brain tissue at 60 min after injection, for both methionines several 14C-labeled metabolites in different amounts, were detected. About half of the 14C-labeled material in the protein-free fraction was found to be methionine. In these three tissues the amount of nonprotein metabolites and (14C)bicarbonate amount ranged from 10% to 17% and 12% to 15% for L-(1-14C)methionine and L-(methyl-14C)methionine, respectively. From these results it can be concluded that the minor metabolic pathways have to be investigated in order to quantitatively model the protein synthesis by PET.

  11. (11)C[double bond, length as m-dash]O bonds made easily for positron emission tomography radiopharmaceuticals.

    PubMed

    Rotstein, Benjamin H; Liang, Steven H; Placzek, Michael S; Hooker, Jacob M; Gee, Antony D; Dollé, Frédéric; Wilson, Alan A; Vasdev, Neil

    2016-08-22

    The positron-emitting radionuclide carbon-11 ((11)C, t1/2 = 20.3 min) possesses the unique potential for radiolabeling of any biological, naturally occurring, or synthetic organic molecule for in vivo positron emission tomography (PET) imaging. Carbon-11 is most often incorporated into small molecules by methylation of alcohol, thiol, amine or carboxylic acid precursors using [(11)C]methyl iodide or [(11)C]methyl triflate (generated from [(11)C]carbon dioxide or [(11)C]methane). Consequently, small molecules that lack an easily substituted (11)C-methyl group are often considered to have non-obvious strategies for radiolabeling and require a more customized approach. [(11)C]Carbon dioxide itself, [(11)C]carbon monoxide, [(11)C]cyanide, and [(11)C]phosgene represent alternative reactants to enable (11)C-carbonylation. Methodologies developed for preparation of (11)C-carbonyl groups have had a tremendous impact on the development of novel PET tracers and provided key tools for clinical research. (11)C-Carbonyl radiopharmaceuticals based on labeled carboxylic acids, amides, carbamates and ureas now account for a substantial number of important imaging agents that have seen translation to higher species and clinical research of previously inaccessible targets, which is a testament to the creativity, utility and practicality of the underlying radiochemistry. PMID:27276357

  12. 11C-Colchicine distribution in tissues of colchicine -sensitive and -resistant neuroblastoma xenografts

    SciTech Connect

    Mehta, B.M.; Levchenko, A.; Broussard, E.

    1995-05-01

    Multidrug resistance (MDR), a major obstacle in chemotherapy of cancer is thought to be due to the overexpression of a membrane P-glycoprotein (Pgp). P-glycoprotein acts as an energy activated efflux pump, reducing the effective drug concentrations from the MDR tumors. Our earlier studies using neuroblastoma cell lines BE(2)-C (-sensitive), and BE(2)-C/CHCb (-resistant) to colchicine (CHC), showed that uptake of 3H-CHC as well as 14C-CHC in sensitive tumors was twice as much as in resistant tumors. In view of this finding we synthesized 11C-CHC to study the distribution in xenografted animals, since 11C-CHC can be used a a Positron Emission Tomography (PET) tracer in humans. Two groups of Balb/c nude mice (5 animals each) xenografted with BE(2)-C and BE(2)-C/CHCb cells (10 x 10{sup 6} cells per animal) were injected iv retroorbitally with 200 {mu}Ci/100 {mu}l of 11C-CHC per animal. One hour after injection animals were sacrificed by cervical dislocation and blood, tissues and tumors were excised to determine the amount of radioactivity. 11C-CHC biodistribution compared well with 3H-CHC and 14C-CHC distribution. Tumor uptake in sensitive was 1.21 {plus_minus} 0.84% ID/g compared to 0.76 {plus_minus} 0.43% ID/g in resistant tumors. Tumor to blood ratios is sensitive and resistant tumors were 1.62 {plus_minus} 0.41 and 0.69 {plus_minus}0.30 respectively. 11C-Isocolchicine, a byproduct of 11C-CHC synthesis, on the other hand had only 25% uptake as compared to 11C-CHC in both sensitive and resistant tumors. We interpret these results to mean that 11C-CHC behaves similarly to other forms of CHC as a marker of the MDR phenotype. In the future, we plan to use 11C-CHC for identification of MDR status of tumors in vivo using PET scanning.

  13. Ammonia oxidation is not required for growth of Group 1.1c soil Thaumarchaeota.

    PubMed

    Weber, Eva B; Lehtovirta-Morley, Laura E; Prosser, James I; Gubry-Rangin, Cécile

    2015-03-01

    Thaumarchaeota are among the most abundant organisms on Earth and are ubiquitous. Within this phylum, all cultivated representatives of Group 1.1a and Group 1.1b Thaumarchaeota are ammonia oxidizers, and play a key role in the nitrogen cycle. While Group 1.1c is phylogenetically closely related to the ammonia-oxidizing Thaumarchaeota and is abundant in acidic forest soils, nothing is known about its physiology or ecosystem function. The goal of this study was to perform in situ physiological characterization of Group 1.1c Thaumarchaeota by determining conditions that favour their growth in soil. Several acidic grassland, birch and pine tree forest soils were sampled and those with the highest Group 1.1c 16S rRNA gene abundance were incubated in microcosms to determine optimal growth temperature, ammonia oxidation and growth on several organic compounds. Growth of Group 1.1c Thaumarchaeota, assessed by qPCR of Group 1.1c 16S rRNA genes, occurred in soil, optimally at 30°C, but was not associated with ammonia oxidation and the functional gene amoA could not be detected. Growth was also stimulated by addition of organic nitrogen compounds (glutamate and casamino acids) but not when supplemented with organic carbon alone. This is the first evidence for non-ammonia oxidation associated growth of Thaumarchaeota in soil. PMID:25764563

  14. Gatekeeper role of brain antigen-presenting CD11c+ cells in neuroinflammation.

    PubMed

    Paterka, Magdalena; Siffrin, Volker; Voss, Jan O; Werr, Johannes; Hoppmann, Nicola; Gollan, René; Belikan, Patrick; Bruttger, Julia; Birkenstock, Jérôme; Jung, Steffen; Esplugues, Enric; Yogev, Nir; Flavell, Richard A; Bopp, Tobias; Zipp, Frauke

    2016-01-01

    Multiple sclerosis is the most frequent chronic inflammatory disease of the CNS. The entry and survival of pathogenic T cells in the CNS are crucial for the initiation and persistence of autoimmune neuroinflammation. In this respect, contradictory evidence exists on the role of the most potent type of antigen-presenting cells, dendritic cells. Applying intravital two-photon microscopy, we demonstrate the gatekeeper function of CNS professional antigen-presenting CD11c(+) cells, which preferentially interact with Th17 cells. IL-17 expression correlates with expression of GM-CSF by T cells and with accumulation of CNS CD11c(+) cells. These CD11c(+) cells are organized in perivascular clusters, targeted by T cells, and strongly express the inflammatory chemokines Ccl5, Cxcl9, and Cxcl10. Our findings demonstrate a fundamental role of CNS CD11c(+) cells in the attraction of pathogenic T cells into and their survival within the CNS. Depletion of CD11c(+) cells markedly reduced disease severity due to impaired enrichment of pathogenic T cells within the CNS. PMID:26612827

  15. Brain regional pharmacokinetics of /sup 11/C-labeled diphenylhydantoin: positron emission tomography in humans

    SciTech Connect

    Baron, J.C.; Roeda, D.; Munari, C.; Crouzel, C.; Chodkiewicz, J.P.; Comar, D.

    1983-05-01

    We used positron emission tomography to study the regional cerebral pharmacokinetics of /sup 11/C-labeled diphenylhydantoin (/sup 11/C-DPH), which was given intravenously to 10 patients (8 intractable partial epileptics and 2 nonepileptics). In the nonaffected hemisphere, /sup 11/C-DPH concentration in gray matter reached equilibrium with blood within 20 minutes but was still rising at 60 minutes in white matter, where equilibrium was too slow to be detected owing to the fast physical decay of /sup 11/C. Brain-blood concentration ratios at 50 minutes were 1.37 and 1.06 in gray and white matter, respectively, similar but less variable than steady-state DPH ratios reported in human brain surgical samples. There was no indication that normal brain regions of medically resistant epileptics bind DPH less effectively than in nonepileptic patients. Brain and blood /sup 11/C-DPH concentrations were well correlated, confirming that the latter gives a reliable estimate of the former in unaffected brain regions.

  16. CD11c expression in adipose tissue and blood and its role in diet-induced obesity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To examine CD11c, a beta(2)-integrin, on adipose tissue (AT) leukocytes, and blood monocytes and its role in diet-induced obesity. High-fat diet-induced obese C57BL/6 mice, CD11c-deficient mice, and obese humans were studied. CD11c, leukocytes, and chemokines/cytokines were examined in AT and/or blo...

  17. Dosimetry of D- and L-enantiomers of /sup 11/C-labeled tryptophan and valine

    SciTech Connect

    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 /sup 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 /sup 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 /sup 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.

  18. [11C]vinpocetine: a prospective peripheral benzodiazepine receptor ligand for primate PET studies.

    PubMed

    Gulyás, Balázs; Halldin, Christer; Vas, Adám; Banati, Richard B; Shchukin, Evgeny; Finnema, Sjoerd; Tarkainen, Jari; Tihanyi, Károly; Szilágyi, Géza; Farde, Lars

    2005-03-15

    Vinpocetine, a synthetic derivative of the Vinca minor alkaloid vincamine, is a widely used drug in neurological practice. We tested the hypothesis that vinpocetine binds to peripheral benzodiazepine binding sites (PBBS) and is therefore a potential ligand of PBBS. Positron emission tomography (PET) measurements in two cynomolgous monkeys showed that pretreatment with vinpocetine markedly reduced the brain uptake of [11C]PK11195, a known PBBS radioligand. On the other hand, whereas pretreatment with PK11195 increased the brain uptake of [11C]vinpocetine due to the blockade of PBBS in the periphery, it significantly reduced the binding potential (BP) values of [11C]vinpocetine in the whole brain and in individual brain structures to PK11195. These findings indicate that, whereas the two ligands have different affinities to PBBS, vinpocetine is a potent ligand of PBBS, which in turn suggests that the pharmacological activity of vinpocetine may involve the regulation of glial functions. PMID:15760643

  19. [11C]PiB PET in Gerstmann-Sträussler-Scheinker disease

    PubMed Central

    Deters, Kacie D; Risacher, Shannon L; Yoder, Karmen K; Oblak, Adrian L; Unverzagt, Frederick W; Murrell, Jill R; Epperson, Francine; Tallman, Eileen F; Quaid, Kimberly A; Farlow, Martin R; Saykin, Andrew J; Ghetti, Bernardino

    2016-01-01

    Gerstmann-Sträussler-Scheinker Disease (GSS) is a familial neurodegenerative disorder characterized clinically by ataxia, parkinsonism, and dementia, and neuropathologically by deposition of diffuse and amyloid plaques composed of prion protein (PrP). The purpose of this study was to evaluate if [11C]Pittsburgh Compound B (PiB) positron emission tomography (PET) is capable of detecting PrP-amyloid in PRNP gene carriers. Six individuals at risk for GSS and eight controls underwent [11C]PiB PET scans using standard methods. Approximately one year after the initial scan, each of the three asymptomatic carriers (two with PRNP P102L mutation, one with PRNP F198S mutation) underwent a second [11C]PiB PET scan. Three P102L carriers, one F198S carrier, and one non-carrier of the F198S mutation were cognitively normal, while one F198S carrier was cognitively impaired during the course of this study. No [11C]PiB uptake was observed in any subject at baseline or at follow-up. Neuropathologic study of the symptomatic individual revealed PrP-immunopositive plaques and tau-immunopositive neurofibrillary tangles in cerebral cortex, subcortical nuclei, and brainstem. PrP deposits were also numerous in the cerebellar cortex. This is the first study to investigate the ability of [11C]PiB PET to bind to PrP-amyloid in GSS F198S subjects. This finding suggests that [11C]PiB PET is not suitable for in vivo assessment of PrP-amyloid plaques in patients with GSS. PMID:27069768

  20. Influence of 11C-choline PET/CT on radiotherapy planning in prostate cancer

    PubMed Central

    López, Escarlata; Lazo, Antonio; Gutiérrez, Antonio; Arregui, Gregorio; Núñez, Isabel; Sacchetti, Antonio

    2014-01-01

    Aim To evaluate the influence of 11C-choline PET/CT on radiotherapy planning in prostate cancer patients. Background Precise information on the extension of prostate cancer is crucial for the choice of an appropriate therapeutic strategy. 11C-choline positron emission tomography (11C-choline PET/CT) has two roles in radiation oncology (RT): (1) patient selection for treatment and (2) target volume selection and delineation. In conjunction with high-accuracy techniques, it might offer an opportunity of dose escalation and better tumour control while sparing healthy tissues. Materials and methods We carried out a retrospective study in order to analyse RT planning modification based on 11C-choline PET/CT in 16 prostate cancer patients. Patients were treated with hypofractionated step-and-shoot Intensity Modulated Radiotherapy (IMRT), or Volumetric Modulated Arc Therapy (VMAT), and a daily cone-beam CT for Image Guided Radiation Therapy (IGRT). All patients underwent a 11C-choline-PET/CT scan prior to radiotherapy. Results In 37.5% of cases, a re-delineation and new dose prescription occurred. Data show good preliminary clinical results in terms of biochemical control and toxicity. No gastrointestinal (GI)/genitourinary (GU) grade III toxicities were observed after a median follow-up of 9.5 months. Conclusions In our experience, concerning the treatment of prostate cancer (PCa), 11C-choline PET/CT may be helpful in radiotherapy planning, either for dose escalation or exclusion of selected sites. PMID:25859399

  1. Bone Marrow CD11c+ Cell-Derived Amphiregulin Promotes Pulmonary Fibrosis.

    PubMed

    Ding, Lin; Liu, Tianju; Wu, Zhe; Hu, Biao; Nakashima, Taku; Ullenbruch, Matthew; Gonzalez De Los Santos, Francina; Phan, Sem H

    2016-07-01

    Amphiregulin (AREG), an epidermal growth factor receptor ligand, is implicated in tissue repair and fibrosis, but its cellular source and role in regeneration versus fibrosis remain unclear. In this study, we hypothesize that AREG induced in bone marrow-derived CD11c(+) cells is essential for pulmonary fibrosis. Thus, the objectives were to evaluate the importance and role of AREG in pulmonary fibrosis, identify the cellular source of AREG induction, and analyze its regulation of fibroblast function and activation. The results showed that lung AREG expression was significantly induced in bleomycin-induced pulmonary fibrosis. AREG deficiency in knockout mice significantly diminished pulmonary fibrosis. Analysis of AREG expression in major lung cell types revealed induction in fibrotic lungs predominantly occurred in CD11c(+) cells. Moreover, depletion of bone marrow-derived CD11c(+) cells suppressed both induction of lung AREG expression and pulmonary fibrosis. Conversely, adoptive transfer of bone marrow-derived CD11c(+) cells from bleomycin-treated donor mice exacerbated pulmonary fibrosis, but not if the donor cells were made AREG deficient prior to transfer. CD11c(+) cell-conditioned media or coculture stimulated fibroblast proliferation, activation, and myofibroblast differentiation in an AREG-dependent manner. Furthermore, recombinant AREG induced telomerase reverse transcriptase, which appeared to be essential for the proliferative effect. Finally, AREG significantly enhanced fibroblast motility, which was associated with increased expression of α6 integrin. These findings suggested that induced AREG specifically in recruited bone marrow-derived CD11c(+) cells promoted bleomycin-induced pulmonary fibrosis by activation of fibroblast telomerase reverse transcriptase-dependent proliferation, motility, and indirectly, myofibroblast differentiation. PMID:27206766

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

    NASA Astrophysics Data System (ADS)

    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

  3. Evaluation of [11C]metergoline as a PET radiotracer for 5HTR in nonhuman primates

    SciTech Connect

    Hooker, J.M.; Hooker, J.M.; Kim, S.W.; Reibel, A.T.; Alexoff, D.; Xu, Y.; Shea, C.

    2010-04-20

    Metergoline, a serotonin receptor antagonist, was labeled with carbon-11 in order to evaluate its pharmacokinetics and distribution in non-human primates using positron emission tomography. [{sup 11}C]Metergoline had moderate brain uptake and exhibited heterogeneous specific binding, which was blocked by pretreatment with metergoline and altanserin throughout the cortex. Non-specific binding and insensitivity to changes in synaptic serotonin limit its potential as a PET radiotracer. However, the characterization of [{sup 11}C]metergoline pharmacokinetics and binding in the brain and peripheral organs using PET improves our understanding of metergoline drug pharmacology.

  4. (/sup 11/C)clorgyline and (/sup 11/C)-L-deprenyl and their use in measuring functional monoamine oxidase activity in the brain using positron emission tomography

    DOEpatents

    Fowler, J.S.; MacGregor, R.R.; Wolf, A.P.

    1986-04-17

    This invention involves a new strategy for imaging the activity of the enzyme monoamine oxidase in the living body by using /sup 11/C-labeled enzyme inhibitors which bind irreversibly to an enzyme as a result of catalysis. By using positron emission tomography to image the distribution of radioactivity produced by the body penetrating radiation emitted by carbon-11, a map of functionally active monoamine oxidase activity is obtained. Clorgyline and L-deprenyl are suicide enzyme inhibitors and irreversibly inhibit monoamine oxidase. When these inhibitors are labeled with carbon-11 they provide selective probes for monoamine oxidase localization and reactivity in vivo using positron emission tomography. 2 figs.

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

    SciTech Connect

    Fowler, J.S.; Volkow, N.D.; Wang, G.J.

    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.

  6. Effects of Ketoconazole on the Biodistribution and Metabolism of [11C]Loperamide and [11C]N-Desmethyl-loperamide in Wild-type and P-gp Knockout Mice

    PubMed Central

    Seneca, Nicholas; Zoghbi, Sami S.; Shetty, H. Umesha; Tuan, Edward; Kannan, Pavitra; Taku, Andrew; Innis, Robert B.; Pike, Victor W.

    2010-01-01

    Introduction [11C]Loperamide and [11C]N-desmethyl-loperamide ([11C]dLop) have been proposed as radiotracers for imaging brain P-glycoprotein (P-gp) function. A major route of [11C]loperamide metabolism is N-demethylation to [11C]dLop. We aimed to test whether inhibition of CYP3A4 with ketoconazole might reduce the metabolism of [11C]loperamide and [11C]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, waspretreated with ketoconazole (50 mg/kg, i.p.) while another such pair was left untreated. Mice were sacrificed at 30 min after injection of [11C]loperamide or [11C]dLop. Whole brain and plasma samples were measured for radioactivity and analyzed with radio-HPLC. Results Ketoconazole increased the plasma concentrations of [11C]loperamide and its main radiometabolite, [11C]dLop, by about two-fold in both wild-type and knockout mice, whereas the most polar radiometabolite was decreased three-fold. Furthermore, ketoconazole increased the brain concentrations of [11C]loperamide and the radiometabolite [11C]dLop by about two-fold 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 [11C]dLop and its radiometabolites in either wild-type or knockout mice, except to increase the low plasma [11C]dLop concentration. The least polar radiometabolite of [11C]dLop was identified with LC-MSn as the N-hydroxymethyl analog of [11C]dLop and this also behaved as a P-gp substrate. Conclusion In this study, ketoconazole (50 mg/kg, i.p.) proved partiallyeffective for inhibiting the N-demethylation of [11C]loperamide in mouse in vivo but had relatively smaller or no effect on [11C

  7. [(11)C]5-HTP and microPET are not suitable for pharmacodynamic studies in the rodent brain.

    PubMed

    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

    2014-01-01

    The PET tracer [(11)C]5-hydroxytryptophan ([(11)C]5-HTP), which is converted to [(11)C]5-hydroxytryptamine ([(11)C]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 [(11)C]5-HTP in rat? Male rats were scanned with [(11)C]5-HTP (60 minutes) after different treatments. Scans included arterial blood sampling and metabolite analysis. 5-HT synthesis rates were calculated by a two-tissue compartment model (2TCM) with irreversible tracer trapping or Patlak analysis. Carbidopa (inhibitor peripheral AADC) dose-dependently increased [(11)C]5-HTP brain uptake, but did not influence 2TCM parameters. Therefore, 10 mg/kg carbidopa was applied in all subsequent study groups. These groups included treatment with NSD 1015 (general AADC inhibitor) or p-chlorophenylalanine (PCPA, inhibitor of tryptophan hydroxylase, TPH). In addition, the effect of a low-tryptophan (Trp) diet was investigated. NSD 1015 or Trp depletion did not affect any model parameters, but PCPA reduced [(11)C]5-HTP uptake, and the k3. This was unexpected as NSD 1015 directly inhibits the enzyme converting [(11)C]5-HTP to [(11)C]5-HT, suggesting that trapping of radioactivity does not distinguish between parent tracer and its metabolites. As different results have been acquired in monkeys and humans, [(11)C]5-HTP-PET may be suitable for measuring 5-HT synthesis in primates, but not in rodents. PMID:24084697

  8. Expression of CD11c Is Associated with Unconventional Activated T Cell Subsets with High Migratory Potential

    PubMed Central

    Cantero, Jon; Tarrats, Antoni; Fernández, Marco Antonio; Sumoy, Lauro; Rodolosse, Annie; McSorley, Stephen J.

    2016-01-01

    CD11c is an α integrin classically employed to define myeloid dendritic cells. Although there is little information about CD11c expression on human T cells, mouse models have shown an association of CD11c expression with functionally relevant T cell subsets. In the context of genital tract infection, we have previously observed increased expression of CD11c in circulating T cells from mice and women. Microarray analyses of activated effector T cells expressing CD11c derived from naïve mice demonstrated enrichment for natural killer (NK) associated genes. Here we find that murine CD11c+ T cells analyzed by flow cytometry display markers associated with non-conventional T cell subsets, including γδ T cells and invariant natural killer T (iNKT) cells. However, in women, only γδ T cells and CD8+ T cells were enriched within the CD11c fraction of blood and cervical tissue. These CD11c+ cells were highly activated and had greater interferon (IFN)-γ secretory capacity than CD11c- T cells. Furthermore, circulating CD11c+ T cells were associated with the expression of multiple adhesion molecules in women, suggesting that these cells have high tissue homing potential. These data suggest that CD11c expression distinguishes a population of circulating T cells during bacterial infection with innate capacity and mucosal homing potential. PMID:27119555

  9. Imaging of brain tumors after administration of L-(/sup 13/N)glutamate: concise communication

    SciTech Connect

    Reiman, R.E.; Benua, R.S.; Gelbard, A.S.; Allen, J.C.; Vomero, J.J.; Laughlin, J.S.

    1982-08-01

    Cyclotron-produced L-(/sup 13/N)glutamate was used to visualize malignant intracranial tumors in 12 pediatric patients who had evidence of recurrent disease as documented by computed transaxial tomography (TCT). Imaging was performed using a rectilinear scanner, gamma camera, or a positron-emission tomograph (PET). The results indicate that /sup 13/N is rapidly taken up by a majority of brain tumors following the administration of L-(/sup 13/N)glutamate, and that /sup 13/N uptake is correlated with breakdown of the blood-brain barrier as demonstrated by contrast TCT or pertechnetate /sup 99m/Tc studies. The feasibility of using this agent in conjunction with PET is established.

  10. Astronomical forcing of an exceptionally long Sahel wet phase during Marine Isotope Stage 11c

    NASA Astrophysics Data System (ADS)

    Prange, Matthias; Rachmayani, Rima; Schulz, Michael

    2016-04-01

    Increased rainfall and expanded vegetation over North Africa during the early-to-mid Holocene was related to an intensified West African monsoon and a northward displacement of the monsoon trough triggered by astronomical forcing. Similar wet phases are evidenced for earlier interglacials including Marine Isotope Stage (MIS) 11c (ca. 425-395 ka before present). We performed a series of time slice simulations using the comprehensive coupled climate model CCSM3 including a dynamic vegetation module in order to examine the dynamics of the MIS 11c humid period. Proxy records from a marine sediment core site off Northwest Africa suggest an extremely long Sahel/Sahara wet phase during MIS 11c between ca. 420 and 405 ka ago, revealing that North African rainfall changes did not simply follow local summer insolation. Instead, the climate model simulations suggest an important role of the obliquity-driven intra-hemispheric insolation gradient in forcing Sahelian rainfall changes. The specific phasing between precession and obliquity during the MIS 11c interglacial resulted in the exceptionally long wet phase in the Sahel region. The early part of this wet phase was primarily induced by northern-hemispheric differential warming in response to maximum obliquity around 416 ka before present. As such, this interval may well serve as an analog for potential future Sahel rainfall increase induced by strong northern hemisphere extratropical warming.

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

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Persons protected by section 11(c). 1977.5 Section 1977.5 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) DISCRIMINATION AGAINST EMPLOYEES EXERCISING RIGHTS UNDER THE WILLIAMS-STEIGER OCCUPATIONAL SAFETY AND HEALTH ACT OF...

  12. 8Be and 9B nuclei in dissociation of relativistic 10B and 11C nuclei

    NASA Astrophysics Data System (ADS)

    Artemenkov, D. A.; Bradnova, V.; Firu, E.; Kornegrutsa, N. K.; Haiduc, M.; Mamatkulov, K. Z.; Kattabekov, R. R.; Neagu, A.; Rukoyatkin, P. A.; Rusakova, V. V.; Stanoeva, R.; Zaitsev, A. A.; Zarubin, P. I.; Zarubina, I. G.

    2016-02-01

    Progress in the study of nuclear clustering in the relativistic 10B and 11C nuclei dissociation in nuclear track emulsion is presented. The contribution of the unbound 8Be and 9B nuclei to their structure is determined on the basis of measurements of the emission angles of relativistic He and H fragments.

  13. 8Be and 9B nuclei in dissociation of relativistic 10C and 11C nuclei

    NASA Astrophysics Data System (ADS)

    Artemenkov, D. A.; Bradnova, V.; Firu, E.; Kornegrutsa, N. K.; Haiduc, M.; Mamatkulov, K. Z.; Kattabekov, R. R.; Neagu, A.; Rukoyatkin, P. A.; Rusakova, V. V.; Stanoeva, R.; Zaitsev, A. A.; Zarubin, P. I.; Zarubina, I. G.

    2016-05-01

    Progress in the study of nuclear clustering in the relativistic 10C and 11C nuclei dissociation in nuclear track emulsion is presented. The contribution of the unbound 8Be and 9B nuclei to their structure is determined on the basis of measurements of the emission angles of relativistic He and H fragments.

  14. ATP11C Facilitates Phospholipid Translocation across the Plasma Membrane of All Leukocytes

    PubMed Central

    Yabas, Mehmet; Jing, Weidong; Shafik, Sarah

    2016-01-01

    Organization of the plasma membrane into specialized substructures in different blood lineages facilitates important biological functions including proper localization of receptors at the plasma membrane as well as the initiation of crucial intracellular signaling cascades. The eukaryotic plasma membrane is a lipid bilayer that consists of asymmetrically distributed phospholipids. This asymmetry is actively maintained by membrane-embedded lipid transporters, but there is only limited data available about the molecular identity of the predominantly active transporters and their substrate specificity in different leukocyte subsets. We demonstrate here that the P4-type ATPase ATP11C mediates significant flippase activity in all murine leukocyte subsets. Loss of ATP11C resulted in a defective internalization of phosphatidylserine (PS) and phosphatidylethanolamine (PE) in comparison to control cells. The diminished flippase activity caused increased PS exposure on 7-aminoactinomycin D− (7-AAD−) viable pro-B cells freshly isolated from the bone marrow of ATP11C-deficient mice, which was corrected upon a 2-hour resting period in vitro. Despite the impaired flippase activity in all immune cell subsets, the only other blood cell type with an accumulation of PS on the surface were viable 7-AAD− developing T cells but this did not result in any discernable effect on their development in the thymus. These findings show that all leukocyte lineages exhibit flippase activity, and identify ATP11C as an aminophospholipid translocase in immune cells. PMID:26799398

  15. 29 CFR 1977.3 - General requirements of section 11(c) of the Act.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false General requirements of section 11(c) of the Act. 1977.3 Section 1977.3 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) DISCRIMINATION AGAINST EMPLOYEES EXERCISING RIGHTS UNDER...

  16. 29 CFR 1977.5 - Persons protected by section 11(c).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 9 2011-07-01 2011-07-01 false Persons protected by section 11(c). 1977.5 Section 1977.5 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) DISCRIMINATION AGAINST EMPLOYEES EXERCISING RIGHTS UNDER THE...

  17. 29 CFR 1977.3 - General requirements of section 11(c) of the Act.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 9 2011-07-01 2011-07-01 false General requirements of section 11(c) of the Act. 1977.3 Section 1977.3 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) DISCRIMINATION AGAINST EMPLOYEES EXERCISING RIGHTS UNDER...

  18. PET evaluation of spinal cord tumor using sup 11 C-methionine

    SciTech Connect

    Higano, S.; Shishido, F.; Nagashima, M.; Tomura, N.; Murakami, M.; Inugami, A.; Fujita, H.; Tabata, K.; Yasui, N.; Uemura, K. )

    1990-03-01

    A cervical cord tumor was examined with positron emission tomography using L-methyl-({sup 11}C)methionine. The radioactive tracer accumulated in the solid parts (but not in the associated cysts) of the neoplasm, which at histology was found to be an ependymoma.

  19. Charge topology of the coherent dissociation of relativistic {sup 11}C and {sup 12}N nuclei

    SciTech Connect

    Artemenkov, D. A.; Bradnova, V.; Zaitsev, A. A.; Zarubin, P. I. Zarubina, I. G.; Kattabekov, R. R.; Kornegrutsa, N. K.; Mamatkulov, K. Z.; Rukoyatkin, P. A.; Rusakova, V. V.; Stanoeva, R.

    2015-09-15

    The charge topology of coherent-dissociation events is presented for {sup 11}C and {sup 12}N nuclei of energy 1.2 GeV per nucleon bombarding nuclear track emulsions. This topology is compared with respective data for {sup 7}Be, {sup 8,10}B, {sup 9,10}C, and {sup 14}N nuclei.

  20. Functional role of CD11c+ monocytes in atherogenesis associated with hypercholesterolemia

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Monocyte activation and migration into the arterial wall are key events in atherogenesis associated with hypercholesterolemia. CD11c/CD18, a beta2 integrin expressed on human monocytes and a subset of mouse monocytes, has been shown to play a distinct role in human monocyte adhesion on endothelial c...

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

    SciTech Connect

    kil K. E.; Biegon A.; Kil, K.-E.; Biegon, A.; Ding, Y.-S.; Fischer, A.; Ferrieri, R.A.; Kim, S.-W.; Pareto, D.; Schueller, M.J.; Fowler, J.S.

    2008-11-10

    Aromatase, a member of the cytochrome P450 family, converts androgens such as androstenedione and testosterone to estrone and estradiol respectively. Letrozole (1-[bis-(4-cyanophenyl)methyl]-1H-1,2,4-triazole, Femara{reg_sign}) is a high affinity aromatase inhibitor (K{sub i}=11.5 nM) which has FDA 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, 3) were prepared in two-step syntheses from 4-cyanobenzyl bromide and 4-bromobenzyl bromide, respectively. The [{sup 11}C]cyano group was introduced via the tetrakis(triphenylphosphine)palladium(0) catalyzed coupling of [{sup 11}C]cyanide with the bromo-precursor (3). PET studies in the baboon brain were carried out to assess regional distribution and kinetics, reproducibility of repeated measures and saturability. The free fraction of letrozole in the plasma, log D, and the [{sup 11}C-cyano]letrozole fraction in the arterial plasma were also measured. [{sup 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/{micro}mol 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. The brain kinetics was not affected by co-injection of unlabeled letrozole (0.1 mg/kg). The free fraction of letrozole in plasma was 48.9% and log D was 1.84. [{sup 11}C-cyano]Letrozole is readily synthesized via a palladium catalyzed coupling reaction with [{sup 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

  2. Imaging Spectrum and Pitfalls of 11C-Methionine Positron Emission Tomography in a Series of Patients with Intracranial Lesions

    PubMed Central

    Matsuda, Hiroshi; Kubota, Kazoo

    2016-01-01

    11C-methionine (Met) positron emission tomography (PET) is one of the most commonly used PET tracers for evaluating brain tumors. However, few reports have described tips and pitfalls of 11C-Met PET for general practitioners. Physiological 11C-Met uptake, anatomical variations, vascular disorders, non-tumorous lesions such as inflammation or dysplasia, benign brain tumors and patient condition during 11C-Met PET examination can potentially affect the image interpretation and cause false positives and negatives. These pitfalls in the interpretation of 11C-Met PET images are important for not only nuclear medicine physicians but also general radiologists. Familiarity with the spectrum and pitfalls of 11C-Met images could help prevent unfavorable clinical results caused by misdiagnoses. PMID:27134530

  3. Imaging Spectrum and Pitfalls of (11)C-Methionine Positron Emission Tomography in a Series of Patients with Intracranial Lesions.

    PubMed

    Ito, Kimiteru; Matsuda, Hiroshi; Kubota, Kazoo

    2016-01-01

    (11)C-methionine (Met) positron emission tomography (PET) is one of the most commonly used PET tracers for evaluating brain tumors. However, few reports have described tips and pitfalls of (11)C-Met PET for general practitioners. Physiological (11)C-Met uptake, anatomical variations, vascular disorders, non-tumorous lesions such as inflammation or dysplasia, benign brain tumors and patient condition during (11)C-Met PET examination can potentially affect the image interpretation and cause false positives and negatives. These pitfalls in the interpretation of (11)C-Met PET images are important for not only nuclear medicine physicians but also general radiologists. Familiarity with the spectrum and pitfalls of (11)C-Met images could help prevent unfavorable clinical results caused by misdiagnoses. PMID:27134530

  4. Preliminary Ionization Efficiencies of {sup 11}C and {sup 14}O with the LBNL ECR Ion Sources

    SciTech Connect

    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.

    1998-10-05

    High charge states, up to fully stripped {sup 11}C and {sup 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 {sup 11}C and {sup 14}O were collected in batch mode with an LN{sub 2} trap and then bled into the ECR ion sources. Ionization efficiency as high as 11% for {sup 11}C{sup 4+} was achieved.

  5. Spectroscopic Classification of Nova M31N 2015-11c

    NASA Astrophysics Data System (ADS)

    Williams, S. C.; Darnley, M. J.

    2015-12-01

    We obtained a spectrum of the M31 nova candidate M31N 2015-11c (PNV J00433852+4128026; ATel #8327) with the SPRAT spectrograph on the 2m Liverpool Telescope (Steele et al. 2004) on 2015 December 3.9 UT. The spectrum shows strong Balmer emission, with numerous Fe II lines also detected in emission (including the 42, 48, 49 and 74 multiplets), along with Na I (D) and [O I] (6300 and 6364 & Aring;).

  6. Production of L-(1-/sup 11/C)valine by HPLC resolution

    SciTech Connect

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

    1982-01-01

    Based on a recently developed analytical technique, preparative high-performance liquid chromatographic (HPLC) resolution of DL-(1-/sup 11/C)valine has been achieved. A conventional reverse-phase HPLC column and a chiral mobile phase (aqueous solution of L-proline, cupric acetate, and sodium acetate) were used. The copper can be removed from the L-valine fraction by precipitation as the sulfide, and final purification by cation-exchange chromatography yields L-(1-/sup 11/C)valine in a form that is acceptable for clinical positron tomographic studies. This purification method does not remove the L-proline introduced in the resolution process, but added L-proline did not affect the tissue distribution of L-(1-/sup 14/C)valine in rats. We have produced up to 60 mCi of L-(1-/sup 11/C)valine in an overall synthesis and resolution time of 50 min. This procedure should be adaptable to the rapid resolution of other C-/sup 11/-labeled amino acid racemates.

  7. Production of L-(1-/sup 11/C)valine by HPLC resolution

    SciTech Connect

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

    1982-01-01

    Based on a recently developed analytical technique, preparative high-performance liquid chromatographic (HPLC) resolution of DL-(1-/sup 11/C)valine has been achieved. A conventional reverse-phase HPLC column and a chiral mobile phase (aqueous solution of L-proline, cupric acetate, and sodium acetate) were used. The copper can be removed from the L-valine fraction by precipitation as the sulfide, and final purification by cation-exchange chromatography yields L-(1-/sup 11/C)valine in a form that is acceptable for clinical positron tomographic studies. This purification method does not remove the L-proline introduced in the resolution process, but added L-proline did not affect the tissue distribution of L-(1-/sup 14/C)valine in rats. We have produced up to 60 mCi of L-(1-/sup 11/C)valine in an overall synthesis and resolution time of 50 min. This procedure should be adapable to the rapid resolution of other C-11-labeled amino acid racemates.

  8. Varenicline-Induced Elevation of Dopamine in Smokers: A Preliminary [(11)C]-(+)-PHNO PET Study.

    PubMed

    Di Ciano, Patricia; Guranda, Mihail; Lagzdins, Dina; Tyndale, Rachel F; Gamaleddin, Islam; Selby, Peter; Boileau, Isabelle; Le Foll, Bernard

    2016-05-01

    Varenicline, a nicotinic partial agonist, is the most effective treatment for tobacco use disorder. However, its mechanism of action is still unclear and may involve stimulating dopaminergic transmission. Here we used PET imaging with [(11)C]-(+)-PHNO to explore for the first time the impact of varenicline on dopamine transmission in the D2-rich striatum and D3-rich extra-striatal regions and its relationship with craving, withdrawal and smoking. Eleven treatment-seeking smokers underwent two PET scans with [(11)C]-(+)-PHNO, each following 12-h overnight smoking abstinence both prior to receiving varenicline and following 10-11 days of varenicline treatment (ie, at steady-state drug levels). Subjective measures of craving and urges to smoke were also assessed on the days of the PET scans. Varenicline treatment significantly reduced [(11)C]-(+)-PHNO binding in the dorsal caudate (p=0.008) and reduced some craving measures. These findings provide the first evidence that varenicline is able to increase DA levels in the human brain, a factor that may contribute to its therapeutic efficacy. PMID:26442600

  9. Efficiency Calibration for Measuring the 12C(n, 2n)11C Cross Section

    NASA Astrophysics Data System (ADS)

    Eckert, Thomas; Gula, August; Vincett, Laurel; Yuly, Mark; Padalino, Stephen; Russ, Megan; Bienstock, Mollie; Simone, Angela; Ellison, Drew; Desmitt, Holly; Sangster, Craig; Regan, Sean; Fitzgerald, Ryan

    2015-11-01

    One possible inertial confinement fusion diagnostic involves tertiary neutron activation via the 12C(n, 2n)11C reaction. A recent experiment to measure this reaction cross-section involved coincidence counting the annihilation gamma rays produced by the positron decay of 11C. This requires an accurate value for the full-peak coincidence efficiency of the NaI detector system. The GEANT 4 toolkit was used to develop a Monte Carlo simulation of the detector system which can be used to calculate the required efficiencies. For validation, simulation predictions have been compared with the results of two experiments. In the first, full-peak coincidence positron annihilation efficiencies were measured for 22Na decay positrons that annihilate in a small plastic scintillator. In the second, a NIST-calibrated 68Ge source was used. A comparison of calculated with measured efficiencies, as well as 12C(n, 2n)11C cross sections are presented. Funded in part by a grant from the DOE through the Laboratory for Laser Energetics.

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

    SciTech Connect

    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.

  11. Analysis of a Measurement of 12C(n,2n)11C Cross Sections

    NASA Astrophysics Data System (ADS)

    Hartshaw, Garrett; Love, Ian; Yuly, Mark; Padalino, Stephen; Russ, Megan; Bienstock, Mollie; Simone, Angela; Ellison, Drew; Desmitt, Holly; Massey, Thomas; Sangster, Craig

    2013-10-01

    In inertial confinement fusion (ICF), nuclear fusion reactions are initiated by bombarding a small fuel pellet with high power lasers. One ICF diagnostic tool involves placing graphite discs within the reaction chamber to determine the number of high-energy neutrons. This diagnostic requires accurate 12C(n, 2n)11C cross sections, which have not been previously well measured. An experiment to measure this cross section was conducted at Ohio University, in which DT neutrons irradiated polyethylene and graphite targets. The neutron flux was determined by counting recoil protons from the polyethylene in a silicon dE-E detector telescope. Preliminary cross sections were calculated using the incident neutron flux and the number of 11C nuclei in the graphite and polyethylene targets determined by counting, in a separate counting station, the gamma rays resulting from the positron decay of 11C. This poster will present the data analysis techniques used to determine these cross sections and the MCNPX simulation used to compute the corrections needed to account for the detector and target geometry. Funded in part by a LLE contract through the DOE.

  12. Reduced blood BDCA-2+ (lymphoid) and CD11c+ (myeloid) dendritic cells in systemic lupus erythematosus

    PubMed Central

    Migita, K; Miyashita, T; Maeda, Y; Kimura, H; Nakamura, M; Yatsuhashi, H; Ishibashi, H; Eguchi, K

    2005-01-01

    Type 1 IFN is thought to be implicated in the autoimmune process of SLE. Plasmacytoid dendric cells (DC), which are natural IFN-α producing cells, play a pivotal epipathogenic role in SLE. The present study was undertaken to investigate the phenotypic characteristics of peripheral blood DC in SLE patients in comparison with those of healthy controls. Samples from 20 SLE patients and 18 healthy controls were studied. Three-colour flow cytometry was performed to identify myeloid DC, as CD11c+ lineage marker−, and HLA-DR+ cells and plasmacytoid DC, as BDCA-2+ linage marker−, and HLA-DR+ cells. We used the whole blood ‘lyse/no-wash’ procedure, which allows precise counting of peripheral blood DC. BDCA-2+ plasmacytoid DC and CD11c+ myeloid DC were reduced in SLE patients compared with controls. Similarly, BDCA-3+ DC were reduced in SLE patients. These results indicated that SLE patients had a reduced number of both BDCA-2+ plasmacytoid DC and CD11c+ myeloid DC. These alternations of the DC subset may drive the autoimmune response in SLE. PMID:16178860

  13. Determinants of [13N]ammonia kinetics in hepatic PET experiments: a minimal recirculatory model.

    PubMed

    Weiss, Michael; Roelsgaard, Klaus; Bender, Dirk; Keiding, Susanne

    2002-12-01

    The aim of this study was the development of a modelling approach for the analysis of the systemic kinetics of the tracer nitrogen-13 ammonia administered for dynamic liver scanning. The radioactive half-life of this tracer is 9.8 min, which limits the time span in which data are available in a positron emission tomography experimental setting. A circulatory pharmacokinetic model was applied to the metabolism of ammonia in anaesthetised pigs, which incorporated data from serial measurements of [(13)N]ammonia and [(13)N]metabolite activity in arterial and portal venous blood together with blood flow rates through the portal vein and through the hepatic artery obtained over 20 min after intravenous injection of [(13)N]ammonia. Model analysis showed that up to 20 min after injection the time course of [(13)N]ammonia concentration in arterial blood is primarily determined by distribution kinetics (steady-state volume of distribution 1,856+/-531 ml kg(-1)). Simultaneous fitting of arterial ammonia and metabolite blood concentrations allowed for estimation of the hepatic [(13)N]ammonia clearance (10.25+/-1.84 ml min(-1) kg(-1)), which accounted for the formation of the circulating metabolites. PMID:12458400

  14. Dynamic study of rectally absorbed ammonia in liver cirrhosis using (13N)ammonia and a positron camera

    SciTech Connect

    Koen, H.; Okuda, K.; Musha, H.; Tateno, Y.; Fukuda, N.; Matsumoto, T.; Shisido, F.; Rikitake, T,; Iinuma, T.; Kurisu, A.; Arimizu, N.

    1980-11-01

    (13N)Ammonia produced by the cyclotron was instilled intrarectally in patients with cirrhosis and other liver diseases to study the turnover of rectally absorbed (12N)ammonia. In the control, (13N)ammonia was absorbed quickly and visualized the liver, whereas in patients with cirrhosis, the lungs and heart were first visualized, and 13N activity over the head was also higher. It was suggested that a large proportion of absorbed (13N)ammonia bypassed hepatocytes and reached peripheral tissues in cirrhosis. The heart/liver ratio of 13N and 13N over the head were correlated with various indices of portal hypertension. The relative proportion of nonammonia 13N metabolites in blood was lower at 5 and 15 min after administration in cirrhosis, suggesting a reduced capacity of the liver to remove and metabolize ammonia.

  15. Kinetic characterization of /sup 13/NH/sub 3/ and (/sup 13/N)glutamine metabolism in rabbit heart

    SciTech Connect

    Krivokapich, J.; Barrio, J.R.; Phelps, M.E.; Watanabe, C.R.; Keen, R.E.; Padgett, H.C.; Douglas, A.; Shine, K.I.

    1984-01-01

    The isolated arterially perfused rabbit interventricular septum was used to study the effects of methionine sulfoximine (MSO) on /sup 13/N-labeled ammonia (/sup 13/NH/sub 3/) and /sup 13/N-labeled glutamine ((/sup 13/N)) metabolism. Tissue time-activity curves were generated from bolus injections of /sup 13/NH/sub 3/ or (/sup 13/N)gln delivered interarterially during control conditions and in the presence of MSO. The fraction of /sup 13/N label retained in the tissue (EF(3)) was significantly less after a bolus of (/sup 13/N)gln than /sup 13/NH/sub 3/. MSO significantly decreased the EF(3) after a bolus of /sup 13/NH/sub 3/ or (/sup 13/N)gln. Chemical analyses using high-pressure liquid chromatography on tissue and effluent samples obtained after bolus injections of /sup 13/NH/sub 3/ and (/sup 13/N)gln with or without MSO present showed the following: 1) after a bolus of /sup 13/NH/sub 3/ or (/sup 13/N)gln the tissue /sup 13/N label is predominantly in (/sup 13/N)gln at 6 min after injection, and 2) MSO significantly decreases the synthesis of (/sup 13/N)gln after an /sup 13/NH/sub 3/ bolus. Thus it would appear that the glutamine synthetase reaction is primarily responsible for the retention of the /sup 13/N label from /sup 13/NH/sub 3/ as (/sup 13/N)gln in rabbit myocardium.

  16. Lifetime Measurement of the 6.79 MeV Excited State of 15O to Help Constrain the 14N(p,gamma)15O Reaction Rate

    NASA Astrophysics Data System (ADS)

    Galinski, Naomi

    2013-12-01

    In main sequence stars such as our Sun, the source of energy comes from converting hydrogen into helium. There are two competing mechanisms via which this can happen: the pp chain and CNO cycle. The latter is a cycle of reactions involving carbon, nitrogen and oxygen which are catalysts for the conversion of hydrogen into helium. The slowest reaction 14N(p, gamma) 15O in the cycle will affect the energy generation timescale and the amount of helium ash produced via the CNO cycle. This has several astrophysical impacts. It affects the evolutionary timescale of main sequence stars from which the ages of globular clusters can be calculated, the nucleosynthesis of heavier elements in H burning shells of red giant stars, and the fraction of energy produced by the CNO cycle compared to the pp chain in our Sun which helps determine the interior composition of the Sun. For main sequence stars the CNO cycle dominates over the pp chain for core temperatures T ≳ 0.02 GK. For the 14N(p, gamma)15O reaction this corresponds to a low center of mass energy Ecm = 30 keV. This is lower than the low energy limit of the reaction rate measurable in the laboratory. This means that we need to extrapolate down to low energy using theory. The largest remaining uncertainty in the theoretical calculations is due to the lifetime tau of the 6.79 MeV state of 15O. In this work the lifetimes of three excited states of 15O were measured using the Doppler shift attenuation method (DSAM) populating the states via the 3He(16O,alpha)15O reaction at a beam energy of 50 MeV. The low lifetime limit measurable using the DSAM is ˜1 fs. The lifetime of the 6.79 MeV state is near that limit, making this measurement challenging. A 1.8 fs upper limit (68.3% C.L.) on this lifetime is reported here. In addition we measured the lifetimes of the 6.17 and 6.86 MeV state in 15O which were < 2.5 fs and 13.3+0.8-1.2 fs (68.3% C.L.) respectively. iii Acknowledgments

  17. Imaging Evaluation of 5HT2C Agonists, [11C]WAY-163909 and [11C]Vabicaserin, Formed by Pictet–Spengler Cyclization

    PubMed Central

    2015-01-01

    The serotonin subtype 2C (5HT2C) receptor is an emerging and promising drug target to treat several disorders of the human central nervous system. In this current report, two potent and selective 5HT2C full agonists, WAY-163909 (2) and vabicaserin (3), were radiolabeled with carbon-11 via Pictet–Spengler cyclization with [11C]formaldehyde and used in positron emission tomography (PET) imaging. Reaction conditions were optimized to exclude the major source of isotope dilution caused by the previously unknown breakdown of N,N-dimethylformamide (DMF) to formaldehyde at high temperature under mildly acid conditions. In vivo PET imaging was utilized to evaluate the pharmacokinetics and distribution of the carbon-11 labeled 5HT2C agonists. Both radiolabeled molecules exhibit high blood–brain barrier (BBB) penetration and nonspecific binding, which was unaltered by preadministration of the unlabeled agonist. Our work demonstrates that Pictet–Spengler cyclization can be used to label drugs with carbon-11 to study their pharmacokinetics and for evaluation as PET radiotracers. PMID:24491146

  18. The CD11c antigen couples concanavalin A binding to generation of superoxide anion in human phagocytes.

    PubMed Central

    Lacal, P M; Balsinde, J; Cabañas, C; Bernabeu, C; Sánchez-Madrid, F; Mollinedo, F

    1990-01-01

    We have found that an anti-CD11c monoclonal antibody (MAb) inhibits the respiratory burst induced in phorbol 12-myristate 13-acetate (PMA)-differentiated U937 cells as well as in human peripheral blood monocytes and neutrophils upon cell stimulation with concanavalin A. The MAb had no effect, however, when the added stimulus was fMet-Leu-Phe or PMA. Flow cytometry analyses indicated that concanavalin A was able to interact with CD11c. The anti-CD11c MAb inhibited significantly concanavalin A binding to differentiated U937 cells, and concanavalin A blocked binding of anti-CD11c MAb to the cells. Binding of labelled concanavalin A to membrane proteins which were separated by PAGE and transferred to nitrocellulose paper indicated that proteins with apparent molecular masses similar to those of CD11c (150 kDa) and CD18 (95 kDa) molecules were the main concanavalin A-binding proteins in differentiated U937 cells as well as in mature neutrophils. Similar experiments carried out in the presence of the anti-CD11c MAb showed a specific and significant inhibition of concanavalin A binding to the CD11c molecule. These results indicate that concanavalin A binds to the CD11c molecule and this binding is responsible for the concanavalin A-induced respiratory burst in PMA-differentiated U937 cells as well as in human mature monocytes and neutrophils. Images Fig. 2. Fig. 3. PMID:1973035

  19. Effect of vehicle on brain uptake of [11C]toluene.

    PubMed

    Gerasimov, Madina R; Logan, Jean; Ferrieri, Richard A; Muller, Ryan D; Alexoff, David; Dewey, Stephen L

    2002-07-01

    With the goal of investigating the pharmacokinetics of the abused solvent, toluene we have adapted the rapid coupling of methyl iodide with tributylphenylstannane mediated by palladium(0) complex to the synthesis of no-carrier-added [11C]toluene starting with 11CH(3)I. Two methods for purification and formulation of the tracer were developed. The first one yielded [11C]toluene dissolved in dimethylacetamide/saline solution, for the second one we adapted supercritical fluid technology where the tracer was purified using and conventional C(18) HPLC column and pure supercritical CO(2) fluid as a mobile phase operating at 2000 psi. Formulation of the tracer in cyclodextrin resulted in a significantly higher integrated uptake and distribution volume values. Additionally, we observed higher uptake and slower clearance of 11C-toluene in white matter, consistent with higher lipid content and neurotoxicological evidence indicating restricted and diffuse white matter changes in toluene abusers. This trend was observed when either DMA or cyclodextrin was used as a vehicle. It appears then, that the choice of a vehicle affected only the degree of bioavailability, but not the regional brain pharmacokinetics. Finally, we demonstrated the effect of a decreased percent difference between DV values for the studies performed on the same day, that is, test/retest variability was lower for all brain regions in beta-cyclodextrin experiments. Present results clearly demonstrate that the choice of a vehicle has a significant effect on tracer uptake and should be considered as a potential factor contributing to the pharmacokinetic measurements. PMID:12088732

  20. Measuring Cigarette Smoking-Induced Cortical Dopamine Release: A [11C]FLB-457 PET Study

    PubMed Central

    Wing, Victoria C; Payer, Doris E; Houle, Sylvain; George, Tony P; Boileau, Isabelle

    2015-01-01

    Striatal dopamine (DA) is thought to have a fundamental role in the reinforcing effects of tobacco smoking and nicotine. Microdialysis studies indicate that nicotine also increases DA in extrastriatal brain areas, but much less is known about its role in addiction. High-affinity D2/3 receptor radiotracers permit the measurement of cortical DA in humans using positron emission tomography (PET). [11C]FLB-457 PET scans were conducted in 10 nicotine-dependent daily smokers after overnight abstinence and reinstatement of smoking. Voxel-wise [11C]-FLB-457-binding potential (BPND) in the frontal lobe, insula, and limbic regions was estimated in the two conditions. Paired t-tests showed BPND values were reduced following smoking (an indirect index of DA release). The overall peak t was located in the cingulate gyrus, which was part of a larger medial cluster (BPND change −12.1±9.4%) and this survived false discovery rate correction for multiple comparisons. Clusters were also identified in the left anterior cingulate cortex/medial frontal gyrus, bilateral prefrontal cortex (PFC), bilateral amygdala, and the left insula. This is the first demonstration of tobacco smoking-induced cortical DA release in humans; it may be the result of both pharmacological (nicotine) and non-pharmacological factors (tobacco cues). Abstinence increased craving but had minimal cognitive effects, thus limiting correlation analyses. However, given that the cingulate cortex, PFC, insula, and amygdala are thought to have important roles in tobacco craving, cognition, and relapse, these associations warrant investigation in a larger sample. [11C]FLB-457 PET imaging may represent a useful tool to investigate individual differences in tobacco addiction severity and treatment response. PMID:25502631

  1. Amino acids labelled with 11C as indicator of the effect of dietary treatment of hyperammonaemia.

    PubMed

    Hardell, L I; Stålnacke, C G; Lundqvist, H; Malmborg, P; Långström, B

    1984-01-01

    Short-lived radioactive carbon, 11C, (T 1/2 = 20 min) was incorporated into an essential amino acid [11C-methyl] -L-methionine, to form a true biological amino acid tracer with external detectability. This was tested in a study of the physiological tracer dynamics in a hyperammonaemic patient before and after a change in the dietary treatment. The protein intake was unchanged between the two investigations but the energy intake was increased from 53 to 63 kcal/kg BW/day. The tracer radioactivity was given per os. In the second investigation a relative decrease of radioactivity in the low molecular weight fraction of blood plasma was seen. Also the external measurements indicated a higher hepatic retention of radioactivity in the second investigation but no increased excretion of tracer. This may reflect an increased ability of the liver to utilize the incoming methionine from the vena porta. The hyperammonaemia remained over the second investigation but seven months later the ammonia content in the blood was almost normalized and the patient had also gained 3 kg in weight. The correlation between changes in tracer dynamics and changes in therapeutical effect of the diet is not further verified in this experiment but the investigation indicates the value of further studies in this topic using 11C-labelled amino acids also including the use of the newly introduced positron tomographic technique. It may be possible to develop this type of nuclide technique further to achieve a clinically useful method of optimizing therapeutic regiments in this type of metabolic disease. PMID:6393522

  2. Evaluation of [(11)C]N-Methyl Lansoprazole as a Radiopharmaceutical for PET Imaging of Tau Neurofibrillary Tangles.

    PubMed

    Shao, Xia; Carpenter, Garrett M; Desmond, Timothy J; Sherman, Phillip; Quesada, Carole A; Fawaz, Maria; Brooks, Allen F; Kilbourn, Michael R; Albin, Roger L; Frey, Kirk A; Scott, Peter J H

    2012-11-01

    [(11)C]N-Methyl lansoprazole ([(11)C]NML, 3) was synthesized and evaluated as a radiopharmaceutical for quantifying tau neurofibrillary tangle (NFT) burden using positron emission tomography (PET) imaging. [(11)C]NML was synthesized from commercially available lansoprazole in 4.6% radiochemical yield (noncorrected RCY, based upon [(11)C]MeI), 99% radiochemical purity, and 16095 Ci/mmol specific activity (n = 5). Log P was determined to be 2.18. A lack of brain uptake in rodent microPET imaging revealed [(11)C]NML to be a substrate for the rodent permeability-glycoprotein 1 (PGP) transporter, but this could be overcome by pretreating with cyclosporin A to block the PGP. Contrastingly, [(11)C]NML was not found to be a substrate for the primate PGP, and microPET imaging in rhesus revealed [(11)C]NML uptake in the healthy primate brain of ∼1600 nCi/cc maximum at 3 min followed by rapid egress to 500 nCi/cc. Comparative autoradiography between wild-type rats and transgenic rats expressing human tau (hTau +/+) revealed 12% higher uptake of [(11)C]NML in the cortex of brains expressing human tau. Further autoradiography with tau positive brain samples from progressive supranuclear palsy (PSP) patients revealed colocalization of [(11)C]NML with tau NFTs identified using modified Bielschowsky staining. Finally, saturation binding experiments with heparin-induced tau confirmed K d and Bmax values of [(11)C]NML as 700 pM and 0.214 fmol/μg, respectively. PMID:24900410

  3. Nuclear reactions with 11C and 14O radioactive ion beams

    SciTech Connect

    Guo, Fanqing

    2004-12-09

    Radioactive ion beams (RIBs) have been shown to be a useful tool for studying proton-rich nuclides near and beyond the proton dripline and for evaluating nuclear models. To take full advantage of RIBs, Elastic Resonance Scattering in Inverse Kinematics with Thick Targets (ERSIKTT), has proven to be a reliable experimental tool for investigations of proton unbound nuclei. Following several years of effort, Berkeley Experiments with Accelerated Radioactive Species (BEARS), a RIBs capability, has been developed at the Lawrence Berkeley National Laboratory's 88-Inch Cyclotron. The current BEARS provides two RIBs: a 11C beam of up to 2x108 pps intensity on target and an 14O beam of up to 3x104 pps intensity. While the development of the 11C beam has been relatively easy, a number of challenges had to be overcome to obtain the 14O beam. The excellent 11C beam has been used to investigate several reactions. The first was the 197Au(11C,xn)208-xnAt reaction, which was used to measure excitation functions for the 4n to 8n exit channels. The measured cross sections were generally predicted quite well using the fusion-evaporation code HIVAP. Possible errors in the branching ratios of ?? decays from At isotopes as well as the presence of incomplete fusion reactions probably contribute to specific overpredictions. 15F has been investigated by the p(14O,p)14O reaction with the ERSIKTT technology. Several 14O+p runs have been performed. Excellent energy calibration was obtained using resonances from the p(14N,p)14N reaction in inverse kinematics, and comparing the results to those obtained earlier with normal kinematics. The differences between 14N+p and 14O+p in the stopping power function have been evaluated for better energy calibration. After careful calibration, the energy levels of 15F were fitted with an R-matrix calculation. Spins and parities were assigned to the two observed resonances. This new measurement of the 15F ground state supports the disappearance of the Z = 8

  4. Synthesis of (11)C-Labeled Thiamine and Fursultiamine for in Vivo Molecular Imaging of Vitamin B1 and Its Prodrug Using Positron Emission Tomography.

    PubMed

    Doi, Hisashi; Mawatari, Aya; Kanazawa, Masakatsu; Nozaki, Satoshi; Nomura, Yukihiro; Kitayoshi, Takahito; Akimoto, Kouji; Suzuki, Masaaki; Ninomiya, Shinji; Watanabe, Yasuyoshi

    2015-06-19

    To enable in vivo analysis of the kinetics of vitamin B1 (thiamine) and its derivatives by positron emission tomography (PET), (11)C-labeled thiamine ([(11)C]-1) has been synthesized. This was carried out via a rapid, multistep synthesis consisting of Pd(0)-mediated C-[(11)C]methylation of a thiazole ring for 3 min and benzylation with 5-(bromomethyl)pyrimidine for 7 min. The [(11)C]-1 was also converted to (11)C-labeled fursultiamine ([(11)C]-2), a prodrug of vitamin B1, by disulfide formation with S-tetrahydrofurfurylthiosulfuric acid sodium salt. Characterization of [(11)C]-1 and [(11)C]-2 showed them to be suitable for use as PET probes for in vivo pharmacokinetic and medical studies. The total durations of the preparations of [(11)C]-1 and [(11)C]-2 were shorter than 60 and 70 min, respectively. The [(11)C]CH3I-based decay-corrected radiochemical yields of [(11)C]-1 and [(11)C]-2 were 9-16% and 4-10%, respectively. The radioactivities of the final injectable solutions of [(11)C]-1 and [(11)C]-2 were 400-700 and 100-250 MBq, respectively. The radiochemical purity of both [(11)C]-1 and [(11)C]-2 was 99%, and the chemical purities of [(11)C]-1 and [(11)C]-2 were 99% and 97-99%, respectively. In vivo PET imaging of normal rats was illustrated by the distribution of [(11)C]-1 and [(11)C]-2 following intravenous injection. PMID:25984933

  5. Cdc13 N-Terminal Dimerization DNA Binding and Telomere Length Regulation

    SciTech Connect

    M Mitchell; J Smith; M Mason; S Harper; D Speicher; F Johnson; E Skordalakes

    2011-12-31

    The essential yeast protein Cdc13 facilitates chromosome end replication by recruiting telomerase to telomeres, and together with its interacting partners Stn1 and Ten1, it protects chromosome ends from nucleolytic attack, thus contributing to genome integrity. Although Cdc13 has been studied extensively, the precise role of its N-terminal domain (Cdc13N) in telomere length regulation remains unclear. Here we present a structural, biochemical, and functional characterization of Cdc13N. The structure reveals that this domain comprises an oligonucleotide/oligosaccharide binding (OB) fold and is involved in Cdc13 dimerization. Biochemical data show that Cdc13N weakly binds long, single-stranded, telomeric DNA in a fashion that is directly dependent on domain oligomerization. When introduced into full-length Cdc13 in vivo, point mutations that prevented Cdc13N dimerization or DNA binding caused telomere shortening or lengthening, respectively. The multiple DNA binding domains and dimeric nature of Cdc13 offer unique insights into how it coordinates the recruitment and regulation of telomerase access to the telomeres.

  6. 13N,15N isotope and kinetic evidence against hyponitrite as an intermediate in dentrification.

    PubMed

    Hollocher, T C; Garber, E; Cooper, A J; Reiman, R E

    1980-06-10

    13N- and 15N-labeling experiments were carried out with Paracoccus denitrificans, grown anaerobically on nitrate, to determine whether hyponitrite might be an obligatory intermediate in denitrification and a precursor of nitrous oxide. From experiments designed to trap [13N]- or [15N,15N]hyponitrite by dilution into authentic hyponitrite it was calculated that the intracellular concentration of a presumptive hyponitrite pool must be less than 0.4 mM. In order for a pool of this size to turn over rapidly enough to handle the flux of nitrogen during dentrifucation, the spontaneous rate of hyponitrite dehydration must be enhanced by a factor of several thousand through enzyme catalysis. Cell extracts failed to catalyze this reaction under a variety of conditions. It is concluded that hyponitrite cannot be an intermediate in dentrification. In addition, the assimilation of inorganic nitrogen was studied in P. denitrificans using 13N as tracer. At low concentrations (less than 10(-8) M) of labeled nitrate and nitrite 5 to 10% of the label was assimilated into non-volatile metabolites and 90 to 95% was reduced to N2. Similarly, with 15 mM [13N]nitrate, 5% of the label went into metabolites and 95% to N2. High pressure liquid chromatography analysis of the labeled metabolites indicated that the major pathway for assimilation of inorganic nitrogen in P. denitrificans under these conditions is through ammonia incorporation via the aspartase reaction. PMID:7372623

  7. Efficient Enzymatic Preparation of (13) N-Labelled Amino Acids: Towards Multipurpose Synthetic Systems.

    PubMed

    da Silva, Eunice S; Gómez-Vallejo, Vanessa; Baz, Zuriñe; Llop, Jordi; López-Gallego, Fernando

    2016-09-12

    Nitrogen-13 can be efficiently produced in biomedical cyclotrons in different chemical forms, and its stable isotopes are present in the majority of biologically active molecules. Hence, it may constitute a convenient alternative to Fluorine-18 and Carbon-11 for the preparation of positron-emitter-labelled radiotracers; however, its short half-life demands for the development of simple, fast, and efficient synthetic processes. Herein, we report the one-pot, enzymatic and non-carrier-added synthesis of the (13) N-labelled amino acids l-[(13) N]alanine, [(13) N]glycine, and l-[(13) N]serine by using l-alanine dehydrogenase from Bacillus subtilis, an enzyme that catalyses the reductive amination of α-keto acids by using nicotinamide adenine dinucleotide (NADH) as the redox cofactor and ammonia as the amine source. The integration of both l-alanine dehydrogenase and formate dehydrogenase from Candida boidinii in the same reaction vessel to facilitate the in situ regeneration of NADH during the radiochemical synthesis of the amino acids allowed a 50-fold decrease in the concentration of the cofactor without compromising reaction yields. After optimization of the experimental conditions, radiochemical yields were sufficient to carry out in vivo imaging studies in small rodents. PMID:27515007

  8. Cryogenic molecular separation system for radioactive {sup 11}C ion acceleration

    SciTech Connect

    Katagiri, K.; Noda, A.; Suzuki, K.; Nagatsu, K.; Nakao, M.; Hojo, S.; Wakui, T.; Noda, K.; Boytsov, A. Yu.; Donets, D. E.; Donets, E. D.; Donets, E. E.; Ramzdorf, A. Yu.

    2015-12-15

    A {sup 11}C molecular production/separation system (CMPS) has been developed as part of an isotope separation on line system for simultaneous positron emission tomography imaging and heavy-ion cancer therapy using radioactive {sup 11}C ion beams. In the ISOL system, {sup 11}CH{sub 4} molecules will be produced by proton irradiation and separated from residual air impurities and impurities produced during the irradiation. The CMPS includes two cryogenic traps to separate specific molecules selectively from impurities by using vapor pressure differences among the molecular species. To investigate the fundamental performance of the CMPS, we performed separation experiments with non-radioactive {sup 12}CH{sub 4} gases, which can simulate the chemical characteristics of {sup 11}CH{sub 4} gases. We investigated the separation of CH{sub 4} molecules from impurities, which will be present as residual gases and are expected to be difficult to separate because the vapor pressure of air molecules is close to that of CH{sub 4}. We determined the collection/separation efficiencies of the CMPS for various amounts of air impurities and found desirable operating conditions for the CMPS to be used as a molecular separation device in our ISOL system.

  9. Practical Radiosynthesis and Preclinical Neuroimaging of [11C]isradipine, A Calcium Channel Antagonist

    PubMed Central

    Rotstein, Benjamin H.; Liang, Steven H.; Belov, Vasily V.; Livni, Eli; Levine, Dylan B.; Bonab, Ali A.; Papisov, Mikhail I.; Perlis, Roy H.; Vasdev, Neil

    2016-01-01

    In the interest of developing in vivo positron emission tomography (PET) probes for neuroimaging of calcium channels, we have prepared a carbon-11 isotopologue of a dihydropyridine Ca2+-channel antagonist, isradipine. Desmethyl isradipine (4-(benzo[c][1,2,5]oxadiazol-4-yl)-5-(isopropoxycarbonyl)-2,6-dimethyl-1,4-dihydropyridine -3-carboxylic acid) was reacted with [11C]CH3I in the presence of tetrabutylammonium hydroxide in DMF in an HPLC injector loop to produce the radiotracer in a good yield (6 ± 3% uncorrected radiochemical yield) and high specific activity (143 ± 90 GBq·μmol−1 at end-of-synthesis). PET imaging of normal rats revealed rapid brain uptake at baseline (0.37 ± 0.08 %ID/cc (percent of injected dose per cubic centimeter) at peak, 15–60 s), which was followed by fast washout. After pretreatment with isradipine (2 mg·kg−1, i.p.), whole brain radioactivity uptake was diminished by 25–40%. This preliminary study confirms that [11C]isradipine can be synthesized routinely for research studies and is brain penetrating. Further work on Ca2+-channel radiotracer development is planned. PMID:26016546

  10. Practical Radiosynthesis and Preclinical Neuroimaging of [11C]isradipine, a Calcium Channel Antagonist.

    PubMed

    Rotstein, Benjamin H; Liang, Steven H; Belov, Vasily V; Livni, Eli; Levine, Dylan B; Bonab, Ali A; Papisov, Mikhail I; Perlis, Roy H; Vasdev, Neil

    2015-01-01

    In the interest of developing in vivo positron emission tomography (PET) probes for neuroimaging of calcium channels, we have prepared a carbon-11 isotopologue of a dihydropyridine Ca2+-channel antagonist, isradipine. Desmethyl isradipine (4-(benzo[c][1,2,5]oxadiazol-4-yl)-5-(isopropoxycarbonyl)-2,6-dimethyl-1,4-dihydropyridine -3-carboxylic acid) was reacted with [11C]CH3I in the presence of tetrabutylammonium hydroxide in DMF in an HPLC injector loop to produce the radiotracer in a good yield (6 ± 3% uncorrected radiochemical yield) and high specific activity (143 ± 90 GBq·µmol-1 at end-of-synthesis). PET imaging of normal rats revealed rapid brain uptake at baseline (0.37 ± 0.08% ID/cc (percent of injected dose per cubic centimeter) at peak, 15-60 s), which was followed by fast washout. After pretreatment with isradipine (2 mg·kg-1, i.p.), whole brain radioactivity uptake was diminished by 25%-40%. This preliminary study confirms that [11C]isradipine can be synthesized routinely for research studies and is brain penetrating. Further work on Ca2+-channel radiotracer development is planned. PMID:26016546

  11. Supercritical CO2 fluid radiochromatography system used to purify [11C]toluene for PET.

    PubMed

    Muller, Ryan D; Ferrieri, Richard A; Gerasimov, Madina; Garza, Victor

    2002-04-01

    Abuse of inhalants in today's society has become such a widespread problem among today's adolescents that in many parts of the world their use exceeds that of many other illicit drugs or alcohol. Even so, little is known how such inhalants affect brain function to an extent that can lead to an abuse liability. While methodologies exist for radiolabeling certain inhalants of interest with short-lived positron emitting radioisotopes that would allow their investigation in human subjects using positron emission tomography (PET), the purification methodologies necessary to separate these volatile substances from the organic starting materials have not been developed. We've adapted supercritical fluid technology to this specific PET application by building a preparative-scale supercritical CO2 fluid radiochromatograph, and applied it to the purification of [11C]toluene. We've demonstrated that [11C]toluene can be separated from the starting materials using a conventional C18 HPLC column and pure supercritical CO2 fluid as the mobile phase operating at 2000 psi and 40 degrees C. We've also shown that the purified radiotracer can be quantitatively captured on Tenax GR, a solid support material, as it exits the supercritical fluid stream, thus allowing for later desorption into a 1.5% cyclodextrin solution that is suitable for human injection, or into a breathing tube for direct inhalation. PMID:11929706

  12. Elevated [11C]-D-Deprenyl Uptake in Chronic Whiplash Associated Disorder Suggests Persistent Musculoskeletal Inflammation

    PubMed Central

    Linnman, Clas; Appel, Lieuwe; Fredrikson, Mats; Gordh, Torsten; Söderlund, Anne; Långström, Bengt; Engler, Henry

    2011-01-01

    There are few diagnostic tools for chronic musculoskeletal pain as structural imaging methods seldom reveal pathological alterations. This is especially true for Whiplash Associated Disorder, for which physical signs of persistent injuries to the neck have yet to be established. Here, we sought to visualize inflammatory processes in the neck region by means Positron Emission Tomography using the tracer 11C-D-deprenyl, a potential marker for inflammation. Twenty-two patients with enduring pain after a rear impact car accident (Whiplash Associated Disorder grade II) and 14 healthy controls were investigated. Patients displayed significantly elevated tracer uptake in the neck, particularly in regions around the spineous process of the second cervical vertebra. This suggests that whiplash patients have signs of local persistent peripheral tissue inflammation, which may potentially serve as a diagnostic biomarker. The present investigation demonstrates that painful processes in the periphery can be objectively visualized and quantified with PET and that 11C-D-deprenyl is a promising tracer for these purposes. PMID:21541010

  13. Elevated [11C]-D-deprenyl uptake in chronic Whiplash Associated Disorder suggests persistent musculoskeletal inflammation.

    PubMed

    Linnman, Clas; Appel, Lieuwe; Fredrikson, Mats; Gordh, Torsten; Söderlund, Anne; Långström, Bengt; Engler, Henry

    2011-01-01

    There are few diagnostic tools for chronic musculoskeletal pain as structural imaging methods seldom reveal pathological alterations. This is especially true for Whiplash Associated Disorder, for which physical signs of persistent injuries to the neck have yet to be established. Here, we sought to visualize inflammatory processes in the neck region by means Positron Emission Tomography using the tracer (11)C-D-deprenyl, a potential marker for inflammation. Twenty-two patients with enduring pain after a rear impact car accident (Whiplash Associated Disorder grade II) and 14 healthy controls were investigated. Patients displayed significantly elevated tracer uptake in the neck, particularly in regions around the spineous process of the second cervical vertebra. This suggests that whiplash patients have signs of local persistent peripheral tissue inflammation, which may potentially serve as a diagnostic biomarker. The present investigation demonstrates that painful processes in the periphery can be objectively visualized and quantified with PET and that (11)C-D-deprenyl is a promising tracer for these purposes. PMID:21541010

  14. Kinetic Analysis of [11C]McN5652: A Serotonin Transporter Radioligand

    PubMed Central

    Szabo, Zsolt; Scheffel, Ursula; Mathews, William B.; Ravert, Hayden T.; Szabo, Katalina; Kraut, Michael; Palmon, Sally; Ricaurte, George A.; Dannals, Robert F.

    2007-01-01

    Summary The impulse response function of a radioligand is the most fundamental way to describe its pharmacokinetics and to assess its tissue uptake and retention pattern. This study investigates the impulse response function of [11C](+)McN5652, a radioligand used for positron emission tomography (PET) imaging of the serotonin transporter (SERT) in the brain. Dynamic PET studies were performed in eight healthy volunteers injected with [11C](+)McN5652 and subsequently with its pharmacologically inactive enantiomer [11C](−)McN5652. The impulse response function was calculated by deconvolution analysis of regional time-activity curves, and its peak value (fmax), its retention value at 75 minutes (fT), and its normalized retention (frel = fr/fmax) were obtained. Alternatively, compartmental models were applied to calculate the apparent total distribution volume (DVT) and its specific binding component (DVS). Both the noncompartmental (fT, frel) and the compartmental parameters (DV) were investigated with and without correction for nonspecific binding by simple subtraction of the corresponding value obtained with [11C](−)McN5652. The impulse response function obtained by deconvolution analysis demonstrated high tracer extraction followed by a slow decline in the form of a monoexponential function. Statistical analysis revealed that the best compartmental model in terms of analysis of variance F and condition number of the parameter variance-covariance matrix was the one that was based on a single tissue compartment with parameters k1and k2 and that also included the parameter of regional cerebral blood volume (BV). The parameter frel demonstrated low between-subject variance (coefficient of variation [CV] = 19%), a midbrain to cerebellum ratio of 1.85, and high correlation with the known density of SERT (r = 0.787 where r is the coefficient of linear correlation between the parameter and the known density of SERT). After correction for nonspecific binding, frel

  15. Dynamic study of supratentorial gliomas with L-methyl-/sup 11/C-methionine and positron emission tomography

    SciTech Connect

    Lilja, A.; Bergstroem, K.H.; Hartvig, P.; Spaennare, B.H.; Halldin, C.; Lundqvist, H.; Langstrom, B.

    1985-07-01

    The regional kinetics of intravenously injected L-methyl-/sup 11/C-methionine (/sup 11/C-L-methionine) in the brain was investigated by positron emission tomography (PET) in 14 patients with gliomas. In both tumor and unaffected brain the tracer uptake reached a nearly constant level in 5 min or less. The ratio between the uptake of /sup 11/C-L-methionine by high-grade tumors and the uptake by unaffected brain was 1.9-4.8. In two cases of low-grade astrocytoma the ratio was 0.8-1.0. High uptakes of /sup 11/C-L-methionine occurred in gliomas even in the absence of blood-brain barrier defects as observed by other methods. This indicates that besides active transport of amino acid, a larger extracellular space in tumor as compared with unaffected brain tissue may also contribute to the increased uptake of /sup 11/C-L-methionine--derived radioactivity. In some patients delineation of the tumors was improved by use of PET with /sup 11/C-L-methionine as compared with computed tomography, angiography, and, in some instances, PET with /sup 68/Ga-EDTA. PET with /sup 11/C-L-methionine permits better evaluation of the tumor extent and may affect preoperative grading.

  16. Differential diagnosis of AH109A tumor and inflammation by radioscintigraphy with L-[methyl-11C]methionine.

    PubMed

    Kubota, K; Matsuzawa, T; Fujiwara, T; Sato, T; Tada, M; Ido, T; Ishiwata, K

    1989-08-01

    For the evaluation of tumor imaging with L-[methyl-11C]methionine (11C-Met), a basic study on the differentiation of tumor from inflammation with 11C-Met and a comparison of the diagnostic value of the image with that obtained using 67Ga citrate, a conventional scintigraphic agent, are important. 11C-Met accumulations into inflammatory lesions, AH109A tumor and normal tissues of rats were examined by means of a tissue distribution study. Aseptic inflammatory lesions on the back of Donryu rats induced by croton oil and 1.5% carrageenan showed significantly lower accumulations of 11C-Met than the AH109A tumor. Histologically, croton oil induced granulomatous inflammation and carrageenan, acute exudative inflammation. Whole-body autoradiography with 14C-Met, a substitute for 11C-Met, was negative in the carrageenan lesion and showed a slightly increased activity at the periphery of the croton oil lesion, in contrast with the high tumor activity. Whole-body autoradiography with 67Ga citrate was performed to compare the imaging ability with that of 14C-Met; it showed high activities in the tumor, bone, and intestine, and a broad increased activity at the periphery of the croton oil lesion, but was negative in the carrageenan lesion. 11C-Met accumulations in the inflammations were very low and clinical application with positron emission tomography, should be useful for the differential diagnosis of tumor from inflammation. PMID:2511187

  17. A singly charged ion source for radioactive 11C ion acceleration

    NASA Astrophysics Data System (ADS)

    Katagiri, K.; Noda, A.; Nagatsu, K.; Nakao, M.; Hojo, S.; Muramatsu, M.; Suzuki, K.; Wakui, T.; Noda, K.

    2016-02-01

    A new singly charged ion source using electron impact ionization has been developed to realize an isotope separation on-line system for simultaneous positron emission tomography imaging and heavy-ion cancer therapy using radioactive 11C ion beams. Low-energy electron beams are used in the electron impact ion source to produce singly charged ions. Ionization efficiency was calculated in order to decide the geometric parameters of the ion source and to determine the required electron emission current for obtaining high ionization efficiency. Based on these considerations, the singly charged ion source was designed and fabricated. In testing, the fabricated ion source was found to have favorable performance as a singly charged ion source.

  18. Transition metal mediated [(11) C]carbonylation reactions: recent advances and applications.

    PubMed

    Kealey, Steven; Gee, Antony; Miller, Philip W

    2014-04-01

    [(11) C]Carbon monoxide is undoubtedly a highly versatile radiolabelling synthon with many potential applications for the synthesis of positron emission tomography (PET) tracer molecules and functional groups, but why has it not found more applications in the PET radiolabelling arena? Today, (11) CO radiolabelling is still primarily viewed as a niche area; however, there are signs that this is beginning to change as some of the technical and chemistry challenges of producing, handling and reacting (11) CO are overcome. This mini review covers the more recent developments of (11) CO-labelling chemistry and is focused on palladium and rhodium-mediated carbonylation reactions that are growing in importance and finding wider application for carbon-11 PET radiotracer development. PMID:24425679

  19. Measurement of human cerebral blood flow with (15O)butanol and positron emission tomography

    SciTech Connect

    Berridge, M.S.; Adler, L.P.; Nelson, A.D.; Cassidy, E.H.; Muzic, R.F.; Bednarczyk, E.M.; Miraldi, F. )

    1991-09-01

    Although H2(15)O is widely used for CBF measurement by positron tomography, it underestimates CBF, especially at elevated flow rates. Several tracers, including butanol, overcome this problem, but the short half-life of 15O provides advantages that cause water to remain the tracer of choice. The authors report the first use and evaluation of 15O-labeled butanol for CBF measurement. Flow measurements made in a similar fashion with water and butanol at 10-min intervals were compared in normal volunteers under resting and hypercapnic conditions. Regional analysis showed good agreement between the tracers at low flows, and significant underestimation of flow by water relative to butanol in regions of elevated flow. The observed relationship between the tracers and the curve-fitted permeability-surface area product for water (133 ml.100 g-1.min-1) follow the known relationship between water and true flow. These observations indicate that (15O)-butanol provided accurate measurements of human regional CBF under conditions of elevated perfusion. They conclude that butanol is a convenient and accurate method for routine CBF determination by positron emission tomography.

  20. Mannosylated polyion complexes for in vivo gene delivery into CD11c(+) dendritic cells.

    PubMed

    Raviv, Lior; Jaron-Mendelson, Michal; David, Ayelet

    2015-02-01

    Dendritic cells (DCs) possess unique abilities in initiating primary immune responses and thus represent prime targets for DNA-based vaccinations. Here, we describe the design and synthesis of mannosylated polyion complexes (PICs) composed of cationic polyethylenimine (PEI) and hydrophilic polyethylene glycol (PEG) segments, and bearing mono- and trivalent mannose as a ligand for targeting mannose receptor (MR/CD206)-positive DCs. Amino-terminated mannose (Man)-containing ligands in mono- and trivalent presentations (Man- and Man3-, respectively) were prepared and conjugated to PEG via an N-hydroxysuccinimide (NHS)-activated terminal. Thiolated PEI was conjugated to the mannosylated PEG via the maleimide (MAL)-activated terminal. The resulting positively charged diblock copolymers bearing mannoses (Man-PEG-b-PEI and Man3-PEG-b-PEI) were self-assembled with DNA to form PICs with lower surface charge than did their PEI building block and mean hydrodynamic diameters in the range of 100-450 nm, depending on the N/P ratio. Man3-PEG-b-PEI demonstrated a 3-4-fold greater transfection efficiency in MR-positive dendritic cell lines (THP-1, DC2.4), relative to Man-PEG-b-PEI, exhibited low cytotoxicity when compared with PEI, and showed low transfection efficiency in nondendritic HeLa cells. In preliminary in vivo experiments, Man-PEG-b-PEI/DNA and Man3-PEG-b-PEI/DNA demonstrated 2-3-fold higher gene delivery efficiency into CD11c(+) DCs collected from inguinal lymph nodes of C57/BL6 mice, when compared to PEI/DNA complexes, as shown by GFP expression measurements, 24 h post subcutaneous injection. The results indicate that the mannosylated PICs are a safe and effective gene delivery system, showing in vivo specificity toward CD11c(+) DCs. PMID:25531245

  1. Alzheimer's disease detection using 11C-PiB with improved partial volume effect correction

    NASA Astrophysics Data System (ADS)

    Raniga, Parnesh; Bourgeat, Pierrick; Fripp, Jurgen; Acosta, Oscar; Ourselin, Sebastien; Rowe, Christopher; Villemagne, Victor L.; Salvado, Olivier

    2009-02-01

    Despite the increasing use of 11C-PiB in research into Alzheimer's disease (AD), there are few standardized analysis procedures that have been reported or published. This is especially true with regards to partial volume effects (PVE) and partial volume correction. Due to the nature of PET physics and acquisition, PET images exhibit relatively low spatial resolution compared to other modalities, resulting in bias of quantitative results. Although previous studies have applied PVE correction techniques on 11C-PiB data, the results have not been quantitatively evaluated and compared against uncorrected data. The aim of this study is threefold. Firstly, a realistic synthetic phantom was created to quantify PVE. Secondly, MRI partial volume estimate segmentations were used to improve voxel-based PVE correction instead of using hard segmentations. Thirdly, quantification of PVE correction was evaluated on 34 subjects (AD=10, Normal Controls (NC)=24), including 12 PiB positive NC. Regional analysis was performed using the Anatomical Automatic Labeling (AAL) template, which was registered to each patient. Regions of interest were restricted to the gray matter (GM) defined by the MR segmentation. Average normalized intensity of the neocortex and selected regions were used to evaluate the discrimination power between AD and NC both with and without PVE correction. Receiver Operating Characteristic (ROC) curves were computed for the binary discrimination task. The phantom study revealed signal losses due to PVE between 10 to 40 % which were mostly recovered to within 5% after correction. Better classification was achieved after PVE correction, resulting in higher areas under ROC curves.

  2. Transcriptional profiling of CD11c-positive microglia accumulating around amyloid plaques in a mouse model for Alzheimer's disease.

    PubMed

    Kamphuis, Willem; Kooijman, Lieneke; Schetters, Sjoerd; Orre, Marie; Hol, Elly M

    2016-10-01

    Amyloid plaques in Alzheimer's disease (AD) mice are surrounded by activated microglia. The functional role of microglia activation in AD is not well understood; both detrimental and beneficial effects on AD progression have been reported. Here we show that the population of activated microglia in the cortex of the APPswe/PS1dE9 mouse AD model is divided into a CD11c-positive and a CD11c-negative subpopulation. Cd11c transcript levels and number of CD11c-positive microglia increase sharply when plaques start to occur and both parameters continue to rise in parallel with the age-related increasing plaque load. CD11c cells are localized near plaques at all stages of the disease development and constitute 23% of all activated microglia. No differences between these two populations were found in terms of proliferation, immunostaining intensity of Iba1, MHC class II, CD45, or immunoproteasome subunit LMP7/β5i. Comparison of the transcriptome of isolated CD11c-positive and CD11c-negative microglia from the cortex of aged APPswe/PS1dE9 with WT microglia showed that gene expression changes had a similar general pattern. However, a differential expression was found for genes involved in immune signaling (Il6, S100a8/Mrp8, S100a9/Mrp14, Spp1, Igf1), lysosome activation, and carbohydrate- and cholesterol/lipid-metabolism (Apoe). In addition, the increased expression of Gpnmb/DC-HIL, Tm7sf4/DC-STAMP, and Gp49a/Lilrb4, suggests a suppressive/tolerizing influence of CD11c cells. We show that amyloid plaques in the APP/PS1 model are associated with two distinct populations of activated microglia: CD11c-positive and CD11c-negative cells. Our findings imply that CD11c-positive microglia can potentially counteract amyloid deposition via increased Aβ-uptake and degradation, and by containing the inflammatory response. PMID:27425031

  3. Phase changes in selected Lennard-Jones X13-nYn clusters.

    PubMed

    Sabo, Dubravko; Predescu, Cristian; Doll, J D; Freeman, David L

    2004-07-01

    Detailed studies of the thermodynamic properties of selected binary Lennard-Jones clusters of the type X13-nYn (where n=1, 2, 3) are presented. The total energy, heat capacity, and first derivative of the heat capacity as a function of temperature are calculated by using the classical and path integral Monte Carlo methods combined with the parallel tempering technique. A modification in the phase change phenomena from the presence of impurity atoms and quantum effects is investigated. PMID:15260616

  4. Low energy proton capture study of the 14N(p, gamma)15O reaction

    NASA Astrophysics Data System (ADS)

    Daigle, Stephen Michael

    The 14N(p,gamma)15O reaction regulates the rate of energy production for stars slightly more massive than the sun throughout stable hydrogen burning on the main sequence. The 14N(p,gamma)15O reaction rate also determines the luminosity for all stars after leaving the main sequence when their cores have exhausted hydrogen fuel, and later when they become red giant stars. The significant role that this reaction plays in stellar evolution has far-reaching consequences, from neutrino production in our Sun, to age estimates of globular clusters in our Galaxy. The weak cross section and inherent coincidence summing in the 15O gamma-ray decay scheme make a precision measurement of the astrophysical S-factor especially challenging, particularly for the ground-state transition. The present study, performed in the Laboratory for Experimental Nuclear Astrophysics (LENA), was aimed at measuring the ground-state transition at low energy by utilizing a new 24-element, position-sensitive, NaI(Tl) detector array. Because the array is highly segmented, the 14N( p,gamma)15O S-factor was evaluated for transitions to the ground, 5.18, 6.18, and 6.79 MeV states without the need for coincidence summing corrections. Additionally, the position-sensitivity of the detector was exploited to measure the angular correlation of the two-photon cascades. Software cuts were made to the data in order to identify single and coincident gamma-ray events and a fraction fit analysis technique was used to extract the characteristic 15O peaks from the composite gamma-ray spectrum. The results from the current work demonstrated a new approach to measuring weak nuclear cross sections near astrophysically relevant energies that, with refinements, has broader applications in gamma-ray spectroscopy.

  5. Tracer kinetic modeling of [(11)C]AFM, a new PET imaging agent for the serotonin transporter.

    PubMed

    Naganawa, Mika; Nabulsi, Nabeel; Planeta, Beata; Gallezot, Jean-Dominique; Lin, Shu-Fei; Najafzadeh, Soheila; Williams, Wendol; Ropchan, Jim; Labaree, David; Neumeister, Alexander; Huang, Yiyun; Carson, Richard E

    2013-12-01

    [(11)C]AFM, or [(11)C]2-[2-(dimethylaminomethyl)phenylthio]-5-fluoromethylphenylamine, is a new positron emission tomography (PET) radioligand with high affinity and selectivity for the serotonin transporter (SERT). The purpose of this study was to determine the most appropriate kinetic model to quantify [(11)C]AFM binding in the healthy human brain. Positron emission tomography data and arterial input functions were acquired from 10 subjects. Compartmental modeling and the multilinear analysis-1(MA1) method were tested using the arterial input functions. The one-tissue model showed a lack of fit in low-binding regions, and the two-tissue model failed to estimate parameters reliably. Regional time-activity curves were well described by MA1. The rank order of [(11)C]AFM binding potential (BPND) matched well with the known regional SERT densities. For routine use of [(11)C]AFM, several noninvasive methods for quantification of regional binding were evaluated, including simplified reference tissue models (SRTM and SRTM2), and multilinear reference tissue models (MRTM and MRTM2). The best methods for region of interest (ROI) analysis were MA1, MRTM2, and SRTM2, with fixed population kinetic values ( or b') for the reference methods. The MA1 and MRTM2 methods were best for parametric imaging. These results showed that [(11)C]AFM is a suitable PET radioligand to image and quantify SERT in humans. PMID:23921898

  6. Optimization and Biodistribution of [(11)C]-TKF, An Analog of Tau Protein Imaging Agent [(18)F]-THK523.

    PubMed

    Kong, Yanyan; Guan, Yihui; Hua, Fengchun; Zhang, Zhengwei; Lu, Xiuhong; Zhu, Tengfang; Zhao, Bizeng; Zhu, Jianhua; Li, Cong; Chen, Jian

    2016-01-01

    The quantification of neurofibrillary tangles (NFTs) using specific PET tracers can facilitate the diagnosis of Alzheimer's disease (AD) and allow monitoring of disease progression and treatment efficacy. [(18)F]-THK523 has shown high affinity and selectivity for tau pathology. However, its high retention in white matter, which makes simple visual inspection difficult, may limit its use in research or clinical settings. In this paper, we optimized the automated radiosynthesis of [(11)C]-TKF and evaluated its biodistribution and toxicity in C57 mice. [(11)C]-TKF can be made by reaction precursor with [(11)C]MeOTf or (11)CH₃I, but [(11)C]MeOTf will give us higher labeling yields and specific activity. [(11)C]-TKF presented better brain uptake in normal mouse than [(18)F]-THK523 (3.23% ± 1.25% ID·g(-1) vs. 2.62% ± 0.39% ID·g(-1) at 2 min post-injection). The acute toxicity studies of [(11)C]-TKF were unremarkable. PMID:27527142

  7. Quantification of the novel N-methyl-d-aspartate receptor ligand [11C]GMOM in man.

    PubMed

    van der Doef, Thalia F; Golla, Sandeep Sv; Klein, Pieter J; Oropeza-Seguias, Gisela M; Schuit, Robert C; Metaxas, Athanasios; Jobse, Ellen; Schwarte, Lothar A; Windhorst, Albert D; Lammertsma, Adriaan A; van Berckel, Bart Nm; Boellaard, Ronald

    2016-06-01

    [(11)C]GMOM (carbon-11 labeled N-(2-chloro-5-thiomethylphenyl)-N'-(3-[(11)C]methoxy-phenyl)-N'-methylguanidine) is a PET ligand that binds to the N-methyl-d-aspartate receptor with high specificity and affinity. The purpose of this first in human study was to evaluate kinetics of [(11)C]GMOM in the healthy human brain and to identify the optimal pharmacokinetic model for quantifying these kinetics, both before and after a pharmacological dose of S-ketamine. Dynamic 90 min [(11)C]GMOM PET scans were obtained from 10 subjects. In six of the 10 subjects, a second PET scan was performed following an S-ketamine challenge. Metabolite corrected plasma input functions were obtained for all scans. Regional time activity curves were fitted to various single- and two-tissue compartment models. Best fits were obtained using a two-tissue irreversible model with blood volume parameter. The highest net influx rate (Ki) of [(11)C]GMOM was observed in regions with high N-methyl-d-aspartate receptor density, such as hippocampus and thalamus. A significant reduction in the Ki was observed for the entire brain after administration of ketamine, suggesting specific binding to the N-methyl-d-aspartate receptors. This initial study suggests that the [(11)C]GMOM could be used for quantification of N-methyl-d-aspartate receptors. PMID:26661185

  8. Quantification of the novel N-methyl-d-aspartate receptor ligand [11C]GMOM in man

    PubMed Central

    van der Doef, Thalia F; Klein, Pieter J; Oropeza-Seguias, Gisela M; Schuit, Robert C; Metaxas, Athanasios; Jobse, Ellen; Schwarte, Lothar A; Windhorst, Albert D; Lammertsma, Adriaan A; van Berckel, Bart NM; Boellaard, Ronald

    2015-01-01

    [11C]GMOM (carbon-11 labeled N-(2-chloro-5-thiomethylphenyl)-N′-(3-[11C]methoxy-phenyl)-N′-methylguanidine) is a PET ligand that binds to the N-methyl-d-aspartate receptor with high specificity and affinity. The purpose of this first in human study was to evaluate kinetics of [11C]GMOM in the healthy human brain and to identify the optimal pharmacokinetic model for quantifying these kinetics, both before and after a pharmacological dose of S-ketamine. Dynamic 90 min [11C]GMOM PET scans were obtained from 10 subjects. In six of the 10 subjects, a second PET scan was performed following an S-ketamine challenge. Metabolite corrected plasma input functions were obtained for all scans. Regional time activity curves were fitted to various single- and two-tissue compartment models. Best fits were obtained using a two-tissue irreversible model with blood volume parameter. The highest net influx rate (Ki) of [11C]GMOM was observed in regions with high N-methyl-d-aspartate receptor density, such as hippocampus and thalamus. A significant reduction in the Ki was observed for the entire brain after administration of ketamine, suggesting specific binding to the N-methyl-d-aspartate receptors. This initial study suggests that the [11C]GMOM could be used for quantification of N-methyl-d-aspartate receptors. PMID:26661185

  9. The effect of nicotine on striatal dopamine release in man: A [11C]raclopride PET study.

    PubMed

    Montgomery, Andrew J; Lingford-Hughes, Anne R; Egerton, Alice; Nutt, David J; Grasby, Paul M

    2007-08-01

    In common with many addictive substances and behaviors nicotine activates the mesolimbic dopaminergic system. Brain microdialysis studies in rodents have consistently shown increases in extrasynaptic DA levels in the striatum after administration of nicotine but PET experiments in primates have given contradicting results. A recent PET study assessing the effect of smoking in humans showed no change in [(11)C]raclopride binding in the brain, but did find that "hedonia" correlated with a reduction in [(11)C]raclopride binding suggesting that DA may mediate the positive reinforcing effects of nicotine. In this experiment we measured the effect of nicotine, administered via a nasal spray, on DA release using [(11)C]raclopride PET, in 10 regular smokers. There was no overall change in [(11)C]raclopride binding after nicotine administration in any of the striatal regions examined. However, the individual change in [(11)C]raclopride binding correlated with change in subjective measures of "amused" and "happiness" in the associative striatum (AST) and sensorimotor striatum (SMST). Nicotine concentration correlated negatively with change in BP in the limbic striatum. Nicotine had significant effects on cardiovascular measures including pulse rate, systolic blood pressure (BPr), and diastolic BPr. Baseline [(11)C]raclopride binding potential (BP) in the AST correlated negatively with the Fagerström score, an index of nicotine dependence. These results support a role for the DA system in nicotine addiction, but reveal a more complex relationship than suggested by studies in animals. PMID:17492764

  10. 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

    PubMed Central

    Nielsen, Ole L; Afzelius, Pia; Bender, Dirk; Schønheyder, Henrik C; Leifsson, Páll S; Nielsen, Karin M; Larsen, Jytte O; Jensen, Svend B; Alstrup, Aage KO

    2015-01-01

    The aim of this study was to compare 111In-labeled leukocyte single-photon emission computed tomography (SPECT) and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) to PET with tracers that potentially could improve detection of osteomyelitis. We chose 11C-methionine, 11C-PK11195 and 68Ga-citrate and validated their diagnostic utility in a porcine haematogenous osteomyelitis model. Four juvenile 14-15 weeks old female pigs were scanned seven days after intra-arterial inoculation in the right femoral artery with a porcine strain of Staphylococcus aureus using a sequential scan protocol with 18F-FDG, 68Ga-citrate, 11C-methionine, 11C-PK11195, 99mTc-Nanocoll and 111In-labelled autologous leukocytes. This was followed by necropsy of the pigs and gross pathology, histopathology and microbial examination. The pigs developed a total of five osteomyelitis lesions, five lesions 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 accumulated in only one lesion. Overall, 18F-FDG PET was superior to 111In-leukocyte SPECT in marking infectious and proliferative, i.e. hyperplastic, lesions. However, leukocyte SPECT was performed as early scans, approximately 6 h after injection of the leukocytes, to match the requirements of the 18 h long scan protocol. 11C-methionine and possibly 68Ga-citrate may be useful for diagnosis of soft issue lesions. PMID:25973338

  11. Comparison of autologous (111)In-leukocytes, (18)F-FDG, (11)C-methionine, (11)C-PK11195 and (68)Ga-citrate for diagnostic nuclear imaging in a juvenile porcine haematogenous staphylococcus aureus osteomyelitis model.

    PubMed

    Nielsen, Ole L; Afzelius, Pia; Bender, Dirk; Schønheyder, Henrik C; Leifsson, Páll S; Nielsen, Karin M; Larsen, Jytte O; Jensen, Svend B; Alstrup, Aage Ko

    2015-01-01

    The aim of this study was to compare (111)In-labeled leukocyte single-photon emission computed tomography (SPECT) and (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) to PET with tracers that potentially could improve detection of osteomyelitis. We chose (11)C-methionine, (11)C-PK11195 and (68)Ga-citrate and validated their diagnostic utility in a porcine haematogenous osteomyelitis model. Four juvenile 14-15 weeks old female pigs were scanned seven days after intra-arterial inoculation in the right femoral artery with a porcine strain of Staphylococcus aureus using a sequential scan protocol with (18)F-FDG, (68)Ga-citrate, (11)C-methionine, (11)C-PK11195, (99m)Tc-Nanocoll and (111)In-labelled autologous leukocytes. This was followed by necropsy of the pigs and gross pathology, histopathology and microbial examination. The pigs developed a total of five osteomyelitis lesions, five lesions 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, (18)F-FDG accumulated in nine, (111)In-leukocytes in eight, (11)C-methionine in six, (68)Ga-citrate in four and (11)C-PK11195 accumulated in only one lesion. Overall, (18)F-FDG PET was superior to (111)In-leukocyte SPECT in marking infectious and proliferative, i.e. hyperplastic, lesions. However, leukocyte SPECT was performed as early scans, approximately 6 h after injection of the leukocytes, to match the requirements of the 18 h long scan protocol. (11)C-methionine and possibly (68)Ga-citrate may be useful for diagnosis of soft issue lesions. PMID:25973338

  12. /sup 13/N-labeled L-amino acids for in vivo assessment of local myocardial metabolism

    SciTech Connect

    Baumgartner, F.J.; Barrio, J.R.; Henze, E.; Schelbert, H.R.; MacDonald, N.S.; Phelps, M.E.; Kuhl, D.E.

    1981-06-01

    The hot cell synthesis of sterile, pyrogen-free /sup 13/N-labeled L-amino acids was accomplished by employing the appropriate immobilized enzymes on a CNBr-activated Sepharose support and using remote, semiautomated systems. The syntheses were completed 6-12 min after cyclotron production of (/sup 13/N)ammonia. Myocardial time-activity curves after intracoronary injection of /sup 13/N-labeled L-amino acids in dogs were triexponential in both normal and ischemic myocardium. Higher retention of /sup 13/N activity was observed in ischemic segments. Positron computed tomography imaging also showed increased uptake of /sup 13/N-labeled L-glutamate and L-alanine in ischemic segments compared with normal myocardium when blood flow corrections were made. Myocardial transaminases are primarily responsible for the observed retention fractions. It suggests the participation of the carbon skeletons of these amino acids in the Krebs cycle.

  13. [{sup 11}C]d-threo-Methylphenidate, a new radiotracer for the dopamine transporter. Characterization in baboon and human brain

    SciTech Connect

    Ding, Y.S.; Volkow, N.D.; Fowler, J.S.

    1995-05-01

    dl-threo Methylphenidate (MP, Ritalin) is a psychostimulant drug which binds to the dopamine transporter (DAT). We evaluated [{sup 11}C]d-threo-methylphenidate ([{sup 11}C]d-MP), the more active enantiomer, as a radiotracer for the DAT in baboons and human brain. Stereoselectivity, saturability and pharmacological specificity and reproducibility were examined. Stereoselectivity was examined in baboons by comparing [{sup 11C}]d-MP,[{sup 11}C]l-MP and [{sup 11}C]dl-MP. Unlabeled MP was used to assess the reversibility and saturability of the binding. GBR 12909,{beta}-(4-iodophenyl)tropane-2-carboxylic acid methyl ester ({beta}-CIT), tomoxetine and citalopram were used to assess the specificity of the binding. The ratios between the radioactivity in the striatum to that in cerebellum (ST/CB) were 3.3,2.2 and 1.1 for [{sup 11}C]d-MP,[{sup 11}C]dl-MP and [{sup 11}C]l-MP respectively. Most of the striatal binding of [{sup 11}C]d-threo-MP was displaced by injection of nonradioactive MP demonstrating reversibility. Pretreatment with MP (0.5 mg/kg), GBR12909 (1.5 mg/kg) or {beta}-CIT (0.3 mg/kg) reduced ST/CB by about 60% and the ratios of distribution volumes at the steady-state for the triatum to cerebellum (DV{sub st/}DV{sub cb}) by about 50%. Pretreatment with tomoxetine (3.0 mg/kg) or citalopram (2.0 mg/kg), inhibitors of the norepinephrine and serotonin transporter, had no effect. Studies of [{sup 11}C]d-MP in the human brain showed highest uptake in basal ganglia with a half clearance time of about 60 minutes. Repeated studies in 6 normal human subjects showed differences in DV{sub st/}DV{sub cb} between -7% and 8%. MP pretreatment decreased BG but no cortical or cerebellar binding and reduced Bmax/Kd by 91%.

  14. An Improved Antagonist Radiotracer for the Kappa Opioid Receptor: Synthesis and Characterization of 11C-LY2459989

    PubMed Central

    Zheng, Ming-Qiang; Kim, Su Jin; Holden, Daniel; Lin, Shu-fei; Need, Anne; Rash, Karen; Barth, Vanessa; Mitch, Charles; Navarro, Antonio; Kapinos, Michael; Maloney, Kathleen; Ropchan, Jim; Carson, Richard E.; Huang, Yiyun

    2016-01-01

    The kappa opioid receptors (KOR) are implicated in a number of neuropsychiatric diseases and addictive disorders. Positron Emission Tomography (PET) with radioligands provides a means to image the KOR in vivo and investigate its function in health and disease. The purpose of this study was to develop the selective KOR antagonist 11C-LY2459989 as a PET radioligand and characterize its imaging performance in non-human primates. Methods LY2459989 was synthesized and assayed for in vitro binding to opioid receptors. Ex vivo studies in rodents were conducted to assess its potential as a tracer candidate. 11C-LY2459989 was synthesized by reaction of its iodophenyl precursor with 11C-cyanide followed by partial hydrolysis of the resulting 11C-cyanophenyl intermediate. Imaging experiments with 11C-LY2459989 were carried out in rhesus monkeys with arterial input function measurement. Imaging data were analyzed with kinetic models to derive in vivo binding parameters. Results LY2459989 is a full antagonist with high binding affinity and selectivity for KOR (Ki = 0.18, 7.68, and 91.3 nM, respectively, for κ, μ, and δ receptors). Ex vivo studies in rats indicated LY2459989 as an appropriate tracer candidate with high specific binding signals, and confirmed its KOR binding selectivity in vivo. 11C-LY2459989 was synthesized in high radiochemical purity and good specific activity. In rhesus monkeys, 11C-LY2459989 displayed a fast rate of peripheral metabolism. Similarly, 11C-LY2459989 displayed fast uptake kinetics in the brain and an uptake pattern consistent with the distribution of KOR in primates. Pretreatment with naloxone (1 mg/kg, i.v.) resulted in a uniform distribution of radioactivity in the brain. Further, specific binding of 11C-LY2459989 was dose-dependently reduced by the selective KOR antagonist LY2456302 and the unlabeled LY2459989. Regional binding potential (BPND) values derived from the multilinear analysis method (MA1), as a measure of in vivo specific

  15. [11C]acetate PET Imaging is not Always Associated with Increased Lipogenesis in Hepatocellular Carcinoma in Mice

    PubMed Central

    Li, Lei; Che, Li; Wang, Chunmei; Blecha, Joseph E.; Li, Xiaolei; VanBrocklin, Henry F.; Calvisi, Diego F.; Puchowicz, Michelle; Chen, Xin; Seo, Youngho

    2015-01-01

    Purpose Altered metabolism, including increased glycolysis and de novo lipogenesis, is one of the hallmarks of cancer. Radiolabeled nutrients, including glucose and acetate, are extensively used for the detection of various tumors, including hepatocellular carcinomas (HCCs). High signal of [11C]acetate positron emission tomography (PET) in tumors is often considered to be associated with increased expression of Fatty Acid Synthase (FASN) and increased de novo lipogenesis in tumor tissues. Defining a subset of tumors with increased [11C]acetate PET signal and thus increased lipogenesis was suggested to help select a group of patients, who may benefit from lipogenesis-targeting therapies. Procedures To investigate whether [11C]acetate PET imaging is truly associated with increased de novo lipogenesis along with hepatocarcinogenesis, we performed [11C]acetate PET imaging in wildtype mice as well as two mouse HCC models, induced by myrAKT/RasV12 (AKT/Ras) and PIK3CA1047R/c-Met (PI3K/Met) oncogene combinations. In addition, we analyzed FASN expression and de novo lipogenesis rate in these mouse liver tissues. Results We found that while HCCs induced by AKT/Ras co-expression showed high levels of [11C]acetate PET signal compared to normal liver, HCCs induced by PI3K/Met overexpression did not. Intriguingly, elevated FASN expression and increased de novo lipogenesis rate were observed in both AKT/Ras and PI3K/Met HCCs. Conclusion Altogether, our study suggests that [11C]acetate PET imaging can be a useful tool for imaging of a subset of HCCs. However, at molecular level, the increased [11C]acetate PET imaging is not always associated with increased FASN expression or de novo lipogenesis. PMID:26567114

  16. In vivo ketamine-induced changes in [11C]ABP688 binding to metabotropic glutamate receptors subtype 5

    PubMed Central

    DeLorenzo, Christine; DellaGioia, Nicole; Bloch, Michael; Sanacora, Gerard; Nabulsi, Nabeel; Abdallah, Chadi; Yang, Jie; Wen, Ruofeng; Mann, J. John; Krystal, John H.; Parsey, Ramin V.; Carson, Richard E.; Esterlis, Irina

    2014-01-01

    Background At subanesthetic doses, ketamine, an N-Methyl-D-aspartate (NMDA) glutamate receptor antagonist, increases glutamate release. Here, we imaged the acute effect of ketamine on brain metabotropic glutamatergic receptors subtype 5 (mGluR5) with a high affinity PET ligand [11C]ABP688 ((E)-3-((6-methylpyridin-2-yl)ethynyl)-cyclohex-2-enone-O-11C-methyl-oxime), a negative allosteric modulator of mGluR5. Methods Ten healthy nonsmoking human volunteers (34±13 years old) received two [11C]ABP688 PET scans on the same day – before (scan 1) and during i.v. ketamine administration (0.23mg/kg over 1min, then 0.58mg/kg over 1h; scan 2). PET data were acquired for 90 min immediately following [11C]ABP688 bolus injection. Input functions were obtained through arterial blood sampling with metabolite analysis. Results A significant reduction in [11C]ABP688 volume of distribution (VT) was observed in scan 2 relative to scan 1 of 21.3 ± 21.4%, on average, in the anterior cingulate, medial prefrontal cortex, orbital prefrontal cortex, ventral striatum, parietal lobe, dorsal putamen, dorsal caudate, amygdala, and hippocampus. There was a significant increase in measurements of dissociative state after ketamine initiation (p<0.05) that resolved after completion of the scan. Discussion This study provides first evidence that ketamine administration decreases [11C]ABP688 binding in vivo in human subjects. Results suggest that [11C]ABP688 binding is sensitive to ketamine-induced effects, although the high individual variation in ketamine response requires further examination. PMID:25156701

  17. Increased striatal dopamine release in Parkinsonian patients with pathological gambling: a [11C] raclopride PET study

    PubMed Central

    Steeves, T. D. L.; Miyasaki, J.; Zurowski, M.; Lang, A. E.; Pellecchia, G.; Van Eimeren, T.; Rusjan, P.; Houle, S.; Strafella, A. P.

    2012-01-01

    Pathological gambling is an impulse control disorder reported in association with dopamine agonists used to treat Parkinson’s disease. Although impulse control disorders are conceptualized as lying within the spectrum of addictions, little neurobiological evidence exists to support this belief. Functional imaging studies have consistently demonstrated abnormalities of dopaminergic function in patients with drug addictions, but to date no study has specifically evaluated dopaminergic function in Parkinson’s disease patients with impulse control disorders. We describe results of a [11C] raclopride positron emission tomography (PET) study comparing dopaminergic function during gambling in Parkinson’s disease patients, with and without pathological gambling, following dopamine agonists. Patients with pathological gambling demonstrated greater decreases in binding potential in the ventral striatum during gambling (13.9%) than control patients (8.1%), likely reflecting greater dopaminergic release. Ventral striatal bindings at baseline during control task were also lower in patients with pathological gambling. Although prior imaging studies suggest that abnormality in dopaminergic binding and dopamine release may be markers of vulnerability to addiction, this study presents the first evidence of these phenomena in pathological gambling. The emergence of pathological gambling in a number of Parkinson’s disease patients may provide a model into the pathophysiology of this disorder. PMID:19346328

  18. (11)C-PBR28 binding to translocator protein increases with progression of Alzheimer's disease.

    PubMed

    Kreisl, William C; Lyoo, Chul Hyoung; Liow, Jeih-San; Wei, Monica; Snow, Joseph; Page, Emily; Jenko, Kimberly J; Morse, Cheryl L; Zoghbi, Sami S; Pike, Victor W; Turner, R Scott; Innis, Robert B

    2016-08-01

    This longitudinal study sought to determine whether the 18 kDa translocator protein (TSPO), a marker of neuroinflammation, increases over time in Alzheimer's disease. Positron emission tomography imaging with the TSPO radioligand (11)C-PBR28 was performed at baseline and after a median follow-up of 2.7 years in 14 amyloid-positive patients and 8 amyloid-negative controls. Patients had a greater increase in TSPO binding than controls in inferior parietal lobule, precuneus, occipital cortex, hippocampus, entorhinal cortex, and combined middle and inferior temporal cortex. TSPO binding in temporoparietal regions increased from 3.9% to 6.3% per annum in patients, but ranged from -0.5% to 1% per annum in controls. The change in TSPO binding correlated with cognitive worsening on clinical dementia rating scale-sum of boxes and reduced cortical volume. The annual rate of increased TSPO binding in temporoparietal regions was about 5-fold higher in patients with clinical progression (n = 9) compared with those who did not progress (n = 5). TSPO may serve as a biomarker of Alzheimer's progression and response to anti-inflammatory therapies. PMID:27318133

  19. Lifetimes of states in {sup 19}Ne above the {sup 15}O+{alpha} breakup threshold

    SciTech Connect

    Mythili, S.; Davids, B.; Ball, G. C.; Chakrawarthy, R. S.; Churchman, R.; Hackman, G.; Padilla, E.; Pearson, C. J.; Ruiz, C.; Ruprecht, G.; Tanihata, I.; Vockenhuber, C.; Walden, P.; Yen, S.; Alexander, T. K.; Chicoine, M.; Forster, J. S.; Gujrathi, S.; Howell, D.; Kanungo, R.

    2008-03-15

    The {sup 15}O({alpha},{gamma}){sup 19}Ne reaction plays a role in the ignition of type I x-ray bursts on accreting neutron stars. The lifetimes of states in {sup 19}Ne above the {sup 15}O+{alpha} threshold of 3.53 MeV are important inputs to calculations of the astrophysical reaction rate. These levels in {sup 19}Ne were populated in the {sup 3}He({sup 20}Ne,{alpha}){sup 19}Ne reaction at a {sup 20}Ne beam energy of 34 MeV. The lifetimes of six states above the threshold were measured with the Doppler-shift attenuation method. The present measurements agree with previous determinations of the lifetimes of these states and in some cases are considerably more precise.

  20. Measurement of the 330-keV resonance in 18F(p,alpha)15O

    SciTech Connect

    Moazen, Brian; Blackmon, Jeff C; Bardayan, Daniel W; Chae, K. Y.; Chipps, K.; Jones, K. L.; Kozub, R. L.; Matei, Catalin; Nesaraja, Caroline D; Pain, Steven D; ShrinerJr., J. F.; Smith, Michael Scott

    2009-03-01

    While recent measurements have substantially improved our understanding of the {sup 18}F(p, {alpha}){sup 15}O reaction that is important in novae, the production of {sup 18}F is still uncertain by more than 2 orders of magnitude, due in large part to the contribution of a resonance located at E{sub cm} = 330 keV. We developed a new technique to study resonant (p, {alpha}) reactions and employed it to measure properties of the E{sub cm} = 183 keV resonance in {sup 17}O(p, {alpha}){sup 14}N which had been previously reported to decrease {sup 18}F production in ONeMg novae by as much as a factor of 10. The previous results were confirmed using the new technique and we now propose to use this technique to study the {sup 18}F(p, {alpha}){sup 15}O reaction.

  1. 15O(alpha,gamma)19Ne breakout reaction and impact on X-ray bursts.

    PubMed

    Tan, W P; Fisker, J L; Görres, J; Couder, M; Wiescher, M

    2007-06-15

    The breakout reaction 15O(alpha,gamma)19Ne, which regulates the flow between the hot CNO cycle and the rp process, is critical for the explanation of the burst amplitude and periodicity of x-ray bursters. We report on the first successful measurement of the critical alpha-decay branching ratios of relevant states in 19Ne populated via 19F(3He,t)19Ne. Based on the experimental results and our previous lifetime measurements of these states, we derive the first experimental rate of 15O(alpha,gamma)19Ne. The impact of our experimental results on the burst pattern and periodicity for a range of accretion rates is analyzed. PMID:17677960

  2. Imaging human brown adipose tissue under room temperature conditions with 11C-MRB, a selective norepinephrine transporter PET ligand

    PubMed Central

    Hwang, Janice J.; Yeckel, Catherine W.; Gallezot, Jean-Dominique; Aguiar, Renata Belfort-De; Ersahin, Devrim; Gao, Hong; Kapinos, Michael; Nabulsi, Nabeel; Huang, Yiyun; Cheng, David; Carson, Richard E.; Sherwin, Robert; Ding, Yu-Shin

    2015-01-01

    Introduction Brown adipose tissue (BAT) plays a critical role in adaptive thermogenesis and is tightly regulated by the sympathetic nervous system (SNS). However, current BAT imaging modalities require cold stimulation and are often unreliable to detect BAT in the basal state, at room temperature (RT). We have shown previously that BAT can be detected in rodents under both RT and cold conditions with 11C-MRB ((S,S)-11C-O-methylreboxetine), a highly selective ligand for the norepinephrine transporter (NET). Here, we evaluate this novel approach for BAT detection in adult humans under RT conditions. Methods Ten healthy, Caucasian subjects (5 M: age 24.6±2.6, BMI 21.6±2.7 kg/m2; 5 F: age 25.4±2.1, BMI 22.1±1.0 kg/m2) underwent 11C-MRB PET-CT imaging for cervical/supraclavicular BAT under RT and cold-stimulated conditions (RPCM Cool vest; enthalpy 15°C) compared to 18F-FDG PET-CT imaging. Uptake of 11C-MRB, was quantified as the distribution volume ratio (DVR) using the occipital cortex as a low NET density reference region. Total body fat and lean body mass were assessed via bioelectrical impedance analysis. Results As expected, 18F-FDG uptake in BAT was difficult to identify at RT but easily detected with cold stimulation (p=0.01). In contrast, BAT 11C-MRB uptake (also normalized for muscle) was equally evident under both RT and cold conditions (BAT DVR: RT 1.0±0.3 vs. cold 1.1±0.3, p=0.31; BAT/muscle DVR: RT 2.3±0.7 vs. cold 2.5±0.5, p=0.61). Importantly, BAT DVR and BAT/muscle DVR of 11C-MRB at RT correlated positively with core body temperature (r=0.76, p=0.05 and r=0.92, p=0.004, respectively), a relationship not observed with 18F-FDG (p=0.63). Furthermore, there were gender differences in 11C-MRB uptake in response to cold (p=0.03), which reflected significant differences in the change in 11C-MRB as a function of both body composition and body temperature. Conclusions Unlike 18F-FDG, the uptake of 11C-MRB in BAT offers a unique opportunity to

  3. The astrophysical reaction rate for the {sup 18}F(p,{alpha}){sup 15}O reaction

    SciTech Connect

    Rehm, K.E.; Paul, M.; Roberts, A.D.

    1996-03-01

    Proton and alpha widths for a 3/2{sup +} ({ell}{sub p} = 0) state in {sup 19}Ne at E{sub x} = 7.1 MeV have been extracted using the results of recent measurements of the {sup 18}F(p,{alpha}){sup 15}O reaction. This {ell}{sub p} = 0 resonance dominates the astrophysical reaction rates at temperatures T{sub 9} > 0.5.

  4. Production of [15O]Water at Low-Energy Proton Cyclotrons

    SciTech Connect

    Powell, James; O'Neil, James P.

    2005-12-12

    We report a simple system for producing [15O]H2O from nitrogen-15 in a nitrogen/hydrogen gas target with recycling of the target nitrogen, allowing production on low-energy proton-only accelerators with minimal consumption of isotopically enriched nitrogen-15. The radiolabeled water is separated from the target gas and radiolytically produced ammonia by temporary freezing in a small trap at -40 C.

  5. Ammonia oxidation is not required for growth of Group 1.1c soil Thaumarchaeota

    PubMed Central

    Weber, Eva B.; Lehtovirta-Morley, Laura E.; Prosser, James I.; Gubry-Rangin, Cécile

    2015-01-01

    Thaumarchaeota are among the most abundant organisms on Earth and are ubiquitous. Within this phylum, all cultivated representatives of Group 1.1a and Group 1.1b Thaumarchaeota are ammonia oxidizers, and play a key role in the nitrogen cycle. While Group 1.1c is phylogenetically closely related to the ammonia-oxidizing Thaumarchaeota and is abundant in acidic forest soils, nothing is known about its physiology or ecosystem function. The goal of this study was to perform in situ physiological characterization of Group 1.1c Thaumarchaeota by determining conditions that favour their growth in soil. Several acidic grassland, birch and pine tree forest soils were sampled and those with the highest Group 1.1c 16S rRNA gene abundance were incubated in microcosms to determine optimal growth temperature, ammonia oxidation and growth on several organic compounds. Growth of Group 1.1c Thaumarchaeota, assessed by qPCR of Group 1.1c 16S rRNA genes, occurred in soil, optimally at 30°C, but was not associated with ammonia oxidation and the functional gene amoA could not be detected. Growth was also stimulated by addition of organic nitrogen compounds (glutamate and casamino acids) but not when supplemented with organic carbon alone. This is the first evidence for non-ammonia oxidation associated growth of Thaumarchaeota in soil. PMID:25764563

  6. Synthesis of [(11)C]MK-1064 as a new PET radioligand for imaging of orexin-2 receptor.

    PubMed

    Gao, Mingzhang; Wang, Min; Zheng, Qi-Huang

    2016-08-01

    The reference standard MK-1064 {5″-chloro-N-((5,6-dimethoxypyridin-2-yl)methyl)-[2,2':5',3″-terpyridine]-3'-carboxamide} was synthesized from methyl 2-chloro-5-iodonicotinate and 5-(chloropyridin-3-yl)boronic acid in 4 steps with 33% overall chemical yield. The precursor desmethyl-MK-1064 {5″-chloro-N-((5-hydroxy-6-methoxypyridin-2-yl)methyl)-[2,2':5',3″-terpyridine]-3'-carboxamide} for radiolabeling was synthesized from 2-bromopyridin-3-ol and 5″-chloro-[2,2':5',3″-terpyridine]-3'-carboxylic acid in 6 steps with 17% overall chemical yield. The target tracer [(11)C]MK-1064 {5″-chloro-N-((5-[(11)C]methoxy-6-methoxypyridin-2-yl)methyl)-[2,2':5',3″-terpyridine]-3'-carboxamide} was prepared by O-[(11)C]methylation of its corresponding precursor desmethyl-MK-1064 with [(11)C]CH3OTf under basic condition and isolated by a simplified solid-phase extraction (SPE) method in 50-60% decay corrected radiochemical yields based on [(11)C]CO2 at end of bombardment (EOB). The overall synthesis time from EOB was 23min, the radiochemical purity was >99%, and the specific activity at end of synthesis (EOS) was 185-555GBq/μmol. PMID:27268698

  7. Design and performance evaluation of single-use whole-sterile "plug & play" kits for routine automated production of [(11)C]choline and [(11)C]methionine with radiopharmaceutical quality.

    PubMed

    Quincoces, Gemma; López-Sánchez, Luisa; Sánchez-Martínez, María; Rodríguez-Fraile, Macarena; Peñuelas, Iván

    2010-12-01

    We herein describe the design and performance evaluation of single-use whole-sterile "plug & play" kits for routine automated production of [(11)C]methionine and [(11)C]choline for human use. Kits were designed for maximal simplicity and ease of using modules from Eckert & Ziegler Modular Lab System. The use of all-disposable sterile medical-grade material, helps ensure safety and cGMP compliance. The quick set-up and removal ("plug & play") also reduces radiation burden to operator. PMID:20685129

  8. Scanning with L-(/sup 13/N) glutamate: Assessment of the response to chemotherapy of a patient with embryonal rhabdomyosarcoma

    SciTech Connect

    Sordillo, P.P.; Reiman, R.E.; Gelbard, A.S.; Benua, R.S.; Magill, G.B.; Laughlin, J.S.

    1982-06-01

    The use of /sup 13/N-labeled L-glutamate as an imaging agent in a patient with embryonal rhabdomyosarcoma is described. Localization of /sup 13/N in a large, poorly defined tumor of the left pectoral region was seen, and clinically occult right axilliary metastases were also detected. A marked reduction in uptake in these areas occurred after chemotherapy, paralleling the clinical disappearance of tumor. These changes were verified on gallium scan. /sup 13/N-labeled glutamate may be useful as an imaging agent, especially in patients with soft-tissue sarcomas.

  9. In vivo kinetics and displacement study of a carbon-11-labeled hallucinogen, N,N-[11C]dimethyltryptamine.

    PubMed

    Yanai, K; Ido, T; Ishiwata, K; Hatazawa, J; Takahashi, T; Iwata, R; Matsuzawa, T

    1986-01-01

    The endogenous hallucinogen, N,N-dimethyltryptamine (DMT), was labeled with carbon-11 and its regional distribution in rat brain studied. [11C]DMT showed higher accumulation in the cerebral cortex, caudate putamen, and amygdaloid nuclei. Studies of the subcellular distribution of [11C]DMT revealed the specific localization in the fractions enriched with serotonin receptors only when a very low dose was injected into rats. The proportions of the radioactivity in receptor-rich fractions were greatly enhanced by pretreatment with the monoamine oxidase inhibitor, pargyline. Specific binding of [11C]DMT to serotonin receptors in dog brain was demonstrated by a positron emission tomographic study in which 5-methoxy-N,N-dimethyltryptamine caused approximately 20% displacement of the radioligand from the receptors. PMID:3489620

  10. Development of a NiO target for the production of 11C at ISAC/TRIUMF

    NASA Astrophysics Data System (ADS)

    Bricault, Pierre G.; Ames, Friedhelm; Dombsky, Marik; Kunz, Peter; Lassen, Jens; Mjøs, Anders; Wong, John

    2016-01-01

    High intensity 11C beams are necessary for the investigation of the formation of 12C via the nuclear reaction 11C(p, γ)12N → 12C + e+ + ν. The production of intense carbon beams on-line is quite challenging due to the thermodynamic properties and chemical reactivity of carbon at high temperatures. A previous attempt, using a medical isotope cyclotron production method in batch mode, was not conclusive. The intensity obtained was at least one order of magnitude too low for a direct proton capture experiment using the DRAGON facility at ISAC/TRIUMF. Producing a 11C beams using the ISOL method requires a target capable of efficiently releasing the carbon isotopes. NiO has been selected as a target material because most of the nickel carbides are not stable at high temperature. The development of carbon beams using a composite NiO/Ni target on-line is described.

  11. Blockade of [11C](+)-PHNO binding in human subjects by the dopamine D3 receptor antagonist ABT-925.

    PubMed

    Graff-Guerrero, Ariel; Redden, Laura; Abi-Saab, Walid; Katz, David A; Houle, Sylvain; Barsoum, Penny; Bhathena, Anahita; Palaparthy, Ramesh; Saltarelli, Mario D; Kapur, Shitij

    2010-04-01

    Dopamine D3 receptors are preferentially localized in the limbic system and midbrain, and thus may be involved in the pathophysiology of neuropsychiatry disorders. [11C](+)-PHNO is the first preferential D3 receptor radioligand in humans, yet there are no blockade studies with a D3 receptor antagonist in humans. This study characterized the blockade of [11C](+)-PHNO binding by ABT-925, a D3 receptor antagonist, in healthy male subjects. Sixteen subjects underwent 2-3 positron emission tomography (PET) scans, at baseline and following one or two doses of ABT-925 ranging from 50 mg to 600 mg. Receptor occupancies were estimated for globus pallidus, substantia nigra, caudate, putamen, and ventral striatum. At the 600-mg dose (n=9), ABT-925 receptor occupancy (mean+/-s.d.) was higher in substantia nigra (75+/-10%) and globus pallidus (64+/-22%) than in ventral striatum (44+/-17%), caudate (40+/-18%) and putamen (38+/-17%) (ANOVA: F4,140=15.02, p<0.001). The fractions of [11C](+)-PHNO binding attributable to D3 receptors in D3 receptor-rich regions were 100% (substantia nigra) and 90% (globus pallidus), and in D2 receptor-rich regions were 55% (caudate) and 53% (putamen). The ED50 of ABT-925 was 4.37 microg/ml across regions. Our results demonstrate that [11C](+)-PHNO binding can be blocked by a D3 receptor antagonist and confirm preclinical findings that [11C](+)-PHNO signal in the substantia nigra and globus pallidus is mainly reflective of its binding to D3 receptors. Thus, [11C](+)-PHNO seems a suitable PET radiotracer to estimate D3 receptor occupancy in humans. PMID:19751545

  12. Investigating expectation and reward in human opioid addiction with [11C]raclopride PET

    PubMed Central

    Watson, Ben J; Taylor, Lindsay G; Reid, Alastair G; Wilson, Sue J; Stokes, Paul R; Brooks, David J; Myers, James F; Turkheimer, Federico E; Nutt, David J; Lingford-Hughes, Anne R

    2014-01-01

    The rewarding properties of some abused drugs are thought to reside in their ability to increase striatal dopamine levels. Similar increases have been shown in response to expectation of a positive drug effect. The actions of opioid drugs on striatal dopamine release are less well characterized. We examined whether heroin and the expectation of heroin reward increases striatal dopamine levels in human opioid addiction. Ten opioid-dependent participants maintained on either methadone or buprenorphine underwent [11C]raclopride positron emission tomography imaging. Opioid-dependent participants were scanned three times, receiving reward from 50-mg intravenous heroin (diamorphine; pharmaceutical heroin) during the first scan to generate expectation of the same reward at the second scan, during which they only received 0.1-mg intravenous heroin. There was no heroin injection during the third scan. Intravenous 50-mg heroin during the first scan induced pronounced effects leading to high levels of expectation at the second scan. There was no detectable increase in striatal dopamine levels to either heroin reward or expectation of reward. We believe this is the first human study to examine whether expectation of heroin reward increases striatal dopamine levels in opioid addiction. The absence of detectable increased dopamine levels to both the expectation and delivery of a heroin-related reward may have been due to the impact of substitute medication. It does however contrast with the changes seen in abstinent stimulant users, suggesting that striatal dopamine release alone may not play such a pivotal role in opioid-maintained individuals. PMID:23829344

  13. BS69/ZMYND11 C-Terminal Domains Bind and Inhibit EBNA2

    PubMed Central

    Shen, Chih-Lung; Gonzalez-Hurtado, Elsie; Zhang, Zhi-Min; Xu, Muyu; Martinez, Ernest; Peng, Chih-Wen; Song, Jikui

    2016-01-01

    Epstein-Barr virus (EBV) nuclear antigen 2 (EBNA2) plays an important role in driving immortalization of EBV-infected B cells through regulating the expression of many viral and cellular genes. We report a structural study of the tumor suppressor BS69/ZMYND11 C-terminal region, comprised of tandem coiled-coil-MYND domains (BS69CC-MYND), in complex with an EBNA2 peptide containing a PXLXP motif. The coiled-coil domain of BS69 self-associates to bring two separate MYND domains in close proximity, thereby enhancing the BS69 MYND-EBNA2 interaction. ITC analysis of BS69CC-MYND with a C-terminal fragment of EBNA2 further suggests that the BS69CC-MYND homodimer synergistically binds to the two EBNA2 PXLXP motifs that are respectively located in the conserved regions CR7 and CR8. Furthermore, we showed that EBNA2 interacts with BS69 and down-regulates its expression at both mRNA and protein levels in EBV-infected B cells. Ectopic BS69CC-MYND is recruited to viral target promoters through interactions with EBNA2, inhibits EBNA2-mediated transcription activation, and impairs proliferation of lymphoblastoid cell lines (LCLs). Substitution of critical residues in the MYND domain impairs the BS69-EBNA2 interaction and abolishes the BS69 inhibition of the EBNA2-mediated transactivation and LCL proliferation. This study identifies the BS69 C-terminal domains as an inhibitor of EBNA2, which may have important implications in development of novel therapeutic strategies against EBV infection. PMID:26845565

  14. Plasma based markers of [11C] PiB-PET brain amyloid burden.

    PubMed

    Kiddle, Steven John; Thambisetty, Madhav; Simmons, Andrew; Riddoch-Contreras, Joanna; Hye, Abdul; Westman, Eric; Pike, Ian; Ward, Malcolm; Johnston, Caroline; Lupton, Michelle Katharine; Lunnon, Katie; Soininen, Hilkka; Kloszewska, Iwona; Tsolaki, Magda; Vellas, Bruno; Mecocci, Patrizia; Lovestone, Simon; Newhouse, Stephen; Dobson, Richard

    2012-01-01

    Changes in brain amyloid burden have been shown to relate to Alzheimer's disease pathology, and are believed to precede the development of cognitive decline. There is thus a need for inexpensive and non-invasive screening methods that are able to accurately estimate brain amyloid burden as a marker of Alzheimer's disease. One potential method would involve using demographic information and measurements on plasma samples to establish biomarkers of brain amyloid burden; in this study data from the Alzheimer's Disease Neuroimaging Initiative was used to explore this possibility. Sixteen of the analytes on the Rules Based Medicine Human Discovery Multi-Analyte Profile 1.0 panel were found to associate with [(11)C]-PiB PET measurements. Some of these markers of brain amyloid burden were also found to associate with other AD related phenotypes. Thirteen of these markers of brain amyloid burden--c-peptide, fibrinogen, alpha-1-antitrypsin, pancreatic polypeptide, complement C3, vitronectin, cortisol, AXL receptor kinase, interleukin-3, interleukin-13, matrix metalloproteinase-9 total, apolipoprotein E and immunoglobulin E--were used along with co-variates in multiple linear regression, and were shown by cross-validation to explain >30% of the variance of brain amyloid burden. When a threshold was used to classify subjects as PiB positive, the regression model was found to predict actual PiB positive individuals with a sensitivity of 0.918 and a specificity of 0.545. The number of APOE [Symbol: see text] 4 alleles and plasma apolipoprotein E level were found to contribute most to this model, and the relationship between these variables and brain amyloid burden was explored. PMID:23028511

  15. Kinetics of 11C-labeled opiates in the brain of rhesus monkeys

    SciTech Connect

    Hartvig, P.; Bergstroem, K.; Lindberg, B.; Lundberg, P.O.; Lundqvist, H.; Langstroem, B.; Svaerd, H.; Rane, A.

    1984-07-01

    The regional uptake in the brain of Rhesus monkeys of i.v. administered 11C-labeled morphine, codeine, heroin and pethidine was studied by means of positron emission tomography. The technique measures the sum of parent drug and radiolabeled metabolites. (For the sake of simplicity the drug derived radioactivity is denoted by the drug name.) Morphine had a limited uptake to discrete areas of the brain. The maximum normalized uptake, with respect to dose per kilogram body weight, was about 0.2, i.e., 20% of the calculated activity if the drug had been evenly distributed throughout the body of the monkey. Maximum radioactivity appeared 30 to 45 min after injection. Morphine left the brain slowly with an estimated half-life of more than 2 hr. An area with a normalized uptake of about 1.0 was detected centrally in the lowest horizontal transsection of the skull. The origin of this area was identified as the pituitary. Codeine, heroin and pethidine were taken up to the brain to a larger extent than morphine, with maximum normalized uptakes of 2.6, 4.6 and 6.3, respectively. Maximum radioactivities of these drugs were achieved earlier and the elimination rates were faster than for morphine. Differences in the uptake of these drugs to the brain, as well as differences in time to maximal normalized uptake and rate of disappearance are considered to reflect differences in the lipophilic character between the drugs. Pethidine had the most rapid and extensive uptake followed by heroin, codeine and morphine in order of decreasing lipophilicity.

  16. Synthesis and Evaluation of [11C]LY2795050 as a Novel Kappa Opioid Receptor Antagonist Radiotracer for PET Imaging

    PubMed Central

    Zheng, Ming-Qiang; Nabulsi, Nabeel; Kim, Su Jin; Tomasi, Giampaolo; Lin, Shu-fei; Mitch, Charles; Quimby, Steven; Barth, Vanessa; Rash, Karen; Masters, John; Navarro, Antonio; Seest, Eric; Morris, Evan E.; Carson, Richard E.; Huang, Yiyun

    2013-01-01

    Kappa opioid receptors (KOR) are believed to be involved in the pathophysiology of depression, anxiety disorders, drug abuse and alcoholism. To date, only one tracer, the kappa opioid receptor agonist [11C]GR103545, has been reported to be able to image KOR in primates. The goal of the present study was to synthesize the selective KOR antagonist [11C]LY2795050 and evaluate its potential as a PET tracer to image KOR in vivo. METHODS In vitro binding affinity of LY2795050 was measured in radioligand competition binding assays. Ex vivo experiments were conducted using microdosing of the unlabelled ligand in Sprague-Dawley rats, as well as wild-type and KOR knock-out mice, to assess the ligand’s potential as a tracer candidate. Imaging experiments with [11C]LY2795050 in monkeys were carried out on the Focus-220 PET scanner with arterial blood input function measurement. Binding parameters were determined with kinetic modeling analysis. RESULTS LY2795050 displays full antagonist activity and high binding affinity and selectivity for KOR. Microdosing studies in rodents and ex vivo analysis of tissue concentrations with LC/MS/MS identified LY2795050 as an appropriate tracer candidate able to provide specific binding signals in vivo. [11C]LY2795050 was prepared in an average yield of 12% and >99% radiochemical purity. In rhesus monkeys, [11C]LY2795050 displayed a moderate rate of peripheral metabolism, with ∼40% of parent compound remaining at 30 min postinjection. In the brain, [11C]LY2795050 displayed fast uptake kinetics (regional activity peak times < 20 min) and an uptake pattern consistent with the distribution of KOR in primates. Pretreatment with naloxone (1 mg/kg, iv) resulted in a uniform distribution of radioactivity. Further, specific binding of [11C]LY2795050 was reduced by the selective KOR antagonist LY2456302 in a dose-dependent manner. CONCLUSION [11C]LY2795050 displayed favorable pharmacokinetic properties and binding profiles in vivo, and therefore

  17. Distinct cerebral lesions in sporadic and 'D90A' SOD1 ALS: studies with [11C]flumazenil PET.

    PubMed

    Turner, M R; Hammers, A; Al-Chalabi, A; Shaw, C E; Andersen, P M; Brooks, D J; Leigh, P N

    2005-06-01

    Five to ten percent of amyotrophic lateral sclerosis (ALS) cases are associated with mutations of the superoxide dismutase-1 (SOD1) gene, and the 'D90A' mutation is associated with a unique phenotype and markedly slower disease progression (mean survival time 14 years). Relative sparing of inhibitory cortical neuronal circuits might be one mechanism contributing to the slower progression in patients homozygous for the D90A mutation (homD90A). The GABA(A) receptor PET ligand [11C]flumazenil has demonstrated motor and extra-motor cortical changes in sporadic ALS. In this study, we used [11C]flumazenil PET to explore differences in the pattern of cortical involvement between sporadic and genetically homogeneous ALS groups. Twenty-four sporadic ALS (sALS) and 10 homD90A patients underwent [11C]flumazenil PET of the brain. In addition, two subjects homozygous for the D90A mutation, but without symptoms or signs ('pre-symptomatic', psD90A), also underwent imaging. Results for each group were compared with those for 24 healthy controls of similar age. Decreases in the binding of [11C]flumazenil in the sALS group were found within premotor regions, motor cortex and posterior motor association areas. In the homD90A group of ALS patients, however, decreases were concentrated in the left fronto-temporal junction and anterior cingulate gyrus. In the two psD90A subjects, a small focus of reduced [11C]flumazenil binding at the left fronto-temporal junction was seen, similar to the pattern seen in the clinically affected patients. Within the sALS group, there was no statistically significant association between decreases in cortical [11C]flumazenil binding and revised ALS functional rating scale (ALSFRS-R score), whereas the upper motor neuron (UMN) score correlated with widespread and marked cortical decreases over the dominant hemisphere. In the homD90A group, there was a stronger statistical association between reduced cortical [11C]flumazenil binding and the ALSFRS-R, rather

  18. Imaging of Carrageenan-Induced Local Inflammation and Adjuvant-Induced Systemic Arthritis with [11C]PBR28 PET

    PubMed Central

    Shao, Xia; Wang, Xueding; English, Sean J; Desmond, Timothy; Sherman, Phillip S; Quesada, Carole A; Piert, Morand R

    2013-01-01

    Introduction [11C]PBR28 binding to translocator protein (TSPO) was evaluated for imaging of acute and chronic inflammation using two established rat models. Methods Acute inflammation was induced by local Carrageenan-injection into the paw of Fisher 344 rats (model A). T-cell mediated adjuvant arthritis was induced by heat-inactivated Mycobacterium butyricum injection in Lewis rats (model B). Micro-PET scan was performed after injection of approximately 35 MBq [11C]PBR28. In model A, volumes of interest (VOIs) were defined in the paw of Fisher 344 rats (n=6) with contralateral sham treatment as control. For model B, VOIs were defined in the tail, sacroiliac joints, hips, knees and thigh muscles of M. butyricum treated animals (n=8) and compared with sham-treated controls (n=4). The peak 11C-PBR28 SUV (SUVpeak) and area under the curve (AUCSUV) of 60-minute time-activity data were calculated. Immunohistochemistry for CD68, a macrophage stain, was performed from paw tissues. In addition, the [11C]PBR28 cell uptake was measured in lipopolysaccharide (LPS)-stimulated and non-stimulated macrophage cultures. Results LPS-stimulated macrophages displayed dose-dependent increased [11C]PBR28 uptake, which was blocked by non-labeled PBR28. In both models, radiotracer uptake of treated lesions increased rapidly within minutes and displayed overall accumulative kinetics. The SUVpeak and AUCSUV of Carrageenan-treated paws was significantly increased compared to controls. Also, the [11C]PBR28 uptake ratio of Carrageenan-treated vs. sham-treated paw correlated significantly with CD68 staining ratios of the same animals. In adjuvant arthritis, significantly increased [11C]PBR28 SUVpeak and AUCSUV values were identified at the tail, knees, and sacroiliac joints, while no significant differences were identified in the lumbar spine and hips. Conclusions Based on our initial data, [11C]PBR28 PET appears to have potential for imaging of various inflammatory processes involving

  19. Kinetics of (/sup 11/C)N,N-dimethylphenylethylamine in mice and humans: potential for measurement of brain MAO-B activity

    SciTech Connect

    Shinotoh, H.; Inoue, O.; Suzuki, K.; Yamasaki, T.; Iyo, M.; Hashimoto, K.; Tominaga, T.; Itoh, T.; Tateno, Y.; Ikehira, H.

    1987-06-01

    Carbon-11-labeled N,N-dimethylphenylethylamine ((/sup 11/C)DMPEA) was synthesized by the reaction of N-methylphenylethylamine with (/sup 11/C)methyl iodide. This newly synthesized radiotracer was developed for the purpose of in vivo measurement of monoamine oxidase-B activity in the brain using a metabolic trapping method. Initially, biodistribution was investigated in mice. The rapid and high uptake of /sup 11/C radioactivity in the brain was observed following intravenous injection of (/sup 11/C)DMPEA, the peak of which was reached at 1 min, followed by a decrease at 1-5 min and slowly thereafter. The kinetics of (/sup 11/C)DMPEA in the human brain were determined using positron emission tomography (PET) and showed that /sup 11/C radioactivity increased gradually over 60 min following initial rapid uptake of /sup 11/C radioactivity, with basal ganglia and thalamus showing high accumulation.

  20. Regional cerebral blood flow measurement with intravenous ( sup 15 O)water bolus and ( sup 18 F)fluoromethane inhalation

    SciTech Connect

    Herholz, K.; Pietrzyk, U.; Wienhard, K.; Hebold, I.; Pawlik, G.; Wagner, R.; Holthoff, V.; Klinkhammer, P.; Heiss, W.D. )

    1989-09-01

    In 20 patients with ischemic cerebrovascular disease, classic migraine, or angiomas, we compared paired dynamic positron emission tomographic measurements of regional cerebral blood flow using both ({sup 15}O)water and ({sup 18}F)fluoromethane as tracers. Cerebral blood flow was also determined according to the autoradiographic technique with a bolus injection of ({sup 15}O)water. There were reasonable overall correlations between dynamic ({sup 15}O)water and ({sup 18}F)fluoromethane values for cerebral blood flow (r = 0.82) and between dynamic and autoradiographic ({sup 15}O)water values for cerebral blood flow (r = 0.83). We found a close correspondence between abnormal pathologic findings and visually evaluated cerebral blood flow tomograms obtained with the two tracers. On average, dynamic ({sup 15}O)water cerebral blood flow was 6% lower than that measured with ({sup 18}F)fluoromethane. There also was a general trend toward a greater underestimation with ({sup 15}O)water in high-flow areas, particularly in hyperemic areas, probably due to incomplete first-pass extraction of ({sup 15}O)water. Underestimation was not detected in low-flow areas or in the cerebellum. Absolute cerebral blood flow values were less closely correlated between tracers and techniques than cerebral blood flow patterns. The variability of the relation between absolute flow values was probably caused by confounding effects of the variation in the circulatory delay time. The autoradiographic technique was most sensitive to this type error.

  1. IL-3 and CSF-1 Interact to Promote Generation of CD11c+ IL-10-Producing Macrophages

    PubMed Central

    Sheng, Kuo-Ching; Herrero, Lara J.; Taylor, Adam; Hapel, Andrew J.; Mahalingam, Suresh

    2014-01-01

    Unraveling the mechanisms of hematopoiesis regulated by multiple cytokines remains a challenge in hematology. IL-3 is an allergic cytokine with the multilineage potential, while CSF-1 is produced in the steady state with restricted lineage coverage. Here, we uncovered an instructive role of CSF-1 in IL-3-mediated hematopoiesis. CSF-1 significantly promoted IL-3-driven CD11c+ cell expansion and dampened basophil and mast cell generation from C57BL/6 bone marrow. Further studies indicated that the CSF-1/CSF-1R axis contributed significantly to IL-3-induced CD11c+ cell generation through enhancing c-Fos-associated monopoiesis. CD11c+ cells induced by IL-3 or IL-3/CSF-1 were competent in cellular maturation and endocytosis. Both IL-3 and IL-3/CSF-1 cells lacked classical dendritic cell appearance and resembled macrophages in morphology. Both populations produced a high level of IL-10, in addition to IL-1, IL-6 and TNFα, in response to LPS, and were relatively poor T cell stimulators. Collectively, these findings reveal a role for CSF-1 in mediating the IL-3 hematopoietic pathway through monopoiesis, which regulates expansion of CD11c+ macrophages. PMID:24743235

  2. Search for new resonant states in 10C and 11C and their impact on the cosmological lithium problem

    NASA Astrophysics Data System (ADS)

    Hammache, F.; Coc, A.; de Séréville, N.; Stefan, I.; Roussel, P.; Ancelin, S.; 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, M.

    2013-12-01

    The observed primordial 7Li abundance in metal-poor halo stars is found to be lower than its Big-Bang nucleosynthesis (BBN) calculated value by a factor of approximately three. Some recent works suggested the possibility that this discrepancy originates from missing resonant reactions which would destroy 7Be, parent of 7Li. The most promising candidate resonances which were found include a possibly missed 1- or 2- narrow state around 15 MeV in the compound nucleus 10C formed by 7Be+3He and a state close to 7.8 MeV in the compound nucleus 11C formed by 7Be+4He. In this work, we studied the high excitation energy region of 10C and the low excitation energy region in 11C via the reactions 10B(3He,t)10C and 11B(3He,t)11C, respectively, at the incident energy of 35 MeV. Our results for 10C do not support 7Be+3He as a possible solution for the 7Li problem. Concerning 11C results, the data show no new resonances in the excitation energy region of interest and this excludes the 7Be+4He reaction channel as an explanation for the 7Li deficit.

  3. Design of Infusion Schemes for Neuroreceptor Imaging: Application to [11C]Flumazenil-PET Steady-State Study

    PubMed Central

    Feng, Ling; Svarer, Claus; Madsen, Karine; Ziebell, Morten; Dyssegaard, Agnete; Ettrup, Anders; Hansen, Hanne Demant; Lehel, Szabolcs; Yndgaard, Stig; Paulson, Olaf Bjarne; Knudsen, Gitte Moos; Pinborg, Lars Hageman

    2016-01-01

    This study aims at developing a simulation system that predicts the optimal study design for attaining tracer steady-state conditions in brain and blood rapidly. Tracer kinetics was determined from bolus studies and used to construct the system. Subsequently, the system was used to design inputs for bolus infusion (BI) or programmed infusion (PI) experiments. Steady-state quantitative measurements can be made with one short scan and venous blood samples. The GABAA receptor ligand [11C]Flumazenil (FMZ) was chosen for this purpose, as it lacks a suitable reference region. Methods. Five bolus [11C]FMZ-PET scans were conducted, based on which population-based PI and BI schemes were designed and tested in five additional healthy subjects. The design of a PI was assisted by an offline feedback controller. Results. The system could reproduce the measurements in blood and brain. With PI, [11C]FMZ steady state was attained within 40 min, which was 8 min earlier than the optimal BI (B/I ratio = 55 min). Conclusions. The system can design both BI and PI schemes to attain steady state rapidly. For example, subjects can be [11C]FMZ-PET scanned after 40 min of tracer infusion for 40 min with venous sampling and a straight-forward quantification. This simulation toolbox is available for other PET-tracers. PMID:27123457

  4. Production of pure quasi-monochromatic 11C beams for accurate radiation therapy and dose delivery verification

    NASA Astrophysics Data System (ADS)

    Lazzeroni, Marta; Brahme, Anders

    2015-09-01

    In the present study we develop a new technique for the production of clean quasi-monochromatic 11C positron emitter beams for accurate radiation therapy and PET-CT dose delivery imaging and treatment verification. The 11C ion beam is produced by projectile fragmentation using a primary 12C ion beam. The practical elimination of the energy spread of the secondary 11C fragments and other beam contaminating fragments is described. Monte Carlo calculation with the SHIELD-HIT10+ code and analytical methods for the transport of the ions in matter are used in the analysis. Production yields, as well as energy, velocity and magnetic rigidity distributions of the fragments generated in a cylindrical target are scored as a function of the depth within 1 cm thick slices for an optimal target consisting of a fixed 20 cm section of liquid hydrogen followed by a variable thickness section of polyethylene. The wide energy and magnetic rigidity spread of the 11C ion beam can be reduced to values around 1% by using a variable monochromatizing wedge-shaped degrader in the beam line. Finally, magnetic rigidity and particle species selection, as well as discrimination of the particle velocity through a combined Time of Flight and Radio Frequency-driven Velocity filter purify the beam from similar magnetic rigidity contaminating fragments (mainly 7Be and 3He fragments). A beam purity of about 99% is expected by the combined method.

  5. Multi-Scale hierarchical generation of PET parametric maps: application and testing on a [11C]DPN study.

    PubMed

    Rizzo, G; Turkheimer, F E; Keihaninejad, S; Bose, S K; Hammers, A; Bertoldo, A

    2012-02-01

    We propose a general approach to generate parametric maps. It consists in a multi-stage hierarchical scheme where, starting from the kinetic analysis of the whole brain, we then cascade the kinetic information to anatomical systems that are akin in terms of receptor densities, and then down to the voxel level. A-priori classes of voxels are generated either by anatomical atlas segmentation or by functional segmentation using unsupervised clustering. Kinetic properties are transmitted to the voxels in each class using maximum a posteriori (MAP) estimation method. We validate the novel method on a [11C]diprenorphine (DPN) test-retest data-set that represents a challenge to estimation given [11C]DPN's slow equilibration in tissue. The estimated parametric maps of volume of distribution (VT) reflect the opioid receptor distributions known from previous [11C]DPN studies. When priors are derived from the anatomical atlas, there is an excellent agreement and strong correlation among voxel MAP and ROI results and excellent test-retest reliability for all subjects but one. Voxel level results did not change when priors were defined through unsupervised clustering. This new method is fast (i.e. 15 min per subject) and applied to [11C]DPN data achieves accurate quantification of VT as well as high quality VT images. Moreover, the way the priors are defined (i.e. using an anatomical atlas or unsupervised clustering) does not affect the estimates. PMID:21924366

  6. 17 CFR 274.11c - Form N-4, registration statement of separate accounts organized as unit investment trusts.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... chapter). Editorial Note: For Federal Register citations affecting Form N-4, see the List of CFR Sections... COMPANY ACT OF 1940 Registration Statements § 274.11c Form N-4, registration statement of separate... filed pursuant to section 8(b) of the Investment Company Act of 1940 by separate accounts that...

  7. The 11C Project:Measurement of Root Exudation at Elevated CO2 Levels in Low and High Nutrient Solutions

    NASA Astrophysics Data System (ADS)

    Leandre, Verida; Howell, Calvin

    2011-03-01

    Understanding the plant kingdom's mechanisms of resource management in variable environments is integral to predicting how plants will respond to an increase in atmospheric CO2 . The goal of this study is to determine the effects of changing nutrient conditions on the root exudation of barley plants at elevated CO2 levels. The 11 C group at the Triangle Universities Nuclear Laboratory (TUNL) tags various species of plants with short-lived positron-emitting radioisotopes in order to analyze metabolite transport in response to changes in the environment. 11 C is produced at TUNL using a tandem Van de Graaff particle accelerator, then transported from TUNL to the Duke Univ. Phytotron (100m) where plants are labeled with 11 C in a growth chamber. The chamber allows researchers to control the light intensity, air temperature, humidity and concentration of CO2 in the air. The plant absorbs 11 CO2 in a leaf that is placed inside a cuvette through which radioactive 11 CO2 gas flows. The sugars in the labeling leaf are tagged with 11 C and translocated throughout the plant similar to 12 C. Scintillation detectors are used to track the tagged sugars as they are translocated through the plant and exudated from the root into the nutrient solution or 11 CO2 gas is respired by the root. The labeling system, detector arrangement, electronics and data analysis will be described and preliminary results will be presented.

  8. Determination of Fatty Acid Metabolism with Dynamic 11C-Palmitate Positron Emission Tomography of Mouse Heart In Vivo

    PubMed Central

    Li, Yinlin; Huang, Tao; Zhang, Xinyue; Zhong, Min; Walker, Natalie N.; He, Jiang; Berr, Stuart S.; Keller, Susanna R.; Kundu, Bijoy K.

    2015-01-01

    The goal of this study was to establish a quantitative method for measuring FA metabolism with partial volume (PV) and spill-over (SP) corrections using dynamic 11C-palmitate PET images of mouse heart in vivo. Methods Twenty-minute dynamic 11C-palmitate PET scans of four 18–20 week old male C57BL/6 mice under isoflurane anesthesia were performed using a Focus 120 PET scanner. A model corrected blood input function (MCIF), by which the input function with SP and PV corrections and the metabolic rate constants (k1−k5) are simultaneously estimated from the dynamic 11C-palmitate PET images of mouse hearts in a 4-compartment tracer kinetic model, was used to determine rates of myocardial FA oxidation (MFAO), myocardial FA esterification (MFAE), myocardial FA utilization (MFAU) and myocardial FA uptake (MFAUp). Results The MFAO thus measured in C57BL/6 mice was 375.03±43.83 nmoles/min/g. This compares well with the MFAO measured in perfused working C57BL/6 mouse hearts ex vivo of about 350 nmoles/g/min and 400 nmoles/min/g. Conclusions FA metabolism was measured for the first time in mouse heart in vivo using dynamic 11C-palmitate PET in a 4-compartment tracer kinetic model. MFAO obtained with this model were validated by results previously obtained with mouse hearts ex vivo. PMID:26462138

  9. Experimental Approach to Evaluate the 11C Perfusion and Diffusion in Small Animal Tissues for HadronPET Applications

    PubMed Central

    Martínez-Rovira, Immaculada; Boisgard, Raphaël; Pottier, Géraldine; Kuhnast, Bertrand; Jan, Sébastien

    2016-01-01

    The development of a reliable dose monitoring system in hadron therapy is essential in order to control the treatment plan delivery. Positron Emission Tomography (PET) is the only method used in clinics nowadays for quality assurance. However, the accuracy of this method is limited by the loss of signal due to the biological washout processes. Up to the moment, very few studies measured the washout processes and there is no database of washout data as a function of the tissue and radioisotope. One of the main difficulties is related to the complexity of such measurements, along with the limited time slots available in hadron therapy facilities. Thus, in this work, we proposed an alternative in vivo methodology for the measurement and modeling of the biological washout parameters without any radiative devices. It consists in the implementation of a point-like radioisotope source by direct injection on the tissues of interest and its measurement by means of high-resolution preclinical PET systems. In particular, the washout of 11C carbonate radioisotopes was assessed, considering that 11C is is the most abundant β+ emitter produced by carbon beams. 11C washout measurements were performed in several tissues of interest (brain, muscle and 9L tumor xenograf) in rodents (Wistar rat). Results show that the methodology presented is sensitive to the washout variations depending on the selected tissue. Finally, a first qualitative correlation between 11C tumor washout properties and tumor metabolism (via 18F-FDG tracer uptake) was found. PMID:27015269

  10. Design of Infusion Schemes for Neuroreceptor Imaging: Application to [(11)C]Flumazenil-PET Steady-State Study.

    PubMed

    Feng, Ling; Svarer, Claus; Madsen, Karine; Ziebell, Morten; Dyssegaard, Agnete; Ettrup, Anders; Hansen, Hanne Demant; Lehel, Szabolcs; Yndgaard, Stig; Paulson, Olaf Bjarne; Knudsen, Gitte Moos; Pinborg, Lars Hageman

    2016-01-01

    This study aims at developing a simulation system that predicts the optimal study design for attaining tracer steady-state conditions in brain and blood rapidly. Tracer kinetics was determined from bolus studies and used to construct the system. Subsequently, the system was used to design inputs for bolus infusion (BI) or programmed infusion (PI) experiments. Steady-state quantitative measurements can be made with one short scan and venous blood samples. The GABAA receptor ligand [(11)C]Flumazenil (FMZ) was chosen for this purpose, as it lacks a suitable reference region. Methods. Five bolus [(11)C]FMZ-PET scans were conducted, based on which population-based PI and BI schemes were designed and tested in five additional healthy subjects. The design of a PI was assisted by an offline feedback controller. Results. The system could reproduce the measurements in blood and brain. With PI, [(11)C]FMZ steady state was attained within 40 min, which was 8 min earlier than the optimal BI (B/I ratio = 55 min). Conclusions. The system can design both BI and PI schemes to attain steady state rapidly. For example, subjects can be [(11)C]FMZ-PET scanned after 40 min of tracer infusion for 40 min with venous sampling and a straight-forward quantification. This simulation toolbox is available for other PET-tracers. PMID:27123457

  11. Experimental Approach to Evaluate the 11C Perfusion and Diffusion in Small Animal Tissues for HadronPET Applications.

    PubMed

    Martínez-Rovira, Immaculada; Boisgard, Raphaël; Pottier, Géraldine; Kuhnast, Bertrand; Jan, Sébastien

    2016-01-01

    The development of a reliable dose monitoring system in hadron therapy is essential in order to control the treatment plan delivery. Positron Emission Tomography (PET) is the only method used in clinics nowadays for quality assurance. However, the accuracy of this method is limited by the loss of signal due to the biological washout processes. Up to the moment, very few studies measured the washout processes and there is no database of washout data as a function of the tissue and radioisotope. One of the main difficulties is related to the complexity of such measurements, along with the limited time slots available in hadron therapy facilities. Thus, in this work, we proposed an alternative in vivo methodology for the measurement and modeling of the biological washout parameters without any radiative devices. It consists in the implementation of a point-like radioisotope source by direct injection on the tissues of interest and its measurement by means of high-resolution preclinical PET systems. In particular, the washout of 11C carbonate radioisotopes was assessed, considering that 11C is is the most abundant β+ emitter produced by carbon beams. 11C washout measurements were performed in several tissues of interest (brain, muscle and 9L tumor xenograf) in rodents (Wistar rat). Results show that the methodology presented is sensitive to the washout variations depending on the selected tissue. Finally, a first qualitative correlation between 11C tumor washout properties and tumor metabolism (via 18F-FDG tracer uptake) was found. PMID:27015269

  12. General last-step labeling of biomolecule-based substrates by [12C], [13C], and [11C] carbon monoxide.

    PubMed

    Cornilleau, Thomas; Audrain, Hélène; Guillemet, Aude; Hermange, Philippe; Fouquet, Eric

    2015-01-16

    Alkaloid-, steroid-, biotin-, carbohydrate-, nucleoside-, and peptide-based bioconjugates are easily labeled with CO by a last-step palladium-catalyzed carbonylation. The choice of the [(12)C], [(13)C], or [(11)C] isotope opens the way to a new class of potential tracers or ligands easily available for various applications. PMID:25562588

  13. Impact of [{sup 11}C]Methionine Positron Emission Tomography for Target Definition of Glioblastoma Multiforme in Radiation Therapy Planning

    SciTech Connect

    Matsuo, Masayuki; Miwa, Kazuhiro; Tanaka, Osamu; Shinoda, Jun; Nishibori, Hironori; Tsuge, Yusuke; Yano, Hirohito; Iwama, Toru; Hayashi, Shinya; Hoshi, Hiroaki; Yamada, Jitsuhiro; Kanematsu, Masayuki; Aoyama, Hidefumi

    2012-01-01

    Purpose: The purpose of this work was to define the optimal margins for gadolinium-enhanced T{sub 1}-weighted magnetic resonance imaging (Gd-MRI) and T{sub 2}-weighted MRI (T{sub 2}-MRI) for delineating target volumes in planning radiation therapy for postoperative patients with newly diagnosed glioblastoma multiforme (GBM) by comparison to carbon-11-labeled methionine positron emission tomography ([{sup 11}C]MET-PET) findings. Methods and Materials: Computed tomography (CT), MRI, and [{sup 11}C]MET-PET were separately performed for radiation therapy planning for 32 patients newly diagnosed with GBM within 2 weeks after undergoing surgery. The extent of Gd-MRI (Gd-enhanced clinical target volume [CTV-Gd]) uptake and that of T{sub 2}-MRI of the CTV (CTV-T{sub 2}) were compared with the extent of [{sup 11}C]MET-PET (CTV--[{sup 11}C]MET-PET) uptake by using CT--MRI or CT--[{sup 11}C]MET-PET fusion imaging. We defined CTV-Gd (x mm) and CTV-T{sub 2} (x mm) as the x-mm margins (where x = 0, 2, 5, 10, and 20 mm) outside the CTV-Gd and the CTV-T{sub 2}, respectively. We evaluated the relationship between CTV-Gd (x mm) and CTV-- [{sup 11}C]MET-PET and the relationship between CTV-T{sub 2} (x mm) and CTV-- [{sup 11}C]MET-PET. Results: The sensitivity of CTV-Gd (20 mm) (86.4%) was significantly higher than that of the other CTV-Gd. The sensitivity of CTV-T{sub 2} (20 mm) (96.4%) was significantly higher than that of the other CTV-T{sub 2} (x = 0, 2, 5, 10 mm). The highest sensitivity and lowest specificity was found with CTV-T{sub 2} (x = 20 mm). Conclusions: It is necessary to use a margin of at least 2 cm for CTV-T{sub 2} for the initial target planning of radiation therapy. However, there is a limit to this setting in defining the optimal margin for Gd-MRI and T{sub 2}-MRI for the precise delineation of target volumes in radiation therapy planning for postoperative patients with GBM.

  14. Synthesis and preliminary evaluation of (S)-[11C]-exaprolol, a novel beta-adrenoceptor ligand for PET.

    PubMed

    van Waarde, Aren; Doorduin, Janine; de Jong, Johan R; Dierckx, Rudi A; Elsinga, Philip H

    2008-01-01

    Positron-emitting beta-adrenoceptor ligands for the CNS could allow determination of changes in beta-adrenoceptor availability after treatment of patients with norepinephrine reuptake inhibitors or tricyclic antidepressants, and differential diagnosis between multiple sclerosis and other brain disorders in an early stage of the disease. No ligands suitable for this purpose are available for human use. In order to prepare a tracer for human studies, we labeled the biologically active enantiomer of the beta-blocker exaprolol with (11)C. Exaprolol has the appropriate lipophilicity (log P + 1.6) for entry of the CNS and is claimed to be a very potent beta-adrenoceptor antagonist. (S)-Desisopropyl-exaprolol was synthesized by reaction of 2-hexylphenol with (S)-glycidyl-nosylate followed by ring opening using ammonia gas. The desisopropyl precursor was reacted with (11)C-acetone in methanol to produce (S)-[(11)C]-exaprolol. Radiochemical purification was performed with RP-HPLC and was followed by Sep-Pak formulation. The labeled product was i.v. injected into male Wistar rats. Brain images were acquired using a microPET Focus 220 and the biodistribution of (11)C was assessed. The radiochemical yield of (S)-[(11)C]-exaprolol was 7% with a total synthesis time of 30 min. Specific activities were >10 GBq/micromol. Brain uptake of the tracer reached a maximum after 15 min. Standardized uptake values were moderate (0.5-0.9) but sufficient for imaging. However, beta-blockade (propranolol, 2.5mg/kg body weight) did not lower tracer uptake in any CNS region and washout from the brain was not accelerated when propranolol was administered 40 min after injection of (S)-[(11)C]-exaprolol. Tracer binding in lung, spleen and erythrocytes was lowered after beta-blockade, but the myocardial uptake of radioactivity was not affected. These data indicate that (S)-[(11)C]-exaprolol is not a suitable beta-adrenoceptor ligand for PET, probably because the in vivo affinity of exaprolol to beta

  15. Trojan Horse method and radioactive ion beams: study of 18F(p,α)15O reaction at astrophysical energies

    NASA Astrophysics Data System (ADS)

    Gulino, M.; Cherubini, S.; Rapisarda, G. G.; Kubono, S.; Lamia, L.; La Cognata, M.; Yamaguchi, H.; Hayakawa, S.; Wakabayashi, Y.; Iwasa, N.; Kato, S.; Komatsubara, H.; Teranishi, T.; Coc, A.; De Séréville, N.; Hammache, F.; Spitaleri, C.

    2013-03-01

    The Trojan Horse Method was applied for the first time to a Radioactive Ion Beam induced reaction to study the reaction 18F(p,α)15O via the three body reaction 18F(d,α 15O)n at the low energies relevant for astrophysics. The abundance of 18F in Nova explosions is an important issue for the understanding of this astrophysical phenomenon. For this reason it is necessary to study the nuclear reactions that produce or destroy 18F in Novae. 18F(p,α)15O is one of the main 18F destruction channels. Preliminary results are presented in this paper.

  16. In vivo visualization of central muscarinic receptors using [11C]quinuclidinyl benzilate and positron emission tomography in baboons.

    PubMed

    Varastet, M; Brouillet, E; Chavoix, C; Prenant, C; Crouzel, C; Stulzaft, O; Bottlaender, M; Cayla, J; Mazière, B; Mazière, M

    1992-03-24

    The muscarinic antagonist, quinuclidinyl benzilate (QNB), labeled with carbon 11 was used as a radioligand to visualize in vivo by positron emission tomography (PET) the central muscarinic acetylcholine receptors (mAChR) in baboons (Papio papio). The binding characteristics of [11C]QNB showed its specific binding to central mAChR. [11C]QNB brain uptake was high in cerebral cortex and striatum, areas that are rich in mAChR, whereas it decreased rapidly in cerebellum, evidencing non-specific binding in this structure that is almost devoid of mAChR. These results are consistent with the known cerebral distribution of mAChR in primates. [11C]QNB specific cerebral binding was enhanced by pretreatment with methyl-QNB, a peripherally acting muscarinic antagonist. Specifically labeled binding sites alone were blocked by prior administration of dexetimide, a muscarinic antagonist. Specific radioactivity was driven out from mAChR-rich regions by atropine and dexetimide, drugs with high affinity for mAChR. This competition was stereospecific since only dexetimide, the pharmacologically active isomer of benzetimide, was able to compete with the radioligand on its binding sites. A relationship between the occupancy of [11C]QNB-labeled receptors by atropine or dexetimide and the concomitant induction of a pharmacological effect was also detected by simultaneous PET scanning and electroencephalographic recording. Since mAChR form an important part of choline receptors in the central nervous system, [11C]QNB appears to be a suitable radiotracer to monitor cerebral physiological or pathological phenomena linked to the cholinergic system in living subjects. PMID:1521561

  17. Molecular imaging of 1p/19q deletion in oligodendroglial tumours with 11C-methionine positron emission tomography

    PubMed Central

    Iwadate, Yasuo; Shinozaki, Natsuki; Matsutani, Tomoo; Uchino, Yoshio; Saeki, Naokatsu

    2016-01-01

    Objective Chromosome 1p/19q deletion is an established prognostic and predictive marker in the WHO grade III oligodendroglial tumours (OT). To estimate the genetic status preoperatively, the authors investigated the correlation between the uptake of 11C-methionine in positron emission tomography (PET) and the 1p/19q status in grades II and III OT. Methods We retrospectively reviewed 144 patients with gliomas who received 11C-methionine PET. 66 cases with grades II–III oligodendrogliomas or oligoastrocytomas underwent fluorescence in situ hybridisation to determine the 1p/19q status. The tissue uptake of 11C-methionine was expressed as the ratio of the maximum standardised uptake value (SUVmax) in tumour areas to the mean SUV (SUVmean) in the contralateral normal brain (tumour-to-normal tissue (T/N) ratio). Results The T/N ratio in 11C-methionine PET was significantly higher in grade III OT than in grade II tumours. The mean T/N ratio of the grade II tumours without 1p/19q deletion was significantly higher than that of the grade II tumours with 1p/19q deletion (mean 2.67 vs 1.94, respectively; p=0.0457). In grade III tumours, the mean T/N ratio of the tumours without 1p/19q deletion was also significantly higher than that of the tumours with 1p/19q deletion (mean 4.83 vs 3.49, respectively; p=0.0261). The rate of IDH1 mutation was lower and the rate of contrast enhancement on MRIs was higher in the 1p/19q non-deleted OT than those with 1p/19q deletion, which may contribute to the high T/N ratio. Conclusions Among suspected OT, 11C-methionine PET may help us preoperatively discriminate tumours with and without 1p/19q deletion. PMID:26848169

  18. Amyloid-β 11C-PiB-PET imaging results from 2 randomized bapineuzumab phase 3 AD trials

    PubMed Central

    Schmidt, Mark E.; Margolin, Richard; Sperling, Reisa; Koeppe, Robert; Mason, Neale S.; Klunk, William E.; Mathis, Chester A.; Salloway, Stephen; Fox, Nick C.; Hill, Derek L.; Les, Andrea S.; Collins, Peter; Gregg, Keith M.; Di, Jianing; Lu, Yuan; Tudor, I. Cristina; Wyman, Bradley T.; Booth, Kevin; Broome, Stephanie; Yuen, Eric; Grundman, Michael; Brashear, H. Robert

    2015-01-01

    Objective: To evaluate the effects of bapineuzumab on brain β-amyloid (Aβ) burden using 11C-Pittsburgh compound B (11C-PiB)-PET. Methods: Two phase 3 clinical trials, 1 each in apolipoprotein APOE ε4 carriers and noncarriers, were conducted in patients with mild to moderate Alzheimer disease dementia. Bapineuzumab, an anti-Aβ monoclonal antibody, or placebo, was administered by IV infusion every 13 weeks for 78 weeks. PET substudies assessed change in brain fibrillar Aβ over 71 weeks using an 11C-PiB-PET standardized uptake value ratio (SUVr) global cortical average (GCA) comprising the average SUVr from 5 cortical regions of interest with cerebellar gray matter as the reference region. Results: A total of 115 carriers and 39 noncarriers were analyzed. The difference (δ) in mean baseline to 71 week change in 11C-PiB-PET GCA between bapineuzumab and placebo was significant in carriers (0.5 mg/kg vs placebo δ = −0.101; p = 0.004) and in pooled analyses of both carriers and noncarriers (0.5 mg/kg vs placebo δ = −0.068; p = 0.027; 1.0 mg/kg vs placebo δ = −0.133; p = 0.028) but not in the noncarrier trial separately. Analyses by individual region of interest and in mild disease yielded findings similar to the main trial results. Conclusions: The 11C-PiB-PET imaging results demonstrated reduction of fibrillar Aβ accumulation in patients with Alzheimer disease treated with bapineuzumab; however, as no clinical benefit was observed, the findings are consistent with the hypotheses that bapineuzumab may not have been initiated early enough in the disease course, the doses were insufficient, or the most critical Aβ species were inadequately targeted. PMID:26208959

  19. [13N] Ammonia Cardiac Program At West Virginia University Health Sciences

    NASA Astrophysics Data System (ADS)

    Armbruster, John M.

    2011-06-01

    Due to the shortage of the more traditional cardiac imagining isotopes, specifically, Technicium-99, the Cardiologists at WVU have had to look to alternative imagining techniques such as PET. This has led to a dramatic increase in the use of [13N] Ammonia PET scans at the Health Sciences Center. The patient load has gone from one to two patients one day a week to typically two to three patients, two days a week, with occasional add-on in-house patients; each patient typically requiring two target irradiations. In this paper, we will discuss the process that is being used to meet this increased demand from the production of the isotope through the final result.

  20. Development of a Monte Carlo code for the data analysis of the {sup 18}F(p,α){sup 15}O reaction at astrophysical energies

    SciTech Connect

    Caruso, A.; Cherubini, S.; Spitaleri, C.; La Cognata, M.; Lamia, L.; Rapisarda, G.; Romano, S.; Sergi, ML.; Crucillà, V.; Gulino, M.; Kubono, S.; Yamaguchi, H.; Hayakawa, S.; Wakabayashi, Y.; Iwasa, N.; Kato, S.; Komatsubara, T.; Teranishi, T.; Coc, A.; Hammache, F.; and others

    2015-02-24

    Novae are astrophysical events (violent explosion) occurring in close binary systems consisting of a white dwarf and a main-sequence star or a star in a more advanced stage of evolution. They are called 'narrow systems' because the two components interact with each other: there is a process of mass exchange with resulting in the transfer of matter from the companion star to the white dwarf, leading to the formation of this last of the so-called accretion disk, rich mainly of hydrogen. Over time, more and more material accumulates until the pressure and the temperature reached are sufficient to trigger nuclear fusion reactions, rapidly converting a large part of the hydrogen into heavier elements. The products of 'hot hydrogen burning' are then placed in the interstellar medium as a result of violent explosions. Studies on the element abundances observed in these events can provide important information about the stages of evolution stellar. During the outbursts of novae some radioactive isotopes are synthesized: in particular, the decay of short-lived nuclei such as {sup 13}N and {sup 18}F with subsequent emission of gamma radiation energy below 511 keV. The gamma rays from products electron-positron annihilation of positrons emitted in the decay of {sup 18}F are the most abundant and the first observable as soon as the atmosphere of the nova starts to become transparent to gamma radiation. Hence the importance of the study of nuclear reactions that lead both to the formation and to the destruction of {sup 18}F. Among these, the {sup 18}F(p,α){sup 15}O reaction is one of the main channels of destruction. This reaction was then studied at energies of astrophysical interest. The experiment done at Riken, Japan, has as its objective the study of the {sup 18}F(p,α){sup 15}O reaction, using a beam of {sup 18}F produced at CRIB, to derive important information about the phenomenon of novae. In this paper we present the experimental technique and the Monte Carlo code

  1. Development of a Monte Carlo code for the data analysis of the 18F(p,α)15O reaction at astrophysical energies

    NASA Astrophysics Data System (ADS)

    Caruso, A.; Cherubini, S.; Spitaleri, C.; Crucillà, V.; Gulino, M.; La Cognata, M.; Lamia, L.; Rapisarda, G.; Romano, S.; Sergi, ML.; Kubono, S.; Yamaguchi, H.; Hayakawa, S.; Wakabayashi, Y.; Iwasa, N.; Kato, S.; Komatsubara, T.; Teranishi, T.; Coc, A.; Hammache, F.; de Séréville, N.

    2015-02-01

    Novae are astrophysical events (violent explosion) occurring in close binary systems consisting of a white dwarf and a main-sequence star or a star in a more advanced stage of evolution. They are called "narrow systems" because the two components interact with each other: there is a process of mass exchange with resulting in the transfer of matter from the companion star to the white dwarf, leading to the formation of this last of the so-called accretion disk, rich mainly of hydrogen. Over time, more and more material accumulates until the pressure and the temperature reached are sufficient to trigger nuclear fusion reactions, rapidly converting a large part of the hydrogen into heavier elements. The products of "hot hydrogen burning" are then placed in the interstellar medium as a result of violent explosions. Studies on the element abundances observed in these events can provide important information about the stages of evolution stellar. During the outbursts of novae some radioactive isotopes are synthesized: in particular, the decay of short-lived nuclei such as 13N and 18F with subsequent emission of gamma radiation energy below 511 keV. The gamma rays from products electron-positron annihilation of positrons emitted in the decay of 18F are the most abundant and the first observable as soon as the atmosphere of the nova starts to become transparent to gamma radiation. Hence the importance of the study of nuclear reactions that lead both to the formation and to the destruction of 18F . Among these, the 18F(p,α)15O reaction is one of the main channels of destruction. This reaction was then studied at energies of astrophysical interest. The experiment done at Riken, Japan, has as its objective the study of the 18F(p,α)15O reaction, using a beam of 18F produced at CRIB, to derive important information about the phenomenon of novae. In this paper we present the experimental technique and the Monte Carlo code developed to be used in the data analysis process.

  2. Synthesis and Evaluation of [N-methyl-11C]N-Desmethyl-loperamide as a New and Improved PET Radiotracer for Imaging P-gp Function

    PubMed Central

    Lazarova, Neva; Zoghbi, Sami S.; Hong, Jinsoo; Seneca, Nicholas; Tuan, Ed; Gladding, Robert L.; Liow, Jeih-San; Taku, Andrew; Innis, Robert B.; Pike, Victor W.

    2009-01-01

    [11C]Loperamide has been proposed for imaging P-glycoprotein (P-gp) function with positron emission tomography (PET), but its metabolism to [N-methyl-11C]N-desmethyl-loperamide ([11C]dLop; [11C]3) precludes quantification. We considered that [11C]3 might itself be a superior radiotracer for imaging brain P-gp function and therefore aimed to prepare [11C]3 and characterize its efficacy. An amide precursor (2) was synthesized and methylated with [11C]iodomethane to give [11C]3. After administration of [11C]3 to wild type mice, brain radioactivity uptake was very low. In P-gp (mdr-1a (−/−)) knockout mice, brain uptake of radioactivity at 30 min increased about 3.5 fold by PET measures, and over seven-fold by ex vivo measures. In knockout mice, brain radioactivity was predominantly (90%) unchanged radiotracer. In monkey PET experiments, brain radioactivity uptake was also very low, but after P-gp blockade increased more than seven-fold. [11C]3 is an effective new radiotracer for imaging brain P-gp function and, in favor of future successful quantification, appears free of extensive brain-penetrant radiometabolites. PMID:18783208

  3. No-carrier-added carbon-11-labeled sn-1,2- and sn-1,3-diacylglycerols by (11C)propyl ketene method

    SciTech Connect

    Imahori, Y.; Fujii, R.; Ueda, S.; Ido, T.; Nishino, H.; Moriyama, Y.; Yamamoto, Y.L.; Nakahashi, H. )

    1991-08-01

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

  4. A continuous [{sup 15}O]H{sub 2}O production and infusion system for PET imaging

    SciTech Connect

    Sajjad, Munawwar; Liow, Jeih-San

    1999-06-10

    A system for continuous production and infusion of [{sup 15}O]H{sub 2}O has been designed for PET cerebral blood flow studies. The injection system consists of a four-port-two-position valve, two Horizon Nxt infusion pumps, and a sterile 50 ml vial. The variation of the production of [{sup 15}O]H{sub 2}O was <1%. The variation of activity delivered measured by scanner counts during the steady state period was <2%.

  5. Uptake of 13N-labeled N2O5 to citric acid aerosol particles

    NASA Astrophysics Data System (ADS)

    Grzinic, Goran; Bartels-Rausch, Thorsten; Birrer, Mario; Türler, Andreas; Ammann, Markus

    2013-04-01

    Dinitrogen pentoxide is a significant reactive intermediate in the night time chemistry of nitrogen oxides. Depending on atmospheric conditions it can act either as a NO3 radical reservoir or as a major NOx sink by heterogeneous hydrolysis on aerosol surfaces. As such, it can influence tropospheric ozone production and therefore the oxidative capacity of the atmosphere. Furthermore it's suspected of being a non negligible source of tropospheric Cl, even over continental areas [1,2]. We used the short-lived radioactive tracer 13N delivered by PSI's PROTRAC facility [3] in conjunction with an aerosol flow tube reactor in order to study N2O5 uptake kinetics on aerosol particles. 13NO is mixed with non labeled NO and O3 in a gas reactor where N2O5 is synthesized under dry conditions to prevent hydrolysis on the reactor walls. The resulting N2O5 flow is fed into an aerosol flow tube reactor together with a humidified aerosol flow. By using movable inlets we can vary the length of the aerosol flow tube and thus the reaction time. The gas feed from the reactor is then directed into a narrow parallel plate diffusion denuder system that allows for selective separation of the gaseous species present in the gas phase. Aerosol particles are trapped on a particle filter placed at the end of the denuder system. The activity of 13N labeled species trapped on the denuder plates and in the particle filter can be monitored via scintillation counters. Aerosol uptake measurements were performed with citric acid aerosols in a humidity range of 27-61.5% RH. The results obtained from our measurements have shown that the uptake coefficient increases with humidity from 1.65±0.3x10-3 (~27% RH) to 1.25±0.3x10-2 (45% RH) and 2.00±0.3x10-2 (61.5% RH). Comparison to literature data shows that this is similar to values reported for some polycarboxylic acids (like malonic acid), while being higher than some others [4]. The increase is likely related to the increasing amount of water associated

  6. Clinicopathologic and 11C-Pittsburgh compound B implications of Thal amyloid phase across the Alzheimer’s disease spectrum

    PubMed Central

    Lowe, Val J.; Graff-Radford, Neill R.; Liesinger, Amanda M.; Cannon, Ashley; Przybelski, Scott A.; Rawal, Bhupendra; Parisi, Joseph E.; Petersen, Ronald C.; Kantarci, Kejal; Ross, Owen A.; Duara, Ranjan; Knopman, David S.; Jack, Clifford R.; Dickson, Dennis W.

    2015-01-01

    Thal amyloid phase, which describes the pattern of progressive amyloid-β plaque deposition in Alzheimer’s disease, was incorporated into the latest National Institute of Ageing – Alzheimer’s Association neuropathologic assessment guidelines. Amyloid biomarkers (positron emission tomography and cerebrospinal fluid) were included in clinical diagnostic guidelines for Alzheimer’s disease dementia published by the National Institute of Ageing – Alzheimer’s Association and the International Work group. Our first goal was to evaluate the correspondence of Thal amyloid phase to Braak tangle stage and ante-mortem clinical characteristics in a large autopsy cohort. Second, we examined the relevance of Thal amyloid phase in a prospectively-followed autopsied cohort who underwent ante-mortem 11C-Pittsburgh compound B imaging; using the large autopsy cohort to broaden our perspective of 11C-Pittsburgh compound B results. The Mayo Clinic Jacksonville Brain Bank case series (n = 3618) was selected regardless of ante-mortem clinical diagnosis and neuropathologic co-morbidities, and all assigned Thal amyloid phase and Braak tangle stage using thioflavin-S fluorescent microscopy. 11C-Pittsburgh compound B studies from Mayo Clinic Rochester were available for 35 participants scanned within 2 years of death. Cortical 11C-Pittsburgh compound B values were calculated as a standard uptake value ratio normalized to cerebellum grey/white matter. In the high likelihood Alzheimer’s disease brain bank cohort (n = 1375), cases with lower Thal amyloid phases were older at death, had a lower Braak tangle stage, and were less frequently APOE-ε4 positive. Regression modelling in these Alzheimer’s disease cases, showed that Braak tangle stage, but not Thal amyloid phase predicted age at onset, disease duration, and final Mini-Mental State Examination score. In contrast, Thal amyloid phase, but not Braak tangle stage or cerebral amyloid angiopathy predicted 11C-Pittsburgh compound

  7. Clinicopathologic and 11C-Pittsburgh compound B implications of Thal amyloid phase across the Alzheimer's disease spectrum.

    PubMed

    Murray, Melissa E; Lowe, Val J; Graff-Radford, Neill R; Liesinger, Amanda M; Cannon, Ashley; Przybelski, Scott A; Rawal, Bhupendra; Parisi, Joseph E; Petersen, Ronald C; Kantarci, Kejal; Ross, Owen A; Duara, Ranjan; Knopman, David S; Jack, Clifford R; Dickson, Dennis W

    2015-05-01

    Thal amyloid phase, which describes the pattern of progressive amyloid-β plaque deposition in Alzheimer's disease, was incorporated into the latest National Institute of Ageing - Alzheimer's Association neuropathologic assessment guidelines. Amyloid biomarkers (positron emission tomography and cerebrospinal fluid) were included in clinical diagnostic guidelines for Alzheimer's disease dementia published by the National Institute of Ageing - Alzheimer's Association and the International Work group. Our first goal was to evaluate the correspondence of Thal amyloid phase to Braak tangle stage and ante-mortem clinical characteristics in a large autopsy cohort. Second, we examined the relevance of Thal amyloid phase in a prospectively-followed autopsied cohort who underwent ante-mortem (11)C-Pittsburgh compound B imaging; using the large autopsy cohort to broaden our perspective of (11)C-Pittsburgh compound B results. The Mayo Clinic Jacksonville Brain Bank case series (n = 3618) was selected regardless of ante-mortem clinical diagnosis and neuropathologic co-morbidities, and all assigned Thal amyloid phase and Braak tangle stage using thioflavin-S fluorescent microscopy. (11)C-Pittsburgh compound B studies from Mayo Clinic Rochester were available for 35 participants scanned within 2 years of death. Cortical (11)C-Pittsburgh compound B values were calculated as a standard uptake value ratio normalized to cerebellum grey/white matter. In the high likelihood Alzheimer's disease brain bank cohort (n = 1375), cases with lower Thal amyloid phases were older at death, had a lower Braak tangle stage, and were less frequently APOE-ε4 positive. Regression modelling in these Alzheimer's disease cases, showed that Braak tangle stage, but not Thal amyloid phase predicted age at onset, disease duration, and final Mini-Mental State Examination score. In contrast, Thal amyloid phase, but not Braak tangle stage or cerebral amyloid angiopathy predicted (11)C-Pittsburgh compound B

  8. Opioid receptor imaging and displacement studies with [6-O-[11C] methyl]buprenorphine in baboon brain.

    PubMed

    Galynker, I; Schlyer, D J; Dewey, S L; Fowler, J S; Logan, J; Gatley, S J; MacGregor, R R; Ferrieri, R A; Holland, M J; Brodie, J; Simon, E; Wolf, A P

    1996-04-01

    Buprenorphine (BPN) is a mixed opiate agonist-antagonist used as an analgesic and in the treatment of opiate addiction. We have used [6-O-[11C]methyl]buprenorphine ([11C]BPN) to measure the regional distribution in baboon brain, the test-retest stability of repeated studies in the same animal, the displacement of the labeled drug by naloxone in vivo, and the tissue distribution in mice. The regional distribution of radioactivity in baboon brain determined with PET was striatum > thalamus > cingulate gyrus > frontal cortex > parietal cortex > occipital cortex > cerebellum. This distribution corresponded to opiate receptor density and to previously published data (37). The tracer uptake in adult female baboons showed no significant variation in serial scans in the same baboon with no intervention in the same scanning session. HPLC analysis of baboon plasma showed the presence of labeled metabolites with 92% +/- 2.2% and 43% +/- 14.4% of the intact tracer remaining at 5 and 30 min, respectively. Naloxone, an opiate receptor antagonist, administered 30-40 min after tracer injection at a dose of 1.0 mg/kg i.v., reduced [11C]BPN binding in thalamus, striatum, cingulate gyrus, and frontal cortex to values 0.25 to 0.60 of that with no intervention. There were minimal (< 15%) effects on cerebellum. Naloxone treatment significantly reduced the slope of the Patlak plot in receptor-containing regions. These results demonstrate that [11C]BPN can be displaced by naloxone in vivo, and they affirm the feasibility of using this tracer and displacement methodology for short-term kinetics studies with PET. Mouse tissue distribution data were used to estimate the radiation dosimetry to humans. The critical organ was the small intestine, with a radiation dose estimate to humans of 117 nrad/mCi. PMID:8782244

  9. 11C-Methionine positron emission tomography-computed tomography in localization of methoxyisobutyl isonitrile negative ectopic parathyroid adenoma

    PubMed Central

    Seniaray, Nikhil; Sharma, Harshul; Arbind, Arpana; Jaimini, Abhinav; D’souza, Maria; Saw, Sanjeev; Hazari, Puja Panwar; Mishra, A. K.; Sharma, Rajnish; Mondal, Anupam

    2016-01-01

    Primary hyperparathyroidism is caused by parathyroid adenomas in 85% of the cases. Since parathyroid adenomas are known for their ectopic location, presurgical localization of the suspected site of adenoma is desirable. However, current imaging modalities are not always successful in localizing ectopic parathyroid adenomas. The aim of this case report is to show that 11C-methionine positron emission tomography could accurately localize ectopic parathyroid adenomas in patients in whom conventional imaging had failed or is inconclusive. PMID:26917896

  10. Unstable nuclei in coherent dissociation of relativistic nuclei 7,9Be, 10B and 10,11C

    NASA Astrophysics Data System (ADS)

    Artemenkov, D. A.; Bradnova, V.; Firu, E.; Kornegrutsa, N. K.; Haiduc, M.; Mamatkulov, K. Z.; Kattabekov, R. R.; Neagu, A.; Rukoyatkin, P. A.; Rusakova, V. V.; Sarkisyan, V. R.; Stanoeva, R.; Zaitsev, A. A.; Zarubin, P. I.; Zarubina, I. G.

    2016-06-01

    Contribution of the unstable nuclei 7Be, 8Be and ®B into coherent dissociation events (“white” stars) of relativistic nuclei 7,9Be, 10B and 10,11C is under study on the basis of a nuclear track emulsion exposed to beams of the JINR Nuclotron. Distributions over the opening angle of α-pairs indicate to a simultaneous presence of virtual 8Beg.s. and 8Be2+ states in the ground states of the 9Be and 10C nuclei. The core 9B is manifested in the 10C nucleus with a probability of (30 ± 4)%, Selection of the 10C “white” stars accompanied by 8Beg.s. (9B) leads to the appearance in the excitation energy distribution of 2α2p “quartets” of the distinct peak with a maximum at 4.1 ± 0.3 MeV. 8Beg.s. decays are presented in 21% 2He + 2H and 19% in the 3He of the all 11C “white” stars. 9Bg.s. decays are identified in “white” stars 11C → 2He + 2H constituting 14% of the 11C “white” stars. The 9B nucleus. is manifested in the “white” stars 10B → 2He + 2H with a probability of (9 ± 1)%. For the 10B case yield of 8Beg.s. nuclei with the respect to 9B is about a factor of 3 higher than 9B.

  11. Synthesis and tissue biodistribution of [{omega}-{sup 11}C]palmitic acid. A novel PET imagining agent for cardiac fatty acid metabolism

    SciTech Connect

    Buckman, B.O.; VanBrocklin, H.F.; Katzenellenbogen, J.A.; Dence, C.S.; Bergmann, S.R.; Welch, M.J.

    1994-12-31

    In order to diagnose patients with medium-chain acyl-CoA dehydrogenase deficiency with a noninvasive diagnostic technique such as positron emission tomography, they have developed a synthesis of [{omega}-{sup 11}C]palmitic acid. The radiochemical synthesis was achieved by coupling an alkylfuran Grignard reagent (7) with [{sup 11}C]methyl iodide, followed by rapid oxidative cleavage of the furan ring to the carboxylate using ruthenium tetraoxide. Tissue biodistribution studies in rags comparing [{omega}-{sup 11}C]palmitic acid and [1-{sup 11}C]palmitic acid show that the %ID/g and %ID/organ in the heart tissue after administration of [{omega}-{sup 11}C]palmitic acid is approximately 50% greater than after administration of [1-{sup 11}C]palmitic acid, due to the diminished metabolism of the [{omega}-{sup 11}C]palmitic acid. These studies show as well, low uptake in nontarget tissues (blood, lung, kidney, and muscle). PET images of a dog heart obtained after administration of [{omega}-{sup 11}C]- and [1-{sup 11}C]palmitic acid show virtually identical uptake and distribution in the myocardium. The differing cardiac washout of labeled palmitates measured by dynamic PET studies may allow diagnosis of disorders in cardiac fatty acid metabolism.

  12. Effective source size, radial, angular and energy spread of therapeutic 11C positron emitter beams produced by 12C fragmentation

    NASA Astrophysics Data System (ADS)

    Lazzeroni, Marta; Brahme, Anders

    2014-02-01

    The use of positron emitter light ion beams in combination with PET (Positron Emission Tomography) and PET-CT (Computed Tomography) imaging could significantly improve treatment verification and dose delivery imaging during radiation therapy. The present study is dedicated to the analysis of the beam quality in terms of the effective source size, as well as radial, angular and energy spread of the 11C ion beam produced by projectile fragmentation of a primary point monodirectional and monoenergetic 12C ion beam in a dedicated range shifter of different materials. This study was performed combining analytical methods describing the transport of particles in matter and the Monte Carlo code SHIELD-HIT+. A high brilliance and production yield of 11C fragments with a small effective source size and emittance is best achieved with a decelerator made of two media: a first liquid hydrogen section of about 20 cm followed by a hydrogen rich section of variable length. The calculated intensity of the produced 11C ion beam ranges from about 5% to 8% of the primary 12C beam intensity depending on the exit energy and the acceptance of the beam transport system. The angular spread is lower than 1 degree for all the materials studied, but the brilliance of the beam is the highest with the proposed mixed decelerator.

  13. Use of ( sup 11 C)aminocyclohexanecarboxylate for the measurement of amino acid uptake and distribution volume in human brain

    SciTech Connect

    Koeppe, R.A.; Mangner, T.; Betz, A.L.; Shulkin, B.L.; Allen, R.; Kollros, P.; Kuhl, D.E.; Agranoff, B.W. )

    1990-09-01

    A quantitative positron emission tomographic (PET) method to measure amino acid blood-brain barrier (BBB) transport rate and tissue distribution volume (DV) has been developed using {sup 11}C-labeled aminocyclohexanecarboxylate (ACHC), a nonmetabolized amino acid analogue. Dynamic PET data were acquired as a series of 15 scans covering a total of 60 min and analyzed by means of a two-compartment, two-parameter model. Functional images were calculated for the amino acid transport rate constants across the BBB and the amino acid DV in the brain. Results show ({sup 11}C)ACHC to have an influx rate constant in gray matter of approximately 0.03-0.04 ml g-1 min-1, indicating a single-pass extraction fraction of approximately 5-7%. The intersubject coefficient of variation was approximately 15% while intrasubject variability of repeat scans was only slightly greater than 5%. Studies were performed in 15 young normal volunteer control subjects, 5 elderly controls, 7 patients with probable Alzheimer's disease, and one patient with phenylketonuria. Results indicate that ({sup 11}C)-ACHC will serve as the basis of a method for measuring amino acid transport rate and DV in the normal and pathological human brain.

  14. Involvement of SOCS3 in regulation of CD11c+ dendritic cell-derived osteoclastogenesis and severe alveolar bone loss.

    PubMed

    Zhang, Xiaoxia; Alnaeeli, Mawadda; Singh, Bhagirath; Teng, Yen-Tung A

    2009-05-01

    To investigate the role of suppressor of cytokine signaling (SOCS) molecules in periodontal immunity and RANKL-mediated dendritic cell (DC)-associated osteoclastogenesis, we analyzed SOCS expression profiles in CD4(+) T cells and the effect of SOCS3 expression in CD11c(+) DCs during periodontal inflammation-induced osteoclastogenesis and bone loss in nonobese diabetic (NOD) versus humanized NOD/SCID mice. Our results of ex vivo and in vitro analyses showed that (i) there is significantly higher SOCS3 expression associated with RANKL(+) T-cell-mediated bone loss in correlation with increased CD11c(+) DC-mediated osteoclastogenesis; (ii) the transfection of CD11c(+) DC using an adenoviral vector carrying a dominant negative SOCS3 gene significantly abrogates TRAP and bone-resorptive activity; and (iii) inflammation-induced TRAP expression, bone resorption, and SOCS3 activity are not associated with any detectable change in the expression levels of TRAF6 and mitogen-activated protein kinase signaling adaptors (i.e., Erk, Jnk, p38, and Akt) in RANKL(+) T cells. We conclude that SOCS3 plays a critical role in modulating cytokine signaling involved in RANKL-mediated DC-derived osteoclastogenesis during immune interactions with T cells and diabetes-associated severe inflammation-induced alveolar bone loss. Therefore, the development of SOCS3 inhibitors may have therapeutic potential as the target to halt inflammation-induced bone loss under pathological conditions in vivo. PMID:19255186

  15. The {sup 14}N(p,gamma){sup 15}O reaction studied at high energy

    SciTech Connect

    Marta, Michele

    2010-03-01

    The {sup 14}N(p,gamma){sup 15}O reaction is the bottleneck of the carbon-nitrogen-oxygen (CNO) cycle. Recent studies of this reaction have been performed in the low energy range E<500 keV. However, also data at higher energy are necessary to extrapolate the S-factor down to the energy range of astrophysical interest. Up to now, only one set of data from an experiment performed in 1987 extends up to 2.5 MeV. A new study has been carried out at the high-current FZD Tandetron in Dresden, in the energy region from 0.6 to 2.5 MeV. The astrophysics motivations, setup and on-going analysis are presented.

  16. Electrical resistivity change in amorphous Ta42Si13N45 films by stress relaxation

    NASA Astrophysics Data System (ADS)

    Nicolet, M.-A.; Ryser, M.; Romano, V.

    2015-03-01

    In a first experiment, a reactively sputtered amorphous Ta42Si13N45 film about 260 nm thick deposited on a flat and smooth alumina substrate was thermally annealed in air for 30 min and let cooled again repeatedly at successively higher temperatures from 200 to 500 °C. This treatment successively and irreversibly increases the room temperature resistivity of the film monotonically from its initial value of 670 μΩ cm to a maximum of 705 μΩ cm (+5.2 %). Subsequent heat treatments at temperatures below 500 °C and up to 6 h have no further effect on the room temperature resistivity. The new value remains unchanged after 3.8 years of storage at room temperature. In a second experiment, the evolution of the initially compressive stress of a film similarly deposited by reactive sputtering on a 2-inch silicon wafer was measured by tracking the wafer curvature during similar thermal annealing cycles. A similar pattern of irreversible and reversible changes of stress was observed as for the film resistivity. Transmission electron micrographs and secondary ion mass profiles of the film taken before and after thermal annealing in air establish that both the structure and the composition of the film scarcely change during the annealing cycles. We reason that the film stress is implicated in the resistivity change. In particular, to interpret the observations, a model is proposed where the interface between the film and the substrate is mechanically unyielding.

  17. Formation and Decay of {sup 24}Mg in the {sup 13}N+{sup 11}B Collision

    SciTech Connect

    P. Figuera; F. Amorini; W. Bradfield-Smith; M. Cabibbo; G. Cardella; T. Davinson; A. DiPietro; W. Galster; P. Leleux; A. Musumarra; A. Ninane; M. Papa; G. Pappalardo; F. Rizzo; A.C. Shotter; C. Sukosd; S. Tudisco; P.J. Woods

    1999-12-31

    Different aspects of the formation and decay of {sup 24}Mg in the collision {sup 13}N+{sup 11}B have been studied using a large solid angle and highly segmented Silicon strip detector. Results concerning the fusion cross section, the 6 {alpha} decay of {sup 24}Mg and the GDR gamma ray emission are discussed.

  18. Formation and decay of {sup 24}Mg in the {sup 13}N+{sup 11}B collision

    SciTech Connect

    Figuera, P.; Amorini, F.; Cabibbo, M.; Papalardo, G.; Rizzo, F.; Tudisco, S.; Bradfield-Smith, W.; Davinson, T.; Di Pietro, A.; Shotter, A. C.; Woods, P. J.; Cardella, G.; Papa, M.; Galster, W.; Leleux, P.; Musumarra, A.; Ninane, A.; Sukosd, C.

    1999-11-16

    Different aspects of the formation and decay of {sup 24}Mg in the collision {sup 13}N+{sup 11}B have been studied using a large solid angle and highly segmented Silicon strip detector. Results concerning the fusion cross section, the 6 {alpha} decay of {sup 24}Mg and the GDR gamma ray emission are discussed.

  19. Molecular characterization and phylogenetics of a reassortant H13N8 influenza virus isolated from gulls in Mongolia

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A double reassortant H13N8 influenza A virus was isolated from gulls in Mongolia. The basic virological characteristics were studied. Complete genome sequence analysis indicated the complicated evolutionary history. The PA gene belongs to classical Avian-like lineage and more likely originated fro...

  20. Cross section measurement of 14N(p ,γ )15O in the CNO cycle

    NASA Astrophysics Data System (ADS)

    Li, Q.; Görres, J.; deBoer, R. J.; Imbriani, G.; Best, A.; Kontos, A.; LeBlanc, P. J.; Uberseder, E.; Wiescher, M.

    2016-05-01

    Background: The CNO cycle is the main energy source in stars more massive than our sun; it defines the energy production and the cycle time that lead to the lifetime of massive stars, and it is an important tool for the determination of the age of globular clusters. In our sun about 1.6% of the total solar neutrino flux comes from the CNO cycle. The largest uncertainty in the prediction of this CNO flux from the standard solar model comes from the uncertainty in the 14N(p ,γ )15O reaction rate; thus, the determination of the cross section at astrophysical temperatures is of great interest. Purpose: The total cross section of the 14N(p ,γ )15O reaction has large contributions from the transitions to the Ex=6.79 MeV excited state and the ground state of 15O. The Ex=6.79 MeV transition is dominated by radiative direct capture, while the ground state is a complex mixture of direct and resonance capture components and the interferences between them. Recent studies have concentrated on cross-section measurements at very low energies, but broad resonances at higher energy may also play a role. A single measurement has been made that covers a broad higher-energy range but it has large uncertainties stemming from uncorrected summing effects. Furthermore, the extrapolations of the cross section vary significantly depending on the data sets considered. Thus, new direct measurements have been made to improve the previous high-energy studies and to better constrain the extrapolation. Methods: Measurements were performed at the low-energy accelerator facilities of the nuclear science laboratory at the University of Notre Dame. The cross section was measured over the proton energy range from Ep=0.7 to 3.6 MeV for both the ground state and the Ex=6.79 MeV transitions at θlab=0∘ , 45∘, 90∘, 135∘, and 150∘. Both TiN and implanted-14N targets were utilized. γ rays were detected by using an array of high-purity germanium detectors. Results: The excitation function as

  1. Labelling of the solvent DMSO as side reaction of methylations with n.c.a. [11C]CH3I.

    PubMed

    Klein, A T; Holschbach, M

    2001-09-01

    Competing labelling of solvent dimethyl sulfoxide (DMSO) can occur during the 11C-methylation of amine precursors. A kinetic analysis of the methylation reaction of DMSO with n.c.a. [11C]CH3I was performed at 120 degrees C resulting in rate constants. The rate constant for the formation of the intermediate, methylated DMSO ([11C]DMSO-M), is compared to the reaction of [11C]CH3I with two tertiary amines, namely Dexetimide and Desmethyloxotremorine-M. The specific activity of the labelled product is reduced due to partial 12C-methylation of the precursor amines by [11C]DMSO-M in cases of significant DMSO labelling as side reaction. PMID:11515652

  2. The fatty acid amide hydrolase C385A variant affects brain binding of the positron emission tomography tracer [11C]CURB

    PubMed Central

    Boileau, Isabelle; Tyndale, Rachel F; Williams, Belinda; Mansouri, Esmaeil; Westwood, Duncan J; Foll, Bernard Le; Rusjan, Pablo M; Mizrahi, Romina; De Luca, Vincenzo; Zhou, Qian; Wilson, Alan A; Houle, Sylvain; Kish, Stephen J; Tong, Junchao

    2015-01-01

    The common functional single-nucleotide polymorphism (rs324420, C385A) of the endocannabinoid inactivating enzyme fatty acid amide hydrolase (FAAH) has been associated with anxiety disorder relevant phenotype and risk for addictions. Here, we tested whether the FAAH polymorphism affects in vivo binding of the FAAH positron emission tomography (PET) probe [11C]CURB ([11C-carbonyl]-6-hydroxy-[1,10-biphenyl]-3-yl cyclohexylcarbamate (URB694)). Participants (n=24) completed one [11C]CURB/PET scan and were genotyped for rs324420. Relative to C/C (58%), A-allele carriers (42%) had 23% lower [11C]CURB binding (λk3) in brain. We report evidence that the genetic variant rs324420 in FAAH is associated with measurable differences in brain FAAH binding as per PET [11C]CURB measurement. PMID:26036940

  3. Dopamine response to psychosocial stress in chronic cannabis users: a PET study with [11C]-+-PHNO.

    PubMed

    Mizrahi, Romina; Suridjan, Ivonne; Kenk, Miran; George, Tony P; Wilson, Alan; Houle, Sylvain; Rusjan, Pablo

    2013-03-01

    A number of addictions have been linked with decreased striatal dopamine (DA) receptor availability and DA release. Stress has a key role in cannabis craving, as well as in modulation of dopaminergic signaling. The present study aimed to assess DA release in response to a laboratory stress task with [(11)C]-(+)-PHNO positron emission tomography in cannabis users (CU). Thirteen healthy CU and 12 healthy volunteers (HV) were scanned during a sensorimotor control task (SMCT) and under a stress condition using the validated Montreal imaging stress task (MIST). The simplified reference tissue model (SRTM) was used to obtain binding potential (BP(ND)) in striatal subdivisions: limbic striatum (LST), associative striatum (AST), and sensorimotor striatum (SMST). Stress-induced DA release (indexed as a percentage of reduction in [(11)C]-(+)-PHNO BP (ND)) between CU and HV was tested with analysis of variance. SMCT BP(ND) was significantly higher in CU compared with HV in the AST (F=10.38, p=0.003), LST (F=4.95, p=0.036), SMST (F=4.33, p=0.048), and whole striatum (F=9.02, p=0.006). Percentage of displacement (change in BP(ND) between SMCT and MIST PET scans) was not significantly different across groups in any brain region, except in the GP (-5.03±14.6 in CU, compared with 6.15±12.1 in HV; F=4.39, p=0.049). Duration of cannabis use was significantly associated with stress-induced [(11)C]-(+)-PHNO displacement by endogenous DA in the LST (r=0.566, p=0.044), with no effect in any other brain region. In conclusion, despite an increase in striatal BP(ND) observed during the control task, chronic cannabis use is not associated with alterations in stress-induced DA release. PMID:23212454

  4. Determination of [11C]Rifampin Pharmacokinetics within Mycobacterium tuberculosis-Infected Mice by Using Dynamic Positron Emission Tomography Bioimaging

    PubMed Central

    DeMarco, Vincent P.; Ordonez, Alvaro A.; Klunk, Mariah; Prideaux, Brendan; Wang, Hui; Zhuo, Zhang; Tonge, Peter J.; Dannals, Robert F.; Holt, Daniel P.; Lee, Carlton K. K.; Weinstein, Edward A.; Dartois, Véronique; Dooley, Kelly E.

    2015-01-01

    Information about intralesional pharmacokinetics (PK) and spatial distribution of tuberculosis (TB) drugs is limited and has not been used to optimize dosing recommendations for new or existing drugs. While new techniques can detect drugs and their metabolites within TB granulomas, they are invasive, rely on accurate resection of tissues, and do not capture dynamic drug distribution in the tissues of interest. In this study, we assessed the in situ distribution of 11C-labeled rifampin in live, Mycobacterium tuberculosis-infected mice that develop necrotic lesions akin to human disease. Dynamic positron emission tomography (PET) imaging was performed over 60 min after injection of [11C]rifampin as a microdose, standardized uptake values (SUV) were calculated, and noncompartmental analysis was used to estimate PK parameters in compartments of interest. [11C]rifampin was rapidly distributed to all parts of the body and quickly localized to the liver. Areas under the concentration-time curve for the first 60 min (AUC0–60) in infected and uninfected mice were similar for liver, blood, and brain compartments (P > 0.53) and were uniformly low in brain (10 to 20% of blood values). However, lower concentrations were noted in necrotic lung tissues of infected mice than in healthy lungs (P = 0.03). Ex vivo two-dimensional matrix-assisted laser desorption ionization (MALDI) imaging confirmed restricted penetration of rifampin into necrotic lung lesions. Noninvasive bioimaging can be used to assess the distribution of drugs into compartments of interest, with potential applications for TB drug regimen development. PMID:26169396

  5. ATP11C is a major flippase in human erythrocytes and its defect causes congenital hemolytic anemia

    PubMed Central

    Arashiki, Nobuto; Takakuwa, Yuichi; Mohandas, Narla; Hale, John; Yoshida, Kenichi; Ogura, Hiromi; Utsugisawa, Taiju; Ohga, Shouichi; Miyano, Satoru; Ogawa, Seishi; Kojima, Seiji; Kanno, Hitoshi

    2016-01-01

    Phosphatidylserine is localized exclusively to the inner leaflet of the membrane lipid bilayer of most cells, including erythrocytes. This asymmetric distribution is critical for the survival of erythrocytes in circulation since externalized phosphatidylserine is a phagocytic signal for splenic macrophages. Flippases are P-IV ATPase family proteins that actively transport phosphatidylserine from the outer to inner leaflet. It has not yet been determined which of the 14 members of this family of proteins is the flippase in human erythrocytes. Herein, we report that ATP11C encodes a major flippase in human erythrocytes, and a genetic mutation identified in a male patient caused congenital hemolytic anemia inherited as an X-linked recessive trait. Phosphatidylserine internalization in erythrocytes with the mutant ATP11C was decreased 10-fold compared to that of the control, functionally establishing that ATP11C is a major flippase in human erythrocytes. Contrary to our expectations phosphatidylserine was retained in the inner leaflet of the majority of mature erythrocytes from both controls and the patient, suggesting that phosphatidylserine cannot be externalized as long as scramblase is inactive. Phosphatidylserine-exposing cells were found only in the densest senescent cells (0.1% of total) in which scramblase was activated by increased Ca2+ concentration: the percentage of these phosphatidylserine-exposing cells was increased in the patient’s senescent cells accounting for his mild anemia. Furthermore, the finding of similar extents of phosphatidylserine exposure by exogenous Ca2+-activated scrambling in both control erythrocytes and the patient’s erythrocytes implies that suppressed scramblase activity rather than flippase activity contributes to the maintenance of phosphatidylserine in the inner leaflet of human erythrocytes. PMID:26944472

  6. Translational characterization of [11C]GSK931145, a PET ligand for the glycine transporter type 1.

    PubMed

    Gunn, Roger N; Murthy, Venkatesha; Catafau, Ana M; Searle, Graham; Bullich, Santiago; Slifstein, Mark; Ouellet, Daniele; Zamuner, Stefano; Herance, Raul; Salinas, Cristian; Pardo-Lozano, Ricardo; Rabiner, Eugenii A; Farre, Magi; Laruelle, Marc

    2011-12-01

    The current interest in developing Glycine transporter Type 1 (GlyT-1) inhibitors, for diseases such as schizophrenia, has led to the demand for a GlyT-1 PET molecular imaging tool to aid drug development and dose selection. We report on [(11) C]GSK931145 as a novel GlyT-1 imaging probe in primate and man. Primate PET studies were performed to determine the level of specific binding following homologous competition with GSK931145 and the plasma-occupancy relationship of the GlyT-1 inhibitor GSK1018921. Human PET studies were performed to determine the test-retest reproducibility of [(11) C]GSK931145 and the plasma-occupancy relationship of GSK1018921. [(11) C]GSK931145 entered primate and human brain and yielded a heterogeneous pattern of uptake which was similar in both species with highest uptake in midbrain, thalamus, and cerebellum. Homologous competition in primates indicated no viable reference region and gave binding potential estimates between 1.5 and 3 for midbrain, thalamus and cerebellum, While the distribution and binding potential values were similar across species, both the plasma free fraction (f(P) : 0.8 vs. 8%) and delivery (K(1) : 0.025 vs. 0.126 ml cm(-3) min(-1) ) were significantly lower in humans. Test-retest reproducibility in humans calculated using a two tissue compartmental model was poor (VAR(V(T) ): 29-38%), but was improved using a pseudo reference tissue model (VAR(BP(ND) ): 16-23%). GSK1018921 EC(50) estimates were 22.5 and 45.7 ng/ml in primates and humans, respectively. PMID:21688322

  7. ATP11C is a major flippase in human erythrocytes and its defect causes congenital hemolytic anemia.

    PubMed

    Arashiki, Nobuto; Takakuwa, Yuichi; Mohandas, Narla; Hale, John; Yoshida, Kenichi; Ogura, Hiromi; Utsugisawa, Taiju; Ohga, Shouichi; Miyano, Satoru; Ogawa, Seishi; Kojima, Seiji; Kanno, Hitoshi

    2016-05-01

    Phosphatidylserine is localized exclusively to the inner leaflet of the membrane lipid bilayer of most cells, including erythrocytes. This asymmetric distribution is critical for the survival of erythrocytes in circulation since externalized phosphatidylserine is a phagocytic signal for splenic macrophages. Flippases are P-IV ATPase family proteins that actively transport phosphatidylserine from the outer to inner leaflet. It has not yet been determined which of the 14 members of this family of proteins is the flippase in human erythrocytes. Herein, we report that ATP11C encodes a major flippase in human erythrocytes, and a genetic mutation identified in a male patient caused congenital hemolytic anemia inherited as an X-linked recessive trait. Phosphatidylserine internalization in erythrocytes with the mutant ATP11C was decreased 10-fold compared to that of the control, functionally establishing that ATP11C is a major flippase in human erythrocytes. Contrary to our expectations phosphatidylserine was retained in the inner leaflet of the majority of mature erythrocytes from both controls and the patient, suggesting that phosphatidylserine cannot be externalized as long as scramblase is inactive. Phosphatidylserine-exposing cells were found only in the densest senescent cells (0.1% of total) in which scramblase was activated by increased Ca(2+) concentration: the percentage of these phosphatidylserine-exposing cells was increased in the patient's senescent cells accounting for his mild anemia. Furthermore, the finding of similar extents of phosphatidylserine exposure by exogenous Ca(2+)-activated scrambling in both control erythrocytes and the patient's erythrocytes implies that suppressed scramblase activity rather than flippase activity contributes to the maintenance of phosphatidylserine in the inner leaflet of human erythrocytes. PMID:26944472

  8. The use of /sup 11/C-glucose and positron emission tomography to measure brain glucose metabolism

    SciTech Connect

    Mintun, M.A.; Raichle, M.E.; Welch, M.J.; Kilbourn, M.R.

    1985-05-01

    To measure regional cerebral metabolism of glucose (CMRGlu) with positron emission tomography (PET), but avoid the potential problems inherent in the use of /sup 18/F-fluoro-deoxyglucose, (e.g. regional variation in regional rate constants and instability of the ''lumped constant''), the authors have developed a method using uniformly labeled /sup 11/C-glucose. The method employs a 4-compartment model that accounts for vascular tracer, transport of tracer in and out of the extravascular space, metabolism of tracer, and the production of labeled carbon dioxide, which is free to leave the tissue with blood flow. The differential equations for this model, when solved for CMRGlu, yield CMRGlu=k/sub 1/ . k/sub 3/ . CBF . C/sub B//(k/sub 1/ . k/sub 3/+CBF/CBV . (k/sub 2/+k/sub 3/)) where CBF and CBV are cerebral blood flow and volume, C/sub B/ is unlabeled blood glucose content, k/sub 1/ and k/sub 2/ are transport rate constants and k/sub 3/ is the metabolism rate constant. The authors have begun implementing this technique in baboons and human subjects by first measuring regional CBV and CBF with extant PET methods, then after injection of 20-40mCi of U-/sup 11/C-glucose, estimating the rate constants from 40 sequential PET scans taken over 20 minutes. Resulting white-to-gray matter range in CMRGlu for one typical human subject was 2.9 to 6.3 mg/(min . 100 mg). Oxygen metabolism (CMRO/sub 2/) was also measured at the same sitting with PET and the molar ratio of CMRO/sub 2//CMRGlu ranged from 5.8 to 6.4 as would be expected. These results demonstrate that it may be feasible to avoid the difficulties of an analogue tracer in the measurement of CMRGlu by using /sup 11/C-glucose.

  9. Rapid analysis for metabolites of 11C-labelled drugs: fate of [11C]-S-4-(tert.-butylamino-2-hydroxypropoxy)-benzimidazol-2-one in the dog.

    PubMed

    Jones, H A; Rhodes, C G; Law, M P; Becket, J M; Clark, J C; Boobis, A R; Taylor, G W

    1991-10-01

    Positron emission tomography (PET) requires the use of compounds labelled with short-lived, positron-emitting isotopes (e.g., t1/2 of 11C approximately 120 min). As the concentration of unbound, non-metabolised drug is required as the input function for modeling, this presents particular problems for the study of the kinetics and metabolism of such compounds. We have now developed a rapid extraction procedure, followed by high-performance liquid chromatography using a short analytical column coupled to an on-line gamma-detector to determine the metabolism and kinetics of a non-selective beta-adrenergic antagonist of high affinity, S-4-(tert.-butylamino-2-hydroxypropoxy)benzimidazol-2-one. This antagonist is potentially well suited to the non-invasive localisation of beta-receptors in vivo. The ligand was rapidly taken up into the beta-receptor pool or excreted in urine, with less than 5% of the drug converted to metabolites. Plasma protein binding was only 16%. No significant metabolism of the ligand was observed in the anaesthetised dog, and, therefore, no correction for blood metabolite concentration is required for kinetic analysis of the 11C-labelled ligand during PET studies in this species. The analytical method reported here should be widely applicable: quantification of metabolites enables accurate estimation of the input function and is critical to the interpretation of PET data. PMID:1686775

  10. Development of 1-N-(11)C-Methyl-L- and -D-Tryptophan for pharmacokinetic imaging of the immune checkpoint inhibitor 1-Methyl-Tryptophan.

    PubMed

    Xie, Lin; Maeda, Jun; Kumata, Katsushi; Yui, Joji; Zhang, Yiding; Hatori, Akiko; Nengaki, Nobuki; Wakizaka, Hidekatsu; Fujinaga, Masayuki; Yamasaki, Tomoteru; Shimoda, Yoko; Higuchi, Makoto; Suhara, Tetsuya; Wang, Feng; Zhang, Ming-Rong

    2015-01-01

    1-Methyl-tryptophan (1MTrp) is known as a specific inhibitor targeting the immune-checkpoint protein indoleamine-2,3-dioxygenase, in two stereoisomers of levorotary (L) and dextrorotary (D). A long-standing debate exists in immunology and oncology: which stereoisomer has the potential of antitumor immunotherapy. Herein, we developed two novel radioprobes, 1-N-(11)C-methyl-L- and -D-tryptophan ((11)C-L-1MTrp and (11)C-D-1MTrp), without modifying the chemical structures of the two isomers, and investigated their utility for pharmacokinetic imaging of the whole body. (11)C-L-1MTrp and (11)C-D-1MTrp were synthesized rapidly with radiochemical yields of 47 ± 6.3% (decay-corrected, based on (11)C-CO2), a radiochemical purity of >98%, specific activity of 47-130 GBq/μmol, and high enantiomeric purity. PET/CT imaging in rats revealed that for (11)C-L-1MTrp, the highest distribution of radioactivity was observed in the pancreas, while for (11)C-D-1MTrp, it was observed in the kidney. Ex vivo biodistribution confirmed the PET/CT results, indicating the differences in pharmacokinetics between the two isomers. Both (11)C-L-1MTrp and (11)C-D-1MTrp are therefore useful PET probes for delineating the distribution and action of the checkpoint inhibitor 1MTrp in vivo. This study represents the first step toward using whole-body and real-time insight to disentangle the antitumor potential of the two stereoisomers of 1MTrp, and it can facilitate the development of 1MTrp immunotherapy. PMID:26552594

  11. Development of 1-N-11C-Methyl-l- and -d-Tryptophan for pharmacokinetic imaging of the immune checkpoint inhibitor 1-Methyl-Tryptophan

    PubMed Central

    Xie, Lin; Maeda, Jun; Kumata, Katsushi; Yui, Joji; Zhang, Yiding; Hatori, Akiko; Nengaki, Nobuki; Wakizaka, Hidekatsu; Fujinaga, Masayuki; Yamasaki, Tomoteru; Shimoda, Yoko; Higuchi, Makoto; Suhara, Tetsuya; Wang, Feng; Zhang, Ming-Rong

    2015-01-01

    1-Methyl-tryptophan (1MTrp) is known as a specific inhibitor targeting the immune- checkpoint protein indoleamine-2,3-dioxygenase, in two stereoisomers of levorotary (l) and dextrorotary (d). A long-standing debate exists in immunology and oncology: which stereoisomer has the potential of antitumor immunotherapy. Herein, we developed two novel radioprobes, 1-N-11C-methyl-l- and -d-tryptophan (11C-l-1MTrp and 11C-d-1MTrp), without modifying the chemical structures of the two isomers, and investigated their utility for pharmacokinetic imaging of the whole body. 11C-l-1MTrp and 11C-d-1MTrp were synthesized rapidly with radiochemical yields of 47 ± 6.3% (decay-corrected, based on 11C-CO2), a radiochemical purity of >98%, specific activity of 47–130 GBq/μmol, and high enantiomeric purity. PET/CT imaging in rats revealed that for 11C-l-1MTrp, the highest distribution of radioactivity was observed in the pancreas, while for 11C-D-1MTrp, it was observed in the kidney. Ex vivo biodistribution confirmed the PET/CT results, indicating the differences in pharmacokinetics between the two isomers. Both 11C-l-1MTrp and 11C-d-1MTrp are therefore useful PET probes for delineating the distribution and action of the checkpoint inhibitor 1MTrp in vivo. This study represents the first step toward using whole-body and real-time insight to disentangle the antitumor potential of the two stereoisomers of 1MTrp, and it can facilitate the development of 1MTrp immunotherapy. PMID:26552594

  12. Range degradation and distal edge behavior of proton radiotherapy beams using 11C activation and Monte Carlo simulation

    NASA Astrophysics Data System (ADS)

    Elmekawy, Ahmed Farouk

    The distal edge of therapeutic proton radiation beams was investigated by different methods. Proton beams produced at the Hampton University Proton Therapy Institute (HUPTI) were used to irradiate a Polymethylmethacrylate (PMMA) phantom for three different ranges (13.5, 17.0 and 21.0 cm) to investigate the distal slope dependence of the Bragg peak. The activation of 11 C was studied by scanning the phantom less than 10 minutes post-irradiation with a Philips Big Bore Gemini(c) PET/CT. The DICOM images were imported into the Varian Eclipse(c) Treatment Planning System (TPS) for analysis and then analyzed by ImageJ(c) . The distal slope ranged from ?0.1671 +/- 0.0036 to -0.1986 +/- 0.0052 (pixel intensity/slice number) for ranges 13.5 to 21.0 cm respectively. A realistic description of the setup was modeled using the GATE 7.0 Monte Carlo simulation tool and compared to the experiment data. The results show the distal slope ranged from -0.1158+/-0.0133 to -0.0787+/-0.002 (Gy/mm). Additionally, low activity, 11C were simulated to study the 11C reconstructed half-life dependence versus the initial activity for six ranges chosen around the previous activation study. The results of the expected/nominal half-life vs. activity ranged from -5 x 10-4 +/- 2.8104 x 10-4 to 1.6 x 10-3 +/- 9.44 x 10-4 (%diff./Bq). The comparison between two experiments with proton beams on a PMMA phantom and multi-layer ion chamber, and two GATE simulations of a proton beam incident on a water phantom and 11C PET study show that: (i) the distal fall-off variation of the steepness of the slopes are found to be similar thus validating the sensitivity of the PET technique to the range degradation and (ii) the average of the super-ratios difference between all studies observed is primarily due to the difference in the dose deposited in the media.

  13. Application of Gray Markov SCGM(1,1)c Model to Prediction of Accidents Deaths in Coal Mining

    PubMed Central

    Lan, Jian-yi; Zhou, Ying

    2014-01-01

    The prediction of mine accident is the basis of aviation safety assessment and decision making. Gray prediction is suitable for such kinds of system objects with few data, short time, and little fluctuation, and Markov chain theory is just suitable for forecasting stochastic fluctuating dynamic process. Analyzing the coal mine accident human error cause, combining the advantages of both Gray prediction and Markov theory, an amended Gray Markov SCGM(1,1)c model is proposed. The gray SCGM(1,1)c model is applied to imitate the development tendency of the mine safety accident, and adopt the amended model to improve prediction accuracy, while Markov prediction is used to predict the fluctuation along the tendency. Finally, the new model is applied to forecast the mine safety accident deaths from 1990 to 2010 in China, and, 2011–2014 coal accidents deaths were predicted. The results show that the new model not only discovers the trend of the mine human error accident death toll but also overcomes the random fluctuation of data affecting precision. It possesses stronger engineering application.

  14. Orthorhombic 11C Pyrrhotite from Michałkowa, Góry Sowie Block, The Sudetes, Poland - Preliminary Report

    NASA Astrophysics Data System (ADS)

    Rybicki, Maciej; Krzykawski, Tomasz

    2014-09-01

    This study provides the preliminary report about first occurrence of orthorhombic 11C pyrrhotite (Fe(i-x)S) from the Sudetes, Poland. Samples of pyrrhotite-containing two-pyroxene gabbro were found in a classic pegmatite locality in Michałkowa near Walim in the Góry Sowie Block. Based on microscopic methods, pyrrhotite is associated with pentlandite, chalcopyrite, chromite, ilmenite, gersdorffite, magnetite, biotite, magnesiohornblende, clinochlore, lizardite and talc. X-Ray diffraction (XRD) indicate that pyrrhotite has orthorhombic 11C structure and it is characterized by: a = 3.433(9) Å, b = 5.99(2) Å, c = 5.7432(5) Å, ß = 90° and d 102 = 2.06906 Å. Mössbauer studies confirmed the XRD data. Pyrrhotite has three sextets with hyperfine parameter values 30.8 T for sextet A, 27.9 T and 25.8 T for sextets B and C respectively, indicating orthorhombic structure, the composition near Fe10S11 and x = 0.0909.

  15. Orthorhombic 11C pyrrhotite from Michałkowa, Góry Sowie Block, The Sudetes, Poland - preliminary report

    NASA Astrophysics Data System (ADS)

    Rybicki, Maciej; Krzykawski, Tomasz

    2014-09-01

    This study provides the preliminary report about first occurrence of orthorhombic 11C pyrrhotite (Fe(1-x)S) from the Sudetes, Poland. Samples of pyrrhotite-containing two-pyroxene gabbro were found in a classic pegmatite locality in Michałkowa near Walim in the Góry Sowie Block. Based on microscopic methods, pyrrhotite is associated with pentlandite, chalcopyrite, chromite, ilmenite, gersdorffite, magnetite, biotite, magnesiohornblende, clinochlore, lizardite and talc. X-Ray diffraction (XRD) indicate that pyrrhotite has orthorhombic 11C structure and it is characterized by: a = 3.433(9) Å, b = 5.99(2) Å, c = 5.7432(5) Å, β = 90º and d102 = 2.06906 Å. Mössbauer studies confirmed the XRD data. Pyrrhotite has three sextets with hyperfine parameter values 30.8 T for sextet A, 27.9 T and 25.8 T for sextets B and C respectively, indicating orthorhombic structure, the composition near Fe10S11 and x = 0.0909

  16. Structure of low-lying states of {sup 10,11}C from proton elastic and inelastic scattering

    SciTech Connect

    Jouanne, C.; Lapoux, V.; Auger, F.; Alamanos, N.; Drouart, A.; Gillibert, A.; Lobo, G.; Musumarra, A.; Nalpas, L.; Pollacco, E.; Sida, J.-L.; Trotta, M.; Blumenfeld, Y.; Khan, E.; Suomijaervi, T.; Zerguerras, T.; Roussel-Chomaz, P.; Savajols, H.; Lagoyannis, A.; Pakou, A.

    2005-07-01

    To probe the ground state and transition densities, elastic and inelastic scattering on a proton target were measured in inverse kinematics for the unstable {sup 10}C and {sup 11}C nuclei at 45.3 and 40.6 MeV/nucleon, respectively. The detection of the recoil proton was performed by the MUST telescope array, in coincidence with a wall of scintillators for the quasiprojectile. The differential cross sections for elastic and inelastic scattering to the first excited states are compared to the optical model calculations performed within the framework of the microscopic nucleon-nucleus Jeukenne-Lejeune-Mahaux potential. Elastic scattering is sensitive to the matter-root-mean square radius found to be 2.42{+-}0.1 and 2.33{+-}0.1 fm, for {sup 10,11}C, respectively. The transition densities from cluster and mean-field models are tested, and the cluster model predicts the correct order of magnitude of cross sections for the transitions of both isotopes. Using the Bohr-Mottelson prescription, a profile for the {sup 10}C transition density from the 0{sup +} ground to the 2{sub 1}{sup +} state is deduced from the data. The corresponding neutron transition matrix element is extracted: M{sub n}=5.51{+-}1.09 fm{sup 2}.

  17. Regional brain distribution of translocator protein using [(11)C]DPA-713 PET in individuals infected with HIV.

    PubMed

    Coughlin, Jennifer M; Wang, Yuchuan; Ma, Shuangchao; Yue, Chen; Kim, Pearl K; Adams, Ashley V; Roosa, Heidi V; Gage, Kenneth L; Stathis, Marigo; Rais, Rana; Rojas, Camilo; McGlothan, Jennifer L; Watkins, Crystal C; Sacktor, Ned; Guilarte, Tomas R; Zhou, Yun; Sawa, Akira; Slusher, Barbara S; Caffo, Brian; Kassiou, Michael; Endres, Christopher J; Pomper, Martin G

    2014-06-01

    Imaging the brain distribution of translocator protein (TSPO), a putative biomarker for glial cell activation and neuroinflammation, may inform management of individuals infected with HIV by uncovering regional abnormalities related to neurocognitive deficits and enable non-invasive therapeutic monitoring. Using the second-generation TSPO-targeted radiotracer, [(11)C]DPA-713, we conducted a positron emission tomography (PET) study to compare the brains of 12 healthy human subjects to those of 23 individuals with HIV who were effectively treated with combination antiretroviral therapy (cART). Compared to PET data from age-matched healthy control subjects, [(11)C]DPA-713 PET of individuals infected with HIV demonstrated significantly higher volume-of-distribution (VT) ratios in white matter, cingulate cortex, and supramarginal gyrus, relative to overall gray matter VT, suggesting localized glial cell activation in susceptible regions. Regional TSPO abnormalities were evident within a sub-cohort of neuro-asymptomatic HIV subjects, and an increase in the VT ratio within frontal cortex was specifically linked to individuals affected with HIV-associated dementia. These findings were enabled by employing a gray matter normalization approach for PET data quantification, which improved test-retest reproducibility, intra-class correlation within the healthy control cohort, and sensitivity of uncovering abnormal regional findings. PMID:24567030

  18. Positron emission tomography ligand [11C]5-hydroxy-tryptophan can be used as a surrogate marker for the human endocrine pancreas.

    PubMed

    Eriksson, Olof; Espes, Daniel; Selvaraju, Ram K; Jansson, Emma; Antoni, Gunnar; Sörensen, Jens; Lubberink, Mark; Biglarnia, Ali-Reza; Eriksson, Jan W; Sundin, Anders; Ahlström, Håkan; Eriksson, Barbro; Johansson, Lars; Carlsson, Per-Ola; Korsgren, Olle

    2014-10-01

    In humans, a well-developed serotonin system is localized to the pancreatic islets while being absent in exocrine pancreas. Assessment of pancreatic serotonin biosynthesis could therefore be used to estimate the human endocrine pancreas. Proof of concept was tested in a prospective clinical trial by comparisons of type 1 diabetic (T1D) patients, with extensive reduction of β-cells, with healthy volunteers (HVs). C-peptide-negative (i.e., insulin-deficient) T1D subjects (n = 10) and HVs (n = 9) underwent dynamic positron emission tomography with the radiolabeled serotonin precursor [(11)C]5-hydroxy-tryptophan ([(11)C]5-HTP). A significant accumulation of [(11)C]5-HTP was obtained in the pancreas of the HVs, with large interindividual variation. A substantial and highly significant reduction (66%) in the pancreatic uptake of [(11)C]5-HTP in T1D subjects was observed, and this was most evident in the corpus and caudal regions of the pancreas where β-cells normally are the major constituent of the islets. [(11)C]5-HTP retention in the pancreas was reduced in T1D compared with nondiabetic subjects. Accumulation of [(11)C]5-HTP in the pancreas of both HVs and subjects with T1D was in agreement with previously reported morphological observations on the β-cell volume, implying that [(11)C]5-HTP retention is a useful noninvasive surrogate marker for the human endocrine pancreas. PMID:24848067

  19. Rapid radiosynthesis of [11C] and [14C]azelaic, suberic, and sebacic acids for in vivo mechanistic studies of systemic acquired resistance in plants

    SciTech Connect

    Best M.; Fowler J.; Best, M.; Gifford, A.N.; Kim, S.W.; Babst, B.; Piel, M.; Roesch, F.; Fowler, J.S.

    2011-11-25

    A recent report that the aliphatic dicarboxylic acid, azelaic acid (1,9-nonanedioic acid) but not related acids, suberic acid (1,8-octanedioic acid) or sebacic (1,10-decanedioic acid) acid induces systemic acquired resistance to invading pathogens in plants stimulated the development of a rapid method for labeling these dicarboxylic acids with {sup 11}C and {sup 14}C for in vivo mechanistic studies in whole plants. {sup 11}C-labeling was performed by reaction of ammonium [{sup 11}C]cyanide with the corresponding bromonitrile precursor followed by hydrolysis with aqueous sodium hydroxide solution. Total synthesis time was 60 min. Median decay-corrected radiochemical yield for [{sup 11}C]azelaic acid was 40% relative to trapped [{sup 11}C]cyanide, and specific activity was 15 GBq/{micro}mol. Yields for [{sup 11}C]suberic and sebacic acids were similar. The {sup 14}C-labeled version of azelaic acid was prepared from potassium [{sup 14}C]cyanide in 45% overall radiochemical yield. Radiolabeling procedures were verified using {sup 13}C-labeling coupled with {sup 13}C-NMR and liquid chromatography-mass spectrometry analysis. The {sup 11}C and {sup 14}C-labeled azelaic acid and related dicarboxylic acids are expected to be of value in understanding the mode-of-action, transport, and fate of this putative signaling molecule in plants.

  20. Using [(11)C]Ro15 4513 PET to characterise GABA-benzodiazepine receptors in opiate addiction: Similarities and differences with alcoholism.

    PubMed

    Lingford-Hughes, Anne; Myers, James; Watson, Ben; Reid, Alastair G; Kalk, Nicola; Feeney, Adrian; Hammers, Alexander; Riaño-Barros, Daniela A; McGinnity, Colm J; Taylor, Lindsay G; Rosso, Lula; Brooks, David J; Turkheimer, Federico; Nutt, David J

    2016-05-15

    The importance of the GABA-benzodiazepine receptor complex and its subtypes are increasingly recognised in addiction. Using the α1/α5 benzodiazepine receptor PET radioligand [(11)C]Ro15 4513, we previously showed reduced binding in the nucleus accumbens and hippocampus in abstinent alcohol dependence. We proposed that reduced [(11)C]Ro15 4513 binding in the nucleus accumbens was a marker of addiction whilst the reduction in hippocampus and positive relationship with memory was a consequence of chronic alcohol abuse. To examine this further we assessed [(11)C]Ro15 4513 binding in another addiction, opiate dependence, and used spectral analysis to estimate contributions of α1 and α5 subtypes to [(11)C]Ro15 4513 binding in opiate and previously acquired alcohol-dependent groups. Opiate substitute maintained opiate-dependent men (n=12) underwent an [(11)C]Ro15 4513 PET scan and compared with matched healthy controls (n=13). We found a significant reduction in [(11)C]Ro15 4513 binding in the nucleus accumbens in the opiate-dependent compared with the healthy control group. There was no relationship between [(11)C]Ro15 4513 binding in the hippocampus with memory. We found that reduced [(11)C]Ro15 4513 binding was associated with reduced α5 but not α1 subtypes in the opiate-dependent group. This was also seen in an alcohol-dependent group where an association between memory performance and [(11)C]Ro15 4513 binding was primarily driven by α5 and not α1 subtype. We suggest that reduced α5 levels in the nucleus accumbens are associated with addiction since we have now shown this in dependence to two pharmacologically different substances, alcohol and opiates. PMID:26876472

  1. Sp1 binds two sites in the CD11c promoter in vivo specifically in myeloid cells and cooperates with AP1 to activate transcription.

    PubMed Central

    Noti, J D; Reinemann, B C; Petrus, M N

    1996-01-01

    The leukocyte integrin gene, CD11c, is transcriptionally regulated and is expressed predominantly on differentiated cells of the myelomonocytic lineage. In this study we have demonstrated that the regions -72 to -63 and -132 to -104 of the CD11c promoter contain elements responsible for phorbol ester-induced differentiation of the myeloid cell line HL60. DNase I footprinting analysis revealed that these regions can bind purified Sp1, and supershift analysis with Sp1 antibody confirmed that Sp1 in HL60 nuclear extracts could bind these regions. Transfection analysis of CD11c promoter-chloramphenicol acetyltransferase constructs containing deletions of these Sp1-binding sites revealed that these sites are essential for expression of the CD11c gene in HL60 cells but not in the T-cell line Molt4 or the cervical carcinoma cell line HeLa. Moreover, cotransfection of pPacSp1 along with these CD11c promoter-chloramphenicol acetyltransferase constructs into Sp1-deficient Drosophila Schneider 2 cells verified that these sites are essential for Sp1-dependent expression of the CD11c promoter. In vivo genomic footprinting revealed that Sp1 contacts the CD11c promoter within the regions -69 to -63 and -116 to -105 in phorbol 12-myristate 13-acetate-differentiated HL60 cells but not in undifferentiated HL60 cells or in Molt4 or HeLa cells. Cotransfection assays in HL60 cells revealed that Sp1 acts synergistically with Ap1 to activate CD11c. Further, both Sp1 sites are capable of cooperating with AP1. In vitro DNase I footprinting analysis with purified Sp1 and c-jun proteins showed that Sp1 binding could facilitate binding of c-jun. We propose that myeloid-specific expression of the CD11c promoter and is facilitated by cooperative interaction between the Sp1- and Ap1-binding sites. PMID:8649405

  2. A two-compartment description and kinetic procedure for measuring regional cerebral ( sup 11 C)nomifensine uptake using positron emission tomography

    SciTech Connect

    Salmon, E.; Brooks, D.J.; Leenders, K.L.; Turton, D.R.; Hume, S.P.; Cremer, J.E.; Jones, T.; Frackowiak, R.S. )

    1990-05-01

    S-(11C)Nomifensine (S-(11C)NMF) is a positron-emitting tracer suitable for positron emission tomography, which binds to both dopaminergic and noradrenergic reuptake sites in the striatum and the thalamus. Modelling of the cerebral distribution of this drug has been hampered by the rapid appearance of glucuronide metabolites in the plasma, which do not cross the blood--brain barrier. To date, (11C)NMF uptake has simply been expressed as regional versus nonspecific cerebellar activity ratios. We have calculated a free NMF input curve from red cell activity curves, using the fact that the free drug rapidly equilibrates between red cells and plasma, while glucuronides do not enter red cells. With this free (11C)NMF input function, all regional cerebral uptake curves could be fitted to a conventional two-compartment model, defining tracer distribution in terms of (11C)NMF regional volume of distribution. Assuming that the cerebellar volume of distribution of (11C)NMF represents the nonspecific volume of distribution of the tracer in striatum and thalamus, we have calculated an equilibrium partition coefficient for (11C)NMF between freely exchanging specific and nonspecific compartments in these regions, representing its binding potential to dopaminergic or noradrenergic uptake sites (or complexes). This partition coefficient was lower in the striatum when the racemate rather than the active S-enantiomer of (11C)NMF was administered. In the striatum of patients suffering from Parkinson's disease and multiple-system atrophy, the specific compartmentation of S-(11C)NMF was significantly decreased compared with that of age-matched volunteers.

  3. Using [11C]Ro15 4513 PET to characterise GABA-benzodiazepine receptors in opiate addiction: Similarities and differences with alcoholism

    PubMed Central

    Lingford-Hughes, Anne; Myers, James; Watson, Ben; Reid, Alastair G.; Kalk, Nicola; Feeney, Adrian; Hammers, Alexander; Riaño-Barros, Daniela A.; McGinnity, Colm J.; Taylor, Lindsay G.; Rosso, Lula; Brooks, David J.; Turkheimer, Federico; Nutt, David J.

    2016-01-01

    The importance of the GABA-benzodiazepine receptor complex and its subtypes are increasingly recognised in addiction. Using the α1/α5 benzodiazepine receptor PET radioligand [11C]Ro15 4513, we previously showed reduced binding in the nucleus accumbens and hippocampus in abstinent alcohol dependence. We proposed that reduced [11C]Ro15 4513 binding in the nucleus accumbens was a marker of addiction whilst the reduction in hippocampus and positive relationship with memory was a consequence of chronic alcohol abuse. To examine this further we assessed [11C]Ro15 4513 binding in another addiction, opiate dependence, and used spectral analysis to estimate contributions of α1 and α5 subtypes to [11C]Ro15 4513 binding in opiate and previously acquired alcohol-dependent groups. Opiate substitute maintained opiate-dependent men (n = 12) underwent an [11C]Ro15 4513 PET scan and compared with matched healthy controls (n = 13). We found a significant reduction in [11C]Ro15 4513 binding in the nucleus accumbens in the opiate-dependent compared with the healthy control group. There was no relationship between [11C]Ro15 4513 binding in the hippocampus with memory. We found that reduced [11C]Ro15 4513 binding was associated with reduced α5 but not α1 subtypes in the opiate-dependent group. This was also seen in an alcohol-dependent group where an association between memory performance and [11C]Ro15 4513 binding was primarily driven by α5 and not α1 subtype. We suggest that reduced α5 levels in the nucleus accumbens are associated with addiction since we have now shown this in dependence to two pharmacologically different substances, alcohol and opiates. PMID:26876472

  4. Quantitative measurement of local cerebral blood flow in humans by positron computed tomography and /sup 15/O-water

    SciTech Connect

    Huang, S.C.; Carson, R.E.; Hoffman, E.J.; Carson, J.; MacDonald, N.; Barrio, J.R.; Phelps, M.E.

    1983-06-01

    A noninvasive method that employs /sup 15/O-water and positron-computed tomography (PCT) was used to measure quantitative local cerebral blood flow (lCBF) in man. /sup 15/O-Water (about 30-50 mCi) was introduced through a single-breath inhalation of /sup 15/O-carbon dioxide or through an intravenous bolus injection of /sup 15/O-water. A sequence of five 2-min PCT scans was initiated at the time of tracer administration. A series of 15-20 blood samples (1 ml each) was withdrawn from the radial artery of the subject over a period of 10 min. Oxygen-15 radioactivities in the blood samples were immediately counted in a well counter to give an input function, which together with the projection data collected by PCT were processed to provide images of 1CBF and local water distribution volume. The method was found to be convenient to use and gave good-quality images of 1CBF. Quantitative values of 1CBF in images were 59 +/- 11 and 20 +/- 4 ml/min/100 g for gray and white matter, respectively, with a gray-to-white matter ratio of 2.93 and a global flow value of 42 +/- 8 ml/min/100 g. Distribution volume of water was 0.85 +/- 0.03, 0.76 +/- 0.03, and 0.81 +/- 0.02 ml/g respectively, for gray matter, white matter, and whole brain.

  5. Cortical activation in profoundly deaf patients during cochlear implant stimulation demonstrated by H sub 2 (15)O PET

    SciTech Connect

    Herzog, H.; Lamprecht, A.; Kuehn, A.R.; Roden, W.; Vosteen, K.H.; Feinendegen, L.E. )

    1991-05-01

    Cochlear implants (CIs) are used to provide sensations of sound to profoundly deaf patients. The performance of the CI is assessed mainly by the subjective reports of patients. The aim of this study was to look for objective cortical responses to the stimulation of the CI. Two postlingually and two prelingually deaf patients were investigated by positron emission tomography (PET) using {sup 15}O-labeled water (H{sub 2}{sup 15}O) to determine the regional cerebral blood flow (rCBF). Instead of quantifying rCBF in absolute terms, it was estimated by referring the regional tissue concentration of H{sub 2}{sup 15}O to the mean whole brain concentration. CI stimulation encoded from white noise and sequential words led to an increased rCBF in the primary and secondary (Wernicke) auditory cortex. Relative elevations of up to 33% were observed bilaterally, although they were higher contralateral to the CI. These results were obtained not only in the postlingually deaf patients but also in two patients who had never been able to hear. Thus, it could be demonstrated that PET measurements of cerebral H{sub 2}{sup 15}O distribution yield objective responses of the central auditory system during electrical stimulation by CIs in profoundly deaf patients.

  6. Lifetime measurement of the 6.79 MeV state in 15O with the AGATA demonstrator

    NASA Astrophysics Data System (ADS)

    Depalo, R.; Michelagnoli, C.; Menegazzo, R.; Ur, C. A.; Bazzacco, D.; Bemmerer, D.; Broggini, C.; Caciolli, A.; Erhard, M.; Farnea, E.; Fülöp, Zs.; Gottardo, A.; Keeley, N.; Lunardi, S.; Marta, M.; Mengoni, D.; Mijatović, T.; Recchia, F.; Rossi-Alvarez, C.; Szücs, T.; Valiente-Dobon, J. J.; Agata Collaboration

    2012-11-01

    The 14N(p,γ)15O reaction is the slowest process of the CN cycle, and thus it is of high astrophysical interest since it regulates the total rate of energy and neutrinos production through the cycle. The 14N+p ground state capture is strongly influenced by a sub-threshold resonance corresponding to the 6.79 MeV state in 15O. The width of this resonance is a major source of uncertainty in the extrapolation of the reaction cross section in the Gamow energy window. Preliminary results of a new Doppler Shift Attenuation measurement of the lifetime of the 6.79 MeV state in 15O are discussed. The level of interest was populated via the 2H(14N,n)15O reaction in inverse kinematics at 32 MeV beam energy. The gamma-rays emitted in the decay of the 6.79 MeV level to the ground state were detected with the AGATA Demonstrator array of high-purity germanium detectors. The sensitivity of the shape of the peak in the gamma-ray energy spectrum to the level lifetime is investigated comparing the experimental peaks with detailed Monte Carlo simulations of the reaction mechanisms and the gamma-ray emission and detection. Nuclear levels in 15N (also populated in the 14N+2H reaction) for which the lifetimes are known in the literature provided a test of the analysis technique.

  7. Structural and functional characterization of TRI3 trichothecene 15-O-acetyltransferase from Fusarium sporotrichioides

    SciTech Connect

    Garvey, Graeme S.; McCormick, Susan P.; Alexander, Nancy J.; Rayment, Ivan

    2009-08-14

    Fusarium head blight is a devastating disease of cereal crops whose worldwide incidence is increasing and at present there is no satisfactory way of combating this pathogen or its associated toxins. There is a wide variety of trichothecene mycotoxins and they all contain a 12,13-epoxytrichothecene skeleton but differ in their substitutions. Indeed, there is considerable variation in the toxin profile across the numerous Fusarium species that has been ascribed to differences in the presence or absence of biosynthetic enzymes and their relative activity. This article addresses the source of differences in acetylation at the C15 position of the trichothecene molecule. Here, we present the in vitro structural and biochemical characterization of TRI3, a 15-O-trichothecene acetyltransferase isolated from F. sporotrichioides and the 'in vivo' characterization of Deltatri3 mutants of deoxynivalenol (DON) producing F. graminearum strains. A kinetic analysis shows that TRI3 is an efficient enzyme with the native substrate, 15-decalonectrin, but is inactive with either DON or nivalenol. The structure of TRI3 complexed with 15-decalonectrin provides an explanation for this specificity and shows that Tri3 and Tri101 (3-O-trichothecene acetyltransferase) are evolutionarily related. The active site residues are conserved across all sequences for TRI3 orthologs, suggesting that differences in acetylation at C15 are not due to differences in Tri3. The tri3 deletion mutant shows that acetylation at C15 is required for DON biosynthesis even though DON lacks a C15 acetyl group. The enzyme(s) responsible for deacetylation at the 15 position of the trichothecene mycotoxins have not been identified.

  8. An apparatus for the preparation of [{sup 15}O]-H{sub 2}O for rapid repetitive PET studies

    SciTech Connect

    Dahl, J. R.; Chaly, T. C.; Matacchieri, R. A.; Yee, A.; Dhawan, V.; Horowitz, S.; Jespersen, K.; Margouleff, D.; Eidelberg, D.

    1999-06-10

    The use of [{sup 15}O]-H{sub 2}O to follow changes in cerebral blood flow using PET has become frequent and widespread, requiring an apparatus easily operated by personnel unfamiliar with the physics and chemistry involved. Oxygen-15 is prepared by the {sup 14}N(d,n){sup 15}O nuclear reaction using a target of UHP nitrogen with 1% UHP hydrogen added, contained in a target chamber similar to that reported for the preparation of [{sup 18}F]-F{sub 2}. Nucleogenic {sup 15}O reacts with hydrogen in the target gas to produce [{sup 15}O]-H{sub 2}O. Some of the N target reacts with hydrogen to produce NH{sub 3}, which must be removed. At the end of bombardment (minimum 6 min.) the target gas is released through a small amount of parenteral water which then flows through approximately 50 mg Dowex 50W-X8 resin (100-200 mesh) to remove the NH{sub 3}. Sufficient 23.4% NaCl solution is added to produce an isotonic solution. The isotonic solution is sterilized by filtration through a 0.22 micron filter into an injection syringe which is sent via pneumatic transport to the PET imaging room. The apparatus, which uses a programmable logic controller and four switches to allow the operator to select standby, refill, collect activity, or deliver dose operations of the production process, provides doses of [{sup 15}O]-H{sub 2}O up to 35 mCi/dose at intervals as frequent as seven minutes with minimal radiation exposure to the operators.

  9. An apparatus for the preparation of [15O]-H2O for rapid repetitive PET studies

    NASA Astrophysics Data System (ADS)

    Dahl, J. R.; Chaly, T. C.; Matacchieri, R. A.; Yee, A.; Dhawan, V.; Horowitz, S.; Jespersen, K.; Margouleff, D.; Eidelberg, D.

    1999-06-01

    The use of [15O]-H2O to follow changes in cerebral blood flow using PET has become frequent and widespread, requiring an apparatus easily operated by personnel unfamiliar with the physics and chemistry involved. Oxygen-15 is prepared by the 14N(d,n)15O nuclear reaction using a target of UHP nitrogen with 1% UHP hydrogen added, contained in a target chamber similar to that reported for the preparation of [18F]-F2. Nucleogenic 15O reacts with hydrogen in the target gas to produce [15O]-H2O. Some of the N target reacts with hydrogen to produce NH3, which must be removed. At the end of bombardment (minimum 6 min.) the target gas is released through a small amount of parenteral water which then flows through approximately 50 mg Dowex 50W-X8 resin (100-200 mesh) to remove the NH3. Sufficient 23.4% NaCl solution is added to produce an isotonic solution. The isotonic solution is sterilized by filtration through a 0.22 micron filter into an injection syringe which is sent via pneumatic transport to the PET imaging room. The apparatus, which uses a programmable logic controller and four switches to allow the operator to select standby, refill, collect activity, or deliver dose operations of the production process, provides doses of [15O]-H2O up to 35 mCi/dose at intervals as frequent as seven minutes with minimal radiation exposure to the operators.

  10. Intensity Modulated Radiation Therapy Dose Painting for Localized Prostate Cancer Using {sup 11}C-choline Positron Emission Tomography Scans

    SciTech Connect

    Chang, Joe H.; Lim Joon, Daryl; Lee, Sze Ting; Gong, Sylvia J.; Anderson, Nigel J.; Scott, Andrew M.; Davis, Ian D.; Clouston, David; Bolton, Damien; Hamilton, Christopher S.; Khoo, Vincent

    2012-08-01

    Purpose: To demonstrate the technical feasibility of intensity modulated radiation therapy (IMRT) dose painting using {sup 11}C-choline positron emission tomography PET scans in patients with localized prostate cancer. Methods and Materials: This was an RT planning study of 8 patients with prostate cancer who had {sup 11}C-choline PET scans prior to radical prostatectomy. Two contours were semiautomatically generated on the basis of the PET scans for each patient: 60% and 70% of the maximum standardized uptake values (SUV{sub 60%} and SUV{sub 70%}). Three IMRT plans were generated for each patient: PLAN{sub 78}, which consisted of whole-prostate radiation therapy to 78 Gy; PLAN{sub 78-90}, which consisted of whole-prostate RT to 78 Gy, a boost to the SUV{sub 60%} to 84 Gy, and a further boost to the SUV{sub 70%} to 90 Gy; and PLAN{sub 72-90}, which consisted of whole-prostate RT to 72 Gy, a boost to the SUV{sub 60%} to 84 Gy, and a further boost to the SUV{sub 70%} to 90 Gy. The feasibility of these plans was judged by their ability to reach prescription doses while adhering to published dose constraints. Tumor control probabilities based on PET scan-defined volumes (TCP{sub PET}) and on prostatectomy-defined volumes (TCP{sub path}), and rectal normal tissue complication probabilities (NTCP) were compared between the plans. Results: All plans for all patients reached prescription doses while adhering to dose constraints. TCP{sub PET} values for PLAN{sub 78}, PLAN{sub 78-90}, and PLAN{sub 72-90} were 65%, 97%, and 96%, respectively. TCP{sub path} values were 71%, 97%, and 89%, respectively. Both PLAN{sub 78-90} and PLAN{sub 72-90} had significantly higher TCP{sub PET} (P=.002 and .001) and TCP{sub path} (P<.001 and .014) values than PLAN{sub 78}. PLAN{sub 78-90} and PLAN{sub 72-90} were not significantly different in terms of TCP{sub PET} or TCP{sub path}. There were no significant differences in rectal NTCPs between the 3 plans. Conclusions: IMRT dose painting for

  11. Brain Regional α-[11C]Methyl-L-Tryptophan Trapping in Medication-Free Patients With Obsessive-Compulsive Disorder

    PubMed Central

    Berney, Alexandre; Leyton, Marco; Gravel, Paul; Sibon, Igor; Sookman, Debbie; Neto, Pedro Rosa; Diksic, Mirko; Nakai, Akio; Pinard, Gilbert; Todorov, Christo; Okazawa, Hidehiko; Blier, Pierre; Nordahl, Thomas Edward; Benkelfat, Chawki

    2013-01-01

    Context The hypothesis of a serotonin (5-hydroxytryptamine [5-HT]) dysfunction in obsessive-compulsive disorder (OCD) stems largely from the clinical efficacy of 5-HT reuptake inhibitors. Serotonergic abnormalities in the unmedicated symptomatic state, however, remain to be fully characterized. Objective To investigate brain regional 5-HT synthesis, as indexed by positron emission tomography and the α-[11C]methyl-L-tryptophan trapping constant (K*), in treatment-free adults meeting criteria for OCD. Design Between-group comparison. Setting Department of Psychiatry and Montreal Neurological Institute, McGill University, and Department of Psychology, McGill University Health Centre, Quebec, Canada. Participants Twenty-one medication-free patients with OCD (15 men with a mean [SD] age of 33.2 [9.3] years and 6 women with a mean [SD] age of 35.8 [7.1] years) and 21 healthy controls matched for age and sex (15 men with a mean [SD] age of 32.9 [10.1] years and 6 women with a mean [SD] age of 36.5.5 [8.6] years). Main Outcome Measure The α-[11C]methyl-L-tryptophan brain trapping constant K*, which was analyzed with Statistical Parametric Mapping (SPM8) and with proportional normalization (extent threshold of 100 voxels with a peak threshold of P≤.005). Results Compared with healthy controls, the patients with OCD exhibited significantly greater α-[11C]methyl-L-tryptophan trapping in the right hippocampus and left temporal gyrus (Brodmann area 20). In the larger sub-sample of all men, these same differences were also evident, as well as higher K* values in the caudate nucleus. Individual differences in symptom severity correlated positively with K* values sampled from the caudate and temporal lobe of the patients with OCD, respectively. There were no regions where the patients exhibited abnormally low K* values. Volumetric analyses found no morphometric alterations that would account for the group differences. Conclusion The results support previous reports of greater

  12. [Detection of tumors in the central zone of the prostate with 11C-Choline PET/CT].

    PubMed

    Garcia, J R; Soler, M; Moragas, M; Ponce, A; Moreno, C; Riera, E

    2014-01-01

    Prostate tumors originate 68% in the peripheral region and 24% in the transitional region where tumors originating in the central zone are rare (8%). However, diagnosis of the tumors in the central zone is important since they exhibit greater aggressiveness conditioned by their location and different biological behavior. Magnetic resonance imaging shows problems in identifying lesions in the central prostate zone, since this region has a heterogeneous signal, mainly after the primary treatment. Ultrasound guided sextant biopsy shows a negative result in 28% of prostate tumors. Therefore, it is advisable to repeat or even to perform saturation biopsies. We present two patients, one of them with suspected biochemical prostate cancer and one with biochemical recurrence after radical treatment. In both, (11)C-Choline PET/CT allowed detection of the tumor focus in the central zone of the prostate, with negative complementary diagnostic test and biopsies. PMID:24119550

  13. [Radiosynthesis and preliminary evaluation of 5-([11C]methyloxy)-L-tryptophan as PET tumor imaging].

    PubMed

    He, Shan-zhen; Wang, Shu-xia; Hu, Kong-zhen; Yao, Bao-guo; Tang, Gang-hua

    2015-05-01

    The PET tracer 5-([11C]methyloxy)-L-tryptophan (5-(11)CMTP) was prepared by nucleophilic fluorination and alkylation reaction via a two-step procedure in order to develop specific tumor probe. The biodistribution and microPET imaging of 5-(11)CMTP were executed. The results unveiled that the overall radiochemical yield with no decay correction was (14.6 ±7.2) %, the radiochemical purity was more than 95% and high uptake and long retention time of 5-(11)CMTP in liver, kidney and blood were observed but low uptake in brain and muscle were found, furthermore, high uptake of 5-(11)CMTP in tumor tissue was observed. It seems that 5-(11)CMTP will be a potential amino acid tracer for tumors imaging with PET. PMID:26234137

  14. Synthesis and bioimaging of positron-emitting 15O-labeled 2-deoxy-D-glucose of two-minute half-life.

    PubMed

    Yorimitsu, Hideki; Murakami, Yoshihiro; Takamatsu, Hiroyuki; Nishimura, Shintaro; Nakamura, Eiichi

    2007-01-01

    In positron emission tomography (PET), which exploits the affinity of a radiopharmaceutical for the target organ, a systematic repertoire of oxygen-15-labeled PET tracers is expected to be useful for bioimaging owing to the ubiquity of oxygen atoms in organic compounds. However, because of the 2-min half-life of 15O, the synthesis of complex biologically active 15O-labeled organic molecules has not yet been achieved. A state-of-the-art synthesis now makes available an 15O-labeled complex organic molecule, 6-[15O]-2-deoxy-D-glucose. Ultrarapid radical hydroxylation of 2,6-dideoxy-6-iodo-D-glucose with molecular oxygen labeled with 15O of two-minute half-life provided the target 15O-labeled molecule. The labeling reaction with 15O was complete in 1.3 min, and the entire operation time starting from the generation of 15O-containing dioxygen by a cyclotron to the purification of the labeled sugar was 7 min. The labeled sugar accumulated in the metabolically active organs as well as in the bladder of mice and rats. 15O-labeling offers the possibility of repetitive scanning and the use of multiple PET tracers in the same body within a short time, and hence should significantly expand the scope of PET studies of small animals. PMID:17441139

  15. Muscarinic Receptor Occupancy and Cognitive Impairment: A PET Study with [11C](+)3-MPB and Scopolamine in Conscious Monkeys

    PubMed Central

    Yamamoto, Shigeyuki; Nishiyama, Shingo; Kawamata, Masahiro; Ohba, Hiroyuki; Wakuda, Tomoyasu; Takei, Nori; Tsukada, Hideo; Domino, Edward F

    2011-01-01

    The muscarinic cholinergic receptor (mAChR) antagonist scopolamine was used to induce transient cognitive impairment in monkeys trained in a delayed matching to sample task. The temporal relationship between the occupancy level of central mAChRs and cognitive impairment was determined. Three conscious monkeys (Macaca mulatta) were subjected to positron emission tomography (PET) scans with the mAChR radioligand N-[11C]methyl-3-piperidyl benzilate ([11C](+)3-MPB). The scan sequence was pre-, 2, 6, 24, and 48 h post-intramuscular administration of scopolamine in doses of 0.01 and 0.03 mg/kg. Occupancy levels of mAChR were maximal 2 h post-scopolamine in cortical regions innervated primarily by the basal forebrain, thalamus, and brainstem, showing that mAChR occupancy levels were 43–59 and 65–89% in doses of 0.01 and 0.03 mg/kg, respectively. In addition, dose-dependent impairment of working memory performance was measured 2 h after scopolamine. A positive correlation between the mAChR occupancy and cognitive impairment 2 and 6 h post-scopolamine was the greatest in the brainstem (P<0.00001). Although cognitive impairment was not observed 24 h post-scopolamine, sustained mAChR occupancy (11–24%) was found with both doses in the basal forebrain and thalamus, but not in the brainstem. These results indicate that a significant degree of mAChRs occupancy is needed to produce cognitive impairment by scopolamine. Furthermore, the importance of the brainstem cholinergic system in working memory in monkey is described. PMID:21430646

  16. Synthesis and Preclinical Evaluation of Sulfonamido-based [11C-Carbonyl]-Carbamates and Ureas for Imaging Monoacylglycerol Lipase

    PubMed Central

    Wang, Lu; Mori, Wakana; Cheng, Ran; Yui, Joji; Hatori, Akiko; Ma, Longle; Zhang, Yiding; Rotstein, Benjamin H.; Fujinaga, Masayuki; Shimoda, Yoko; Yamasaki, Tomoteru; Xie, Lin; Nagai, Yuji; Minamimoto, Takafumi; Higuchi, Makoto; Vasdev, Neil; Zhang, Ming-Rong; Liang, Steven H.

    2016-01-01

    Monoacylglycerol lipase (MAGL) is a 33 kDa member of the serine hydrolase superfamily that preferentially degrades 2-arachidonoylglycerol (2-AG) to arachidonic acid in the endocannabinoid system. Inhibition of MAGL is not only of interest for probing the cannabinoid pathway but also as a therapeutic and diagnostic target for neuroinflammation. Limited attempts have been made to image MAGL in vivo and a suitable PET ligand for this target has yet to be identified and is urgently sought to guide small molecule drug development in this pathway. Herein we synthesized and evaluated the physiochemical properties of an array of eleven sulfonamido-based carbamates and ureas with a series of terminal aryl moieties, linkers and leaving groups. The most potent compounds were a novel MAGL inhibitor, N-((1-(1H-1,2,4-triazole-1-carbonyl)piperidin-4-yl) methyl)-4-chlorobenzenesulfonamide (TZPU; IC50 = 35.9 nM), and the known inhibitor 1,1,1,3,3,3-hexafluoropropan-2-yl 4-(((4-chlorophenyl)sulfonamido) methyl)piperidine-1-carboxylate (SAR127303; IC50 = 39.3 nM), which were also shown to be selective for MAGL over fatty acid amide hydrolase (FAAH), and cannabinoid receptors (CB1 & CB2). Both of these compounds were radiolabeled with carbon-11 via [11C]COCl2, followed by comprehensive ex vivo biodistribution and in vivo PET imaging studies in normal rats to determine their brain permeability, specificity, clearance and metabolism. Whereas TZPU did not show adequate specificity to warrant further evaluation, [11C]SAR127303 was advanced for preliminary PET neuroimaging studies in nonhuman primate. The tracer showed good brain permeability (ca. 1 SUV) and heterogeneous regional brain distribution which is consistent with the distribution of MAGL. PMID:27279908

  17. D-(U-11C)glucose uptake and metabolism in the brain of insulin-dependent diabetic subjects

    SciTech Connect

    Gutniak, M.; Blomqvist, G.; Widen, L.; Stone-Elander, S.; Hamberger, B.; Grill, V. )

    1990-05-01

    We used D-(U-11C)glucose to evaluate transport and metabolism of glucose in the brain in eight nondiabetic and six insulin-dependent diabetes mellitus (IDDM) subjects. IDDM subjects were treated by continuous subcutaneous insulin infusion. Blood glucose was regulated by a Biostator-controlled glucose infusion during a constant insulin infusion. D-(U-11C)-glucose was injected for positron emission tomography studies during normoglycemia as well as during moderate hypoglycemia (arterial plasma glucose 2.74 +/- 0.14 in nondiabetic and 2.80 +/- 0.26 mmol/l (means +/- SE) in IDDM subjects). Levels of free insulin were constant and similar in both groups. The tracer data were analyzed using a three-compartment model with a fixed correction for 11CO2 egression. During normoglycemia the influx rate constant (k1) and blood-brain glucose flux did not differ between the two groups. During hypoglycemia k1 increased significantly and similarly in both groups (from 0.061 +/- 0.007 to 0.090 +/- 0.006 in nondiabetic and from 0.061 +/- 0.006 to 0.093 +/- 0.013 ml.g-1.min-1 in IDDM subjects). During normoglycemia the tracer-calculated metabolism of glucose was higher in the whole brain in the nondiabetic than in the diabetic subjects (22.0 +/- 1.9 vs. 15.6 +/- 1.1 mumol.100 g-1.min-1, P less than 0.01). During hypoglycemia tracer-calculated metabolism was decreased by 40% in nondiabetic subjects and by 28% in diabetic subjects. The results indicate that uptake of glucose is normal, but some aspect of glucose metabolism is abnormal in a group of well-controlled IDDM subjects.

  18. Decreased Norepinephrine Transporter Availability in Obesity: Positron Emission Tomography Imaging with (S,S)-[11C]O-Methylreboxetine

    PubMed Central

    Li, Chiang-shan R.; Potenza, Marc N.; Lee, Dianne E.; Planeta, Beata; Gallezot, Jean-Dominique; Labaree, David; Henry, Shannan; Nabulsi, Nabeel; Sinha, Rajita; Ding, Yu-Shin; Carson, Richard E.; Neumeister, Alexander

    2013-01-01

    Objectives Noradrenergic dysfunction is implicated in obesity. The norepinephrine transporter (NET) regulates the synaptic availability of norepinephrine. However, NET availability has not been previously characterized in vivo in obese people using Positron Emission Tomography (PET) imaging. Here we report findings evaluating NET availability in individuals with obesity and matched lean (i.e., normal weight) comparison subjects. Methods Seventeen obese but otherwise healthy individuals with a mean±SD body mass index (BMI) of 34.7±2.6 and 17 lean individuals with a mean±SD BMI of 23.1±1.4 were studied using a High-Resolution Research Tomograph (HRRT) and (S,S)-[11C]O-methylreboxetine ([11C]-MRB), a radioligand selective for the NET. The regional brain NET binding potential (BPND) was estimated by the multilinear reference tissue model 2 (MRTM2) with the occipital cortex as a reference region. BPND for regions of interest were obtained with the Automated Anatomic Labeling (AAL) template registered to individual’s structural MR scans. Results Obese individuals had lower NET BPND values in the thalamus (p<0.038, 27% reduction) including within the pulvinar (p<0.083, 30% reduction), but not in the hypothalamus, locus coeruleus or the raphe nuclei, compared to lean individuals. When age was included as a covariate, the difference in NET BPND values remained significant in the thalamus (p<0.025) and pulvinar (p<0.042). Conclusions These results indicate that NET availability is decreased in the thalamus, including the pulvinar, in obese individuals. These findings further support data indicating noradrenergic dysfunction in obesity and suggest impaired NE clearance in obesity. PMID:24121204

  19. Direct measurement of the {sup 11}C({alpha},p){sup 14}N reaction at CRIB: A path from pp-chain to CNO

    SciTech Connect

    Hayakawa, S.; Kubono, S.; Kahl, D.; Yamaguchi, H.; Binh, D. N.; Hashimoto, T.; Wakabayashi, Y.; He, J. J.; Iwasa, N.; Kato, S.; Komatsubara, T.; Kwon, Y. K.; Teranishi, T.; Wanajo, S.

    2012-11-20

    We determined the total reaction rate of the {sup 11}C({alpha},p){sup 14}N reaction relevant to the nucleosynthesis in explosive hydrogen-burning stars. The measurement was performed by means of the thick target method in inverse kinematics with {sup 11}C RI beams. We performed the identification of the ground-state transition and excited-state transitions using time-of-flight information for the first time.

  20. Direct measurement of the breakout reaction {sup 11}C({alpha},p){sup 14}N in explosive hydrogen-burning process

    SciTech Connect

    Hayakawa, S.; Kubono, S.; Kahl, D.; Yamaguchi, H.; Binh, Dam N.; Hashimoto, T.; Wakabayashi, Y.; He, J. J.; Iwasa, N.; Kato, S.; Komatsubara, T.; Kwon, Y. K.; Teranishi, T.; Wanajo, S.

    2012-11-12

    We determined the {sup 11}C({alpha},p){sup 14}N reaction rate relevant to the nucleosynthesis in explosive hydrogen-burning stars. The measurement was performed by means of the thick target method in inverse kinematics with {sup 11}C RI beams. We derived the excitation functions for the ground-state transition and excited-state transitions using time-of-flight information for the first time. The present reaction rate is compared to the previous one.

  1. Characterisation of the contribution of the GABA-benzodiazepine α1 receptor subtype to [11C]Ro15-4513 PET images

    PubMed Central

    Myers, James FM; Rosso, Lula; Watson, Ben J; Wilson, Sue J; Kalk, Nicola J; Clementi, Nicoletta; Brooks, David J; Nutt, David J; Turkheimer, Federico E; Lingford-Hughes, Anne R

    2012-01-01

    This positron emission tomography (PET) study aimed to further define selectivity of [11C]Ro15-4513 binding to the GABARα5 relative to the GABARα1 benzodiazepine receptor subtype. The impact of zolpidem, a GABARα1-selective agonist, on [11C]Ro15-4513, which shows selectivity for GABARα5, and the nonselective benzodiazepine ligand [11C]flumazenil binding was assessed in humans. Compartmental modelling of the kinetics of [11C]Ro15-4513 time-activity curves was used to describe distribution volume (VT) differences in regions populated by different GABA receptor subtypes. Those with low α5 were best fitted by one-tissue compartment models; and those with high α5 required a more complex model. The heterogeneity between brain regions suggested spectral analysis as a more appropriate method to quantify binding as it does not a priori specify compartments. Spectral analysis revealed that zolpidem caused a significant VT decrease (∼10%) in [11C]flumazenil, but no decrease in [11C]Ro15-4513 binding. Further analysis of [11C]Ro15-4513 kinetics revealed additional frequency components present in regions containing both α1 and α5 subtypes compared with those containing only α1. Zolpidem reduced one component (mean±s.d.: 71%±41%), presumed to reflect α1-subtype binding, but not another (13%±22%), presumed to reflect α5. The proposed method for [11C]Ro15-4513 analysis may allow more accurate selective binding assays and estimation of drug occupancy for other nonselective ligands. PMID:22214903

  2. Confirmation of fenfluramine effect on 5-HT1B receptor binding of [11C]AZ10419369 using an equilibrium approach

    PubMed Central

    Finnema, Sjoerd J; Varrone, Andrea; Hwang, Tzung-Jeng; Halldin, Christer; Farde, Lars

    2012-01-01

    Assessment of serotonin release in the living brain with positron emission tomography (PET) may have been hampered by the lack of suitable radioligands. We previously reported that fenfluramine caused a dose-dependent reduction in specific binding in monkeys using a classical displacement paradigm with bolus administration of [11C]AZ10419369. The aim of this study was to confirm our previous findings using an equilibrium approach in monkey. A total of 24 PET measurements were conducted using a bolus infusion protocol of [11C]AZ10419369 in three cynomolgus monkeys. Initial PET measurements were performed to assess suitable Kbol values. The fenfluramine effect on [11C]AZ10419369 binding was evaluated in a displacement and pretreatment paradigm. The effect of fenfluramine on [11C]AZ10419369 binding potential (BPND) was dose-dependent in the displacement paradigm and confirmed in the pretreatment paradigm. After pretreatment administration of fenfluramine (5.0 mg/kg), the mean BPND of the occipital cortex decreased by 39%, from 1.38±0.04 to 0.84±0.09. This study confirms that the new 5-HT1B receptor radioligand [11C]AZ10419369 is sensitive to fenfluramine-induced changes in endogenous serotonin levels in vivo. The more advanced methodology is suitable for exploring the sensitivity limit to serotonin release as measured using [11C]AZ10419369 and PET. PMID:22167236

  3. Increase of 20-HETE synthase after brain ischemia in rats revealed by PET study with 11C-labeled 20-HETE synthase-specific inhibitor

    PubMed Central

    Kawasaki, Toshiyuki; Marumo, Toshiyuki; Shirakami, Keiko; Mori, Tomoko; Doi, Hisashi; Suzuki, Masaaki; Watanabe, Yasuyoshi; Chaki, Shigeyuki; Nakazato, Atsuro; Ago, Yukio; Hashimoto, Hitoshi; Matsuda, Toshio; Baba, Akemichi; Onoe, Hirotaka

    2012-01-01

    20-Hydroxyeicosatetraenoic acid (20-HETE), an arachidonic acid metabolite known to be produced after cerebral ischemia, has been implicated in ischemic and reperfusion injury by mediating vasoconstriction. To develop a positron emission tomography (PET) probe for 20-HETE synthase imaging, which might be useful for monitoring vasoconstrictive processes in patients with brain ischemia, we synthesized a 11C-labeled specific 20-HETE synthase inhibitor, N′(4-dimethylaminohexyloxy)phenyl imidazole ([11C]TROA). Autoradiographic study showed that [11C]TROA has high-specific binding in the kidney and liver consistent with the previously reported distribution of 20-HETE synthase. Using transient middle cerebral artery occlusion in rats, PET study showed significant increases in the binding of [11C]TROA in the ipsilateral hemisphere of rat brains after 7 and 10 days, which was blocked by co-injection of excess amounts of TROA (10 mg/kg). The increased [11C]TROA binding on the ipsilateral side returned to basal levels within 14 days. In addition, quantitative real-time PCR revealed that increased expression of 20-HETE synthase was only shown on the ipsilateral side on day 7. These results indicate that [11C]TROA might be a useful PET probe for imaging of 20-HETE synthase in patients with cerebral ischemia. PMID:22669478

  4. A microPET comparison of the effects of etifoxine and diazepam on [(11)C]flumazenil uptake in rat brains.

    PubMed

    Bouillot, Caroline; Bonnefoi, Frédéric; Liger, François; Zimmer, Luc

    2016-01-26

    Using positron emission tomography (PET), the present study assessed the binding of [(11)C]flumazenil to GABA-A receptors in anesthetized rats following a single intravenous injection of an active dose of either etifoxine (25mg/kg) or diazepam (1mg/kg), which are both anxiolytic drugs. [(11)C]flumazenil binding was measured in five discrete brain structures, namely the caudate putamen, hippocampus, cerebellum, occipital cortex and parietal cortex. As expected, diazepam injection produced a significant decrease in [(11)C]flumazenil binding, which was interpreted as benzodiazepine GABA-A receptor occupancy, whereas etifoxine increased the binding of [(11)C]flumazenil. This first use of in vivo imaging after etifoxine administration revealed the activated binding pattern of [(11)C]flumazenil and highlighted the pharmacological differences between etifoxine and benzodiazepines. Using the same [(11)C]flumazenil radiotracer, PET neuroimaging could be applied to larger animals and, ultimately, to human subjects, thus providing new perspectives for better defining the molecular pharmacology of etifoxine. PMID:26644334

  5. Kinetic modeling of 11C-LY2795050, a novel antagonist radiotracer for PET imaging of the kappa opioid receptor in humans

    PubMed Central

    Naganawa, Mika; Zheng, Ming-Qiang; Nabulsi, Nabeel; Tomasi, Giampaolo; Henry, Shannan; Lin, Shu-Fei; Ropchan, Jim; Labaree, David; Tauscher, Johannes; Neumeister, Alexander; Carson, Richard E; Huang, Yiyun

    2014-01-01

    11C-LY2795050 is a novel kappa opioid receptor (KOR) antagonist tracer for positron emission tomography (PET) imaging. The purpose of this first-in-human study was to determine the optimal kinetic model for analysis of 11C-LY2795050 imaging data. Sixteen subjects underwent baseline scans and blocking scans after oral naltrexone. Compartmental modeling and multilinear analysis-1 (MA1) were applied using the arterial input functions. Two-tissue compartment model and MA1 were found to be the best models to provide reliable measures of binding parameters. The rank order of 11C-LY2795050 distribution volume (VT) matched the known regional KOR densities in the human brain. Blocking scans with naltrexone indicated no ideal reference region for 11C-LY2795050. Three methods for calculation of the nondisplaceable distribution volume (VND) were assessed: (1) individual VND estimated from naltrexone occupancy plots, (2) mean VND across subjects, and (3) a fixed fraction of cerebellum VT. Approach (3) produced the lowest intersubject variability in the calculation of binding potentials (BPND, BPF, and BPP). Therefore, binding potentials of 11C-LY2795050 can be determined if the specific binding fraction in the cerebellum is presumed to be unchanged by diseases and experimental conditions. In conclusion, results from the present study show the suitability of 11C-LY2795050 to image and quantify KOR in humans. PMID:25182664

  6. Kinetic modeling of (11)C-LY2795050, a novel antagonist radiotracer for PET imaging of the kappa opioid receptor in humans.

    PubMed

    Naganawa, Mika; Zheng, Ming-Qiang; Nabulsi, Nabeel; Tomasi, Giampaolo; Henry, Shannan; Lin, Shu-Fei; Ropchan, Jim; Labaree, David; Tauscher, Johannes; Neumeister, Alexander; Carson, Richard E; Huang, Yiyun

    2014-11-01

    (11)C-LY2795050 is a novel kappa opioid receptor (KOR) antagonist tracer for positron emission tomography (PET) imaging. The purpose of this first-in-human study was to determine the optimal kinetic model for analysis of (11)C-LY2795050 imaging data. Sixteen subjects underwent baseline scans and blocking scans after oral naltrexone. Compartmental modeling and multilinear analysis-1 (MA1) were applied using the arterial input functions. Two-tissue compartment model and MA1 were found to be the best models to provide reliable measures of binding parameters. The rank order of (11)C-LY2795050 distribution volume (VT) matched the known regional KOR densities in the human brain. Blocking scans with naltrexone indicated no ideal reference region for (11)C-LY2795050. Three methods for calculation of the nondisplaceable distribution volume (VND) were assessed: (1) individual VND estimated from naltrexone occupancy plots, (2) mean VND across subjects, and (3) a fixed fraction of cerebellum VT. Approach (3) produced the lowest intersubject variability in the calculation of binding potentials (BPND, BPF, and BPP). Therefore, binding potentials of (11)C-LY2795050 can be determined if the specific binding fraction in the cerebellum is presumed to be unchanged by diseases and experimental conditions. In conclusion, results from the present study show the suitability of (11)C-LY2795050 to image and quantify KOR in humans. PMID:25182664

  7. Advanced [18F]FDG and [11C]flumazenil PET analysis for individual outcome prediction after temporal lobe epilepsy surgery for hippocampal sclerosis

    PubMed Central

    Yankam Njiwa, J.; Gray, K.R.; Costes, N.; Mauguiere, F.; Ryvlin, P.; Hammers, A.

    2014-01-01

    Purpose We have previously shown that an imaging marker, increased periventricular [11C]flumazenil ([11C]FMZ) binding, is associated with failure to become seizure free (SF) after surgery for temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS). Here, we investigated whether increased preoperative periventricular white matter (WM) signal can be detected on clinical [18F]FDG-PET images. We then explored the potential of periventricular FDG WM increases, as well as whole-brain [11C]FMZ and [18F]FDG images analysed with random forest classifiers, for predicting surgery outcome. Methods Sixteen patients with MRI-defined HS had preoperative [18F]FDG and [11C]FMZ-PET. Fifty controls had [18F]FDG-PET (30), [11C]FMZ-PET (41), or both (21). Periventricular WM signal was analysed using Statistical Parametric Mapping (SPM8), and whole-brain image classification was performed using random forests implemented in R (http://www.r-project.org). Surgery outcome was predicted at the group and individual levels. Results At the group level, non-seizure free (NSF) versus SF patients had periventricular increases with both tracers. Against controls, NSF patients showed more prominent periventricular [11C]FMZ and [18F]FDG signal increases than SF patients. All differences were more marked for [11C]FMZ. For individuals, periventricular WM signal increases were seen at optimized thresholds in 5/8 NSF patients for both tracers. For SF patients, 1/8 showed periventricular signal increases for [11C]FMZ, and 4/8 for [18F]FDG. Hence, [18F]FDG had relatively poor sensitivity and specificity. Random forest classification accurately identified 7/8 SF and 7/8 NSF patients using [11C]FMZ images, but only 4/8 SF and 6/8 NSF patients with [18F]FDG. Conclusion This study extends the association between periventricular WM increases and NSF outcome to clinical [18F]FDG-PET, but only at the group level. Whole-brain random forest classification increases [11C]FMZ-PET's performance for predicting

  8. 15-O-Acetyl-3-O-benzoylcharaciol and helioscopinolide A, two diterpenes isolated from Euphorbia helioscopia suppress microglia activation.

    PubMed

    Wang, Hao; Liu, Yu; Zhang, Jingling; Xu, Jing; Cui, Chun-Ai; Guo, Yuanqiang; Jin, Da-Qing

    2016-01-26

    Microglia activation plays an important role in the pathogenesis of various neurodegenerative diseases by producing neurotoxic factors. In the present study, we found that two diterpenes isolated from Euphorbia helioscopia, 15-O-Acetyl-3-O-benzoylcharaciol and helioscopinolide A suppressed NO and PGE2 production by inhibition of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in lipopolysaccharide (LPS)-stimulated BV2 microglia cells. The diterpenes also inhibited the production of ROS and proinflammatory cytokines including interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α, the mechanism involved the NF-κB but not Akt and mitogen-activated protein kinase (MAPK) pathway. Moreover, the two diterpenes also attenuate microglia activation-mediated neuronal death. These results suggest that 15-O-Acetyl-3-O-benzoylcharaciol and helioscopinolide A may provide potential therapeutic strategy for various neuroinflammatory diseases. PMID:26683904

  9. Determination of Complex Structures from Powder Diffraction Data: The Crystal Structure of La 3Ti 5Al 15O 37

    NASA Astrophysics Data System (ADS)

    Morris, Russell E.; Owen, Jonathan J.; Stalick, Judith K.; Cheetham, Anthony K.

    1994-07-01

    The applicability of powder diffraction techniques to structure determination has improved substantially in recent times, but it has only been successfully utilized in the solution of relatively simple structures of up to 29 atoms in the asymmetric unit. The structure La 3Ti 5Al 15O 37, which has 60 atoms in the asymmetric unit, has been solved using a combination of synchrotron X-ray and neutron powder diffraction. This represents a considerable advance in the size of structure that has been solved using powder diffraction techniques. The structure of La 3Ti 5Al 15O 37 consists of small regions of simpler structure types in the La/Ti/Al/O system, interleaved to form a complex 3D network.

  10. Proton-transfer study of unbound ^19Ne states via ^2H(^18F,α+^15O)n

    NASA Astrophysics Data System (ADS)

    Brune, C. R.; Adekola, A.; Heinen, Z.; Hornish, M. J.; Massey, T. N.; Voinov, A. V.; Bardayan, D. W.; Blackmon, J. C.; Nesaraja, C. D.; Smith, M. S.; Chae, K.; Ma, Z.; Champagne, A. E.; Visser, D. W.; Jones, K. L.; Pain, S. D.; Thomas, J. S.; Greife, U.; Livesay, R.; Porter-Peden, M.; Sarazin, F.; Johnson, M.; Domizioli, C.; Kozub, R. L.; Moazen, B.

    2006-04-01

    The nuclear structure of ^19Ne near the proton threshold is of interest for understanding the rates of proton-induced reactions on ^18F in novae. The proton transfer reaction ^18F(d,n)^19Ne has been measured by bombarding a 720-μg/cm^2 CD2 target with a 150-MeV ^18F^9+ beam at ORNL's Holifield Radioactive Ion Beam Facility. The ^19Ne states of interest near the proton threshold decay by breakup into α+^15O which are detected in coincidence with position-sensitive E-δE Si telescopes. The reconstruction of the relative energy reveals the excited states of ^19Ne which are populated. The mirror reaction ^2H(^18F,α+^15N)p has been measured simultaneously. The implications for the ^18F(p,α)^15O reaction and ^19Ne-^19F mirror symmetry will be discussed.

  11. Microdialysis with radiometric monitoring of L-[β-11C]DOPA to assess dopaminergic metabolism: effect of inhibitors of L-amino acid decarboxylase, monoamine oxidase, and catechol-O-methyltransferase on rat striatal dialysate.

    PubMed

    Okada, Maki; Nakao, Ryuji; Hosoi, Rie; Zhang, Ming-Rong; Fukumura, Toshimitsu; Suzuki, Kazutoshi; Inoue, Osamu

    2011-01-01

    The catecholamine, dopamine (DA), is synthesized from 3,4-dihydroxy-L-phenylalanine (L-DOPA) by aromatic L-amino acid decarboxylase (AADC). Dopamine metabolism is regulated by monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT). To measure dopaminergic metabolism, we used microdialysis with radiometric detection to monitor L-[β-(11)C]DOPA metabolites in the extracellular space of the rat striatum. We also evaluated the effects of AADC, MAO, and COMT inhibitors on metabolite profiles. The major early species measured after administration of L-[β-(11)C]DOPA were [(11)C]3,4-dihydroxyphenylacetic acid ([(11)C]DOPAC) and [(11)C]homovanillic acid ([(11)C]HVA) in a 1:1 ratio, which shifted toward [(11)C]HVA with time. An AADC inhibitor increased the uptake of L-[β-(11)C]DOPA and L-3-O-methyl-[(11)C]DOPA and delayed the accumulation of [(11)C]DOPAC and [(11)C]HVA. The MAO and COMT inhibitors increased the production of [(11)C]3-methoxytyramine and [(11)C]DOPAC, respectively. These results reflect the L-DOPA metabolic pathway, suggesting that this method may be useful for assessing dopaminergic metabolism. PMID:20407462

  12. Lifetime measurement of the 6.79 MeV state in {sup 15}O with the AGATA demonstrator

    SciTech Connect

    Michelagnoli, C.; Depalo, R.; Ur, C. A.; Menegazzo, R.; Broggini, C.; Bazzacco, D.; Caciolli, A.; Farnea, E.; Lunardi, S.; Bemmerer, D.; Keeley, N.; Erhard, M.; Fueloep, Zs.; Gottardo, A.; Marta, M.; Mengoni, D.; Mijatovic, T.; Recchia, F.; Rossi-Alvarez, C.; Szuecs, T.; and others

    2012-11-12

    The preliminary results of a new direct measurement of the lifetime of the first excited 3/2{sup +} state in {sup 15}O are discussed. An accurate evaluation of this lifetime is of paramount importance for the determination of the cross section of the {sup 14}N(p,{gamma}){sup 15}O reaction, the slowest one in the CNO cycle, at the energies of the solar Gamow peak. The {sup 2}H({sup 14}N,{sup 15}O)n reaction in inverse kinematics at 32MeV beam energy (XTU Tandem, LNL) was used to populate the level of interest, which decays via a 6.79 MeV E1 gamma-ray transition to the ground state. Gamma rays were detected with 4 triple clusters of HPGe detectors of the AGATA Demonstrator array. The energy resolution and position sensitivity of this state-of-the-art gamma-ray spectrometer have been exploited to investigate the Doppler Shift Attenuation effect on the lineshape of the gamma-ray peak in the energy spectrum. The deconvolution of the lifetime effects from those due to the kinematics of the emitting nuclei has been performed using detailed Monte Carlo simulations of the gamma emission and detection. CDCC-CRC calculations for the nucleon transfer process have been used for this purpose and preliminary results are shown.

  13. Lifetime measurement of the 6.79 MeV state in 15O with the AGATA demonstrator

    NASA Astrophysics Data System (ADS)

    Michelagnoli, C.; Depalo, R.; Ur, C. A.; Menegazzo, R.; Broggini, C.; Bazzacco, D.; Caciolli, A.; Farnea, E.; Lunardi, S.; Bemmerer, D.; Keeley, N.; Erhard, M.; Fülöp, Zs.; Gottardo, A.; Marta, M.; Mengoni, D.; Mijatović, T.; Recchia, F.; Rossi-Alvarez, C.; Szücs, T.; Valiente-Dobon, J. J.

    2012-11-01

    The preliminary results of a new direct measurement of the lifetime of the first excited 3/2+ state in 15O are discussed. An accurate evaluation of this lifetime is of paramount importance for the determination of the cross section of the 14N(p,γ)15O reaction, the slowest one in the CNO cycle, at the energies of the solar Gamow peak. The 2H(14N,15O)n reaction in inverse kinematics at 32MeV beam energy (XTU Tandem, LNL) was used to populate the level of interest, which decays via a 6.79 MeV E1 gamma-ray transition to the ground state. Gamma rays were detected with 4 triple clusters of HPGe detectors of the AGATA Demonstrator array. The energy resolution and position sensitivity of this state-of-the-art gamma-ray spectrometer have been exploited to investigate the Doppler Shift Attenuation effect on the lineshape of the gamma-ray peak in the energy spectrum. The deconvolution of the lifetime effects from those due to the kinematics of the emitting nuclei has been performed using detailed Monte Carlo simulations of the gamma emission and detection. CDCC-CRC calculations for the nucleon transfer process have been used for this purpose and preliminary results are shown.

  14. Multicompartmental analysis of (/sup 11/C)-carfentanil binding to opiate receptors in humans measured by positron emission tomography

    SciTech Connect

    Frost, J.J.; Douglass, K.H.; Mayberg, H.S.; Dannals, R.F.; Links, J.M.; Wilson, A.A.; Ravert, H.T.; Crozier, W.C.; Wagner, H.N. Jr.

    1989-06-01

    (11C)-Carfentanil is a high affinity opiate agonist that can be used to localize mu opiate receptors in humans by positron emission tomography (PET). A four-compartment model was used to obtain quantitative estimates of rate constants for receptor association and dissociation. PET studies were performed in five normal subjects in the absence and presence of 1 mg/kg naloxone. Arterial plasma concentration of (11C)-carfentanil and its labeled metabolites were determined during each PET study. The value of k3/k4 = Bmax/kD was determined for each subject in the presence and absence of naloxone. There was a significant reduction in the value of k3/k4 from 3.4 +/- 0.92 to 0.26 +/- 0.13 in the thalamus (p less than 0.01) and from 1.8 +/- 0.33 to 0.16 +/- 0.065 in the frontal cortex (p less than 0.001). Mean values of frontal cortex/occipital cortex and thalamus/occipital cortex ratios were determined for the interval 35-70 min after injection when receptor binding is high relative to nonspecific binding. The relationship between the measured region/occipital cortex values and the corresponding values of k3/k4 in the presence and absence of naloxone was: regions/occipital cortex = 0.95 + 0.74 (k3/k4) with r = 0.98 (n = 20). Simulation studies also demonstrated a linear relationship between the thalamus/occipital cortex or frontal cortex/occipital cortex ratio and k3/k4 for less than twofold increases or decreases in k3/k4. Simulation studies in which thalamic blood flow was varied demonstrated no significant effect on the region/occipital cortex ratio at 35-70 min for a twofold increase or fourfold decrease in blood flow. Therefore, the region/occipital cortex ratio can be used to quantitate changes in k3/k4 when tracer kinetic modeling is not feasible.

  15. Evaluation of [11C]MRB for assessment of occupancy of norepinephrine transporters: Studies with atomoxetine in non-human primates

    PubMed Central

    Gallezot, Jean-Dominique; Weinzimmer, David; Nabulsi, Nabeel; Lin, Shu-Fei; Fowles, Krista; Sandiego, Christine; McCarthy, Timothy J.; Maguire, R. Paul; Carson, Richard E.; Ding, Yu-Shin

    2013-01-01

    [11C]MRB is one of the most promising radioligands used to measure brain norepinephrine transporters (NET) with positron emission tomography (PET). The objective of this study was to evaluate the suitability of [11C]MRB for drug occupancy studies of NET using atomoxetine (ATX), a NET uptake inhibitor used in the treatment of depression and attention-deficit hyperactivity disorder (ADHD). A second goal of the study was identification of a suitable reference region. Ten PET studies were performed in three anesthetized rhesus monkeys following an infusion of ATX or placebo. [11C]MRB arterial input functions and ATX plasma levels were also measured. A dose-dependent reduction of [11C]MRB volume of distribution was observed after correction for [11C]MRB plasma free fraction. ATX IC50 was estimated to be 31±10 ng/mL plasma. This corresponds to an effective dose (ED50) of 0.13 mg/kg, which is much lower than the therapeutic dose of ATX in ADHD (1.0–1.5 mg/kg). [11C]MRB binding potential BPND in the thalamus was estimated to be 1.8±0.3. Defining a reference region for a NET radiotracer is challenging due to the widespread and relatively uniform distribution of NET in the brain. Three regions were evaluated for use as reference region: caudate, putamen and occipital cortex. Caudate was found to be the most suitable for preclinical drug occupancy studies in rhesus monkeys. The IC50 estimate obtained using MRTM2 BPND without arterial blood sampling was 21±3 ng/mL (using caudate as the reference region). This study demonstrated that [11C]MRB is suitable for drug occupancy studies of NET. PMID:20869448

  16. Predictive efficacy of (11)C-PD153035 PET imaging for EGFR-tyrosine kinase inhibitor sensitivity in non-small cell lung cancer patients.

    PubMed

    Dai, Dong; Li, Xiao-Feng; Wang, Jian; Liu, Jian-Jing; Zhu, Yan-Jia; Zhang, Ying; Wang, Qi; Xu, Wen-Gui

    2016-02-15

    To determine the correlation of (11)C-PD153035 uptake with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) sensitivity and phosphorylated EGFR (pEGFR) expression in non-small cell lung cancer (NSCLC) cell lines with different EGFR-TKI sensitivities and in their corresponding xenografts. Four human NSCLC cell lines (HCC827, PC9, A549, and H1975) in the logarithmic phase were co-incubated with (11)C-PD153035 to analyze the correlation of (11)C-PD153035 uptake with EGFR-TKI sensitivity, and EGFR/pEGFR expression. Nude mice xenograft models bearing the four NSCLCs were prepared. (11)C-PD153035 positron-emission tomography (PET)-computed tomography (CT) was used to image the xenografts and observe radioactive uptakes. Correlation of the in vivo uptakes with EGFR-TKI sensitivity, and EGFR/pEGFR expression was analyzed. HCC827 and PC9 cells, which were highly sensitive to EGFR-TKIs, exhibited higher (11)C-PD153035 uptakes than the other cells. A549 cells, which were moderately sensitive to EGFR-TKIs, showed higher uptake than the EGFR-TKI-resistant H1975 cells, which showed little or no uptake. Radioactive uptakes were positively correlated with pEGFR expression in all cells. PET-CT showed that radioactivity was highest in HCC827 xenografts. The radioactivity in PC9 xenografts was higher than that in A549 and H1975 xenografts. Tumor vs. non-tumor tissue ratio values were positively correlated with pEGFR expression in HCC827 and PC9 xenografts, but not in A549 and H1975 xenografts. In conclusion, (11)C-PD153035 can serve as an EGFR imaging agent in vitro and in vivo, and predicts sensitivity to EGFR-TKIs. This will provide an experimental basis for clinical applications of (11)C-PD153035 and individualized NSCLC therapy. PMID:26334931

  17. A priori predictions of the rotational constants for HC13N, HC15N, C5O

    NASA Technical Reports Server (NTRS)

    DeFrees, D. J.; McLean, A. D.

    1989-01-01

    Ab initio molecular orbital theory is used to estimate the rotational constant for several carbon-chain molecules that are candidates for discovery in interstellar space. These estimated rotational constants can be used in laboratory or astronomical searches for the molecules. The rotational constant for HC13N is estimated to be 0.1073 +/- 0.0002 GHz and its dipole moment 5.4 D. The rotational constant for HC15N is estimated to be 0.0724 GHz, with a somewhat larger uncertainty. The rotational constant of C5O is estimated to be 1.360 +/- 2% GHz and its dipole moment 4.4. D.

  18. S-Factor measurement of the 12C(p,γ)13N reaction in inverse kinematics

    NASA Astrophysics Data System (ADS)

    Stöckel, Klaus; Reinhardt, Tobias P.; Akhmadaliev, S.; Bemmerer, D.; Gohl, St.; Reinicke, S.; Schmidt, K.; Serfling, M.; Szücs, T.; Takács, M. P.; Wagner, L.; Zuber, K.

    2015-05-01

    Hydrogen rich solid targets have been developed and produced to investigate the 12C(p, γ)13N reaction in inverse kinematics. The SRIM simulation software has been used to determine the parameters for ion implantation in various materials. Nuclear Resonant Reacton Analysis (NRRA) with the resonant reaction 15N(p, αγ)12C has been carried out to measure the hydrogen content of the produced targets. Measurements of the produced targets at the energy range from Ecm = 577 keV down to Ecm = 191 keV, were performed at the 3-MV Tandetron of Helmholtz-Zentrum Dresden-Rossendorf (HZDR).

  19. Ablating the aryl hydrocarbon receptor (AhR) in CD11c+ cells perturbs intestinal epithelium development and intestinal immunity

    PubMed Central

    Chng, Song Hui; Kundu, Parag; Dominguez-Brauer, Carmen; Teo, Wei Ling; Kawajiri, Kaname; Fujii-Kuriyama, Yoshiaki; Mak, Tak Wah; Pettersson, Sven

    2016-01-01

    Diet and microbiome derived indole derivatives are known to activate the ligand induced transcription factor, the Aryl hydrocarbon Receptor (AhR). While the current understanding of AhR biology has confirmed its role in mucosal lymphocytes, its function in intestinal antigen presenting cells (APCs) is poorly understood. Here, we report that Cre-mediated deletion of AhR in CD11c-expressing cells in C57/BL6 mice is associated with altered intestinal epithelial morphogenesis in vivo. Moreover, when co-cultured with AhR-deficient DCs ex vivo, intestinal organoids showed reduced SRY (sex determining region Y)-box 9 and increased Mucin 2 expression, which correlates with reduced Paneth cells and increased goblet cell differentiation, similar to the data obtained in vivo. Further, characterization of intestinal APC subsets, devoid of AhR, revealed an expression pattern associated with aberrant intrinsic Wnt pathway regulation. At a functional level, the loss of AhR in APCs resulted in a dysfunctional epithelial barrier, associated with a more aggressive chemically induced colitis compared to wild type animals. Our results are consistent with a model whereby the AhR signalling pathway may participate in the regulation of innate immunity through intestinal epithelium development and mucosal immunity. PMID:27068235

  20. Limitations of SRTM, Logan graphical method, and equilibrium analysis for measuring transient dopamine release with [(11)C]raclopride PET.

    PubMed

    Sullivan, Jenna M; Kim, Su Jin; Cosgrove, Kelly P; Morris, Evan D

    2013-01-01

    Conventional PET methods to estimate [(11)C]raclopride binding potential (BP ND) assume that endogenous dopamine concentration does not change during the scan time. However, this assumption is purposely violated in studies using pharmacological or behavioral stimuli to invoke acute dopamine release. When the assumption of steady-state dopamine is violated, conventional analysis methods may produce biased or even unusable estimates of BP ND. To illustrate this problem, we examined the effect of scan duration on ΔBP ND estimated by three common analysis methods (simplified reference tissue model, Logan graphical reference method, and equilibrium analysis) applied to simulated and experimental single-scan activation studies. The activation - dopamine release - in both the simulated and experimental studies was brief. Simulations showed ΔBP ND to be highly dependent on the window of data used to determine BP ND in the activation state. A similar pattern was seen in the data from human smoking studies. No such pattern of ΔBP ND dependence on the window of data used was apparent in simulations where dopamine was held constant. The dependence of ΔBP ND on the duration of data analyzed illustrates the inability of conventional methods to reliably quantify short-lived increases in endogenous dopamine. PMID:23638336

  1. First direct measurement of the 11C (α ,p )14N stellar reaction by an extended thick-target method

    NASA Astrophysics Data System (ADS)

    Hayakawa, S.; Kubono, S.; Kahl, D.; Yamaguchi, H.; Binh, D. N.; Hashimoto, T.; Wakabayashi, Y.; He, J. J.; Iwasa, N.; Kato, S.; Komatsubara, T.; Kwon, Y. K.; Teranishi, T.

    2016-06-01

    The 11C(α,p ) 14N reaction is an important α -induced reaction competing with β -limited hydrogen-burning processes in high-temperature explosive stars. We directly measured its reaction cross sections both for the ground-state transition (α ,p0) and the excited-state transitions (α ,p1) and (α ,p2) at relevant stellar energies 1.3-4.5 MeV by an extended thick-target method featuring time of flight for the first time. We revised the reaction rate by numerical integration including the (α ,p1) and (α ,p2) contributions and also low-lying resonances of (α ,p0) using both the present and the previous experimental data which were totally neglected in the previous compilation works. The present total reaction rate lies between the previous (α ,p0) rate and the total rate of the Hauser-Feshbach statistical model calculation, which is consistent with the relevant explosive hydrogen-burning scenarios such as the ν p process.

  2. D2 dopamine receptors in neuroleptic-naive schizophrenic patients. A positron emission tomography study with (11C)raclopride

    SciTech Connect

    Farde, L.; Wiesel, F.A.; Stone-Elander, S.; Halldin, C.; Nordstroem, A.L.H.; Hall, H.; Sedvall, G. )

    1990-03-01

    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 ({sup 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.

  3. N-(/sup 11/C)-methyl-p-substituted phentermine analogs as potential brain blood flow agents for positron tomography

    SciTech Connect

    Kizuka, H.; Elmaleh, D.R.; Boudreaux, G.J.; Anderton, K.D.; Strauss, H.W.; Ackerman, R.H.; Brownell, G.L.

    1984-01-01

    The addition of a methyl group to the ..cap alpha..-position of amphetamine increases both the lipophilicity of the agent and its resistance to metabolism by monoamine oxidase. In addition, since tritium substituted phenteramine analog studies suggested that the p-halo phentermines had a greater concentration in the brain and prolonged retention time, the authors evaluated the biological behavior of positron labeled ..cap alpha..-methylamphetamine (phenteramine) in rats, dogs and monkeys. The N-(/sup 11/C) methyl analogs of p-chloro (I) and p-fluoro (II) phentermines were prepared by methylation of their primary amines using /sup 11/Ch/sub 3/I. Biodistribution studies in rats shows brain uptake is in the range of 1% dose/gr at 5 and 15 min for both agents. The activity in blood and eyes is low. Sequential images of the dogs' brain over 1 hour revealed a clearance of <15%. Images of the monkey brain were also obtained using a MGH positron camera PCR-I.

  4. Dynamics of CD11c+ dendritic cell subsets in lymph nodes draining the site of intestinal nematode infection

    PubMed Central

    Balic, Adam; Smith, Katherine A.; Harcus, Yvonne; Maizels, Rick M.

    2009-01-01

    Helminth parasites drive dominant Th2 responses through an as yet unidentified pathway. We have previously shown that the rodent gastrointestinal nematode Nippostrongylus brasiliensis secretes products which selectively activate in vitro-derived dendritic cells to induce Th2 responses on in vivo transfer. We now show that, during active infection with this parasite, the draining mesenteric lymph node dendritic cell population is altered significantly. Although there is substantial expansion of DC numbers during infection, the CD86hi-CD8αint-CD11b− subset is markedly diminished, and expression levels of CD40, CD86 and CD103 are reduced. Notably, the reduced frequency of CD8αint DCs is evident only in those mesenteric lymph nodes draining the anterior site of infestation. In infections with the longer lived Heligmosomoides polygyrus, the proportion of CD8αint DCs in the MLNC falls to below 10% of total DC numbers by 35 days post-infection. Further, infection alters TLR responsiveness, as IL-12 production (as measured by ex vivo intracellular staining of CD11c+ DCs) in response to LPS stimulation is reduced, while IL-6, TNF-α and in particular, IL-10 all increase following infection with either nematode parasite. These changes suggest the possibility that helminth parasites modulate gastrointestinal immunity both by inhibiting migration of CD8αint DCs to the draining lymph nodes, and modifying DC responsiveness in a manner which favours a Th2 outcome. PMID:19766674

  5. Ablating the aryl hydrocarbon receptor (AhR) in CD11c+ cells perturbs intestinal epithelium development and intestinal immunity.

    PubMed

    Chng, Song Hui; Kundu, Parag; Dominguez-Brauer, Carmen; Teo, Wei Ling; Kawajiri, Kaname; Fujii-Kuriyama, Yoshiaki; Mak, Tak Wah; Pettersson, Sven

    2016-01-01

    Diet and microbiome derived indole derivatives are known to activate the ligand induced transcription factor, the Aryl hydrocarbon Receptor (AhR). While the current understanding of AhR biology has confirmed its role in mucosal lymphocytes, its function in intestinal antigen presenting cells (APCs) is poorly understood. Here, we report that Cre-mediated deletion of AhR in CD11c-expressing cells in C57/BL6 mice is associated with altered intestinal epithelial morphogenesis in vivo. Moreover, when co-cultured with AhR-deficient DCs ex vivo, intestinal organoids showed reduced SRY (sex determining region Y)-box 9 and increased Mucin 2 expression, which correlates with reduced Paneth cells and increased goblet cell differentiation, similar to the data obtained in vivo. Further, characterization of intestinal APC subsets, devoid of AhR, revealed an expression pattern associated with aberrant intrinsic Wnt pathway regulation. At a functional level, the loss of AhR in APCs resulted in a dysfunctional epithelial barrier, associated with a more aggressive chemically induced colitis compared to wild type animals. Our results are consistent with a model whereby the AhR signalling pathway may participate in the regulation of innate immunity through intestinal epithelium development and mucosal immunity. PMID:27068235

  6. 11C-Methionine-PET: A novel and sensitive tool for monitoring of early response to treatment in multiple myeloma

    PubMed Central

    Albert, Christa; Herrmann, Ken; Jörg, Gerhard; Samnick, Samuel; Einsele, Herrmann; Knop, Stefan; Buck, Andreas K.

    2015-01-01

    Multiple myeloma (MM) remains an essentially incurable hematologic malignancy. However, new treatment modalities and novel drugs have been introduced and thus additional tools for therapy monitoring are increasingly needed. Therefore, we evaluated the radiotracers 11C-Methionine (paraprotein-biosynthesis) and 18F-FDG (glucose-utilization) for monitoring response to anti-myeloma-therapy and outcome prediction. Influence of proteasome-inhibition on radiotracer-uptake of different MM cell-lines and patient-derived CD138+ plasma cells was analyzed and related to tumor-biology. Mice xenotransplanted with MM.1S tumors underwent MET- and FDG-μPET. Tumor-to-background ratios before and after 24 h, 8 and 15 days treatment with bortezomib were correlated to survival. Treatment reduced both MET and FDG uptake; changes in tracer-retention correlated with a switch from high to low CD138-expression. In xenotransplanted mice, MET-uptake significantly decreased by 30–79% as early as 24 h after bortezomib injection. No significant differences were detected thus early with FDG. This finding was confirmed in patient-derived MM cells. Importantly, early reduction of MET- but not FDG-uptake correlated with improved survival and reduced tumor burden in mice. Our results suggest that MET is superior to FDG in very early assessment of response to anti-myeloma-therapy. Early changes in MET-uptake have predictive potential regarding response and survival. MET-PET holds promise to individualize therapies in MM in future. PMID:25762625

  7. CD11c(+) monocyte/macrophages promote chronic Helicobacter hepaticus-induced intestinal inflammation through the production of IL-23.

    PubMed

    Arnold, I C; Mathisen, S; Schulthess, J; Danne, C; Hegazy, A N; Powrie, F

    2016-03-01

    In inflammatory bowel diseases, a breakdown in host microbial interactions accompanies sustained activation of immune cells in the gut. Functional studies suggest a key role for interleukin-23 (IL-23) in orchestrating intestinal inflammation. IL-23 can be produced by various mononuclear phagocytes (MNPs) following acute microbial stimulation, but little is known about the key cellular sources of IL-23 that drive chronic intestinal inflammation. Here we have addressed this question using a physiological model of bacteria-driven colitis. By combining conditional gene ablation and gene expression profiling, we found that IL-23 production by CD11c(+) MNPs was essential to trigger intestinal immunopathology and identified MHCII(+) monocytes and macrophages as the major source of IL-23. Expression of IL-23 by monocytes was acquired during their differentiation in the intestine and correlated with the expression of major histocompatibility complex class II (MHCII) and CD64. In contrast, Batf3-dependent CD103(+) CD11b(-) dendritic cells were dispensable for bacteria-induced colitis in this model. These studies reinforce the pathogenic role of monocytes in dysregulated responses to intestinal bacteria and identify production of IL-23 as a key component of this response. Further understanding of the functional sources of IL-23 in diverse forms of intestinal inflammation may lead to novel therapeutic strategies aimed at interrupting IL-23-driven immune pathology. PMID:26242598

  8. A comparison study of 11C-methionine and 18F-fluorodeoxyglucose positron emission tomography-computed tomography scans in evaluation of patients with recurrent brain tumors

    PubMed Central

    Sharma, Rajnish; D’Souza, Maria; Jaimini, Abhinav; Hazari, Puja Panwar; Saw, Sanjeev; Pandey, Santosh; Singh, Dinesh; Solanki, Yachna; Kumar, Nitin; Mishra, Anil K.; Mondal, Anupam

    2016-01-01

    Introduction: 11C-methonine ([11C]-MET) positron emission tomography-computed tomography (PET-CT) is a well-established technique for evaluation of tumor for diagnosis and treatment planning in neurooncology. [11C]-MET reflects amino acid transport and has been shown to be more sensitive than magnetic resonance imaging (MRI) in stereotactic biopsy planning. This study compared fluorodeoxyglucose (FDG) PET-CT and MET PET-CT in the detection of various brain tumors. Materials and Methods: Sixty-four subjects of brain tumor treated by surgery, chemotherapy, and/or radiotherapy were subjected to [18F]-FDG, [11C]-MET, and MRI scan. The lesion was analyzed semiquantitatively using tumor to normal contralateral ratio. The diagnosis was confirmed by surgery, stereotactic biopsy, clinical follow-up, MRI, or CT scans. Results: Tumor recurrence was found in 5 out of 22 patients on [F-18] FDG scan while [11C]-MET was able to detect recurrence in 18 out of 22 patients in low-grade gliomas. Two of these patients were false positive for the presence of recurrence of tumor and later found to be harboring necrosis. Among oligodendroglioma, medulloblastoma and high-grade glioma out of 42 patients 39 were found to be concordant MET and FDG scans. On semiquantitative analysis, mean T/NT ratio was found to be 2.96 ± 0.94 for lesions positive for recurrence of tumors and 1.18 ± 0.74 for lesions negative for recurrence of tumor on [11C]-MET scan. While the ratio for FDG scan on semiquantitative analysis was found to be 2.05 ± 1.04 for lesions positive for recurrence of tumors and 0.52 ± 0.15 for lesions negative for recurrence of tumors. Conclusion: The study highlight that [11C]-MET is superior to [18F]-FDG PET scans to detect recurrence in low-grade glioma. A cut-off value of target to nontarget value of 1.47 is a useful parameter to distinguish benign from malignant lesion on an [11C]-MET Scan. Both [18F]-FDG and [11C]-MET scans were found to be useful in high-grade astrocytoma

  9. Brain and Whole-Body Imaging in Rhesus Monkeys of 11C-NOP-1A, a Promising PET Radioligand for Nociceptin/Orphanin FQ Peptide Receptors

    PubMed Central

    Kimura, Yasuyuki; Fujita, Masahiro; Hong, Jinsoo; Lohith, Talakad G.; Gladding, Robert L.; Zoghbi, Sami S.; Tauscher, Johannes A.; Goebl, Nancy; Rash, Karen S.; Chen, Zhaogen; Pedregal, Concepcion; Barth, Vanessa N.; Pike, Victor W.; Innis, Robert B.

    2011-01-01

    Our laboratory developed (S)-3-(2′-fluoro-6′,7′-dihydrospiro [piperidine-4,4′-thieno[3,2-c]pyran]-1-yl)-2-(2-fluorobenzyl)-N-methylpropanamide (11C-NOP-1A), a new radioligand for the nociceptin/orphanin FQ peptide (NOP) receptor, with high affinity (Ki, 0.15 nM) and appropriate lipophilicity (measured logD, 3.4) for PET brain imaging. Here, we assessed the utility of 11C-NOP-1A for quantifying NOP receptors in the monkey brain and estimated the radiation safety profile of this radioligand based on its biodistribution in monkeys. Methods Baseline and blocking PET scans were acquired from head to thigh for 3 rhesus monkeys for approximately 120 min after 11C-NOP-1A injection. These 6 PET scans were used to quantify NOP receptors in the brain and to estimate radiation exposure to organs of the body. In the blocked scans, a selective nonradioactive NOP receptor antagonist (SB-612111; 1 mg/kg intravenously) was administered before 11C-NOP-1A. In all scans, arterial blood was sampled to measure the parent radioligand 11C-NOP-1A. Distribution volume (VT; a measure of receptor density) was calculated with a compartment model using brain and arterial plasma data. Radiation-absorbed doses were calculated using the MIRD Committee scheme. Results After 11C-NOP-1A injection, peak uptake of radioactivity in the brain had a high concentration (~5 standardized uptake value), occurred early (~12 min), and thereafter washed out quickly. VT (mL cm−3) was highest in the neocortex (~20) and lowest in hypothalamus and cerebellum (~13). SB-612111 blocked approximately 50%–70% of uptake and reduced VT in all brain regions to approximately 7 mL cm−3. Distribution was well identified within 60 min of injection and stable for the remaining 60 min, consistent with only parent radioligand and not radiometabolites entering the brain. Whole-body scans confirmed that the brain had specific (i.e., displaceable) binding but could not detect specific binding in peripheral organs. The

  10. Estimating Endogenous Dopamine Levels at D2 and D3 Receptors in Humans using the Agonist Radiotracer [11C]-(+)-PHNO

    PubMed Central

    Caravaggio, Fernando; Nakajima, Shinichiro; Borlido, Carol; Remington, Gary; Gerretsen, Philip; Wilson, Alan; Houle, Sylvain; Menon, Mahesh; Mamo, David; Graff-Guerrero, Ariel

    2014-01-01

    Using positron emission tomography (PET) and an acute dopamine depletion challenge it is possible to estimate endogenous dopamine levels occupying dopamine D2/3 receptors (D2/3R) in humans in vivo. Our group has developed [11C]-(+)-PHNO, the first agonist radiotracer with preferential in vivo affinity for D3R. Thus, the use of [11C]-(+)-PHNO offers the novel possibility of (i) estimating in vivo endogenous dopamine levels at D2/3R using an agonist radiotracer, and (ii) estimating endogenous dopamine levels at D3R in extrastriatal regions such as the substantia nigra, hypothalamus, and ventral pallidum. Ten healthy participants underwent a [11C]-(+)-PHNO PET scan under baseline conditions and another under acute endogenous dopamine depletion achieved via oral administration of alpha-methyl-para-tyrosine (64 mg/kg). [11C]-(+)-PHNO binding was sensitive to acute dopamine depletion, allowing in vivo estimates of endogenous dopamine in D2R-rich regions (caudate and putamen), mixed D2/3R-rich regions (ventral striatum and globus pallidus), and extrastriatal D3R-rich regions (hypothalamus and ventral pallidum). Dopamine depletion decreased self-reported vigor, which was correlated with the reduction in dopamine levels in the globus pallidus. [11C]-(+)-PHNO is a suitable radiotracer for use in estimating endogenous dopamine levels at D2R and D3R in neuropsychiatric populations. PMID:24874713

  11. Quantification of [(11)C]PIB PET for imaging myelin in the human brain: a test-retest reproducibility study in high-resolution research tomography.

    PubMed

    Veronese, Mattia; Bodini, Benedetta; García-Lorenzo, Daniel; Battaglini, Marco; Bongarzone, Salvatore; Comtat, Claude; Bottlaender, Michel; Stankoff, Bruno; Turkheimer, Federico E

    2015-11-01

    An accurate in vivo measure of myelin content is essential to deepen our insight into the mechanisms underlying demyelinating and dysmyelinating neurological disorders, and to evaluate the effects of emerging remyelinating treatments. Recently [(11)C]PIB, a positron emission tomography (PET) tracer originally conceived as a beta-amyloid marker, has been shown to be sensitive to myelin changes in preclinical models and humans. In this work, we propose a reference-region methodology for the voxelwise quantification of brain white-matter (WM) binding for [(11)C]PIB. This methodology consists of a supervised procedure for the automatic extraction of a reference region and the application of the Logan graphical method to generate distribution volume ratio (DVR) maps. This approach was assessed on a test-retest group of 10 healthy volunteers using a high-resolution PET tomograph. The [(11)C]PIB PET tracer binding was shown to be up to 23% higher in WM compared with gray matter, depending on the image reconstruction. The DVR estimates were characterized by high reliability (outliers <1%) and reproducibility (intraclass correlation coefficient (ICC) >0.95). [(11)C]PIB parametric maps were also found to be significantly correlated (R(2)>0.50) to mRNA expressions of the most represented proteins in the myelin sheath. On the contrary, no correlation was found between [(11)C]PIB imaging and nonmyelin-associated proteins. PMID:26058700

  12. Manipulation of [11C]-5-hydroxytryptophan and 6-[18F]fluoro-3,4-dihydroxy-L-phenylalanine accumulation in neuroendocrine tumor cells.

    PubMed

    Neels, Oliver C; Koopmans, Klaas P; Jager, Pieter L; Vercauteren, Laya; van Waarde, Aren; Doorduin, Janine; Timmer-Bosscha, Hetty; Brouwers, Adrienne H; de Vries, Elisabeth G E; Dierckx, Rudi A J O; Kema, Ido P; Elsinga, Philip H

    2008-09-01

    [(11)C]-5-Hydroxytryptophan ([(11)C]HTP) and 6-[(18)F]fluoro-3,4-dihydroxy-l-phenylalanine ([(18)F]FDOPA) are used to image neuroendocrine tumors with positron emission tomography. The precise mechanism by which these tracers accumulate in tumor cells is unknown. We aimed to study tracer uptake via large amino acid transporters, peripheral decarboxylation (inhibited by carbidopa), and intracellular breakdown by monoamine oxidase (MAO). [(11)C]HTP and [(18)F]FDOPA tracer accumulation was assessed in a human neuroendocrine tumor cell line, BON. The carbidopa experiments were done in a tumor-bearing mouse model. Intracellular [(11)C]HTP accumulation was 2-fold higher than that of [(18)F]FDOPA. Cellular transport of both tracers was inhibited by amino-2-norbornanecarboxylic acid. The MAO inhibitors clorgyline and pargyline increased tracer accumulation in vitro. Carbidopa did not influence tracer accumulation in vitro but improved tumor imaging in vivo. Despite lower accumulation in vitro, visualization of [(18)F]FDOPA is superior to [(11)C]HTP in the neuroendocrine pancreatic tumor xenograft model. This could be a consequence of the serotonin saturation of BON cells in the in vivo model. PMID:18757434

  13. Characterisation of [11C]PR04.MZ in Papio anubis baboon: A selective high-affinity radioligand for quantitative imaging of the dopamine transporter

    SciTech Connect

    Riss P. J.; Fowler J.; Riss, P.J.; Hooker, J.M.; Shea, C.; Xu, Y.; Carter, P.; Warner, D.; Ferrari V.; Kim, S.W.; Aigbirhio, F.I.; Fowler, J.S.; Roesch, F.

    2011-10-25

    N-(4-fluorobut-2-yn-1-yl)-2{beta}-carbomethoxy-3{beta}-(4{prime}-tolyl)nortropane (PR04.MZ, 1) is a PET radioligand for the non-invasive exploration of the function of the cerebral dopamine transporter (DAT). A reliable automated process for routine production of the carbon-11 labelled analogue [{sup 11}C]PR04.MZ ([{sup 11}C]-1) has been developed using GMP compliant equipment. An adult female Papioanubis baboon was studied using a test-retest protocol with [{sup 11}C]-1 in order to assess test-retest reliability, metabolism and CNS distribution profile of the tracer in non-human primates. Blood sampling was performed throughout the studies for determination of the free fraction in plasma (fP), plasma input functions and metabolic degradation of the radiotracer [{sup 11}C]-1. Time-activity curves were derived for the putamen, the caudate nucleus, the ventral striatum, the midbrain and the cerebellum. Distribution volumes (VT) and non-displaceable binding potentials (BPND) for various brain regions and the blood were obtained from kinetic modelling. [{sup 11}C]-1 shows promising results as aselective marker of the presynaptic dopamine transporter. With the reliable visualisation of the extra-striatal dopaminergic neurons and no indication on labelled metabolites, the tracer provides excellent potential for translation into man.

  14. Radiosynthesis of [11C]SNAP-7941—the first PET-tracer for the melanin concentrating hormone receptor 1 (MCHR1)

    PubMed Central

    Philippe, C.; Schirmer, E.; Mitterhauser, M.; Shanab, K.; Lanzenberger, R.; Karanikas, G.; Spreitzer, H.; Viernstein, H.; Wadsak, W.

    2012-01-01

    The melanin concentrating hormone (MCH) system is a new target to treat human disorders. Our aim was the preparation of the first PET-tracer for the MCHR1. [11C]SNAP-7941 is a carbon-11 labeled analog of the published MCHR1 antagonist SNAP-7941. The optimum reaction conditions were 2 min reaction time, ≤25 °C reaction temperature, and 2 mg/mL precursor (SNAP-acid) in acetonitrile, using [11C]CH3OTf as methylation agent. [11C]SNAP-7941 was prepared in a reliable and feasible manner with high radiochemical yields (2.9±1.6 GBq; 11.5±6.4% EOB, n=15). PMID:22858577

  15. Parameter evaluation and fully-automated radiosynthesis of [(11)C]harmine for imaging of MAO-A for clinical trials.

    PubMed

    Philippe, C; Zeilinger, M; Mitterhauser, M; Dumanic, M; Lanzenberger, R; Hacker, M; Wadsak, W

    2015-03-01

    The aim of the present study was the evaluation and automation of the radiosynthesis of [(11)C]harmine for clinical trials. The following parameters have been investigated: amount of base, precursor concentration, solvent, reaction temperature and time. The optimum reaction conditions were determined to be 2-3mg/mL precursor activated with 1eq. 5M NaOH in DMSO, 80°C reaction temperature and 2min reaction time. Under these conditions 6.1±1GBq (51.0±11% based on [(11)C]CH3I, corrected for decay) of [(11)C]harmine (n=72) were obtained. The specific activity was 101.32±28.2GBq/µmol (at EOS). All quality control parameters were in accordance with the standards for parenteral human application. Due to its reliability and high yields, this fully-automated synthesis method can be used as routine set-up. PMID:25594603

  16. The Gene Expression Profile of CD11c+CD8α− Dendritic Cells in the Pre-Diabetic Pancreas of the NOD Mouse

    PubMed Central

    Beumer, Wouter; Welzen-Coppens, Jojanneke M. C.; van Helden-Meeuwsen, Cornelia G.; Gibney, Sinead M.; Drexhage, Hemmo A.; Versnel, Marjan A.

    2014-01-01

    Two major dendritic cell (DC) subsets have been described in the pancreas of mice: The CD11c+CD8α− DCs (strong CD4+ T cell proliferation inducers) and the CD8α+CD103+ DCs (T cell apoptosis inducers). Here we analyzed the larger subset of CD11c+CD8α− DCs isolated from the pancreas of pre-diabetic NOD mice for genome-wide gene expression (validated by Q-PCR) to elucidate abnormalities in underlying gene expression networks. CD11c+CD8α− DCs were isolated from 5 week old NOD and control C57BL/6 pancreas. The steady state pancreatic NOD CD11c+CD8α− DCs showed a reduced expression of several gene networks important for the prime functions of these cells, i.e. for cell renewal, immune tolerance induction, migration and for the provision of growth factors including those for beta cell regeneration. A functional in vivo BrdU incorporation test showed the reduced proliferation of steady state pancreatic DC. The reduced expression of tolerance induction genes (CD200R, CCR5 and CD24) was supported on the protein level by flow cytometry. Also previously published functional tests on maturation, immune stimulation and migration confirm the molecular deficits of NOD steady state DC. Despite these deficiencies NOD pancreas CD11c+CD8α− DCs showed a hyperreactivity to LPS, which resulted in an enhanced pro-inflammatory state characterized by a gene profile of an enhanced expression of a number of classical inflammatory cytokines. The enhanced up-regulation of inflammatory genes was supported by the in vitro cytokine production profile of the DCs. In conclusion, our data show that NOD pancreatic CD11c+CD8α− DCs show various deficiencies in steady state, while hyperreactive when encountering a danger signal such as LPS. PMID:25166904

  17. Amphetamine Decreases α2C-Adrenoceptor Binding of [11C]ORM-13070: A PET Study in the Primate Brain

    PubMed Central

    Hughes, Zoë A; Haaparanta-Solin, Merja; Stepanov, Vladimir; Nakao, Ryuji; Varnäs, Katarina; Varrone, Andrea; Arponen, Eveliina; Marjamäki, Päivi; Pohjanoksa, Katariina; Vuorilehto, Lauri; Babalola, Phebian A; Solin, Olof; Grimwood, Sarah; Sallinen, Jukka; Farde, Lars; Scheinin, Mika; Halldin, Christer

    2015-01-01

    Background: The neurotransmitter norepinephrine has been implicated in psychiatric and neurodegenerative disorders. Examination of synaptic norepinephrine concentrations in the living brain may be possible with positron emission tomography (PET), but has been hampered by the lack of suitable radioligands. Methods: We explored the use of the novel α2C-adrenoceptor antagonist PET tracer [11C]ORM-13070 for measurement of amphetamine-induced changes in synaptic norepinephrine. The effect of amphetamine on [11C]ORM-13070 binding was evaluated ex vivo in rat brain sections and in vivo with PET imaging in monkeys. Results: Microdialysis experiments confirmed amphetamine-induced elevations in rat striatal norepinephrine and dopamine concentrations. Regional [11C]ORM-13070 receptor binding was high in the striatum and low in the cerebellum. After injection of [11C]ORM-13070 in rats, mean striatal specific binding ratios, determined using cerebellum as a reference region, were 1.4±0.3 after vehicle pretreatment and 1.2±0.2 after amphetamine administration (0.3mg/kg, subcutaneous). Injection of [11C]ORM-13070 in non-human primates resulted in mean striatal binding potential (BP ND) estimates of 0.65±0.12 at baseline. Intravenous administration of amphetamine (0.5 and 1.0mg/kg, i.v.) reduced BP ND values by 31–50%. Amphetamine (0.3mg/kg, subcutaneous) increased extracellular norepinephrine (by 400%) and dopamine (by 270%) in rat striata. Conclusions: Together, these results indicate that [11C]ORM-13070 may be a useful tool for evaluation of synaptic norepinephrine concentrations in vivo. Future studies are required to further understand a potential contribution of dopamine to the amphetamine-induced effect. PMID:25522417

  18. [11C]MADAM Used as a Model for Understanding the Radiometabolism of Diphenyl Sulfide Radioligands for Positron Emission Tomography (PET)

    PubMed Central

    Gourand, Fabienne; Amini, Nahid; Jia, Zhisheng; Stone-Elander, Sharon; Guilloteau, Denis; Barré, Louisa; Halldin, Christer

    2015-01-01

    In quantitative PET measurements, the analysis of radiometabolites in plasma is essential for determining the exact arterial input function. Diphenyl sulfide compounds are promising PET and SPECT radioligands for in vivo quantification of the serotonin transporter (SERT) and it is therefore important to investigate their radiometabolism. We have chosen to explore the radiometabolic profile of [11C]MADAM, one of these radioligands widely used for in vivo PET-SERT studies. The metabolism of [11C]MADAM/MADAM was investigated using rat and human liver microsomes (RLM and HLM) in combination with radio-HPLC or UHPLC/Q-ToF-MS for their identification. The effect of carrier on the radiometabolic rate of the radioligand [11C]MADAM in vitro and in vivo was examined by radio-HPLC. RLM and HLM incubations were carried out at two different carrier concentrations of 1 and 10 μM. Urine samples after perfusion of [11C]MADAM/MADAM in rats were also analysed by radio-HPLC. Analysis by UHPLC/Q-ToF-MS identified the metabolites produced in vitro to be results of N-demethylation, S-oxidation and benzylic hydroxylation. The presence of carrier greatly affected the radiometabolism rate of [11C]MADAM in both RLM/HLM experiments and in vivo rat studies. The good concordance between the results predicted by RLM and HLM experiments and the in vivo data obtained in rat studies indicate that the kinetics of the radiometabolism of the radioligand [11C]MADAM is dose-dependent. This issue needs to be addressed when the diarylsulfide class of compounds are used in PET quantifications of SERT. PMID:26367261

  19. Fully automated preparation of [11C]choline and [18F]fluoromethylcholine using TracerLab synthesis modules and facilitated quality control using analytical HPLC.

    PubMed

    Shao, Xia; Hockley, Brian G; Hoareau, Raphaël; Schnau, Paul L; Scott, Peter J H

    2011-02-01

    Modifications of a GE TracerLab FX(C-Pro), which can be implemented for solid-phase [(11)C]methylation are described. The simplified procedure for synthesis of [(11)C]choline uses a single Sep-Pak CM-Light cation-exchange cartridge for both solid-supported reaction and purification. Compared with the commonly used two Sep-Pak method, the low back-pressure of this Sep-Pak enables efficient and reliable production of [(11)C]choline using a TracerLab FX(C-Pro) without requirement for any gas pressure adjustment. Typical radiochemical yields (RCY) are >60%, radiochemical purity (RCP) is 99.9% and levels of residual precursor in the final product, which may inhibit the uptake of [(11)C]choline, are reduced to 1 μg/mL. Similarly, modification of a GE TracerLab FX(FN) is reported which enables gas-phase production of [(18)F]fluoromethylcholine, suitable for pre-clinical use, (in 4-6% RCY and >99.7% RCP) using a related Sep-Pak method. These modifications can be utilized for solid-phase [(11)C]methylation and [(18)F]fluoromethylation of other radiotracers, and allow straightforward switching to other module configurations for solution-phase radiochemistry or loop chemistry. In addition, we report a convenient HPLC ion chromatography method, which can monitor residual precursor and the radiochemical purity of product at the same time, providing highly efficient quality control for routine clinical application. The reported HPLC method is appropriate for analysis of doses of both [(11)C]choline and [(18)F]fluoromethylcholine, and eliminates the need for a GC method to determine residual precursor levels. PMID:21115355

  20. Visualization of angiogenesis during cancer development in the polyoma middle T breast cancer model: molecular imaging with (R)-[11C]PAQ

    PubMed Central

    2014-01-01

    Background Vascular endothelial growth factor receptor 2 (VEGFR2) is a crucial mediator of tumour angiogenesis. High expression levels of the receptor have been correlated to poor prognosis in cancer patients. Reliable imaging biomarkers for stratifying patients for anti-angiogenic therapy could therefore be valuable for increasing treatment success rates. The aim of this study was to investigate the pharmacokinetics and angiogenesis imaging abilities of the VEGFR2-targeting positron emission tomography (PET) tracer (R)-[11C]PAQ. Methods (R)-[11C]PAQ was evaluated in the mouse mammary tumour virus-polyoma middle T (MMTV-PyMT) model of metastatic breast cancer. Mice at different stages of disease progression were imaged with (R)-[11C]PAQ PET, and results were compared to those obtained with [18 F]FDG PET and magnetic resonance imaging. (R)-[11C]PAQ uptake levels were also compared to ex vivo immunofluorescence analysis of tumour- and angiogenesis-specific biomarkers. Additional pharmacokinetic studies were performed in rat and mouse. Results A heterogeneous uptake of (R)-[11C]PAQ was observed in the tumorous mammary glands. Ex vivo analysis confirmed the co-localization of areas with high radioactivity uptake and areas with elevated levels of VEGFR2. In some animals, a high focal uptake was observed in the lungs. The lung uptake correlated to metastatic and angiogenic activity, but not to uptake of [18 F]FDG PET. The pharmacokinetic studies revealed a limited metabolism and excretion during the 1-h scan and a distribution of radioactivity mainly to the liver, kidneys and lungs. In rat, a high uptake was additionally observed in adrenal and parathyroid glands. Conclusion The results indicate that (R)-[11C]PAQ is a promising imaging biomarker for visualization of angiogenesis, based on VEGFR2 expression, in primary tumours and during metastasis development. PMID:24670127

  1. Apparatus and method for preparing oxygen-15 labeled water H{sub 2}[{sup 15}O] in an injectable form for use in positron emission tomography

    DOEpatents

    Ferrieri, R.A.; Schlyer, D.J.; Alexoff, D.

    1996-01-09

    A handling and processing apparatus is revealed for preparing Oxygen-15 labeled water (H{sub 2}[{sup 15}O]) in injectable form for use in Positron Emission Tomography from preferably H{sub 2}[{sup 15}O] produced by irradiating a flowing gas target of nitrogen and hydrogen. The apparatus includes a collector for receiving and directing a gas containing H{sub 2}[{sup 15}O] gas and impurities, mainly ammonia (NH{sub 3}) gas into sterile water to trap the H{sub 2}[{sup 15}O] and form ammonium (NH{sub 4}{sup +}) in the sterile water. A device for displacing the sterile water containing H{sub 2}[{sup 15}O] and NH{sub 4}{sup +} through a cation resin removes NH{sub 4}{sup +} from the sterile water. A device for combining the sterile water containing H{sub 2}[{sup 15}O] with a saline solution produces an injectable solution. Preferably, the apparatus includes a device for delivering the solution to a syringe for injection into a patient. Also, disclosed is a method for preparing H{sub 2}[{sup 15}O] in injectable form for use in Positron Emission Tomography in which the method neither requires isotopic exchange reaction nor application of high temperature. 7 figs.

  2. Apparatus and method for preparing oxygen-15 labeled water H.sub.2 [.sup.15 O] in an injectable form for use in positron emission tomography

    DOEpatents

    Ferrieri, Richard A.; Schlyer, David J.; Alexoff, David

    1996-01-09

    A handling and processing apparatus for preparing Oxygen-15 labeled water (H.sub.2 [.sup.15 O]) in injectable form for use in Positron Emission Tomography from preferably H.sub.2 [.sup.15 O] produced by irradiating a flowing gas target of nitrogen and hydrogen. The apparatus includes a collector for receiving and directing a gas containing H.sub.2 [.sup.15 O] gas and impurities, mainly ammonia (NH.sub.3) gas into sterile water to trap the H.sub.2 [.sup.15 O] and form ammonium (NH.sub.4.sup.+) in the sterile water. A device for displacing the sterile water containing H.sub.2 [.sup.15 O] and NH.sub.4.sup.+ through a cation resin removes NH.sub.4.sup.+ from the sterile water. A device for combining the sterile water containing H.sub.2 [.sup.15 O] with a saline solution produces an injectable solution. Preferably, the apparatus includes a device for delivering the solution to a syringe for injection into a patient. Also, disclosed is a method for preparing H.sub.2 [.sup.15 O] in injectable form for use in Positron Emission Tomography in which the method neither requires isotopic exchange reaction nor application of high temperature.

  3. {sup 11}C-methionine PET improves the target volume delineation of meningiomas treated with stereotactic fractionated radiotherapy

    SciTech Connect

    Grosu, Anca-Ligia . E-mail: anca-ligia.grosu@lrz.tum.de; Weber, Wolfgang A.; Astner, Sabrina T.; Adam, Markus; Krause, Bernd J.; Schwaiger, Markus; Molls, Michael; Nieder, Carsten

    2006-10-01

    Purpose: To evaluate the role of {sup 11}C-methionine positron emission tomography (MET-PET) in target volume delineation for meningiomas and to determine the interobserver variability. Methods and Materials: Two independent observers performed treatment planning in 10 patients according to a prospective written protocol. In the first step, they used coregistered computed tomography (CT) and magnetic resonance imaging (MRI). In the second step, MET-PET was added to CT/MRI (image fusion based on mutual information). Results: The correlation between gross tumor volume (GTVs) delineated by the two observers based on CT/MRI was r = 0.855 (Spearman's correlation coefficient, p = 0.002) and r = 0.988 (p = 0.000) when MET-PET/CT/MRI were used. The number of patients with agreement in more then 80% of the outlined volume increased with the availability of MET-PET from 1 in 10 to 5 in 10. The median volume of intersection between the regions delineated by two observers increased significantly from 69% (from the composite volume) to 79%, by the addition of MET-PET (p = 0.005). The information of MET-PET was useful to delineate GTV in the area of cavernous sinus, orbit, and base of the skull. Conclusions: The hypothesis-generating findings of potential normal tissue sparing and reduced interobserver variability provide arguments for invasive studies of the correlation between MET-PET images and histologic tumor extension and for prospective trials of target volume delineation with CT/MRI/MET-PET image fusion.

  4. A plasmacytoid dendritic cell (CD123+/CD11c-) based assay system to predict contact allergenicity of chemicals

    PubMed Central

    Ayehunie, Seyoum; Snell, Maureen; Child, Matthew; Klausner, Mitchell

    2009-01-01

    A predictive allergenicity test system for assessing the contact allergenicity of chemicals is needed by the cosmetic and pharmaceutical industry to monitor product safety in the marketplace. Development of such non-animal alternative assay systems for skin sensitization and hazard identification has been pursued by policy makers and regulatory agencies. We investigated whether phenotypic and functional changes to a subset of dendritic cells (DC), plasmacytoid DC (pDC), could be used to identify contact allergens. To achieve this goal, normal human DC were generated from CD34+ progenitor cells and cryopreserved. Frozen DC were thawed and the pDC fraction (CD123+/CD11c-) was harvested using FACS sorting. The pDC were cultured, expanded, and exposed to chemical allergens (N=26) or non-allergens (N=22). Concentrations of each chemical that resulted in >50% viability was determined using FACS analysis of propidium iodide stained cells using pDC from 2-5 donors. Expression of the surface marker, CD86, which has been implicated in dendritic cell maturation, was used as a marker of allergenicity. CD86 expression increased (≥ 1.5 fold) for 25 of 26 allergens (sensitivity = 96%) but did not increase for 19 of 22 non-allergens (specificity = 86%). In a direct comparison to historical data for the regulatory approved, mouse local lymph node assay (LLNA) for 23 allergens and 22 non-allergens, the pDC method had sensitivity and specificity of 96% and 86%, respectively, while the sensitivity and specificity of the LLNA assay was 83% and 82%, respectively. In conclusion, CD86 expression in pDC appears to be a sensitive and specific indicator to identify contact allergenicity. Such an assay method utilizing normal human cells will be useful for high throughput screening of chemicals for allergenicity. PMID:19665512

  5. Nonuniform Cardiac Denervation Observed by 11C-meta-Hydroxyephedrine PET in 6-OHDA-Treated Monkeys

    PubMed Central

    Joers, Valerie; Seneczko, Kailie; Goecks, Nichole C.; Kamp, Timothy J.; Hacker, Timothy A.; Brunner, Kevin G.; Engle, Jonathan W.; Barnhart, Todd E.; Nickles, R. Jerome; Holden, James E.; Emborg, Marina E.

    2012-01-01

    Parkinson's disease presents nonmotor complications such as autonomic dysfunction that do not respond to traditional anti-parkinsonian therapies. The lack of established preclinical monkey models of Parkinson's disease with cardiac dysfunction hampers development and testing of new treatments to alleviate or prevent this feature. This study aimed to assess the feasibility of developing a model of cardiac dysautonomia in nonhuman primates and preclinical evaluations tools. Five rhesus monkeys received intravenous injections of 6-hydroxydopamine (total dose: 50 mg/kg). The animals were evaluated before and after with a battery of tests, including positron emission tomography with the norepinephrine analog 11C-meta-hydroxyephedrine. Imaging 1 week after neurotoxin treatment revealed nearly complete loss of specific radioligand uptake. Partial progressive recovery of cardiac uptake found between 1 and 10 weeks remained stable between 10 and 14 weeks. In all five animals, examination of the pattern of uptake (using Logan plot analysis to create distribution volume maps) revealed a persistent region-specific significant loss in the inferior wall of the left ventricle at 10 (P<0.001) and 14 weeks (P<0.01) relative to the anterior wall. Blood levels of dopamine, norepinephrine (P<0.05), epinephrine, and 3,4-dihydroxyphenylacetic acid (P<0.01) were notably decreased after 6-hydroxydopamine at all time points. These results demonstrate that systemic injection of 6-hydroxydopamine in nonhuman primates creates a nonuniform but reproducible pattern of cardiac denervation as well as a persistent loss of circulating catecholamines, supporting the use of this method to further develop a monkey model of cardiac dysautonomia. PMID:22539969

  6. Nanostructured copper, chromium, and tin oxide multicomponent materials as catalysts for methanol decomposition: 11C-radiolabeling study.

    PubMed

    Tsoncheva, Tanya; Sarkadi-Priboczki, Eva; Dimitrov, Momtchil; Genova, Izabela

    2013-01-01

    Copper and chromium modified tin oxide nanocomposites were obtained via incipient wetness impregnation of high surface area nanosized SnO(2) with the corresponding metal acetylacetonates and their further decomposition in air. Powder X-ray diffraction (XRD), Nitrogen physisorption, UV-Vis, and Temperature-programmed reduction (TPR) with hydrogen were applied for the samples characterization. The catalytic activity of the obtained materials was tested in methanol conversion. A new approach based on the selective coverage of the surface with (11)C-methanol was used for the characterization of the catalytic sites. It was demonstrated that the products distribution could be controlled by the surface coverage with methanol and the role of different active sites was discussed. The modification of SnO(2) with copper oxide increased the activity in methanol decomposition to CO(2)via dioxymethylene intermediates, but the catalyst suffered considerable loss of activity due to the reduction transformations by the reaction medium and formation of an inactive intermetallic alloy. The modification with chromium changed the acid-basic properties of SnO(2) by the formation of Cr(2)O(3) nanoparticles as well as anchored to the support chromate species. The former particles facilitated the formation of dimethyl ether (DME), while the latter species converted methanol predominantly to hydrocarbons. The fraction of chromate species increased in Cu-Cr-Sn oxide multicomponent nanocomposites and promoted the formation of hydrocarbons over DME at low temperatures, while at higher temperatures, the activity of the copper species leading to CO(2) formation was more pronounced. PMID:23031492

  7. Nonuniform cardiac denervation observed by 11C-meta-hydroxyephedrine PET in 6-OHDA-treated monkeys.

    PubMed

    Joers, Valerie; Seneczko, Kailie; Goecks, Nichole C; Kamp, Timothy J; Hacker, Timothy A; Brunner, Kevin G; Engle, Jonathan W; Barnhart, Todd E; Nickles, R Jerome; Holden, James E; Emborg, Marina E

    2012-01-01

    Parkinson's disease presents nonmotor complications such as autonomic dysfunction that do not respond to traditional anti-parkinsonian therapies. The lack of established preclinical monkey models of Parkinson's disease with cardiac dysfunction hampers development and testing of new treatments to alleviate or prevent this feature. This study aimed to assess the feasibility of developing a model of cardiac dysautonomia in nonhuman primates and preclinical evaluations tools. Five rhesus monkeys received intravenous injections of 6-hydroxydopamine (total dose: 50 mg/kg). The animals were evaluated before and after with a battery of tests, including positron emission tomography with the norepinephrine analog (11)C-meta-hydroxyephedrine. Imaging 1 week after neurotoxin treatment revealed nearly complete loss of specific radioligand uptake. Partial progressive recovery of cardiac uptake found between 1 and 10 weeks remained stable between 10 and 14 weeks. In all five animals, examination of the pattern of uptake (using Logan plot analysis to create distribution volume maps) revealed a persistent region-specific significant loss in the inferior wall of the left ventricle at 10 (P<0.001) and 14 weeks (P<0.01) relative to the anterior wall. Blood levels of dopamine, norepinephrine (P<0.05), epinephrine, and 3,4-dihydroxyphenylacetic acid (P<0.01) were notably decreased after 6-hydroxydopamine at all time points. These results demonstrate that systemic injection of 6-hydroxydopamine in nonhuman primates creates a nonuniform but reproducible pattern of cardiac denervation as well as a persistent loss of circulating catecholamines, supporting the use of this method to further develop a monkey model of cardiac dysautonomia. PMID:22539969

  8. Sea surface temperature and salinity patterns in the northern North Atlantic and the Arctic during interglacial MIS 11c: Implications for oceanic circulation reconstruction

    NASA Astrophysics Data System (ADS)

    Kandiano, E.; van der Meer, M.; Schouten, S.; Fahl, K.; Polyak, L. V.; Cronin, T. M.; Bauch, H. A.; Sinninghe Damste, J. S.

    2013-12-01

    Sea surface temperature (SST) patterns in the northern North Atlantic, the Nordic seas, and the western Arctic Ocean (AO) were reconstructed across the MIS 11c interglacial, a potential future climate analogue, using planktic foraminiferal abundances, alkenone-based Uk'37 and glycerol dialkyl glycerol tetraether (GDGT)-based TEX86 analyses. Foraminiferal SST reconstructions were supported by foraminiferal counts of small-sized fractions and rare foraminiferal species, stable oxygen isotope measurements on benthic and planktic foraminifers, and ice rafted debris records. Additionally, the hydrogen isotopic (δD) compositions of long chain alkenones were determined to assess variations in paleo sea surface salinity in the North Atlantic. In the North Atlantic our newly produced TEX86 -based SSTs range between 14 and 19 °C in agreement with summer foraminiferal SST (13 and 18 °C) and alkenone SSTs (13 and 16 °C). However, the former showed higher fluctuations than SSTs based on foraminiferal abundances. In concordance with δ18O records TEX86 SSTs demonstrate notable variability in the middle of MIS 11c, between 400 and 410 ka, which is consistent with the intra-MIS 11c cold event in the Arctic indicated by planktic foraminifers. This pattern implies that the interglacial MIC 11c climate was probably not as stable as it widely believed. The preliminary alkenone δD data show that during MIS 11c salinity values in the North Atlantic were similar to Holocene values. Foraminiferal SST records imply that during MIS 11c at least parts of the AO experienced unusually warm and probably ice free conditions, whereas the Nordic seas remained rather cold, especially during the early phase of this period, as it is inferred from foraminiferal and alkenone SSTs. At the same time all our SST records show that the North Atlantic was 1-2°C warmer than present during MIS 11c. This pattern suggests that during MIS 11c the North Atlantic Current was deflected to the west, which

  9. Brain and Whole-Body Imaging of Nociceptin/Orphanin FQ Peptide Receptor in Humans Using the PET Ligand 11C-NOP-1A

    PubMed Central

    Lohith, Talakad G.; Zoghbi, Sami S.; Morse, Cheryl L.; Araneta, Maria F.; Barth, Vanessa N.; Goebl, Nancy A.; Tauscher, Johannes T.; Pike, Victor W.; Innis, Robert B.; Fujita, Masahiro

    2013-01-01

    Nociceptin/orphanin FQ peptide (NOP) receptor is a new class of opioid receptor that may play a pathophysiologic role in anxiety and drug abuse and is a potential therapeutic target in these disorders. We previously developed a high-affinity PET ligand, 11C-NOP-1A, which yielded promising results in monkey brain. Here, we assessed the ability of 11C-NOP-1A to quantify NOP receptors in human brain and estimated its radiation safety profile. Methods After intravenous injection of 11C-NOP-1A, 7 healthy subjects underwent brain PET for 2 h and serial sampling of radial arterial blood to measure parent radioligand concentrations. Distribution volume (VT; a measure of receptor density) was determined by compartmental (1- and 2-tissue) and noncompartmental (Logan analysis and Ichise’s bilinear analysis [MA1]) methods. A separate group of 9 healthy subjects underwent whole-body PET to estimate whole-body radiation exposure (effective dose). Results After 11C-NOP-1A injection, the peak concentration of radioactivity in brain was high (~5–7 standardized uptake values), occurred early (~10 min), and then washed out quickly. The unconstrained 2-tissue-compartment model gave excellent VT identifiability (~1.1% SE) and fitted the data better than a 1-tissue-compartment model. Regional VT values (mL·cm−3) ranged from 10.1 in temporal cortex to 5.6 in cerebellum. VT was well identified in the initial 70 min of imaging and remained stable for the remaining 50 min, suggesting that brain radioactivity was most likely parent radioligand, as supported by the fact that all plasma radiometabolites of 11C-NOP-1A were less lipophilic than the parent radioligand. Voxel-based MA1 VT values correlated well with results from the 2-tissue-compartment model, showing that parametric methods can be used to compare populations. Whole-body scans showed radioactivity in brain and in peripheral organs expressing NOP receptors, such as heart, pancreas, and spleen. 11C-NOP-1A was significantly

  10. 11C-choline vs. 18F-FDG PET/CT in assessing bone involvement in patients with multiple myeloma

    PubMed Central

    Nanni, Cristina; Zamagni, Elena; Cavo, Michele; Rubello, Domenico; Tacchetti, Paola; Pettinato, Cinzia; Farsad, Mohsen; Castellucci, Paolo; Ambrosini, Valentina; Montini, Gian Carlo; Al-Nahhas, Adil; Franchi, Roberto; Fanti, Stefano

    2007-01-01

    Background Multiple Myeloma (MM) is a B cell neoplasm causing lytic or osteopenic bone abnormalities. Whole body skeletal survey (WBSS), Magnetic resonance (MR) and 18F-FDG PET/CT are imaging techniques routinely used for the evaluation of bone involvement in MM patients. Aim As MM bone lesions may present low 18F-FDG uptake; the aim of this study was to assess the possible added value and limitations of 11C-Choline to that of 18F-FDG PET/CT in patients affected with MM. Methods Ten patients affected with MM underwent a standard 11C-Choline PET/CT and an 18F-FDG PET/CT within one week. The results of the two scans were compared in terms of number, sites and SUVmax of lesions. Results Four patients (40%) had a negative concordant 11C-Choline and 18F-FDG PET/CT scans. Two patients (20%) had a positive 11C-Choline and 18F-FDG PET/CT scans that identified the same number and sites of bone lesions. The remaining four patients (40%) had a positive 11C-Choline and 18F-FDG PET/CT scan, but the two exams identified different number of lesions. Choline showed a mean SUVmax of 5 while FDG showed a mean SUVmax of 3.8 (P = 0.042). Overall, 11C-Choline PET/CT scans detected 37 bone lesions and 18F-FDG PET/CT scans detected 22 bone lesions but the difference was not significant (P = 0.8). Conclusion According to these preliminary data, 11C-Choline PET/CT appears to be more sensitive than 18F-FDG PET/CT for the detection of bony myelomatous lesions. If these data are confirmed in larger series of patients, 11C-Choline may be considered a more appropriate functional imaging in association with MRI for MM bone staging. PMID:17584499

  11. a Coupled GCM Comparison of Marine Isotope Stages 1, 5e, 11c and 31 IN Relation to Lake El'gygytgyn, NE Russia

    NASA Astrophysics Data System (ADS)

    Coletti, A. J.; DeConto, R.; Melles, M.; Brigham-Grette, J.; Minyuk, P.

    2012-12-01

    The lack of scientific data concerning interglacials of the Pleistocene in the Arctic has been a major obstacle within the climate community. Study of the interglacials of Marine Isotope Stage(s) (MIS) 1, 5e, 11c and 31 in high latitudes is important to decoding Arctic sensitivity and providing us with a potential analogue for a future Arctic with climate change. Data from a sediment core recovered from Lake El'Gygytgyn in northeastern (NE) Russia gives a continuous, high-resolution record of the Arctic spanning the past 2.8 million years whilst recording these interglacials. The data was used to correlate simulated interglacial Arctic climate with Arctic climate derived from sediment core proxy studies. Here, we use a Global Circulation Model (GCM) with a coupled atmosphere and land-surface scheme complete with an interactive vegetation component to simulate marine isotope stages 1, 5e, 11c and 31 in the Arctic. GCM simulations of MIS 5e and 31 in the Arctic both show a warmer arctic climate that can be explained by high obliquity, high eccentricity, high CO2 (287 ppmv ,325 ppmv , respectively) and precession that aligns perihelion with boreal summer. Consequently, MIS 5e showed the greatest summer warming compared to the other interglacials and pre-industrial control. However, the distinctly higher values of mean temperature of the warmest month (MTWM) and annual precipitation during stage 11c cannot readily be explained by summer orbital forcings and greenhouse gas (GHG) concentrations. Montane forest is seen migrating northward in stages 1, 5e and 31 as the surface insolation increases and sea ice melts, whereas in 11c, the warmest of the interglacials, evergreen forest takes over and migrates pole ward toward the coast. Feedback from low albedo forest biome was studied and conclusions suggest the increase in temperature due to forest cover is insignificant in creating a significantly warm regional climate. The warming associated with a lack of a Greenland Ice

  12. Relevance of a scoring system including CD11c expression in the identification of splenic diffuse red pulp small B-cell lymphoma (SRPL).

    PubMed

    Baseggio, L; Traverse-Glehen, A; Callet-Bauchu, E; Morel, D; Magaud, J P; Berger, F; Salles, G; Felman, P

    2011-03-01

    'Splenic red pulp lymphoma with numerous basophilic villous lymphocytes' (SRPL), recently described, is characterized by clinical, morphologic, immunologic, cytogenetic and molecular features distinct from SMZL/SLVL and HCL. In particular, the intensity of CD11c staining (expressed as fluorescence intensity -RFI-) in SRPL is significantly different from the RFI in SMZL/SLVL and HCL. Moreover the use of a scoring system based on the expression of CD11c, CD22, CD76, CD38 and CD27 appears to improve the differential diagnosis between SRPL and SMZL/SLVL and emphasizes that SRPL is an entity closed to but distinct from SMZL/SLVL. PMID:20677173

  13. Kinetics of /sup 13/N-ammonia uptake in myocardial single cells indicating potential limitations in its applicability as a marker of myocardial blood flow

    SciTech Connect

    Rauch, B.; Helus, F.; Grunze, M.; Braunwell, E.; Mall, G.; Hasselbach, W.; Kuebler, W.

    1985-02-01

    To study kinetics and principles of cellular uptake of /sup 13/N-ammonia, a marker of coronary perfusion in myocardial scintigraphy, heart muscle cells of adult rats were isolated by perfusion with collagenase and hyaluronidase. Net uptake of /sup 13/N, measured by flow dialysis, reached equilibrium within 20 sec in the presence of sodium bicarbonate and carbon dioxide (pH 7.4, 37 degrees C). Total extraction, 80 sec after the reaction start, was 786 +/- 159 mumol/ml cell volume. Cells destroyed by calcium overload were unable to extract /sup 13/N-ammonia. Omission of bicarbonate and carbon dioxide reduced total extraction to 36% of control. /sup 13/N-Ammonia uptake could also be reduced by 50 muM 4,4' diisothiocyanostilbene 2,2' disulfonic acid, by 100 micrograms/ml 1-methionine sulfoximine, and by preincubation with 5 muM free oleic acid. These results indicate that in addition to metabolic trapping by glutamine synthetase, the extraction of /sup 13/N-ammonia by myocardial cells is influenced by cell membrane integrity, intracellular-extracellular pH gradient, and possibly an anion exchange system for bicarbonate. For this reason, the uptake of /sup 13/N-ammonia may not always provide a valid measurement of myocardial perfusion.

  14. Semiconductor to metallic type transition in Ni1.5Fe1.5O4 ferrite

    NASA Astrophysics Data System (ADS)

    Aneeshkumar K., S.; Bhowmik, R. N.

    2016-05-01

    We have investigated electrical properties of Ni1.5Fe1.5O4 ferrite. The sample has been prepared by chemical coprecipitation route. The dc limit of conductivity has been derived from the fitting of ac conductivity data using Johnscher power law and Cole-Cole plot of impedance spectrum. The temperature dependence of dc conductivity data indicated a semiconductor to metallic type transition at 373K and metallic to semiconductor transition at 413K. Such electrical transition may be attributed to the effect of localization and de-localization of charge carriers in the hopping paths (Fe3+-O-Fe3+) and (Ni2+-O-Ni3+).

  15. Trojan Horse Method and RIBs: The {sup 18}F(p,{alpha}){sup 15}O reaction at astrophysical energies

    SciTech Connect

    Cherubini, S.; Gulino, M.; Rapisarda, G. G.; Spitaleri, C.; La Cognata, M.; Lamia, L.; Kubono, S.; Yamaguchi, H.; Hayakawa, S.; Wakabayashi, Y.; Iwasa, N.; Kato, S.; Komatsubara, H.; Teranishi, T.; Coc, A.; De Sereville, N.; Hammache, F.

    2012-11-12

    The abundance of {sup 18}F in Nova explosions is an important issue for the understanding of this astrophysical phenomenon. For this reason it is necessary to study the nuclear reactions that produce or destroy this isotope in novae. Among these latter processes, the {sup 18}F(p,{alpha}){sup 15}O is one of the main {sup 18}F destruction channels. We report here on the preliminary results of the first experiment that applies the Trojan Horse Method to a Radioactive Ion Beam induced reaction. The experiment was performed using the CRIB apparatus of the Center for Nuclear Study of The Tokyo University.

  16. Emission computed tomography of /sup 18/F-fluorodeoxyglucose and /sup 13/N-ammonia in stroke and epilepsy

    SciTech Connect

    Kuhl, D.E.; Phelps, M.E.; Engel, J. Jr.

    1980-01-01

    The ECAT Positron Tomograph was used to scan normal control subjects, stroke patients at various times during recovery, and patients with partial epilepsy during EEG monitoring. /sup 18/F-fluorodeoxyglucose (/sup 18/FDG) and /sup 13/N-Ammonia (/sup 13/NH/sub 3/) were used as indicators of abnormalities in local cerebral glucose utilization (LCMR/sub glc/) and relative perfusion, respectively. Hypometabolism, due to deactivation or minimal damage, was demonstrated with the /sup 18/FDG scan in deep structures and broad zones of cerebral cortex which appeared normal on x-ray CT (XCT) and /sup 99m/Tc pertechnetate scans. In patients with partial epilepsy, who had unilateral or focal electrical abnormalities, interictal /sup 18/FDG scan patterns clearly showed localized regions of decreased (20 to 50%) LCMR/sub glc/, which correlated anatomically with the eventual EEG localization.

  17. Reproducibility and Accuracy of Quantitative Myocardial Blood Flow Using 82Rb-PET: Comparison with 13N-Ammonia

    PubMed Central

    Fakhri, Georges El

    2011-01-01

    82Rb cardiac PET allows the assessment of myocardial perfusion using a column generator in clinics that lack a cyclotron. We and others have previously shown that quantitation of myocardial blood flow (MBF) and coronary flow reserve (CFR) is feasible using dynamic 82Rb PET and factor and compartment analyses. The aim of the present work was to determine the intra- and inter-observer variability of MBF estimation using 82Rb PET as well as the reproducibility of our generalized factor + compartment analyses methodology to estimate MBF and assess its accuracy by comparing, in the same subjects, 82Rb estimates of MBF to those obtained using 13N-ammonia. Methods Twenty-two subjects were included in the reproducibility and twenty subjects in the validation study. Patients were injected with 60±5mCi of 82Rb and imaged dynamically for 6 minutes at rest and during dipyridamole stress Left and right ventricular (LV+RV) time-activity curves were estimated by GFADS and used as input to a 2-compartment kinetic analysis that estimates parametric maps of myocardial tissue extraction (K1) and egress (k2), as well as LV+RV contributions (fv,rv). Results Our results show excellent reproducibility of the quantitative dynamic approach itself with coefficients of repeatability of 1.7% for estimation of MBF at rest, 1.4% for MBF at peak stress and 2.8% for CFR estimation. The inter-observer reproducibility between the four observers that participated in this study was also very good with correlation coefficients greater than 0.87 between any two given observers when estimating coronary flow reserve. The reproducibility of MBF in repeated 82Rb studies was good at rest and excellent at peak stress (r2=0.835). Furthermore, the slope of the correlation line was very close to 1 when estimating stress MBF and CFR in repeated 82Rb studies. The correlation between myocardial flow estimates obtained at rest and during peak stress in 82Rb and 13N-ammonia studies was very good at rest (r2

  18. Measurement of the sup 12 C( p ,. pi. sup 0 ) sup 13 N reaction by recoil detection

    SciTech Connect

    Homolka, J.; Schott, W.; Wagner, W.; Wilhelm, W. ); Saber, M.; Segel, R.E. ); Bent, R.D.; Fatyga, M.; Pollock, R.E. ); Kienle, P. ); Rehm, K.E. )

    1992-03-01

    Differential cross sections for the neutral pion production reaction {sup 12}C({ital p},{pi}{sup 0}){sup 13}N{sub g.s.} have been measured at 153.5, 166.1, 186.0, and 204.0 MeV bombarding energy using recoil detection. The shape of the angular distribution agrees well with that of the mirror reaction {sup 12}C({ital p},{pi}{sup +}){sup 13}C{sub g.s.}. Isospin invariance predicts for the ratio of the cross sections {sigma}({ital p},{pi}{sup +})/{sigma}({ital p},{pi}{sup 0})=2. At 153.5, 166.1, and 186.0, MeV, where ({ital p},{pi}{sup +}) cross sections have been reported previously by other groups at the same reduced pion momentum {eta}={ital p}{sub {pi}}/{ital m}{sub {pi}}{ital c}=0.34,0.55,0.78, the ratio of the total cross sections is 2.02{plus minus}0.14, 3.14{plus minus}0.12, and 2.12{plus minus}0.16, respectively. The ({ital p},{pi}{sup 0}) cross sections at 166 MeV is therefore 1.57{plus minus}0.06 times larger than expected. For {ital T}{sub {ital p}}{lt}160 MeV, the experimental cross sections are larger than predicted by a phase space and Coulomb barrier penetration calculation that fits the higher-energy data. Differential cross sections were also obtained for the {sup 12}C({ital p},{pi}{sup {minus}}){sup 13}O reaction, and upper limits set for differential cross sections for radiative capture to the ground state of {sup 13}N.

  19. Comparison of [11C]cocaine binding at tracer and pharmacological doses of baboon brain: A PET study

    SciTech Connect

    Volkow, N.D.; Fowler, J.S.; Logan, J.

    1994-05-01

    In vitro studies have shown that cocaine (C) binds to both high and low affinity sites on the dopamine transporter (DAT). We have previously characterized the binding of tracer doses of [{sup 11}C]cocaine (C*)to a high affinity site on the DAT. To assess if in vivo C also binds to low affinity sites we used PET to compare binding of tracer doses (17.8{plus_minus}12.2 {mu}g C) of C* to pharmacological doses (8 mg of C coadministered with C*). Sixteen paired studies were done to assess test/retest variability, specific versus non specific binding and to characterize binding profile. Dynamic scans were started immediately after injection of C* (5-8 mCi) for 50 min on the CTI-931 (6 x 6 x 6.5 mm FWHM). Time activity curves for tissue concentration and for unchanged tracer in plasma were used to calculate the transport constant between plasma and tissue (K1) and to obtain the distribution volume (DV). The ratio of the DV in striatum (ST) to that in cerebellum (CB) (which corresponds to Bmax/Kd-1) was used as model parameter. Peak brain uptake of C* was significantly higher for tracer than for pharmacological doses (0.041 versus 0.033 % dose/cc), as were the values for K1 (1.07{plus_minus}0.21 versus 0.68{plus_minus}0.26 (t=3.0 p<0.01)). Repeated measures were reproducible for tracer ({plus_minus}2%) and pharmacological doses of C* ({plus_minus}4%). Tracer dose C* showed highest binding and slowest clearance in ST which was reduced by C (0.5-2.0 mg/kg iv, -25 to -30%) and by drugs that inhibit DAT (2mg/kg nomifensine - 21%, 0.5 mg/kg methylphenidate -12%) and was increased by serotonin transporter inhibitors (5HT-Ti) (2 mg/kg citalopram +11%, 0.5 mg/kg fluoxetine +6%) and not changed by NE transporter inhibitors (0.5 mg/kg desipramine or 2 mg/kg tomoxetine). The increase with (5HT-Ti) may reflect neurotransmitter interactions or changes in bioavailability. At pharmacological doses C* showed homogeneous distribution and was not changed by C nor by any of the above drugs.

  20. A case of mistaken identity: CD11c-eYFP(+) cells in the normal mouse brain parenchyma and neural retina display the phenotype of microglia, not dendritic cells.

    PubMed

    Dando, Samantha J; Naranjo Golborne, Cecilia; Chinnery, Holly R; Ruitenberg, Marc J; McMenamin, Paul G

    2016-08-01

    Under steady-state conditions the central nervous system (CNS) is traditionally thought to be devoid of antigen presenting cells; however, putative dendritic cells (DCs) expressing enhanced yellow fluorescent protein (eYFP) are present in the retina and brain parenchyma of CD11c-eYFP mice. We previously showed that these mice carry the Crb1(rd8) mutation, which causes retinal dystrophic lesions; therefore we hypothesized that the presence of CD11c-eYFP(+) cells within the CNS may be due to pathology associated with the Crb1(rd8) mutation. We generated CD11c-eYFP Crb1(wt/wt) mice and compared the distribution and immunophenotype of CD11c-eYFP(+) cells in CD11c-eYFP mice with and without the Crb1(rd8) mutation. The number and distribution of CD11c-eYFP(+) cells in the CNS was similar between CD11c-eYFP Crb1(wt/wt) and CD11c-eYFP Crb1(rd8/rd8) mice. CD11c-eYFP(+) cells were distributed throughout the inner retina, and clustered in brain regions that receive input from the external environment or lack a blood-brain barrier. CD11c-eYFP(+) cells within the retina and cerebral cortex of CD11c-eYFP Crb1(wt/wt) mice expressed CD11b, F4/80, CD115 and Iba-1, but not DC or antigen presentation markers, whereas CD11c-eYFP(+) cells within the choroid plexus and pia mater expressed CD11c, I-A/I-E, CD80, CD86, CD103, DEC205, CD8α and CD135. The immunophenotype of CD11c-eYFP(+) cells and microglia within the CNS was similar between CD11c-eYFP Crb1(wt/wt) and CD11c-eYFP Crb1(rd8/rd8) mice; however, CD11c and I-A/I-E expression was significantly increased in CD11c-eYFP Crb1(rd8/rd8) mice. This study demonstrates that the overwhelming majority of CNS CD11c-eYFP(+) cells do not display the phenotype of DCs or their precursors and are most likely a subpopulation of microglia. GLIA 2016. GLIA 2016;64:1331-1349. PMID:27189804

  1. Synthesis and biodistribution of [11C]A-836339, a new potential radioligand for PET imaging of cannabinoid type 2 receptors (CB2)

    PubMed Central

    Horti, Andrew G.; Gao, Yongjun; Ravert, Hayden T.; Finley, Paige; Valentine, Heather; Wong, Dean F.; Endres, Christopher J.; Savonenko, Alena V.; Dannals, Robert F.

    2010-01-01

    Recently, A-836339 [2,2,3,3-tetramethylcyclopropanecarboxylic acid [3-(2-methoxyethyl)-4,5-dimethyl-3H-thiazol-(2Z)-ylidene]amide] (1) was reported to be a selective CB2 agonist with high binding affinity. Here we describe the radiosynthesis of [11C]A-836339 ([11C]1) via its desmethyl precursor as a candidate radioligand for imaging CB2 receptors with positron emission tomography (PET). Whole body and the regional brain distribution of [11C]1 in control CD1 mice demonstrated that this radioligand exhibits specific uptake in the CB2-rich spleen and little specific in vivo binding in the control mouse brain. However, [11C]1 shows specific cerebral uptake in the lipopolysaccharide (LPS)-induced mouse model of neuroinflammation and in the brain areas with Aβ-amyloid plaque deposition in a mouse model of Alzheimer's disease (APPswe/PS1dE9 mice). These data establish a proof of principle that CB2 receptors binding in the neuroinflammation and related disorders can be measured in vivo. PMID:20554448

  2. Direct one-step labeling of cysteine residues on peptides with [(11)C]methyl triflate for the synthesis of PET radiopharmaceuticals.

    PubMed

    Chin, Joshua; Vesnaver, Matthew; Bernard-Gauthier, Vadim; Saucke-Lacelle, Erin; Wängler, Björn; Wängler, Carmen; Schirrmacher, Ralf

    2013-11-01

    Radiolabeled peptides have emerged as an attractive platform for the diagnostic and therapeutic oncology. However, the (11)C-radiolabeling of peptides for positron emission tomography (PET) has been poorly explored, owing to the relatively short half-life of carbon-11 (t 1/2 = 20.3 min) and time-consuming multi-step radiochemical reactions. Existing methods have found limited use and are not routinely encountered in the production of radiotracers. Herein, we propose a facile one-step direct (11)C-methylation of cysteine residues in peptides using [(11)C]methyl triflate under ambient temperatures (20 °C) and short reaction times, on the order of seconds. Good regioselectivity of this method was demonstrated by HPLC in a simple peptide (glutathione, GSH) and a more complex test decapeptide (Trp-Tyr-Trp-Ser-Arg-Cys-Lys-Trp-Thr-Gly) bearing multiple nucleophilic sites. In addition, we extend this method towards the synthesis of [(11)C]Cys(Me)-[Tyr(3)-octreotate] as a demonstration of applicability for peptides of biological interest. This octreotate derivative was obtained in non-decay-corrected radiochemical yields of 11 ± 2 % (n = 3) with a synthesis time of approx. 30 min. PMID:23921782

  3. Cutting Edge: IL-4, IL-21, and IFN-γ Interact To Govern T-bet and CD11c Expression in TLR-Activated B Cells.

    PubMed

    Naradikian, Martin S; Myles, Arpita; Beiting, Daniel P; Roberts, Kenneth J; Dawson, Lucas; Herati, Ramin Sedaghat; Bengsch, Bertram; Linderman, Susanne L; Stelekati, Erietta; Spolski, Rosanne; Wherry, E John; Hunter, Christopher; Hensley, Scott E; Leonard, Warren J; Cancro, Michael P

    2016-08-15

    T-bet and CD11c expression in B cells is linked with IgG2c isotype switching, virus-specific immune responses, and humoral autoimmunity. However, the activation requisites and regulatory cues governing T-bet and CD11c expression in B cells remain poorly defined. In this article, we reveal a relationship among TLR engagement, IL-4, IL-21, and IFN-γ that regulates T-bet expression in B cells. We find that IL-21 or IFN-γ directly promote T-bet expression in the context of TLR engagement. Further, IL-4 antagonizes T-bet induction. Finally, IL-21, but not IFN-γ, promotes CD11c expression independent of T-bet. Using influenza virus and Heligmosomoides polygyrus infections, we show that these interactions function in vivo to determine whether T-bet(+) and CD11c(+) B cells are formed. These findings suggest that T-bet(+) B cells seen in health and disease share the common initiating features of TLR-driven activation within this circumscribed cytokine milieu. PMID:27430719

  4. Comparative double-tracer whole-body autoradiography: uptake of 11C-, 18F- and 3H-labeled compounds in rat tumors.

    PubMed

    d'Argy, R; Paul, R; Frankenberg, L; Stålnacke, C G; Lundqvist, H; Kangas, L; Halldin, C; Någren, K; Roeda, D; Haaparanta, M

    1988-01-01

    The uptake of various labeled compounds by tumors was studied by double-tracer whole-body autoradiography (DTWBA) in rats. Each animal carried two types of tumors: mammary carcinomas and the Walker 256 carcinosarcomas. The markers used were [18F]- and [3H]fluorodeoxyglucose (glucose utilization), [3H]thymidine (cell proliferation), [11C]methionine (amino acid metabolism) and [11C]- and [3H]toremifene (estrogen-receptor-avid agents). In each experiment, the distribution of a substance labeled with short-lived radionuclide (11C or 18F) was compared with that of another substance labeled with a long-lived nuclide (3H). Quantification was done by combining computerized image analysis of the autoradiograms with liquid scintillation counting of punched tissue pieces obtained from the cryosections. The relationships between the uptakes of the various radiopharmaceuticals were recorded in tumors and normal tissues. The dynamics of [18F]fluorodeoxyglucose and [11C]methionine were determined in tumors and some selected tissues by positron emission tomography (PET). The uptake rate between fluorodeoxyglucose and thymidine in the mammary tumor was five times higher than the ratio in the Walker tumor. The corresponding figure for FDG/methionine was four times. Thymidine, compared with methionine, was twice as efficient. Thus, the mammary tumors were best imaged with FDG or thymidine. The non-steroid antiestrogen toremifene was taken up in very low amounts by these tumors. By DTWBA, experimental tumors may serve as their own control. PMID:2978293

  5. A new approach of weighted integration technique based on accumulated images using dynamic PET and H2(15)O

    SciTech Connect

    Yokoi, T.; Kanno, I.; Iida, H.; Miura, S.; Uemura, K. )

    1991-05-01

    We developed a new technique of weighted integration for the measurement of local cerebral blood flow (LCBF) and the blood-tissue partition coefficient (p) using dynamic positron emission tomography (PET) and H2(15)O. The weighted integration in the new technique is carried out on the equation of the first time integration of the Kety-Schmidt differential equation. Practically, serially accumulated images with sequentially prolonged accumulation times are weighted by two arbitrary functions. The weighting functions do not have to be differentiated because of the exclusion of the differential term in the starting equation. Consequently, the method does not require data at the end of the scan. The technique was applied to H2(15)O dynamic PET performed on four normal subjects, and was verified to provide a better signal-to-noise ratio than the previously developed integrated projection (IP) technique. Computer simulations were carried out to investigate the effects of statistical noise, tissue heterogeneity, and time delay and dispersion in arterial input function. The simulation showed that the new technique provided about a 1.4 times lower statistical error in both LCBF and p at 50 ml 100 g-1 min-1 compared to the IP technique, and it should be noted that the new technique was less sensitive to the shape of the weighting functions. The new technique provides a new strategy with respect to the statistical error for estimation of LCBF and p.

  6. Improved electrochemical properties of BiOF-coated 5 V spinel Li[Ni 0.5Mn 1.5]O 4 for rechargeable lithium batteries

    NASA Astrophysics Data System (ADS)

    Kang, Han-Byeol; Myung, Seung-Taek; Amine, Khalil; Lee, Sung-Man; Sun, Yang-Kook

    The electrochemical properties of BiOF-coated 5 V spinel Li[Ni 0.5Mn 1.5]O 4 were investigated at elevated temperatures (55 °C). As observed by scanning and transmission electron microscopy, BiOF nanolayers with ∼10 nm thickness were coated on the surface of Li[Ni 0.5Mn 1.5]O 4. The BiOF coating layer protected the surface of the active materials from HF generated by the decomposition of LiPF 6 in the electrolyte during electrochemical cycling. The dissolution of transition metal elements was also suppressed upon cycling. Therefore, the capacity retention of the BiOF-coated Li[Ni 0.5Mn 1.5]O 4 was obviously improved compared to the pristine Li[Ni 0.5Mn 1.5]O 4 at 55 °C.

  7. Extrapolation of astrophysical S factors for the reaction {sup 14}N((p, {gamma}) {sup 15}O to near-zero energies

    SciTech Connect

    Artemov, S. V.; Igamov, S. B. Tursunmakhatov, Q. I.; Yarmukhamedov, R.

    2012-03-15

    The astrophysical S factors for the radiative-capture reaction {sup 14}N(p, {gamma}){sup 15}O in the region of ultralow energies were calculated on the basis of the R-matrix approach. The values of the radiative and protonic widths were fitted to new experimental data. The contribution of direct radiative capture to bound states of the {sup 15}O nucleus was determined with the aid of asymptotic normalization coefficients, whose values were refined in the present study on the basis of the results obtained from an analysis of the reaction {sup 14}N({sup 3}He, d){sup 15}O at three different energies of incident helium ions. A value of S(0) = 1.79 {+-} 0.31 keV b was obtained for the total astrophysical S factor, and the reaction rate was determined for the process {sup 14}N(p, {gamma}){sup 15}O.

  8. [18F]DPA-714: Direct Comparison with [11C]PK11195 in a Model of Cerebral Ischemia in Rats

    PubMed Central

    Boutin, Hervé; Prenant, Christian; Maroy, Renaud; Galea, James; Greenhalgh, Andrew D.; Smigova, Alison; Cawthorne, Christopher; Julyan, Peter; Wilkinson, Shane M.; Banister, Samuel D.; Brown, Gavin; Herholz, Karl; Kassiou, Michael; Rothwell, Nancy J.

    2013-01-01

    Purpose Neuroinflammation is involved in several brain disorders and can be monitored through expression of the translocator protein 18 kDa (TSPO) on activated microglia. In recent years, several new PET radioligands for TSPO have been evaluated in disease models. [18F]DPA-714 is a TSPO radiotracer with great promise; however results vary between different experimental models of neuroinflammation. To further examine the potential of [18F]DPA-714, it was compared directly to [11C]PK11195 in experimental cerebral ischaemia in rats. Methods Under anaesthesia, the middle cerebral artery of adult rats was occluded for 60 min using the filament model. Rats were allowed recovery for 5 to 7 days before one hour dynamic PET scans with [11C]PK11195 and/or [18F]DPA-714 under anaesthesia. Results Uptake of [11C]PK11195 vs [18F]DPA-714 in the ischemic lesion was similar (core/contralateral ratio: 2.84±0.67 vs 2.28±0.34 respectively), but severity of the brain ischemia and hence ligand uptake in the lesion appeared to vary greatly between animals scanned with [11C]PK11195 or with [18F]DPA-714. To solve this issue of inter-individual variability, we performed a direct comparison of [11C]PK11195 and [18F]DPA-714 by scanning the same animals sequentially with both tracers within 24 h. In this direct comparison, the core/contralateral ratio (3.35±1.21 vs 4.66±2.50 for [11C]PK11195 vs [18F]DPA-714 respectively) showed a significantly better signal-to-noise ratio (1.6 (1.3–1.9, 95%CI) fold by linear regression) for [18F]DPA-714. Conclusions In a clinically relevant model of neuroinflammation, uptake for both radiotracers appeared to be similar at first, but a high variability was observed in our model. Therefore, to truly compare tracers in such models, we performed scans with both tracers in the same animals. By doing so, our result demonstrated that [18F]DPA-714 displayed a higher signal-to-noise ratio than [11C]PK11195. Our results suggest that, with the longer half-life of

  9. In vivo imaging of microglial activation by positron emission tomography with [(11)C]PBR28 in the 5XFAD model of Alzheimer's disease.

    PubMed

    Mirzaei, Nazanin; Tang, Sac Pham; Ashworth, Sharon; Coello, Christopher; Plisson, Christophe; Passchier, Jan; Selvaraj, Vimal; Tyacke, Robin J; Nutt, David J; Sastre, Magdalena

    2016-06-01

    Microglial activation has been linked with deficits in neuronal function and synaptic plasticity in Alzheimer's disease (AD). The mitochondrial translocator protein (TSPO) is known to be upregulated in reactive microglia. Accurate visualization and quantification of microglial density by PET imaging using the TSPO tracer [(11)C]-R-PK11195 has been challenging due to the limitations of the ligand. In this study, it was aimed to evaluate the new TSPO tracer [(11)C]PBR28 as a marker for microglial activation in the 5XFAD transgenic mouse model of AD. Dynamic PET scans were acquired following intravenous administration of [(11)C]PBR28 in 6-month-old 5XFAD mice and in wild-type controls. Autoradiography with [(3)H]PBR28 was carried out in the same brains to further confirm the distribution of the radioligand. In addition, immunohistochemistry was performed on adjacent brain sections of the same mice to evaluate the co-localization of TSPO with microglia. PET imaging revealed that brain uptake of [(11)C]PBR28 in 5XFAD mice was increased compared with control mice. Moreover, binding of [(3)H]PBR28, measured by autoradiography, was enriched in cortical and hippocampal brain regions, coinciding with the positive staining of the microglial marker Iba-1 and amyloid deposits in the same areas. Furthermore, double-staining using antibodies against TSPO demonstrated co-localization of TSPO with microglia and not with astrocytes in 5XFAD mice and human post-mortem AD brains. The data provided support of the suitability of [(11)C]PBR28 as a tool for in vivo monitoring of microglial activation and assessment of treatment response in future studies using animal models of AD. PMID:26959396

  10. Heightened D3 Dopamine Receptor Levels in Cocaine Dependence and Contributions to the Addiction Behavioral Phenotype: A Positron Emission Tomography Study with [11C]-(+)-PHNO

    PubMed Central

    Payer, Doris E; Behzadi, Arian; Kish, Stephen J; Houle, Sylvain; Wilson, Alan A; Rusjan, Pablo M; Tong, Junchao; Selby, Peter; George, Tony P; McCluskey, Tina; Boileau, Isabelle

    2014-01-01

    The dopamine system is a primary treatment target for cocaine dependence (CD), but research on dopaminergic abnormalities (eg, D2 receptor system deficiencies) has so far failed to translate into effective treatment strategies. The D3 receptor system has recently attracted considerable clinical interest, and D3 antagonism is now under investigation as a novel avenue for addiction treatment. The objective here was to evaluate the status and behavioral relevance of the D3 receptor system in CD, using the positron emission tomography (PET) radiotracer [11C]-(+)-PHNO. Fifteen CD subjects (many actively using, but all abstinent 7–240 days on scan day) and fifteen matched healthy control (HC) subjects completed two PET scans: one with [11C]-(+)-PHNO to assess D3 receptor binding (BPND; calculated regionally using the simplified reference tissue model), and for comparison, a second scan with [11C]raclopride to assess D2/3 binding. CD subjects also completed a behavioral battery to characterize the addiction behavioral phenotype. CD subjects showed higher [11C]-(+)-PHNO BPND than HC in the substantia nigra, which correlated with behavioral impulsiveness and risky decision making. In contrast, [11C]raclopride BPND was lower across the striatum in CD, consistent with previous literature in ⩾2 week abstinence. The data suggest that in contrast to a D2 deficiency, CD individuals may have heightened D3 receptor levels, which could contribute to addiction-relevant traits. D3 upregulation is emerging as a biomarker in preclinical models of addiction, and human PET studies of this receptor system can help guide novel pharmacological strategies for treatment. PMID:23921256

  11. Heightened D3 dopamine receptor levels in cocaine dependence and contributions to the addiction behavioral phenotype: a positron emission tomography study with [11C]-+-PHNO.

    PubMed

    Payer, Doris E; Behzadi, Arian; Kish, Stephen J; Houle, Sylvain; Wilson, Alan A; Rusjan, Pablo M; Tong, Junchao; Selby, Peter; George, Tony P; McCluskey, Tina; Boileau, Isabelle

    2014-01-01

    The dopamine system is a primary treatment target for cocaine dependence (CD), but research on dopaminergic abnormalities (eg, D2 receptor system deficiencies) has so far failed to translate into effective treatment strategies. The D3 receptor system has recently attracted considerable clinical interest, and D3 antagonism is now under investigation as a novel avenue for addiction treatment. The objective here was to evaluate the status and behavioral relevance of the D3 receptor system in CD, using the positron emission tomography (PET) radiotracer [(11)C]-(+)-PHNO. Fifteen CD subjects (many actively using, but all abstinent 7-240 days on scan day) and fifteen matched healthy control (HC) subjects completed two PET scans: one with [(11)C]-(+)-PHNO to assess D3 receptor binding (BPND; calculated regionally using the simplified reference tissue model), and for comparison, a second scan with [(11)C]raclopride to assess D2/3 binding. CD subjects also completed a behavioral battery to characterize the addiction behavioral phenotype. CD subjects showed higher [(11)C]-(+)-PHNO BPND than HC in the substantia nigra, which correlated with behavioral impulsiveness and risky decision making. In contrast, [(11)C]raclopride BPND was lower across the striatum in CD, consistent with previous literature in 2 week abstinence. The data suggest that in contrast to a D2 deficiency, CD individuals may have heightened D3 receptor levels, which could contribute to addiction-relevant traits. D3 upregulation is emerging as a biomarker in preclinical models of addiction, and human PET studies of this receptor system can help guide novel pharmacological strategies for treatment. PMID:23921256

  12. Higher binding of the dopamine D3 receptor-preferring ligand [11C]-(+)-PHNO in Methamphetamine Polydrug Users: A Positron Emission Tomography Study

    PubMed Central

    Boileau, Isabelle; Payer, Doris; Houle, Sylvain; Behzadi, Arian; Rusjan, Pablo M.; Tong, Junchao; Wilkins, Diana; Selby, Peter; George, Tony P.; Zack, Martin; Furukawa, Yoshiaki; McCluskey, Tina; Wilson, Alan A.; Kish, Stephen J.

    2012-01-01

    Positron emission tomography (PET) findings suggesting lower D2-type dopamine receptors and dopamine concentration in brains of stimulant users have prompted speculation that increasing dopamine signaling might help in drug-treatment. However, this strategy needs to consider the possibility, based on animal and postmortem human data, that dopaminergic activity at the related D3 receptor might, in contrast, be elevated, and thereby contribute to drug-taking behavior. We tested the hypothesis that D3 receptor binding is above-normal in methamphetamine (MA) polydrug users, using PET and the D3-preferring ligand [11C]-(+)-PHNO. Sixteen control subjects and 16 polydrug users reporting MA as their primary drug of abuse underwent PET scanning following [11C]-(+)-PHNO. Compared to control subjects, drug users had higher [11C]-(+)-PHNO binding in the D3-rich midbrain substantia nigra (SN, +46%, p<0.02) and in the globus pallidus (+9%, p=0.06) and ventral pallidum (+11%, p=0.1), whereas binding was slightly lower in the D2-rich dorsal striatum (~−4%, NS; −12% in heavy users, p=0.01) and related to drug-use severity. [11C]-(+)-PHNO binding ratio in D3-rich SN vs. D2-rich dorsal striatum was 55% higher in MA users (p=0.004), with heavy but not moderate users having ratios significantly different from controls. [11C]-(+)-PHNO binding in SN was related to self-reported “drug-wanting.” We conclude that the dopamine D3 receptor, unlike the D2 receptor, might be upregulated in brains of MA polydrug users although lower dopamine levels in MA users could have contributed to the finding. Pharmacological studies are needed to establish whether normalization of D3 receptor function could reduce vulnerability to relapse in stimulant abuse. PMID:22279219

  13. Test-retest reproducibility of binding parameters in humans with 11C-LY2795050, an antagonist PET radiotracer for the kappa opioid receptor

    PubMed Central

    Naganawa, Mika; Zheng, Ming-Qiang; Henry, Shannan; Nabulsi, Nabeel; Lin, Shu-Fei; Ropchan, Jim; Labaree, David; Najafzadeh, Soheila; Kapinos, Michael; Tauscher, Johannes; Neumeister, Alexander; Carson, Richard E.; Huang, Yiyun

    2015-01-01

    11C-LY2795050 is a new antagonist PET radioligand for the kappa opioid receptor (KOR). In this study, we assessed the reproducibility of the binding parameters of 11C-LY2795050 in healthy human subjects. Methods Sixteen healthy subjects (11 men, 5 women) underwent two separate 90-min PET scans with arterial input function and plasma free fraction measurements. The two-tissue compartment model and multilinear analysis-1 were applied to calculate five outcome measures in 14 brain regions: distribution volume (VT), distribution volume normalized by plasma free fraction (VT/fP), and three binding potentials (BPND, BPP, BPF). Since KOR is distributed ubiquitously throughout the brain, there are no suitable reference regions. We used a fixed fraction of individual cerebellum VT value as the non-displaceable distribution volume VND (= VT CER/1.17). The relative and absolute test-retest variability and intra-class correlation coefficient were evaluated for the outcome measures of 11C-LY2795050. Results The test-retest variability of 11C-LY2795050 for VT was ≤ 10% in all regions, and 12% in the amygdala. For binding potentials (BPND and BPP), the test-retest variability was good in regions of moderate and high KOR density (BPND > 0.4) and poor in regions of low density. Correction by fP (VT/fP or BPF) did not improve the test-retest performance. Conclusion Our results suggest that quantification of 11C-LY2795050 imaging is reproducible and reliable in the regions with moderate and high KOR density. Therefore we conclude that this first antagonist radiotracer is highly useful for PET studies of KOR. PMID:25593119

  14. Quantification of human opiate receptor concentration and affinity using high and low specific activity ( sup 11 C)diprenorphine and positron emission tomography

    SciTech Connect

    Sadzot, B.; Price, J.C.; Mayberg, H.S.; Douglass, K.H.; Dannals, R.F.; Lever, J.R.; Ravert, H.T.; Wilson, A.A.; Wagner, H.N. Jr.; Feldman, M.A. )

    1991-03-01

    (11C)Diprenorphine, a weak partial opiate agonist, and positron emission tomography were used to obtain noninvasive regional estimates of opiate receptor concentration (Bmax) and affinity (Kd) in human brain. Different compartmental models and fitting strategies were compared statistically to establish the most reliable method of parameter estimation. Paired studies were performed in six normal subjects using high (769-5,920 Ci/mmol) and low (27-80 Ci/mmol) specific activity (SA) (11C)diprenorphine. Two subjects were studied a third time using high SA (11C)diprenorphine after a pretreatment with 1-1.5 mg/kg of the opiate antagonist naloxone. After the plasma radioactivity was corrected for metabolites, the brain data were analyzed using a three-compartment model and nonlinear least-squares curve fitting. Linear differential equations were used to describe the high SA (low receptor occupancy) kinetics. The k3/k4 ratio varied from 1.0 +/- 0.2 (occipital cortex) to 8.6 +/- 1.6 (thalamus). Nonlinear differential equations were used to describe the low SA (high receptor occupancy) kinetics and the curve fits provided the konf2 product. The measured free fraction of (11C)diprenorphine in plasma (f1) was 0.30 +/- 0.03, the average K1/k2 ratio from the two naloxone studies was 1.1 +/- 0.2, and the calculated free fraction of (11C)diprenorphine in the brain (f2) was 0.3. Using the paired SA studies, the estimated kinetic parameters, and f2, separate estimates of Bmax and Kd were obtained. Bmax varied from 2.3 +/- 0.5 (occipital cortex) to 20.6 +/- 7.3 (cingulate cortex) nM. The average Kd (eight brain regions) was 0.85 +/- 0.17 nM.

  15. CD11c-positive cells from brain, spleen, lung, and liver exhibit site-specific immune phenotypes and plastically adapt to new environments.

    PubMed

    Immig, Kerstin; Gericke, Martin; Menzel, Franziska; Merz, Felicitas; Krueger, Martin; Schiefenhövel, Fridtjof; Lösche, Andreas; Jäger, Kathrin; Hanisch, Uwe-Karsten; Biber, Knut; Bechmann, Ingo

    2015-04-01

    The brain's immune privilege has been also attributed to the lack of dendritic cells (DC) within its parenchyma and the adjacent meninges, an assumption, which implies maintenance of antigens rather than their presentation in lymphoid organs. Using mice transcribing the green fluorescent protein under the promoter of the DC marker CD11c (itgax), we identified a juxtavascular population of cells expressing this DC marker and demonstrated their origin from bone marrow and local microglia. We now phenotypically compared this population with CD11c/CD45 double-positive cells from lung, liver, and spleen in healthy mice using seven-color flow cytometry. We identified unique, site-specific expression patterns of F4/80, CD80, CD86, CX3CR1, CCR2, FLT3, CD103, and MHC-II. Furthermore, we observed the two known CD45-positive populations (CD45(high) and CD45(int) ) in the brain, whereas liver, lung, and spleen exhibited a homogeneous CD45(high) population. CD11c-positive microglia lacked MHC-II expression and CD45(high) /CD11c-positive cells from the brain have a lower percentage of MHC-II-positive cells. To test whether phenotypical differences are fixed by origin or specifically develop due to environmental factors, we transplanted brain and spleen mononuclear cells on organotypic slice cultures from brain (OHSC) and spleen (OSSC). We demonstrate that adaption and ramification of MHC-II-positive splenocytes is paralleled by down-regulation of MHC-II, whereas brain-derived mononuclear cells neither ramified nor up-regulated MHC-II in OSSCs. Thus, brain-derived mononuclear cells maintain their MHC-II-negative phenotype within the environment of an immune organ. Intraparenchymal CD11c-positive cells share immunophenotypical characteristics of DCs from other organs but remain unique for their low MHC-II expression. PMID:25471735

  16. Comparative study of 18F-DOPA, 13N-Ammonia and F18-FDG PET/CT in primary brain tumors

    PubMed Central

    Jacob, Mattakarottu J; Pandit, Aniruddha G; Jora, Charu; Mudalsha, Ravina; Sharma, Amit; Pathak, Harish C

    2011-01-01

    Aim: To determine the diagnostic reliability of 18F-FDOPA, 13N-Ammonia and F18-FDG PET/CT in primary brain tumors. We evaluated the amino acid and glucose metabolism of brain tumors by using PET with 18F-FDOPA, 13N-Ammonia and F18-FDG PET/CT. Materials and Methods: Nine patients undergoing evaluation for brain tumors were studied. Tracer uptake was quantified by the use of standardized uptake values and the ratio of tumor uptake to normal identical area of contra lateral hemisphere (T/N). In addition, PET uptake with 18F-FDOPA was quantified by use of ratio of tumor uptake to striatum uptake (T/S). The results were correlated with the patient's clinical profile. Results: Both high-grade and low-grade tumors were well visualized with 18F-FDOPA. The sensitivity for identifying tumors was substantially higher with 18F-FDOPA PET than with F18-FDG and 13N-Ammonia PET as determined by simple visual inspection. The sensitivity for identifying recurrence in low grade gliomas is higher with 13N-Ammonia than with F18-FDG. Conclusion: 18F-FDOPA PET is more reliable than F18-FDG and 13N-Ammonia PET for evaluating brain tumors. PMID:23326065

  17. Comparison of qualitative and quantitative imaging characteristics of [11C]PiB and [18F]flutemetamol in normal control and Alzheimer's subjects

    PubMed Central

    Mountz, James M.; Laymon, Charles M.; Cohen, Ann D.; Zhang, Zheng; Price, Julie C.; Boudhar, Sanaa; McDade, Eric; Aizenstein, Howard J.; Klunk, William E.; Mathis, Chester A.

    2015-01-01

    Introduction Neuritic amyloid plaques and neurofibrillary tangles, the hallmark pathologic lesions of Alzheimer's disease, are thought to develop before the symptoms of brain failure are clinically detectable. Imaging methods capable of detecting the presence of neuritic amyloid plaques should improve a clinician's ability to identify Alzheimer's disease during the earliest symptomatic phase and to identify at-risk individuals presymptomatically. Currently the best studied amyloid imaging ligand is [11C]Pittsburgh Compound B ([11C]PiB). However, the 20-minute half-life of this radiotracer limits its use. This study is designed to evaluate the performance characteristics of [18F]flutemetamol and to independently compare results to [11C]PiB in the same subjects. Methods Twenty-three subjects, 15 cognitively normal (NL) and 8 with a clinical diagnosis of Alzheimer's Dementia (AD), underwent [11C]PiB and [18F]flutemetamol PET scans within 28 days of study enrollment. We studied both normal and AD subjects to assess the uptake characteristics across a range of amyloid positivity. Blinded visual reads were conducted by five raters. Correlation analyses were performed between cortical SUVR for the two tracers and also between rater scores and SUVR for each tracer. Overall reader accuracy for classifying scans as amyloid positive or negative was determined for each tracer using SUVR classification as the standard. Results The linear correlation coefficient between global cortical SUVR for the two tracers was R2 = 0.85, indicating that both tracers have similar retention characteristics. The two tracers were well correlated for rater-determined AD-like positivity (Cohen κ = 0.82). Averaged visual ratings and global cortical SUVR disagreed on their classification in 2/23 [11C]PiB scans and 4/23 [18F]flutemetamol scans. Conclusions [11C]PiB and [18F]flutemetamol have similar retention characteristics across a range of amyloid negative to positive subjects. Both tracers

  18. Is There an Additional Value of {sup 11}C-Choline PET-CT to T2-weighted MRI Images in the Localization of Intraprostatic Tumor Nodules?

    SciTech Connect

    Van den Bergh, Laura; Koole, Michel; Isebaert, Sofie; Joniau, Steven; Deroose, Christophe M.; Oyen, Raymond; Lerut, Evelyne; Budiharto, Tom; Mottaghy, Felix; Bormans, Guy; Van Poppel, Hendrik; Haustermans, Karin

    2012-08-01

    Purpose: To investigate the additional value of {sup 11}C-choline positron emission tomography (PET)-computed tomography (CT) to T2-weighted (T2w) magnetic resonance imaging (MRI) for localization of intraprostatic tumor nodules. Methods and Materials: Forty-nine prostate cancer patients underwent T2w MRI and {sup 11}C-choline PET-CT before radical prostatectomy and extended lymphadenectomy. Tumor regions were outlined on the whole-mount histopathology sections and on the T2w MR images. Tumor localization was recorded in the basal, middle, and apical part of the prostate by means of an octant grid. To analyze {sup 11}C-choline PET-CT images, the same grid was used to calculate the standardized uptake values (SUV) per octant, after rigid registration with the T2w MR images for anatomic reference. Results: In total, 1,176 octants were analyzed. Sensitivity, specificity, and accuracy of T2w MRI were 33.5%, 94.6%, and 70.2%, respectively. For {sup 11}C-choline PET-CT, the mean SUV{sub max} of malignant octants was significantly higher than the mean SUV{sub max} of benign octants (3.69 {+-} 1.29 vs. 3.06 {+-} 0.97, p < 0.0001) which was also true for mean SUV{sub mean} values (2.39 {+-} 0.77 vs. 1.94 {+-} 0.61, p < 0.0001). A positive correlation was observed between SUV{sub mean} and absolute tumor volume (Spearman r = 0.3003, p = 0.0362). No correlation was found between SUVs and prostate-specific antigen, T-stage or Gleason score. The highest accuracy (61.1%) was obtained with a SUV{sub max} cutoff of 2.70, resulting in a sensitivity of 77.4% and a specificity of 44.9%. When both modalities were combined (PET-CT or MRI positive), sensitivity levels increased as a function of SUV{sub max} but at the cost of specificity. When only considering suspect octants on {sup 11}C-choline PET-CT (SUV{sub max} {>=} 2.70) and T2w MRI, 84.7% of these segments were in agreement with the gold standard, compared with 80.5% for T2w MRI alone. Conclusions: The additional value of {sup

  19. Experimental study of the 15O(2p, γ)17Ne cross section by Coulomb Dissociation for the rp process

    NASA Astrophysics Data System (ADS)

    Marganiec, J.; Warners, F.; Aksouh, F.; Aksyutina, Y.; Alvarez Pol, H.; Aumann, T.; Beceiro, S.; Bertulani, C.; Boretzky, K.; Borge, M. J.; Chartier, M.; Chatillon, A.; Chulkov, L.; Cortina-Gil, D.; Egorova, I.; Emling, H.; Ershova, O.; Forssén, C.; Fraile, L. M.; Fynbo, H.; Galaviz, D.; Geissel, H.; Grigorenko, L.; Heil, M.; Hoffmann, D. H. H.; Hoffmann, J.; Johansson, H.; Jonson, B.; Karakoç, M.; Karagiannis, C.; Kiselev, O.; Kratz, J. V.; Kulessa, R.; Kurz, N.; Langer, C.; Lantz, M.; Larsson, K.; Le Bleis, T.; Lemmon, R.; Litvinov, Yu A.; Mahata, K.; Müntz, C.; Nilsson, T.; Nociforo, C.; Nyman, G.; Ott, W.; Panin, V.; Parfenova, Yu; Paschalis, S.; Perea, A.; Plag, R.; Reifarth, R.; Richter, A.; Riisager, K.; Rodríguez Tajes, C.; Rossi, D.; Schrieder, G.; Shulgina, N.; Simon, H.; Stroth, J.; Sümmerer, K.; Taylor, J.; Tengblad, O.; Tengborn, E.; Weick, H.; Wiescher, M.; Wimmer, C.; Zhukov, M.

    2016-01-01

    The time-reversed reaction 15O(2p, γ)17Ne has been studied by the Coulomb dissociation technique. Secondary 17Ne ion beams at 500 AMeV have been produced by fragmentation reactions of 20Ne in a beryllium production target and dissociated on a secondary Pb target. The incoming beam and the reaction products have been identified with the kinematically complete LAND-R3B experimental setup at GSI. The excitation energy prior to decay has been reconstructed by using the invariant-mass method. The preliminary differential and integral Coulomb Dissociation cross sections (σCoul) have been calculated, which provide a photoabsorption (σphoto) and a radiative capture cross section (σcap). Additionally, important information about the nuclear structure of the 17Ne nucleus will be obtained. The analysis is in progress.

  20. Trojan Horse measurement of the 18F(p,α)15O astrophysical S(E)-factor

    NASA Astrophysics Data System (ADS)

    Pizzone, R. G.; Roeder, B. T.; McCleskey, M.; Trache, L.; Tribble, R. E.; Spitaleri, C.; Bertulani, C. A.; Cherubini, S.; Gulino, M.; Indelicato, I.; La Cognata, M.; Lamia, L.; Rapisarda, G. G.; Spartá, R.

    2016-02-01

    Crucial information on novae nucleosynthesis is linked to the abundance of 18F , which, due to great improvements in gamma-ray astronomy, can be detected in explosive environments. Therefore, the reaction network producing and destroying this radioactive isotope has been extensively studied in the last years. Among those reactions, the 18F(p,α)15O cross section has been measured by means of several dedicated experiments, both using direct and indirect methods. The presence of resonances in the energy region of astrophysical interest has been reported by many authors. In the present work a report on a recent experiment performed via the Trojan Horse Method (THM) is presented and the results are given and compared with the ones known in the literature, both direct and indirect. Data arising from THM measurements are then averaged and the reaction rate calculated in the novae energy range.

  1. Effects of single-dose irradiation in tumor blood flow studied by 15O decay after proton activation in situ.

    PubMed

    Emami, B; Ten Haken, R K; Nussbaum, G H; Hughes, W L

    1981-10-01

    A noninvasive technique employing photon activation of tissue oxygen in situ and detection of subsequent 15O positron decay was used to study the effects of single-dose 60Co irradiation on capillary blood flow in transplanted rat rhabdomyosarcomas. Tumor blood flow was measured before irradiation with 16.5, 38.5, or 60.5 Gy and at several intervals afterward (0-72 hr.). Pre-irradiation values of volume-averaged blood flow in the tumor ranged from 7 to 44 ml/min./100 g. Several hours after irradiation, blood flow fell by up to 50% for 60.5 Gy and up to 35% for 16.5 Gy. However, 24 hours after irradiation, tumor blood flow had recovered completely in the 16.5-Gy group and substantially in the others. For smaller doses such as the fractions typically employed in radiotherapy, no changes in tumor blood flow were observed. PMID:7291527

  2. Direct measurement of the {sup 18}F(p,{alpha}){sup 15}O reaction at nova temperatures

    SciTech Connect

    Beer, C. E.; Laird, A. M.; Bentley, M. A.; Diget, C. A.; Fox, S. P.; Fulton, B. R.; Murphy, A. St. J.; Davinson, T.; Salter, P.; Buchman, L.; Davids, B.; Hager, U.; Howell, D.; Martin, L.; Ruiz, C.; Ruprecht, G.; Vockenhuber, C.; Walden, P.

    2011-04-15

    The {sup 18}F(p,{alpha}){sup 15}O reaction rate is crucial for understanding the final abundance of {sup 18}F predicted by nova models. The {gamma}-ray emission in the first few hours after a nova outburst is expected to be dominated by 511 keV annihilation photons from the decay of {sup 18}F, and so understanding its production can provide important constraints on the conditions during the outburst when compared with observations. Results are presented from the lowest-energy direct measurement to date, performed at the Isotope Separator and Accelerator radioactive beam facility at the TRIUMF laboratory, Canada. Cross section measurements at center-of-mass energies of 250, 330, 453, and 673 keV are obtained and the results compared to previous data and R-matrix calculations. The implications for the overall reaction rate in the context of nova explosions have been discussed.

  3. Validity of using a 3-dimensional PET scanner during inhalation of 15O-labeled oxygen for quantitative assessment of regional metabolic rate of oxygen in man

    NASA Astrophysics Data System (ADS)

    Hori, Yuki; Hirano, Yoshiyuki; Koshino, Kazuhiro; Moriguchi, Tetsuaki; Iguchi, Satoshi; Yamamoto, Akihide; Enmi, Junichiro; Kawashima, Hidekazu; Zeniya, Tsutomu; Morita, Naomi; Nakagawara, Jyoji; Casey, Michael E.; Iida, Hidehiro

    2014-09-01

    Use of 15O labeled oxygen (15O2) and positron emission tomography (PET) allows quantitative assessment of the regional metabolic rate of oxygen (CMRO2) in vivo, which is essential to understanding the pathological status of patients with cerebral vascular and neurological disorders. The method has, however, been challenging, when a 3D PET scanner is employed, largely attributed to the presence of gaseous radioactivity in the trachea and the inhalation system, which results in a large amount of scatter and random events in the PET assessment. The present study was intended to evaluate the adequacy of using a recently available commercial 3D PET scanner in the assessment of regional cerebral radioactivity distribution during an inhalation of 15O2. Systematic experiments were carried out on a brain phantom. Experiments were also performed on a healthy volunteer following a recently developed protocol for simultaneous assessment of CMRO2 and cerebral blood flow, which involves sequential administration of 15O2 and C15O2. A particular intention was to evaluate the adequacy of the scatter-correction procedures. The phantom experiment demonstrated that errors were within 3% at the practically maximum radioactivity in the face mask, with the greatest radioactivity in the lung. The volunteer experiment demonstrated that the counting rate was at peak during the 15O gas inhalation period, within a verified range. Tomographic images represented good quality over the entire FOV, including the lower part of the cerebral structures and the carotid artery regions. The scatter-correction procedures appeared to be important, particularly in the process to compensate for the scatter originating outside the FOV. Reconstructed images dramatically changed if the correction was carried out using inappropriate procedures. This study demonstrated that accurate reconstruction could be obtained when the scatter compensation was appropriately carried out. This study also suggested the

  4. [Detection of second tumors in 11C-choline PET/CT studies performed due to biochemical recurrence of prostate cancer].

    PubMed

    García, J R; Ponce, A; Canales, M; Ayuso, J; Moragas, M; Soler, M

    2014-01-01

    Early localization of biochemical recurrence in patients after radical treatment of prostate cancer is a widely accepted clinical indication of (11)C-choline PET/CT. Its widespread clinical use has prompted the depiction of incidentalomas, unusual sites of metastatic lesions, as well as false positive and negative cases. Over the last 6 years, a total of 454 (11)C-choline PET/CT studies have been performed in our institution to locate biochemical recurrence of patients with prostate cancer. With these studies, a second neoplasm has been found in 7 patients (1.54%): 3 lung, 2 colorectal, 1 esophagus and 1 esophageal junction, respectively. Although the clinical usefulness of this technique for detecting cancer lesions other than prostate origin is known for those patients who undergo this technique in the accepted indication, the diagnosis of a second tumor has a significant impact on their therapeutic management. PMID:23499124

  5. Approaching complete inhibition of P-glycoprotein at the human blood-brain barrier: an (R)-[11C]verapamil PET study.

    PubMed

    Bauer, Martin; Karch, Rudolf; Zeitlinger, Markus; Philippe, Cécile; Römermann, Kerstin; Stanek, Johann; Maier-Salamon, Alexandra; Wadsak, Wolfgang; Jäger, Walter; Hacker, Marcus; Müller, Markus; Langer, Oliver

    2015-05-01

    As P-glycoprotein (Pgp) inhibition at the blood-brain barrier (BBB) after administration of a single dose of tariquidar is transient, we performed positron emission tomography (PET) scans with the Pgp substrate (R)-[(11)C]verapamil in five healthy volunteers during continuous intravenous tariquidar infusion. Total distribution volume (VT) of (R)-[(11)C]verapamil in whole-brain gray matter increased by 273 ± 78% relative to baseline scans without tariquidar, which was higher than previously reported VT increases. During tariquidar infusion whole-brain VT was comparable to VT in the pituitary gland, a region not protected by the BBB, which suggested that we were approaching complete Pgp inhibition at the human BBB. PMID:25669913

  6. Design, Synthesis, and Evaluation of a Low-Molecular-Weight (11)C-Labeled Tetrazine for Pretargeted PET Imaging Applying Bioorthogonal in Vivo Click Chemistry.

    PubMed

    Denk, Christoph; Svatunek, Dennis; Mairinger, Severin; Stanek, Johann; Filip, Thomas; Matscheko, Dominik; Kuntner, Claudia; Wanek, Thomas; Mikula, Hannes

    2016-07-20

    A low-molecular-weight tetrazine labeled with the short-lived positron emitter carbon-11 was developed as a bioorthogonal PET probe for pretargeted imaging. A method for efficient and fast synthesis of this imaging agent is presented using radiolabeling of a readily available precursor. High reactivity with trans-cyclooctenes was observed and in vivo investigations including PET/MR scanning showed homogeneous biodistribution, good metabolic stability, and rapid excretion in naive mice. These properties are key to the success of bioorthogonal (11)C-PET imaging, which has been shown in a simple pretargeting experiment using TCO-modified mesoporous silica nanoparticles. Overall, this (11)C-labeled tetrazine represents a highly versatile and advantageous chemical tool for bioorthogonal PET imaging and enables pretargeting approaches using carbon-11 for the first time. PMID:27308894

  7. Approaching complete inhibition of P-glycoprotein at the human blood–brain barrier: an (R)-[11C]verapamil PET study

    PubMed Central

    Bauer, Martin; Karch, Rudolf; Zeitlinger, Markus; Philippe, Cécile; Römermann, Kerstin; Stanek, Johann; Maier-Salamon, Alexandra; Wadsak, Wolfgang; Jäger, Walter; Hacker, Marcus; Müller, Markus; Langer, Oliver

    2015-01-01

    As P-glycoprotein (Pgp) inhibition at the blood–brain barrier (BBB) after administration of a single dose of tariquidar is transient, we performed positron emission tomography (PET) scans with the Pgp substrate (R)-[11C]verapamil in five healthy volunteers during continuous intravenous tariquidar infusion. Total distribution volume (VT) of (R)-[11C]verapamil in whole-brain gray matter increased by 273±78% relative to baseline scans without tariquidar, which was higher than previously reported VT increases. During tariquidar infusion whole-brain VT was comparable to VT in the pituitary gland, a region not protected by the BBB, which suggested that we were approaching complete Pgp inhibition at the human BBB. PMID:25669913

  8. High Precision Determination of the β Decay QEC Value of 11C and Implications on the Tests of the Standard Model

    NASA Astrophysics Data System (ADS)

    Gulyuz, K.; Bollen, G.; Brodeur, M.; Bryce, R. A.; Cooper, K.; Eibach, M.; Izzo, C.; Kwan, E.; Manukyan, K.; Morrissey, D. J.; Naviliat-Cuncic, O.; Redshaw, M.; Ringle, R.; Sandler, R.; Schwarz, S.; Sumithrarachchi, C. S.; Valverde, A. A.; Villari, A. C. C.

    2016-01-01

    We report the determination of the QEC value of the mirror transition of 11C by measuring the atomic masses of 11C and 11B using Penning trap mass spectrometry. More than an order of magnitude improvement in precision is achieved as compared to the 2012 Atomic Mass Evaluation (Ame2012) [Chin. Phys. C 36, 1603 (2012)]. This leads to a factor of 3 improvement in the calculated F t value. Using the new value, QEC=1981.690 (61 ) keV , the uncertainty on F t is no longer dominated by the uncertainty on the QEC value. Based on this measurement, we provide an updated estimate of the Gamow-Teller to Fermi mixing ratio and standard model values of the correlation coefficients.

  9. High Precision Determination of the β Decay Q(EC) Value of (11)C and Implications on the Tests of the Standard Model.

    PubMed

    Gulyuz, K; Bollen, G; Brodeur, M; Bryce, R A; Cooper, K; Eibach, M; Izzo, C; Kwan, E; Manukyan, K; Morrissey, D J; Naviliat-Cuncic, O; Redshaw, M; Ringle, R; Sandler, R; Schwarz, S; Sumithrarachchi, C S; Valverde, A A; Villari, A C C

    2016-01-01

    We report the determination of the Q(EC) value of the mirror transition of (11)C by measuring the atomic masses of (11)C and (11)B using Penning trap mass spectrometry. More than an order of magnitude improvement in precision is achieved as compared to the 2012 Atomic Mass Evaluation (Ame2012) [Chin. Phys. C 36, 1603 (2012)]. This leads to a factor of 3 improvement in the calculated Ft value. Using the new value, Q(EC)=1981.690(61)  keV, the uncertainty on Ft is no longer dominated by the uncertainty on the Q(EC) value. Based on this measurement, we provide an updated estimate of the Gamow-Teller to Fermi mixing ratio and standard model values of the correlation coefficients. PMID:26799013

  10. Missense mutations in β-1,3-N-acetylglucosaminyltransferase 1 (B3GNT1) cause Walker–Warburg syndrome

    PubMed Central

    Buysse, Karen; Riemersma, Moniek; Powell, Gareth; van Reeuwijk, Jeroen; Chitayat, David; Roscioli, Tony; Kamsteeg, Erik-Jan; van den Elzen, Christa; van Beusekom, Ellen; Blaser, Susan; Babul-Hirji, Riyana; Halliday, William; Wright, Gavin J.; Stemple, Derek L.; Lin, Yung-Yao; Lefeber, Dirk J.; van Bokhoven, Hans

    2013-01-01

    Several known or putative glycosyltransferases are required for the synthesis of laminin-binding glycans on alpha-dystroglycan (αDG), including POMT1, POMT2, POMGnT1, LARGE, Fukutin, FKRP, ISPD and GTDC2. Mutations in these glycosyltransferase genes result in defective αDG glycosylation and reduced ligand binding by αDG causing a clinically heterogeneous group of congenital muscular dystrophies, commonly referred to as dystroglycanopathies. The most severe clinical form, Walker–Warburg syndrome (WWS), is characterized by congenital muscular dystrophy and severe neurological and ophthalmological defects. Here, we report two homozygous missense mutations in the β-1,3-N-acetylglucosaminyltransferase 1 (B3GNT1) gene in a family affected with WWS. Functional studies confirmed the pathogenicity of the mutations. First, expression of wild-type but not mutant B3GNT1 in human prostate cancer (PC3) cells led to increased levels of αDG glycosylation. Second, morpholino knockdown of the zebrafish b3gnt1 orthologue caused characteristic muscular defects and reduced αDG glycosylation. These functional studies identify an important role of B3GNT1 in the synthesis of the uncharacterized laminin-binding glycan of αDG and implicate B3GNT1 as a novel causative gene for WWS. PMID:23359570

  11. Detection of Local, Regional, and Distant Recurrence in Patients With PSA Relapse After External-Beam Radiotherapy Using {sup 11}C-Choline Positron Emission Tomography

    SciTech Connect

    Breeuwsma, Anthonius J.; Pruim, Jan; Bergh, Alphons C.M. van den; Leliveld, Anna M.; Nijman, Rien J.M.; Dierckx, Rudi A.J.O.; Jong, Igle J. de

    2010-05-01

    Purpose: An elevated serum prostate-specific antigen (PSA) level cannot distinguish between local-regional recurrences and the presence of distant metastases after treatment with curative intent for prostate cancer. With the advent of salvage treatment such as cryotherapy, it has become important to localize the site of recurrence (local or distant). In this study, the potential of {sup 11}C-choline positron emission tomography (PET) to identify site of recurrence was investigated in patients with rising PSA after external-beam radiotherapy (EBRT). Methods and Materials: Seventy patients with histologically proven prostate cancer treated with EBRT and showing biochemical recurrence as defined by American Society for Therapeutic Radiology and Oncology consensus statement and 10 patients without recurrence underwent a PET scan using 400 MBq {sup 11}C-choline intravenously. Biopsy-proven histology from the site of suspicion, findings with other imaging modalities, clinical follow-up and/or response to adjuvant therapy were used as comparative references. Results: None of the 10 patients without biochemical recurrence had a positive PET scan. Fifty-seven of 70 patients with biochemical recurrence (median PSA 9.1 ng/mL; mean PSA 12.3 ng/mL) showed an abnormal uptake pattern (sensitivity 81%). The site of recurrence was only local in 41 of 57 patients (mean PSA 11.1 ng/mL at scan), locoregionally and/or distant in 16 of 57 patients (mean PSA 17.7 ng/mL). Overall the positive predictive value and negative predictive value for {sup 11}C-choline PET scan were 1.0 and 0.44 respectively. Accuracy was 84%. Conclusions: {sup 11}C-choline PET scan is a sensitive technique to identify the site of recurrence in patients with PSA relapse after EBRT for prostate cancer.

  12. Brain PET measurement of PDE10A occupancy by TAK-063, a new PDE10A inhibitor, using [(11) C]T-773 in nonhuman primates.

    PubMed

    Takano, Akihiro; Stepanov, Vladimir; Nakao, Ryuji; Amini, Nahid; Gulyás, Balázs; Kimura, Haruhide; Halldin, Christer

    2016-06-01

    Because phosphodiesterase 10A (PDE10A) degrades both cyclic adenosine monophosphate and cyclic guanosine monophosphate and is distributed mainly in the striatum, PDE10A inhibitors have been considered to potentially be useful therapeutic agents for psychiatric and neurodegenerative diseases such as schizophrenia and Huntington's disease. We measured striatal PDE10A occupancy by TAK-063, a newly developed compound with high affinity and selectivity for PDE10A, using PET with [(11) C]T-773 in nonhuman primates. Two 123-min dynamic PET measurements were performed on three female rhesus monkeys, once at baseline and again after intravenous administration of different doses of TAK-063 (0.2-1.6 mg/kg). Total distribution volume (VT ) was calculated with a two-tissue compartment model using metabolite-corrected plasma input. Although the in vitro autoradiography did not show high specific binding to [(11) C]T-773 in the cerebellum, VT in the cerebellum decreased after TAK-063 treatment. The specific binding to PDE10A (VS ) was calculated as the difference of the VT between the target regions and the cerebellum. PDE10A occupancy was calculated as the percent change of VS . The average PDE10A occupancy of the caudate nucleus and putamen was 35.2% at 0.2 mg/kg and 83.2% at 1.6 mg/kg. In conclusion, this nonhuman primate PET study demonstrated that [(11) C]T-773 is useful to estimate the PDE10A occupancy by TAK-063 in the striatum although there is in vivo interaction of the uptake between [(11) C]T-773 and TAK-063 in the cerebellum. These results warrant further clinical occupancy study for TAK-063. Synapse 70:253-263, 2016. © 2016 Wiley Periodicals, Inc. PMID:26878349

  13. Imaging glutamate homeostasis in cocaine addiction with the mGluR5 PET radiotracer [11C]ABP688 and Magnetic Resonance Spectroscopy

    PubMed Central

    Martinez, Diana; Slifstein, Mark; Nabulsi, Nabeel; Grassetti, Alexander; Urban, Nina; Perez, Audrey; Liu, Fei; Lin, Shu-fei; Ropchan, Jim; Mao, Xiangling; Kegeles, Lawrence S.; Shungu, Dikoma C.; Carson, Richard E.; Huang, Yiyun

    2014-01-01

    Background Preclinical studies demonstrate that glutamate homeostasis in the striatum is disrupted following cocaine exposure, including a decrease in metabotropic glutamate receptor type 5 (mGluR5) expression and reduced glutamate turnover. The goal of this study was to use imaging of the human brain to investigate alterations in the glutamate signaling in cocaine addiction. Methods Positron Emission tomography (PET) imaging with the radiotracer [11C]ABP688 was used to measure mGluR5 binding and magnetic resonance spectroscopy (MRS) was used to measure glutamate-glutamine levels in the striatum of cocaine addicted participants (n=15) compared to healthy controls (n=15). Following the scans, the cocaine addicted volunteers performed cocaine self-administration sessions in order to investigate the correlation between cocaine seeking behavior and mGluR5 receptor binding. Results The results of the study showed that cocaine addiction was associated with a 20–22% reduction in [11C]ABP688 binding in the striatum. A secondary analysis of cortical and subcortical regions other than the striatum showed a similar reduction in [11C]ABP688 binding, suggesting that the decrease is widespread. No between-group differences were seen in the MRS measures of glutamate-glutamine in the left striatum. In addition, no correlation was seen between [11C]ABP688 binding in the striatum and the choice to self-administer cocaine. Conclusions Overall, these results show that long-term cocaine use is associated with a decrease in mGluR5 availability compared to matched healthy controls and suggests that this receptor may serve as a viable target for treatment development for this disorder. PMID:24035345

  14. Spinal Cord Dopamine D2/D3 Receptors: In Vivo and Ex Vivo Imaging in the Rat using 18F/11C-Fallypride

    PubMed Central

    Kaur, Jasmeet; Khararjian, Armen; Coleman, Robert A.; Constantinescu, Cristian C.; Pan, Min-Liang; Mukherjee, Jogeshwar

    2014-01-01

    Objectives Spinal cord is known to be innervated with dopaminergic cells with catecholaminergic projections arising from the medulla and pons and dopaminergic transmission in the spinal cord is vital for sensory and motor function. Our goal was to evaluate and compare the imaging capability of dopamine D2/D3 receptors in the rat spinal cord using PET ligands 18F-fallypride and 11C-fallypride. Methods Male Sprague-Dawley rats were used in all in vitro and in vivo studies. Spinal cord and brain sections were used for in vitro autoradiography and ex vivo autoradiography. For in vivo studies animals received a 18F-fallypride scan or a 11C-fallypride PET scan. The spinal cord and the brain were then harvested, flash-frozen and imaged ex vivo. For in vivo analysis Logan plots with cerebellum as a reference was used to evaluate binding potentials (BP). Tissue ratios were used for ex vivo analysis. Drug effects were evaluated using clozapine, haloperidol and dopamine were evaluated on spinal cord sections in vitro. Results In vitro studies showed 18F-fallypride binding to superficial dorsal horn (SDH), dorsal horn (DH), ventral horn (VH) and the pars centralis (PC). In the cervical section, the greatest amount of binding appeared to be in the SDH. Ex vivo studies showed approximately 6% of 18F-fallypride in SDH compared to that observed in the striatum. In vivo analysis of both 18F-fallypride and 11C-fallypride in the spinal cord were comparable to that in the extrastriatal regions. Haloperidol and clozapine displaced more than 75% of the 18F-fallypride in spinal cord sections. Conclusions Our studies showed 18F-fallypride and 11C-fallypride binding in the spinal cord in vitro and in vivo. The binding pattern correlates well with the known distribution of dopamine D2/D3 receptors in the spinal cord. PMID:25199843

  15. Variability of Gross Tumor Volume in Nasopharyngeal Carcinoma Using 11C-Choline and 18F-FDG PET/CT.

    PubMed

    Jiang, Jun; Wu, Hubing; Huang, Meiyan; Wu, Yao; Wang, Quanshi; Zhao, Jianqi; Yang, Wei; Chen, Wufan; Feng, Qianjin

    2015-01-01

    This study was conducted to evaluate the variability of gross tumor volume (GTV) using 11C-Choline and 18F-FDG PET/CT images for nasopharyngeal carcinomas boundary definition. Assessment consisted of inter-observer and inter-modality variation analysis. Four radiation oncologists were invited to manually contour GTV by using PET/CT fusion obtained from a cohort of 12 patients with nasopharyngeal carcinoma (NPC) and who underwent both 11C-Choline and 18F-FDG scans. Student's paired-sample t-test was performed for analyzing inter-observer and inter-modality variability. Semi-automatic segmentation methods, including thresholding and region growing, were also validated against the manual contouring of the two types of PET images. We observed no significant variation in the results obtained by different oncologists in terms of the same type of PET/CT volumes. Choline fusion volumes were significantly larger than the FDG volumes (p < 0.0001, mean ± SD = 18.21 ± 8.19). While significantly consistent results were obtained between the oncologists and the standard references in Choline volumes compared with those in FDG volumes (p = 0.0025). Simple semi-automatic delineation methods indicated that 11C-Choline PET images could provide better results than FDG volumes (p = 0.076, CI = [-0.29, 0.025]). 11C-Choline PET/CT may be more advantageous in GTV delineation for the radiotherapy of NPC than 18F-FDG. Phantom simulations and clinical trials should be conducted to prove the possible improvement of the treatment outcome. PMID:26161910

  16. Validation of a tracer kinetic model for the quantification of 5-HT(2A) receptors in human brain with [(11)C]MDL 100,907.

    PubMed

    Hinz, Rainer; Bhagwagar, Zubin; Cowen, Philip J; Cunningham, Vincent J; Grasby, Paul M

    2007-01-01

    The positron emission tomography (PET) ligand [(11)C]MDL 100,907 has previously been introduced to image the serotonin 2A (5-HT(2A)) receptor in human brain. The aim of this work was to contribute to the verification of the tracer kinetic modelling in human studies. Five healthy volunteers were scanned twice after intravenous bolus injection of approximately 370 MBq [(11)C]MDL 100,907 using dynamic PET. One scan was performed under baseline condition, the other scan commenced 90 mins after a single oral dose of 30 mg of the antidepressant mirtazapine, which binds to the 5-HT(2A) receptor. There did not appear to be radiolabelled metabolites of [(11)C]MDL 100,907 in human plasma, which are likely to cross the blood-brain barrier. Total volumes of distribution VD in 11 different brain regions were estimated using a reversible, two tissue, four rate constants compartment model with a variable fractional blood volume term and the metabolite-corrected plasma input function. There were no significant changes of the VD in the cerebellum between the baseline and the blocked scans confirming the cerebellum as a region devoid of displaceable binding. Regional estimates of binding potential were then obtained indirectly using the cerebellar VD and occupancies calculated. The mean occupancy with this clinically effective dose of mirtazapine was 60% without significant regional differences. This study confirmed the use of an arterial input kinetic model for the quantification of 5-HT(2A) receptor binding with [(11)C]MDL 100,907 and the use of the cerebellum as a reference region for the free and nonspecific binding. PMID:16685260

  17. Evaluation in Monkey of Two Candidate PET Radioligands, [11C]RX-1 and [18F]RX-2, for Imaging Brain 5-HT4 Receptors

    PubMed Central

    LOHITH, TALAKAD G.; XU, RONG; TSUJIKAWA, TETSUYA; MORSE, CHERYL L.; ANDERSON, KACEY B.; GLADDING, ROBERT L.; ZOGHBI, SAMI S.; FUJITA, MASAHIRO; INNIS, ROBERT B.; PIKE, VICTOR W.

    2014-01-01

    The serotonin subtype-4 (5-HT4) receptor, which is known to be involved physiologically in learning and memory, and pathologically in Alzheimer’s disease, anxiety and other neuropsychiatric disorders – has few radioligands readily available for imaging in vivo. We have previously reported two novel 5-HT4 receptor radioligands, namely [methoxy-11C](1-butylpiperidin-4-yl)methyl 4-amino-3-methoxybenzoate; [11C]RX-1) and the [18F]3-fluoromethoxy analog ([18F]RX-2), and in this study we evaluated them by PET in rhesus monkey. Brain scans were performed at baseline, receptor preblock or displacement conditions using SB 207710, a 5-HT4 receptor antagonist, on the same day for [11C]RX-1 and on different days for [18F]RX-2. Specific-to-nondisplaceable ratio (BPND) was measured with the simplified reference tissue model from all baseline scans. To determine specific binding, total distribution volume (VT) was also measured in some monkeys by radiometabolite-corrected arterial input function after ex vivo inhibition of esterases from baseline and blocked scans. Both radioligands showed moderate to high peak brain uptake of radioactivity (2–6 SUV). Regional BPND values were in the rank order of known 5-HT4 receptor distribution with a trend for higher BPND values from [18F]RX-2. One-tissue compartmental model provided good fits with well identified VT values for both radioligands. In the highest 5-HT4 receptor density region, striatum, 50–60% of total binding was specific. The VT in receptor-poor cerebellum reached stable values by about 60 min for both radioligands indicating little influence of radiometabolites on brain signal. In conclusion, both [11C]RX-1 and [18F]RX-2 showed positive attributes for PET imaging of brain 5-HT4 receptors, validating the radioligand design strategy. PMID:25088028

  18. Human SLC4A11-C functions as a DIDS-stimulatable H+(OH−) permeation pathway: partial correction of R109H mutant transport

    PubMed Central

    Kao, Liyo; Azimov, Rustam; Abuladze, Natalia; Newman, Debra

    2014-01-01

    The SLC4A11 gene mutations cause a variety of genetic corneal diseases, including congenital hereditary endothelial dystrophy 2 (CHED2), Harboyan syndrome, some cases of Fuchs' endothelial dystrophy (FECD), and possibly familial keratoconus. Three NH2-terminal variants of the human SLC4A11 gene, named SLC4A11-A, -B, and -C are known. The SLC4A11-B variant has been the focus of previous studies. Both the expression of the SLC4A11-C variant in the cornea and its functional properties have not been characterized, and therefore its potential pathophysiological role in corneal diseases remains to be explored. In the present study, we demonstrate that SLC4A11-C is the predominant SLC4A11 variant expressed in human corneal endothelial mRNA and that the transporter functions as an electrogenic H+(OH−) permeation pathway. Disulfonic stilbenes, including 4,4′-diisothiocyano-2,2′-stilbenedisulfonate (DIDS), 4,4′-diisothiocyanatodihydrostilbene-2,2′-disulfonate (H2DIDS), and 4-acetamido-4′-isothiocyanato-stilbene-2,2′-disulfonate (SITS), which are known to bind covalently, increased SLC4A11-C-mediated H+(OH−) flux by 150–200% without having a significant effect in mock-transfected cells. Noncovalently interacting 4,4′-diaminostilbene-2,2′-disulfonate (DADS) was without effect. We tested the efficacy of DIDS on the functionally impaired R109H mutant (SLC4A11-C numbering) that causes CHED2. DIDS (1 mM) increased H+(OH−) flux through the mutant transporter by ∼40–90%. These studies provide a basis for future testing of more specific chemically modified dilsulfonic stilbenes as potential therapeutic agents to improve the functional impairment of specific SLC4A11 mutant transporters. PMID:25394471

  19. Test-retest reproducibility of [11C]-(+)-propyl-hexahydro-naphtho-oxazin positron emission tomography using the bolus plus constant infusion paradigm.

    PubMed

    Lee, Dianne E; Gallezot, Jean-Dominique; Zheng, Ming-Qiang; Lim, Keunpoong; Ding, Yu-Shin; Huang, Yiyun; Carson, Richard E; Morris, Evan D; Cosgrove, Kelly P

    2013-01-01

    We examined the reproducibility of using the constant infusion paradigm for equilibrium measurement of D2/3 receptors using [11C]-(+)-propyl-hexahydro-naphtho-oxazin (PHNO) positron emission tomography (PET). Six subjects were scanned with a bolus plus constant infusion (Kbol = 80 minutes) of [11C]-(+)-PHNO. Binding potential (BPND) was computed using the equilibrium approach and compared to a simplified reference tissue model (SRTM). The rate of change in the concentration-activity curve from 60 to 90 minutes was -5 ± 13%/h in the caudate, putamen, substantia nigra, thalamus, and cerebellum but was 15 ± 15%/h in the ventral striatum and pallidum. Test-retest variability was lower in striatal compared to extrastriatal regions (4 ± 8% vs -8 ± 22%, respectively) using the equilibrium approach, with comparable results with SRTM. The equilibrium ratio and SRTM yielded reliable BPND estimates (intraclass correlation coefficient = 0.88 and 0.82, respectively). These studies support the reproducibility of the bolus plus constant infusion paradigm with [11C]-(+)-PHNO PET. PMID:23415395

  20. Quantification of delta-opioid receptors in human brain with N1'-([11C]methyl) naltrindole and positron emission tomography.

    PubMed

    Smith, J S; Zubieta, J K; Price, J C; Flesher, J E; Madar, I; Lever, J R; Kinter, C M; Dannals, R F; Frost, J J

    1999-09-01

    The regional binding of N1'-([11C]methyl)naltrindole (MeNTI), a selective delta-opioid antagonist, was studied in healthy human subjects with positron emission tomography (PET). After the bolus intravenous administration of high specific activity [11C]MeNTI, PET was performed over 90 minutes. Arterial plasma samples were obtained during the scanning period and assayed for the presence of radiolabeled metabolites. The data were analyzed with various kinetic (two- and three-compartment models, Patlak graphical analysis) and nonkinetic (apparent volume of distribution and activity at a late scanning time) approaches. This tracer showed irreversible binding characteristics during the scanning period used. The results of the analyses also were compared with the density and distribution of delta-opioid receptors in the human brain in vitro. Additionally, computer simulations were performed to assess the effects of changes in receptor binding and tracer transport changes on the perceived binding parameters obtained with the models. A constrained three-compartment kinetic model was demonstrated to be superior to other quantification models for the description of MeNTI kinetics and quantification of delta receptor binding in the human brain with 11C-labeled MeNTI. PMID:10478647

  1. In vivo (R)-[(11)C]PK11195 PET imaging of 18kDa translocator protein in recent onset psychosis.

    PubMed

    van der Doef, Thalia F; de Witte, Lot D; Sutterland, Arjen L; Jobse, Ellen; Yaqub, Maqsood; Boellaard, Ronald; de Haan, Lieuwe; Eriksson, Jonas; Lammertsma, Adriaan A; Kahn, René S; van Berckel, Bart N M

    2016-01-01

    Evidence is accumulating that immune dysfunction is involved in the pathophysiology of schizophrenia. It has been hypothesized that microglia activation is present in patients with schizophrenia. Various in vivo and post-mortem studies have investigated this hypothesis, but as yet with inconclusive results. Microglia activation is associated with elevations in 18 kDa translocator protein (TSPO) levels, which can be measured with the positron emission tomography (PET) tracer (R)-[(11)C]PK11195. The purpose of the present study was to investigate microglia activation in psychosis in vivo at an early stage of the disease. (R)-[(11)C]PK11195 binding potential (BPND) was measured in 19 patients with recent onset psychosis and 17 age and gender-matched healthy controls. Total gray matter, as well as five gray matter regions of interest (frontal cortex, temporal cortex, parietal cortex, striatum, and thalamus) were defined a priori. PET data were analysed using a reference tissue approach and a supervised cluster analysis algorithm to identify the reference region. No significant difference in (R)-[(11)C]PK11195 BPND between patients and controls was found in total gray matter, nor one of the regions of interest. These findings suggest that microglia activation is not present in recent onset psychosis or that it is a subtle phenomenon that could not be detected using the design of the present study. PMID:27602389

  2. In vivo (R)-[11C]PK11195 PET imaging of 18kDa translocator protein in recent onset psychosis

    PubMed Central

    van der Doef, Thalia F; de Witte, Lot D; Sutterland, Arjen L; Jobse, Ellen; Yaqub, Maqsood; Boellaard, Ronald; de Haan, Lieuwe; Eriksson, Jonas; Lammertsma, Adriaan A; Kahn, René S; van Berckel, Bart N M

    2016-01-01

    Evidence is accumulating that immune dysfunction is involved in the pathophysiology of schizophrenia. It has been hypothesized that microglia activation is present in patients with schizophrenia. Various in vivo and post-mortem studies have investigated this hypothesis, but as yet with inconclusive results. Microglia activation is associated with elevations in 18 kDa translocator protein (TSPO) levels, which can be measured with the positron emission tomography (PET) tracer (R)-[11C]PK11195. The purpose of the present study was to investigate microglia activation in psychosis in vivo at an early stage of the disease. (R)-[11C]PK11195 binding potential (BPND) was measured in 19 patients with recent onset psychosis and 17 age and gender-matched healthy controls. Total gray matter, as well as five gray matter regions of interest (frontal cortex, temporal cortex, parietal cortex, striatum, and thalamus) were defined a priori. PET data were analysed using a reference tissue approach and a supervised cluster analysis algorithm to identify the reference region. No significant difference in (R)-[11C]PK11195 BPND between patients and controls was found in total gray matter, nor one of the regions of interest. These findings suggest that microglia activation is not present in recent onset psychosis or that it is a subtle phenomenon that could not be detected using the design of the present study. PMID:27602389

  3. Acute effect of the anti-addiction drug bupropion on extracellular dopamine concentrations in the human striatum: an [11C]raclopride PET study.

    PubMed

    Egerton, Alice; Shotbolt, John P; Stokes, Paul R A; Hirani, Ella; Ahmad, Rabia; Lappin, Julia M; Reeves, Suzanne J; Mehta, Mitul A; Howes, Oliver D; Grasby, Paul M

    2010-03-01

    Bupropion is an effective medication in treating addiction and is widely used as an aid to smoking cessation. Bupropion inhibits striatal dopamine reuptake via dopamine transporter blockade, but it is unknown whether this leads to increased extracellular dopamine levels at clinical doses in man. The effects of bupropion on extracellular dopamine levels in the striatum were investigated using [(11)C]raclopride positron emission tomography (PET) imaging in rats administered saline, 11 or 25 mg/kg bupropion i.p. and in healthy human volunteers administered either placebo or 150 mg bupropion (Zyban Sustained-Release). A cognitive task was used to stimulate dopamine release in the human study. In rats, bupropion significantly decreased [(11)C]raclopride specific binding in the striatum, consistent with increases in extracellular dopamine concentrations. In man, no significant decreases in striatal [(11)C]raclopride specific binding were observed. Levels of dopamine transporter occupancy in the rat at 11 and 25 mg/kg bupropion i.p. were higher than predicted to occur in man at the dose used. Thus, these data indicate that, at the low levels of dopamine transporter occupancy achieved in man at clinical doses, bupropion does not increase extracellular dopamine levels. These findings have important implications for understanding the mechanism of action underlying bupropions' therapeutic efficacy and for the development of novel treatments for addiction and depression. PMID:19969097

  4. Imaging the cannabinoid CB1 receptor in humans with [11C]OMAR: assessment of kinetic analysis methods, test-retest reproducibility, and gender differences.

    PubMed

    Normandin, Marc D; Zheng, Ming-Qiang; Lin, Kuo-Shyan; Mason, N Scott; Lin, Shu-Fei; Ropchan, Jim; Labaree, David; Henry, Shannan; Williams, Wendol A; Carson, Richard E; Neumeister, Alexander; Huang, Yiyun

    2015-08-01

    The Radiotracer [(11)C]OMAR was developed for positron emission tomography (PET) imaging of cannabinoid type-1 receptors (CB1R). The objectives of the present study were to evaluate kinetic analysis methods, determine test-retest reliability, and assess gender differences in receptor availability. Dynamic PET data were acquired in 10 human subjects, and analyzed with one-tissue (1T) and two-tissue (2T) compartment models and by the Logan and multilinear analysis (MA1) methods to estimate regional volume of distribution (VT). The 2T model inclusive of a vascular component (2TV) and MA1 were the preferred techniques. Test-retest reliability of VT was good (mean absolute deviation ~9%; intraclass correlation coefficient ~0.7). Tracer parent fraction in plasma was lower in women (P<0.0001). Cerebral uptake normalized by body weight and injected dose was higher in men by 17% (P<0.0001), but VT was significantly greater in women by 23% (P<0.0001). These findings show that [(11)C]OMAR binding can be reliably quantified by the 2T model or MA1 method and demonstrate the utility of this tracer for in vivo imaging of CB1R. In addition, results from the present study indicate that gender difference in receptor binding should be taken into consideration when [(11)C]OMAR is used to quantify CB1R availability in neuropsychiatric disorders. PMID:25833345

  5. Imaging the cannabinoid CB1 receptor in humans with [11C]OMAR: assessment of kinetic analysis methods, test–retest reproducibility, and gender differences

    PubMed Central

    Normandin, Marc D; Zheng, Ming-Qiang; Lin, Kuo-Shyan; Mason, N Scott; Lin, Shu-Fei; Ropchan, Jim; Labaree, David; Henry, Shannan; Williams, Wendol A; Carson, Richard E; Neumeister, Alexander; Huang, Yiyun

    2015-01-01

    The Radiotracer [11C]OMAR was developed for positron emission tomography (PET) imaging of cannabinoid type-1 receptors (CB1R). The objectives of the present study were to evaluate kinetic analysis methods, determine test–retest reliability, and assess gender differences in receptor availability. Dynamic PET data were acquired in 10 human subjects, and analyzed with one-tissue (1T) and two-tissue (2T) compartment models and by the Logan and multilinear analysis (MA1) methods to estimate regional volume of distribution (VT). The 2T model inclusive of a vascular component (2TV) and MA1 were the preferred techniques. Test–retest reliability of VT was good (mean absolute deviation ~9% intraclass correlation coefficient ~0.7). Tracer parent fraction in plasma was lower in women (P<0.0001). Cerebral uptake normalized by body weight and injected dose was higher in men by 17% (P<0.0001), but VT was significantly greater in women by 23% (P<0.0001). These findings show that [11C]OMAR binding can be reliably quantified by the 2T model or MA1 method and demonstrate the utility of this tracer for in vivo imaging of CB1R. In addition, results from the present study indicate that gender difference in receptor binding should be taken into consideration when [11C]OMAR is used to quantify CB1R availability in neuropsychiatric disorders. PMID:25833345

  6. [11C]-Labeled Metformin Distribution in the Liver and Small Intestine Using Dynamic Positron Emission Tomography in Mice Demonstrates Tissue-Specific Transporter Dependency.

    PubMed

    Jensen, Jonas B; Sundelin, Elias I; Jakobsen, Steen; Gormsen, Lars C; Munk, Ole L; Frøkiær, Jørgen; Jessen, Niels

    2016-06-01

    Metformin is the most commonly prescribed oral antidiabetic drug, with well-documented beneficial preventive effects on diabetic complications. Despite being in clinical use for almost 60 years, the underlying mechanisms for metformin action remain elusive. Organic cation transporters (OCT), including multidrug and toxin extrusion proteins (MATE), are essential for transport of metformin across membranes, but tissue-specific activity of these transporters in vivo is incompletely understood. Here, we use dynamic positron emission tomography with [(11)C]-labeled metformin ([(11)C]-metformin) in mice to investigate the role of OCT and MATE in a well-established target tissue, the liver, and a putative target of metformin, the small intestine. Ablation of OCT1 and OCT2 significantly reduced the distribution of metformin in the liver and small intestine. In contrast, inhibition of MATE1 with pyrimethamine caused accumulation of metformin in the liver but did not affect distribution in the small intestine. The demonstration of OCT-mediated transport into the small intestine provides evidence of direct effects of metformin in this tissue. OCT and MATE have important but separate roles in uptake and elimination of metformin in the liver, but this is not due to changes in biliary secretion. [(11)C]-Metformin holds great potential as a tool to determine the pharmacokinetic properties of metformin in clinical studies. PMID:26993065

  7. PET imaging of serotoninergic neurotransmission with [11C]DASB and [18F]altanserin after focal cerebral ischemia in rats

    PubMed Central

    Martín, Abraham; Szczupak, Boguslaw; Gómez-Vallejo, Vanessa; Plaza, Sandra; Padró, Daniel; Cano, Ainhoa; Llop, Jordi

    2013-01-01

    The use of selective serotonin reuptake inhibitors has shown functional improvement after stroke. Despite this, the role of serotoninergic neurotransmission after cerebral ischemia evolution and its involvement in functional recovery processes are still largely unknown. For this purpose, we performed in parallel in vivo magnetic resonance imaging and positron emission tomography (PET) with [11C]DASB and [18F]altanserin at 1, 3, 7, 14, 21, and 28 days after middle cerebral artery occlusion (MCAO) in rats. In the ischemic territory, PET with [11C]DASB and [18F]altanserin showed a dramatic decline in serotonin transporter (SERT) and 5-HT2A binding potential in the cortex and striatum after cerebral ischemia. Interestingly, a slight increase in [11C]DASB binding was observed from days 7 to 21 followed by the uppermost binding at day 28 in the ipsilateral midbrain. In contrast, no changes were observed in the contralateral hemisphere by using both radiotracers. Likewise, both functional and behavior testing showed major impaired outcome at day 1 after ischemia onset followed by a recovery of the sensorimotor function and dexterity from day 21 to day 28 after cerebral ischemia. Taken together, these results might evidence that SERT changes in the midbrain could have a key role in the functional recovery process after cerebral ischemia. PMID:23982048

  8. Biodistribution of the radionuclides (18)F-FDG, (11)C-methionine, (11)C-PK11195, and (68)Ga-citrate in domestic juvenile female pigs and morphological and molecular imaging of the tracers in hematogenously disseminated Staphylococcus aureus lesions.

    PubMed

    Afzelius, Pia; Nielsen, Ole L; Alstrup, Aage Ko; Bender, Dirk; Leifsson, Páll S; Jensen, Svend B; Schønheyder, Henrik C

    2016-01-01

    Approximately 5-7% of acute-care patients suffer from bacteremia. Bacteremia may give rise to bacterial spread to different tissues. Conventional imaging procedures as X-ray, Computed Tomography (CT), Magnetic Resonance Imaging (MRI), and ultrasound are often first-line imaging methods for identification and localization of infection. These methods are, however, not always successful. Early identification and localization of infection is critical for the appropriate and timely selection of therapy. The aim of this study was thus; a head to head comparison of (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) to PET with tracers that potentially could improve uncovering of infectious lesions in soft tissues. We chose (11)C-methionine, (11)C-PK11195, and (68)Ga-citrate as tracers and besides presenting their bio-distribution we validated their diagnostic utility in pigs with experimental bacterial infection. Four juvenile 14-15 weeks old female domestic pigs were scanned seven days after intra-arterial inoculation in the right femoral artery with a porcine strain of S. aureus using a sequential scanning protocol with (18)F-FDG, (11)C-methionine, (11)C-PK11195 and (68)Ga-citrate. This was followed by necropsy of the pigs consisting of gross pathology, histopathology and microbial examination. The pigs primarily developed lesions in lungs and neck muscles. (18)F-FDG had higher infection to background ratios and accumulated in most infectious foci caused by S. aureus, while (11)C-methionine and particularly (11)C-PK11195 and (68)Ga-citrate accumulated to a lesser extent in infectious foci. (18)F-FDG-uptake was seen in the areas of inflammatory cells and to a much lesser extent in reparative infiltration surrounding necrotic regions. PMID:27069765

  9. Biodistribution of the radionuclides 18F-FDG, 11C-methionine, 11C-PK11195, and 68Ga-citrate in domestic juvenile female pigs and morphological and molecular imaging of the tracers in hematogenously disseminated Staphylococcus aureus lesions

    PubMed Central

    Afzelius, Pia; Nielsen, Ole L; Alstrup, Aage KO; Bender, Dirk; Leifsson, Páll S; Jensen, Svend B; Schønheyder, Henrik C

    2016-01-01

    Approximately 5-7% of acute-care patients suffer from bacteremia. Bacteremia may give rise to bacterial spread to different tissues. Conventional imaging procedures as X-ray, Computed Tomography (CT), Magnetic Resonance Imaging (MRI), and ultrasound are often first-line imaging methods for identification and localization of infection. These methods are, however, not always successful. Early identification and localization of infection is critical for the appropriate and timely selection of therapy. The aim of this study was thus; a head to head comparison of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) to PET with tracers that potentially could improve uncovering of infectious lesions in soft tissues. We chose 11C-methionine, 11C-PK11195, and 68Ga-citrate as tracers and besides presenting their bio-distribution we validated their diagnostic utility in pigs with experimental bacterial infection. Four juvenile 14-15 weeks old female domestic pigs were scanned seven days after intra-arterial inoculation in the right femoral artery with a porcine strain of S. aureus using a sequential scanning protocol with 18F-FDG, 11C-methionine, 11C-PK11195 and 68Ga-citrate. This was followed by necropsy of the pigs consisting of gross pathology, histopathology and microbial examination. The pigs primarily developed lesions in lungs and neck muscles. 18F-FDG had higher infection to background ratios and accumulated in most infectious foci caused by S. aureus, while 11C-methionine and particularly 11C-PK11195 and 68Ga-citrate accumulated to a lesser extent in infectious foci. 18F-FDG-uptake was seen in the areas of inflammatory cells and to a much lesser extent in reparative infiltration surrounding necrotic regions. PMID:27069765

  10. Radiation Dosimetry and Biodistribution of the Translocator Protein Radiotracer [11C]DAA1106 Determined with PET/CT in Healthy Human Volunteers

    PubMed Central

    Brody, Arthur L.; Okita, Kyoji; Shieh, Jennifer; Liang, Lidia; Hubert, Robert; Mamoun, Michael; Farahi, Judah; Mandelkern, Mark A.

    2014-01-01

    Introduction When microglia become activated (an integral part of neuroinflammation), cellular morphology changes and expression of translocator protein (TSPO) 18 kDa is increased. Over the past several years, [11C]DAA1106 has emerged as a reliable radiotracer for labeling TSPO with high affinity during positron emission tomography (PET) scanning. While [11C]DAA1106 PET scanning has been used in several research studies, a radiation dosimetry study of this radiotracer in humans has not yet been published. Methods Twelve healthy participants underwent full body dynamic [11C]DAA1106 PET scanning, with 8 sequential whole body scans (approximately 12 bed positions each), following a single injection. Regions of interest were drawn manually and time activity curves (TACs) were obtained for 15 organs. OLINDA/EXM 1.1 was used to compute radiation absorbed doses to the target organs, as well as effective dose (ED) and effective dose equivalent (EDE). Results The ED and EDE were 4.06 ± 0.58 μSv/MBq and 5.89 ± 0.83 μSv/MBq, respectively. The highest absorbed doses were to the heart wall, kidney, liver, pancreas, and spleen. TACs revealed that peak dose rates are during the first scan (at 6 min) for all organs other than the urinary bladder wall, which had its peak dose rate during the fourth scan (at 30 min). Conclusions The recently developed radiotracer [11C]DAA1106 has its EDE and target-organ absorbed dose such that, for a single administration, its radiation dosimetry is well within the U.S. FDA guidelines for basic research studies in adults. This dose level implies that the dosimetry for multiple [11C]DAA1106 scans within a given year also falls within FDA guidelines, and this favorable property makes this radiotracer suitable for examining microglial activation repeatedly over time, which may in the future be useful for longitudinal tracking of disease progression and monitoring of therapy response in conditions marked by neuroinflammation (e.g., head trauma and

  11. Isolation and characterization of two Saccharomyces cerevisiae genes that encode proteins that bind to (TG1-3)n single strand telomeric DNA in vitro.

    PubMed Central

    Lin, J J; Zakian, V A

    1994-01-01

    By screening lambda gt11 libraries with a radiolabeled (TG1-3)n oligonucleotide, two Saccharomyces cerevisiae genes were identified that encode polypeptides that recognize the single-stranded telomeric repeat sequence (TG1-3)n. The first gene, NSR1, a previously identified gene, encodes a protein involved in ribosomal RNA maturation and possibly in transport of proteins into the nucleus. The second gene, GBP2 (G-strand Binding Protein), is an anonymous open reading frame from chromosome III. These two genes contain RNA recognition motifs (RRMs) that are found in proteins that interact with RNA. Both Nsr1p and Gbp2p bind specifically to yeast single strand (TG1-3)n DNA in vitro. To test whether these two proteins associate with telomeres in vivo, strains were constructed in which one or both of these genes were either disrupted or overexpressed. None of these alterations affected telomere length or telomere position effect. The potential role of these two (TG1-3)n binding proteins is discussed. Images PMID:7800479

  12. Reaction Mechanisms in Collisions Induced by Halo and/or Weakly Bound Nuclei Around the Barrier: the 13N+9Be and 6He+64Zn Collisions

    SciTech Connect

    Figuera, P.; Cardella, G.; Di Pietro, A.; Lu, J.; Marchetta, C.; Papa, M.; Tian, W.; Amorini, F.; Cherubini, S.; Lattuada, M.; Musumarra, A.; Pizzone, R. G.; Rizzo, F.; Scuderi, V.; Angulo, C.; Casarejos, E.; Pellegriti, M. G.; Raabe, R.; Sida, J. L.

    2006-08-14

    The study of reaction mechanisms in collisions induced by halo and/or weakly bound nuclei around the barrier has recently been the subject of many theoretical and experimental papers. Here we discuss our recent results concerning the study of the systems 13N+9Be and 6He+64Zn.

  13. N-(3,4-Dimethylisoxazol-5-yl)piperazine-4-[4-(2-fluoro-4-[(11)C]methylphenyl)thiazol-2-yl]-1-carboxamide: A promising positron emission tomography ligand for fatty acid amide hydrolase.

    PubMed

    Shimoda, Yoko; Fujinaga, Masayuki; Hatori, Akiko; Yui, Joji; Zhang, Yiding; Nengaki, Nobuki; Kurihara, Yusuke; Yamasaki, Tomoteru; Xie, Lin; Kumata, Katsushi; Ishii, Hideki; Zhang, Ming-Rong

    2016-02-15

    To visualize fatty acid amide hydrolase (FAAH) in brain in vivo, we developed a novel positron emission tomography (PET) ligand N-(3,4-dimethylisoxazol-5-yl)piperazine-4-[4-(2-fluoro-4-[(11)C]methylphenyl)thiazol-2-yl]-1-carboxamide ([(11)C]DFMC, [(11)C]1). DFMC (1) was shown to have high binding affinity (IC50: 6.1nM) for FAAH. [(11)C]1 was synthesized by C-(11)C coupling reaction of arylboronic ester 2 with [(11)C]methyl iodide in the presence of Pd catalyst. At the end of synthesis, [(11)C]1 was obtained with a radiochemical yield of 20±10% (based on [(11)C]CO2, decay-corrected, n=5) and specific activity of 48-166GBq/μmol. After the injection of [(11)C]1 in mice, high uptake of radioactivity (>2% ID/g) was distributed in the lung, liver, kidney, and brain, organs with high FAAH expression. PET images of rat brains for [(11)C]1 revealed high uptakes in the cerebellar nucleus (SUV=2.4) and frontal cortex (SUV=2.0), two known brain regions with high FAAH expression. Pretreatment with the FAAH-selective inhibitor URB597 reduced the brain uptake. Higher than 90% of the total radioactivity in the rat brain was irreversible at 30min after the radioligand injection. The present results indicate that [(11)C]1 is a promising PET ligand for imaging of FAAH in living brain. PMID:26740152

  14. Investigation of the CNO-break-out reaction: 15O(2p,γ)17Ne by the Coulomb dissociation of 17Ne

    NASA Astrophysics Data System (ADS)

    Marganiec, Justyna; Aumann, Thomas; Heil, Michael; Plag, Ralf; Warners, Felix; LAND-RB Collaboration

    2012-02-01

    By the Coulomb dissociation of 17Ne, the time-reversed reaction 15O(2p, γ)17Ne has been investigated. This reaction might play an important role in the rp process, as a bypass of the 15O waiting point. The secondary 17Ne ion beam of 500 AMeV has been dissociated on a Pb target, and the reaction products have been recorded with the LAND-R3B experimental setup (GSI). This experiment allows to determine the Coulomb dissociation cross section σCoul, which can be converted into a photo-absorption cross section σphoto, and a radiative-capture cross section σcap for the 15O(2p,γ) 17Ne reaction. Additionally, informations about the structure of the 17Ne nucleus, a possible two-proton halo, may be obtained. The analysis is still in progress.

  15. Graphene wrapped ordered LiNi0.5Mn1.5O4 nanorods as promising cathode material for lithium-ion batteries

    PubMed Central

    Tang, Xiao; Jan, S. Savut; Qian, Yanyan; Xia, Hui; Ni, Jiangfeng; Savilov, Serguei V.; Aldoshin, Serguei M.

    2015-01-01

    LiNi0.5Mn1.5O4 nanorods wrapped with graphene nanosheets have been prepared and investigated as high energy and high power cathode material for lithium-ion batteries. The structural characterization by X-ray diffraction, Raman spectroscopy, and Fourier transform infrared spectroscopy indicates the LiNi0.5Mn1.5O4 nanorods prepared from β-MnO2 nanowires have ordered spinel structure with P4332 space group. The morphological characterization by scanning electron microscopy and transmission electron microscopy reveals that the LiNi0.5Mn1.5O4 nanorods of 100–200 nm in diameter are well dispersed and wrapped in the graphene nanosheets for the composite. Benefiting from the highly conductive matrix provided by graphene nanosheets and one-dimensional nanostructure of the ordered spinel, the composite electrode exhibits superior rate capability and cycling stability. As a result, the LiNi0.5Mn1.5O4-graphene composite electrode delivers reversible capacities of 127.6 and 80.8 mAh g−1 at 0.1 and 10 C, respectively, and shows 94% capacity retention after 200 cycles at 1 C, greatly outperforming the bare LiNi0.5Mn1.5O4 nanorod cathode. The outstanding performance of the LiNi0.5Mn1.5O4-graphene composite makes it promising as cathode material for developing high energy and high power lithium-ion batteries. PMID:26148558

  16. Resonance strengths in the {sup 14}N(p,gamma){sup 15}O and {sup 15}N(p,alphagamma){sup 12}C reactions

    SciTech Connect

    Marta, Michele; Trompler, Erik; Bemmerer, Daniel; Beyer, Roland; Grosse, Eckart; Hannaske, Roland; Junghans, Arnd R.; Nair, Chithra; Schwengner, Ronald; Wagner, Andreas; Yakorev, Dmitry; Broggini, Carlo; Caciolli, Antonio; Erhard, Martin; Menegazzo, Roberto; Fueloep, Zsolt; Gyuerky, Gyoergy; Szuecs, Tamas; Vezzu, Simone

    2010-05-15

    The {sup 14}N(p,gamma){sup 15}O reaction is the slowest reaction of the carbon-nitrogen-oxygen cycle of hydrogen burning in stars. As a consequence, it determines the rate of the cycle. The {sup 15}N(p,alphagamma){sup 12}C reaction is frequently used in inverse kinematics for hydrogen depth profiling in materials. The {sup 14}N(p,gamma){sup 15}O and {sup 15}N(p,alphagamma){sup 12}C reactions have been studied simultaneously, using titanium nitride targets of natural isotopic composition and a proton beam. The strengths of the resonances at E{sub p} = 1058 keV in {sup 14}N(p,gamma){sup 15}O and at E{sub p} = 897 and 430 keV in {sup 15}N(p,alphagamma){sup 12}C have been determined with improved precision, relative to the well-known resonance at E{sub p} = 278 keV in {sup 14}N(p,gamma){sup 15}O. The new recommended values are omegagamma=0.353+-0.018, 362+-20, and 21.9+-1.0 eV for their respective strengths. In addition, the branching ratios for the decay of the E{sub p} = 1058 keV resonance in {sup 14}N(p,gamma){sup 15}O have been redetermined. The data reported here should facilitate future studies of off-resonant capture in the {sup 14}N(p,gamma){sup 15}O reaction that are needed for an improved R-matrix extrapolation of the cross section. In addition, the data on the 430 keV resonance in {sup 15}N(p,alphagamma){sup 12}C may be useful for hydrogen depth profiling.

  17. Graphene wrapped ordered LiNi0.5Mn1.5O4 nanorods as promising cathode material for lithium-ion batteries.

    PubMed

    Tang, Xiao; Jan, S Savut; Qian, Yanyan; Xia, Hui; Ni, Jiangfeng; Savilov, Serguei V; Aldoshin, Serguei M

    2015-01-01

    LiNi0.5Mn1.5O4 nanorods wrapped with graphene nanosheets have been prepared and investigated as high energy and high power cathode material for lithium-ion batteries. The structural characterization by X-ray diffraction, Raman spectroscopy, and Fourier transform infrared spectroscopy indicates the LiNi0.5Mn1.5O4 nanorods prepared from β-MnO2 nanowires have ordered spinel structure with P4332 space group. The morphological characterization by scanning electron microscopy and transmission electron microscopy reveals that the LiNi0.5Mn1.5O4 nanorods of 100-200 nm in diameter are well dispersed and wrapped in the graphene nanosheets for the composite. Benefiting from the highly conductive matrix provided by graphene nanosheets and one-dimensional nanostructure of the ordered spinel, the composite electrode exhibits superior rate capability and cycling stability. As a result, the LiNi0.5Mn1.5O4-graphene composite electrode delivers reversible capacities of 127.6 and 80.8 mAh g(-1) at 0.1 and 10 C, respectively, and shows 94% capacity retention after 200 cycles at 1 C, greatly outperforming the bare LiNi0.5Mn1.5O4 nanorod cathode. The outstanding performance of the LiNi0.5Mn1.5O4-graphene composite makes it promising as cathode material for developing high energy and high power lithium-ion batteries. PMID:26148558

  18. The first science result with the JENSA gas-jet target: Confirmation and study of a strong subthreshold 18F (p , α)15O resonance

    NASA Astrophysics Data System (ADS)

    Bardayan, D. W.; Chipps, K. A.; Ahn, S.; Blackmon, J. C.; deBoer, R. J.; Greife, U.; Jones, K. L.; Kontos, A.; Kozub, R. L.; Linhardt, L.; Manning, B.; Matoš, M.; O'Malley, P. D.; Ota, S.; Pain, S. D.; Peters, W. A.; Pittman, S. T.; Sachs, A.; Schmitt, K. T.; Smith, M. S.; Thompson, P.

    2015-12-01

    The astrophysical 18F (p , α)15O rate determines, in large part, the extent to which the observable radioisotope 18F is produced in novae. This rate, however, has been extremely uncertain owing to the unknown properties of a strong subthreshold resonance and its possible interference with higher-lying resonances. The new Jet Experiments in Nuclear Structure and Astrophysics (JENSA) gas-jet target has been used for the first time to determine the spin of this important resonance and significantly reduce uncertainties in the 18F (p , α)15O rate.

  19. Insight into the Atomic Structure of High-Voltage Spinel LiNi0.5Mn1.5O4 Cathode Material in the First Cycle

    DOE PAGESBeta

    Huang, Xuejie; Yu, Xiqian; Lin, Mingxiang; Ben, Liubin; Sun, Yang; Wang, Hao; Yang, Zhenzhong; Gu, Lin; Yang, Xiao -Qing; Zhao, Haofei; et al

    2014-12-22

    Application of high-voltage spinel LiNi0.5Mn1.5O4 cathode material is the closest and the most realistic approach to meeting the midterm goal of lithium-ion batteries for electric vehicles (EVs) and plug-in hybrid electric vehicles (HEVs). However, this application has been hampered by long-standing issues, such as capacity degradation and poor first-cycle Coulombic efficiency of LiNi0.5Mn1.5O4 cathode material. Although it is well-known that the structure of LiNi0.5Mn1.5O4 into which Li ions are reversibly intercalated plays a critical role in the above issues, performance degradation related to structural changes, particularly in the first cycle, are not fully understood. Here, we report detailed investigations ofmore » local atomic-level and average structure of LiNi0.5Mn1.5O4 during first cycle (3.5–4.9 V) at room temperature. We observed two types of local atomic-level migration of transition metals (TM) ions in the cathode of a well-prepared LiNi0.5Mn1.5O4//Li half-cell during first charge via an aberration-corrected scanning transmission electron microscopy (STEM). Surface regions (~2 nm) of the cycled LiNi0.5Mn1.5O4 particles show migration of TM ions into tetrahedral Li sites to form a Mn3O4-like structure. However, subsurface regions of the cycled particles exhibit migration of TM ions into empty octahedral sites to form a rocksalt-like structure. The migration of these TM ions are closely related to dissolution of Ni/Mn ions and building-up of charge transfer impedance, which contribute significantly to the capacity degradation and the poor first-cycle Coulombic efficiency of spinel LiNi0.5Mn1.5O4 cathode material. Accordingly, we provide suggestions of effective stabilization of LiNi0.5Mn1.5O4 structure to obtain better electrochemical performance.« less

  20. The synthesis and biodistribution of [(11)C]metformin as a PET probe to study hepatobiliary transport mediated by the multi-drug and toxin extrusion transporter 1 (MATE1) in vivo.

    PubMed

    Hume, W Ewan; Shingaki, Tomotaka; Takashima, Tadayuki; Hashizume, Yoshinobu; Okauchi, Takashi; Katayama, Yumiko; Hayashinaka, Emi; Wada, Yasuhiro; Kusuhara, Hiroyuki; Sugiyama, Yuichi; Watanabe, Yasuyoshi

    2013-12-15

    In order to develop a new positron emission tomography (PET) probe to study hepatobiliary transport mediated by the multi-drug and toxin extrusion transporter 1 (MATE1), (11)C-labelled metformin was synthesized and then evaluated as a PET probe. [(11)C]Metformin ([(11)C]4) was synthesized in three steps, from [(11)C]methyl iodide. Evaluation by small animal PET of [(11)C]4 showed that there was increased concentrations of [(11)C]4 in the livers of mice pre-treated with pyrimethamine, a potential inhibitor of MATEs, inhibiting the hepatobiliary excretion of metformin. Radiometabolite analysis showed that [(11)C]4 was not degraded in vivo during the PET scan. Biodistribution studies were undertaken and the organ distributions were extrapolated into a standard human model. In conclusion, [(11)C]4 may be useful as a PET probe to non-invasively study the in vivo function of hepatobiliary transport and drug-drug interactions, mediated by MATE1 in future clinical investigations. PMID:24238901

  1. Enhanced rate performance of LiNi0.5Mn1.5O4 fibers synthesized by electrospinning

    SciTech Connect

    Xu, Rui; Zhang, Xiaofeng; chamoun, rita; Shui, Jianglan; Li, James; Lu, Jun; Amine, Khalil; Belharouak, IB

    2015-05-29

    Spinel LiNi0.5Mn1.5O4 (LNMO) provides a high working potential as a cathode material for lithium-ion batteries. Yet there is a phase transition from cubic to tetragonal structure in LNMO during the ~3 V charge/discharge region. To suppress the large volume change and capacity fade inherent with bulk-sized LNMO particles when discharged to below 3.0 V, one-dimensional nano-structured LNMO was prepared by an electrospinning method and a subsequent heat treatment. The well-separated nanofiber precursors combat the growth and aggregation of LNMO particles during the heating procedure and lead to improved capacity, better cycling stability, and improved rate capability of the final LMNO nanofibers. The as-prepared LMNO nanofibers have a diameter as thin as 50–100 nm, which is the thinnest of this kind of complex compounds that contain multi-transition metal elements produced through the electrospinning method. In coin cell tests of this material at a current density of 27 mA g-1, the initial discharge capacity was 130 mAh g-1 over a voltage range of 3.5–4.8 V and 300 mAh g-1 over a voltage range of 2.0–4.8 V.

  2. Microglial activity in people at ultra high risk of psychosis and in schizophrenia; an [11C]PBR28 PET brain imaging study

    PubMed Central

    Veronese, Mattia; Rizzo, Gaia; Bertoldo, Alessandra; Owen, David R; Bloomfield, Michael AP; Bonoldi, Ilaria; Kalk, Nicola; Turkheimer, Federico; McGuire, Philip

    2016-01-01

    Objective To determine whether microglial activity, measured using translocator-protein positron emission tomographic imaging (PET), is increased in unmedicated subjects presenting with sub-clinical symptoms indicating they are at ultra high risk of psychosis, and to determine if it is elevated in schizophrenia after controlling for a translocator specific genetic polymorphism. Method Here we use the second generation radioligand [11C]PBR28 and PET to image microglial activity in the brains of subjects at ultra high risk for psychosis. Subjects were recruited from early intervention centres. We also imaged a cohort of patients with schizophrenia and healthy controls for comparison, in total 56 subjects completed the study. At screening, subjects were genotyped to account for the rs6971 polymorphism in the gene encoding the 18Kd Translocator Protein. The main outcome measure was total grey matter [11C]PBR28 binding ratio, representing microglial activity. Results [11C]PBR28 binding ratio in grey matter was elevated in ultra high risk subjects, compared to matched controls, (p=0.004, F= 10.3, Cohen’s d >1.2), and was positively correlated with symptom severity (r= 0.730, p<0.01). Patients with schizophrenia also demonstrated elevated microglial activity with respect to matched controls (p<0.001, F= 20.8, Cohen’s d >1.7). Conclusion Microglial activity is elevated in schizophrenia and in subjects with sub-clinical symptoms who are at ultra high risk of psychosis, and is related to at risk symptom severity. This indicates that neuroinflammation is linked to the risk of psychosis and related disorders, and the expression of sub-clinical symptoms. Follow up of ultra high risk subjects will determine whether this is specific to the later development of schizophrenia or risk factors in general. PMID:26472628

  3. Ictal lack of binding to brain parenchyma suggests integrity of the blood-brain barrier for 11C-dihydroergotamine during glyceryl trinitrate-induced migraine.

    PubMed

    Schankin, Christoph J; Maniyar, Farooq H; Seo, Youngho; Kori, Shashidar; Eller, Michael; Chou, Denise E; Blecha, Joseph; Murphy, Stephanie T; Hawkins, Randall A; Sprenger, Till; VanBrocklin, Henry F; Goadsby, Peter J

    2016-07-01

    SEE DREIER DOI 101093/AWW112 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: For many decades a breakdown of the blood-brain barrier has been postulated to occur in migraine. Hypothetically this would facilitate access of medications, such as dihydroergotamine or triptans, to the brain despite physical properties otherwise restricting their entry. We studied the permeability of the blood-brain barrier in six migraineurs and six control subjects at rest and during acute glyceryl trinitrate-induced migraine attacks using positron emission tomography with the novel radioligand (11)C-dihydroergotamine, which is chemically identical to pharmacologically active dihydroergotamine. The influx rate constant Ki, average dynamic image and time activity curve were assessed using arterial blood sampling and served as measures for receptor binding and thus blood-brain barrier penetration. At rest, there was binding of (11)C-dihydroergotamine in the choroid plexus, pituitary gland, and venous sinuses as expected from the pharmacology of dihydroergotamine. However, there was no binding to the brain parenchyma, including the hippocampus, the area with the highest density of the highest-affinity dihydroergotamine receptors, and the raphe nuclei, a postulated brainstem site of action during migraine, suggesting that dihydroergotamine is not able to cross the blood-brain barrier. This binding pattern was identical in migraineurs during glyceryl trinitrate-induced migraine attacks as well as in matched control subjects. We conclude that (11)C-dihydroergotamine is unable to cross the blood-brain barrier interictally or ictally demonstrating that the blood-brain barrier remains tight for dihydroergotamine during acute glyceryl trinitrate-induced migraine attacks. PMID:27234268

  4. Intravenous ethanol increases dopamine release in the ventral striatum in humans: PET study using bolus-plus-infusion administration of [11C]raclopride

    PubMed Central

    Aalto, Sargo; Ingman, Kimmo; Alakurtti, Kati; Kaasinen, Valtteri; Virkkala, Jussi; Någren, Kjell; Rinne, Juha O; Scheinin, Harry

    2015-01-01

    Ethanol increases the interstitial dopamine (DA) concentration in the nucleus accumbens (NAcc) of experimental animals, but positron emission tomography (PET) studies using the single-bolus protocol of the [11C]-raclopride competition paradigm have yielded conflicting results in humans. To resolve disparate previous findings, we utilized the bolus-plus-infusion (B/I) method, allowing both baseline and intervention quantification of [11C]raclopride binding during a single 105-minute PET scan, to investigate possible ethanol-induced DA release in nine healthy male subjects. A 25-minute intravenous ethanol (7.6%) infusion, resulting in a 1.3 g/L mean blood ethanol concentration, was administered using masked timing during the PET scan. Automated region-of-interest analysis testing the difference between baseline (40–50 minutes) and intervention (60–85 minutes) revealed an average 12.6% decrease in [11C]raclopride binding in the ventral striatum (VST, P=0.003) including the NAcc. In addition, a shorter time interval from the start of ethanol infusion to the first subjective effect was associated with a greater binding potential decrease bilaterally in the VST (r=0.92, P=0.004), and the feeling of pleasure was associated with a decrease in binding potential values in both the caudate nucleus (r=−0.87, P=0.003) and putamen (r=−0.74; P=0.02). These results confirm that ethanol induces rapid DA release in the limbic striatum, which can be reliably estimated using the B/I method in one imaging session. PMID:25492110

  5. Comparison of the Pharmacokinetics of Different Analogs of 11C-Labeled TZTP for Imaging Muscarinic M2 Receptors with PET

    PubMed Central

    Reid, Alicia E.; Ding, Yu-Shin; Eckelman, William C.; Logan, Jean; Alexoff, David; Shea, Colleen; Xu, Youwen; Fowler, Joanna S.

    2011-01-01

    Introduction The only radiotracer available for the selective imaging of muscarinic M2 receptors in vivo is 3-(3-{3-[18F]fluoropropyl)thio}-1,2,5-thiadiazol-4-yl)-1,2,5,6-tetrahydro-1-methylpyridine) ([18F]FP-TZTP). We have prepared and labeled FP-TZTP and two other TZTP derivatives with 11C at the methylpyridine moiety to explore the potential of using C-11 labeled FP-TZTP for PET imaging of M2 receptors and to compare the effect of small structural changes on tracer pharmacokinetics (PK) in brain and peripheral organs. Methods 11C radiolabeled [FP-TZTP, 3], 3-(3-propyl)-TZTP [P-TZTP, 6], 3,3,3-(3-(3-trifluoropropyl)-TZTP [F3P-TZTP, 10] were prepared and log D, plasma protein binding (PPB), affinity constants, time-activity curves (TACs), area under the curve (AUC) for arterial plasma, distribution volumes (DV) and pharmacological blockade in baboons were compared. Results Values for log D, PPB and affinity constants were similar for 3, 6 and 10. The fraction of parent radiotracer in the plasma was higher and the AUC lower for 10 than for 3 and 6. TACs for brain regions were similar for 3 and 6, which showed PK similar to the F-18 tracer, while 10 showed slower uptake and little clearance over 90 min. DV’s for 3 and 6 were similar to the F-18 tracer but higher for 10. Uptake of the three tracers was significantly reduced by coinjection of unlabeled 3 and 6. Conclusion Small structural variations on the TZTP structure greatly altered the PK in brain and behavior in blood with little change in the log D, PPB or affinity. The study suggests that 11C radiolabeled 3 will be a suitable alternative to [18F]FP-TZTP for translational studies in humans. PMID:18355684

  6. Dose-dependent, Saturable Occupancy of the Metabotropic Glutamate Subtype 5 Receptor by Fenobam as Measured with [11C]ABP688 PET Imaging

    PubMed Central

    KUWABARA, HIROTO; STANSFIELD, KIRSTIE; VALENTINE, HEATHER; ALEXANDER, MOHAB; KUMAR, ANIL; HILTON, JOHN; DANNALS, ROBERT F.; WONG, DEAN F.; GASPARINI, FABRIZIO

    2014-01-01

    Fenobam is a negative allosteric modulator of the metabotropic glutamate receptor subtype 5 (mGluR5) with inverse agonist activity and is expected to contribute to the treatment of neuropsychiatric disorders involving dysfunction of mGluR5 including Fragile × syndrome. This study examined whether [11C]ABP688, an antagonist PET radioligand, competes with fenobam for the same binding site in the non-human primate brain and would allow examination of occupancy-plasma concentration relationships in the evaluation of the drug for target disorders in the human brain. Four paired PET studies with [11C]ABP688 were performed in baboons at a baseline condition and after intravenous treatment with fenobam at different dose levels (0.3 - 1.33 mg/kg). Total distribution volume (VT) and binding potential (BPND) using the cerebellum as a reference region were obtained by the plasma reference graphical method. Then it was examined whether occupancy follows a dose-dependent, saturating pattern that was predicted by a modified first-order Hill equation in individual regions. Baseline regional VT and BPND values agreed with previously published data. Occupancy showed dose-dependent and saturating patterns in individual regions, reaching >90% occupancy at 1.33 mg/kg dose of fenobam in the majority of regions. To our knowledge, this is the first use of PET to characterize the mGluR5 therapeutic drug fenobam. This study demonstrates a proof of principle for determining the in vivo occupancy of fenobam in primates. The results indicate that [11C]ABP688 and PET may be useful for examination of occupancy of mGluR5 by fenobam, which should prove to be useful for designing future studies and treatment of human disease states. PMID:25098663

  7. Dose-dependent, saturable occupancy of the metabotropic glutamate subtype 5 receptor by fenobam as measured with [(11) C]ABP688 PET imaging.

    PubMed

    Mathews, William B; Kuwabara, Hiroto; Stansfield, Kirstie; Valentine, Heather; Alexander, Mohab; Kumar, Anil; Hilton, John; Dannals, Robert F; Wong, Dean F; Gasparini, Fabrizio

    2014-08-01

    Fenobam is a negative allosteric modulator of the metabotropic glutamate receptor subtype 5 (mGluR5) with inverse agonist activity and is expected to contribute to the treatment of neuropsychiatric disorders involving dysfunction of mGluR5 including Fragile X syndrome. This study examined whether [(11) C]ABP688, an antagonist PET radioligand, competes with fenobam for the same binding site in the nonhuman primate brain and would allow examination of occupancy-plasma concentration relationships in the evaluation of the drug for target disorders in the human brain. Four paired PET studies with [(11) C]ABP688 were performed in baboons at a baseline condition and after intravenous treatment with fenobam at different dose levels (0.3-1.33 mg/kg). Total distribution volume (VT ) and binding potential (BPND ) using the cerebellum as a reference region were obtained by the plasma reference graphical method. Then it was examined whether occupancy follows a dose-dependent, saturating pattern that was predicted by a modified first-order Hill equation in individual regions. Baseline regional VT and BPND values agreed with previously published data. Occupancy showed dose-dependent and saturating patterns in individual regions, reaching >90% occupancy at 1.33 mg/kg dose of fenobam in the majority of regions. To our knowledge, this is the first use of PET to characterize the mGluR5 therapeutic drug fenobam. This study demonstrates a proof of principle for determining the in vivo occupancy of fenobam in primates. The results indicate that [(11) C]ABP688 and PET may be useful for examination of occupancy of mGluR5 by fenobam, which should prove to be useful for designing future studies and treatment of human disease states. Synapse, 2014. © 2014 Wiley Periodicals, Inc. PMID:25098663

  8. Ictal lack of binding to brain parenchyma suggests integrity of the blood–brain barrier for 11C-dihydroergotamine during glyceryl trinitrate-induced migraine

    PubMed Central

    Schankin, Christoph J.; Maniyar, Farooq H.; Seo, Youngho; Kori, Shashidar; Eller, Michael; Chou, Denise E.; Blecha, Joseph; Murphy, Stephanie T.; Hawkins, Randall A.; Sprenger, Till; VanBrocklin, Henry F.

    2016-01-01

    See Dreier (doi: 10.1093/aww112) for a scientific commentary on this article. For many decades a breakdown of the blood–brain barrier has been postulated to occur in migraine. Hypothetically this would facilitate access of medications, such as dihydroergotamine or triptans, to the brain despite physical properties otherwise restricting their entry. We studied the permeability of the blood–brain barrier in six migraineurs and six control subjects at rest and during acute glyceryl trinitrate-induced migraine attacks using positron emission tomography with the novel radioligand 11C-dihydroergotamine, which is chemically identical to pharmacologically active dihydroergotamine. The influx rate constant Ki, average dynamic image and time activity curve were assessed using arterial blood sampling and served as measures for receptor binding and thus blood–brain barrier penetration. At rest, there was binding of 11C-dihydroergotamine in the choroid plexus, pituitary gland, and venous sinuses as expected from the pharmacology of dihydroergotamine. However, there was no binding to the brain parenchyma, including the hippocampus, the area with the highest density of the highest-affinity dihydroergotamine receptors, and the raphe nuclei, a postulated brainstem site of action during migraine, suggesting that dihydroergotamine is not able to cross the blood–brain barrier. This binding pattern was identical in migraineurs during glyceryl trinitrate-induced migraine attacks as well as in matched control subjects. We conclude that 11C-dihydroergotamine is unable to cross the blood–brain barrier interictally or ictally demonstrating that the blood–brain barrier remains tight for dihydroergotamine during acute glyceryl trinitrate-induced migraine attacks. PMID:27234268

  9. Use of an Isogenic Mutant Constructed in Moraxella catarrhalis To Identify a Protective Epitope of Outer Membrane Protein B1 Defined by Monoclonal Antibody 11C6

    PubMed Central

    Luke, Nicole R.; Russo, Thomas A.; Luther, Neal; Campagnari, Anthony A.

    1999-01-01

    Moraxella catarrhalis-induced otitis media continues to be a significant cause of infection in young children, prompting increased efforts at identifying effective vaccine antigens. We have previously demonstrated that M. catarrhalis expresses specific outer membrane proteins (OMPs) in response to iron limitation and that this organism can utilize transferrin and lactoferrin for in vitro growth. One of these proteins, which binds human transferrin, is OMP B1. As the human host presents a naturally iron-limited environment, proteins, like OMP B1, which are expressed in response to this nutritional stress are potential vaccine antigens. In this study, we have developed monoclonal antibody (MAb) 11C6, which reacts to a surface-exposed epitope of OMP B1 expressed by M. catarrhalis 7169. This antibody was used to clone ompB1, and sequence analysis suggested that OMP B1 is the M. catarrhalis homologue to the transferrin binding protein B described for pathogenic Neisseriaceae, Haemophilus influenzae, Actinobacillus pleuropneumoniae, and M. catarrhalis. Expression of recombinant OMP B1 on the surface of Escherichia coli confers transferrin binding activity, confirming that this protein is likely involved in iron acquisition. In addition, ompB1 was used to construct an isogenic mutant in M. catarrhalis 7169. This mutant, termed 7169b12, was used as the control in bactericidal assays designed to determine if OMP B1 elicits protective antibodies. In the presence of MAb 11C6 and human complement, wild-type 7169 demonstrated a 99% decline in viability, whereas the ompB1 isogenic mutant was resistant to this bactericidal activity. Further analysis with MAb 11C6 revealed the presence of this OMP B1 epitope on 31% of the clinical isolates tested. These data suggest that OMP B1 is a potential vaccine antigen against M. catarrhalis infections. PMID:9916077

  10. Deep-Towed Sidescan Sonar Studies of Amagmatic Spreading Centres: the Mid-Atlantic Ridge at 13N

    NASA Astrophysics Data System (ADS)

    Mallows, C.; Searle, R. C.; Party, J. S.

    2007-12-01

    rotation and subsequent termination of the footwall. References Smith, D.K., Cann, J.R. & Escartin, J. Widespread active detachment faulting and core complex formation near 13N on the Mid-Atlantic Ridge, Nature, v.442/27, p.440-443, 2006.

  11. 11C-Choline and 18F-FDG PET/CT in the Detection of Occult Prostate Cancer in the Context of a Paraneoplastic Syndrome.

    PubMed

    Jiménez-Bonilla, Julio; Quirce, Remedios; Banzo, Ignacio; Martínez-Rodríguez, Isabel; Carril, José Manuel

    2015-08-01

    In a 73-year-old man, an occult neoplasm was suspected after 2 consecutive deep venous thrombosis, the latter under anticoagulant therapy and previous axonopathy. After normal CT and MRI findings, a requested (18)F-FDG PET/CT showed a focal uptake in the prostate. Because FDG uptake in the prostate is infrequent, a (11)C-choline PET/CT was indicated revealing a focal uptake in the same location. No other abnormalities were detected in the rest of the body. A guided biopsy by ultrasonography was performed revealing a prostate carcinoma and inflammation in both prostatic lobes. PMID:26018697

  12. Activated MAO-B in the brain of Alzheimer patients, demonstrated by [11C]-L-deprenyl using whole hemisphere autoradiography.

    PubMed

    Gulyás, Balázs; Pavlova, Elena; Kása, Péter; Gulya, Károly; Bakota, Lidia; Várszegi, Szilvia; Keller, Eva; Horváth, Mónika Csilla; Nag, Sangram; Hermecz, István; Magyar, Kálmán; Halldin, Christer

    2011-01-01

    In the human brain the monoaminooxidase-B enzyme or MAO-B is highly abundant in astrocytes. As astrocyte activity and, consequently, the activity of the MAO-B enzyme, is up-regulated in neuroinflammatory processes, radiolabelled analogues of deprenyl may serve as an imaging biomarker in neuroinflammation and neurodegeneration, including Alzheimer's disease. In the present study [(11)C]-L-deprenyl, the PET radioligand version of L-deprenyl or selegiline®, a selective irreversible MAO-B inhibitor was used in whole hemisphere autoradiographic experiments in human brain sections in order to test the radioligand's binding to the MAO-B enzyme in human brain tissue, with an eye on exploring the radioligand's applicability as a molecular imaging biomarker in human PET studies, with special regard to diagnostic detection of reactive astrogliosis. Whole hemisphere brain sections obtained from Alzheimer patients and from age matched control subjects were examined. In control brains the binding of [(11)C]-L-deprenyl was the highest in the hippocampus, in the basal ganglia, the thalamus, the substantia nigra, the corpus geniculatum laterale, the nucleus accumbens and the periventricular grey matter. In Alzheimer brains significantly higher binding was observed in the temporal lobes and the white matter. Furthermore, in the Alzheimer brains in the hippocampus, temporal lobe and white matter the binding negatively correlated with Braak stages. The highest binding was observed in Braak I-II, whereas it decreased with increasing Braak grades. The increased regional binding in Alzheimer brains coincided with the presence of an increased number of activated astrocytes, as demonstrated by correlative immunohistochemical studies with GFAP in adjacent brain slices. Deprenyl itself as well as the MAO-B antagonist rasagiline did effectively block the binding of the radioligand, whereas the MAO-A antagonist pirlindole did not affect it. Compounds with high affinity for the PBR system did

  13. Positron Emission Tomography studies with [11C]PBR28 in the Healthy Rodent Brain: Validating SUV as an Outcome Measure of Neuroinflammation

    PubMed Central

    Häggkvist, Jenny; Varrone, Andrea; Amini, Nahid; Halldin, Christer; Gulyás, Balázs

    2015-01-01

    Molecular imaging of the 18 kD Translocator protein (TSPO) with positron emission tomography (PET) is of great value for studying neuroinflammation in rodents longitudinally. Quantification of the TSPO in rodents is, however, quite challenging. There is no suitable reference region and the use of plasma-derived input is not an option for longitudinal studies. The aim of this study was therefore to evaluate the use of the standardized uptake value (SUV) as an outcome measure for TSPO imaging in rodent brain PET studies, using [11C]PBR28. In the first part of the study, healthy male Wistar rats (n = 4) were used to determine the correlation between the distribution volume (VT, calculated with Logan graphical analysis) and the SUV. In the second part, healthy male Wistar rats (n = 4) and healthy male C57BL/6J mice (n = 4), were used to determine the test-retest variability of the SUV, with a 7-day interval between measurements. Dynamic PET scans of 63 minutes were acquired with a nanoScan PET/MRI and nanoScan PET/CT. An MRI scan was made for anatomical reference with each measurement. The whole brain VT of [11C]PBR28 in rats was 42.9 ± 1.7. A statistically significant correlation (r2 = 0.96; p < 0.01) was found between the VT and the SUV. The test-retest variability in 8 brain region ranged from 8 to 20% in rats and from 7 to 23% in mice. The interclass correlation coefficient (ICC) was acceptable to excellent for rats, but poor to acceptable for mice. In conclusion: The SUV of [11C]PBR28 showed a high correlation with VT as well as good test-retest variability. For future longitudinal small animal PET studies the SUV can thus be used to describe [11C]PBR28 uptake in healthy brain tissue. Based on the present observations, further studies are needed to explore the applicability of this approach in small animal disease models, with special regard to neuroinflammatory models. PMID:25996996

  14. New measurement of the 10B(p,α0)7Be reaction cross section at low energies and the structure of 11C

    NASA Astrophysics Data System (ADS)

    Lombardo, I.; Dell'Aquila, D.; Conte, F.; Francalanza, L.; La Cognata, M.; Lamia, L.; La Torre, R.; Spadaccini, G.; Spitaleri, C.; Vigilante, M.

    2016-05-01

    We report preliminary results of a new measurement of the 10B(p,α0)7Be cross section in the 0.6 - 1.0 MeV bombarding energy domain. In this region very few data have been reported in the literature. Excitation functions at both forward and backward angles have been obtained. Angular distributions testify the contribution due to several excited states in the 11C compound nucleus. The experimental S-factor is about 30% lower than the one reported in the literature and based on activation methods.

  15. Awake Nonhuman Primate Brain PET Imaging with Minimal Head Restraint: Evaluation of GABAA Benzodiazepine Binding with [11C]Flumazenil in Awake and Anesthetized Animals

    PubMed Central

    Sandiego, Christine M.; Jin, Xiao; Mulnix, Tim; Fowles, Krista; Labaree, David; Ropchan, Jim; Huang, Yiyun; Cosgrove, Kelly; Castner, Stacy A.; Williams, Graham V.; Wells, Lisa; Rabiner, Eugenii A.; Carson, Richard E.

    2013-01-01

    Neuroreceptor imaging in the nonhuman primate (NHP) is valuable for translational research approaches in humans. However, the majority of NHP studies are conducted under anesthesia, which affects the interpretability of receptor binding measures. The aims of this study are to develop awake NHP imaging with minimal head restraint and to compare in vivo binding of GABAA-benzodiazepine radiotracer [11C]flumazenil under anesthetized and awake conditions. We hypothesized that [11C]flumazenil binding potential (BPND) would be higher in isoflurane-anesthetized monkeys. Methods The Focus-220 small animal PET scanner was fitted to a mechanical device that raised and tilted the scanner 45° while the awake NHP was tilted back 35° in a custom chair for optimal brain positioning. This required acclimation of the animals to the chair, touch-screen tasks, i.v. catheter insertion, and tilting. For PET studies, the bolus plus constant infusion (B/I) method was used for [11C]flumazenil administration. Two rhesus monkeys were scanned under the awake (n=6 scans) and isoflurane-anesthetized (n=4 scans) conditions. The Vicra infrared camera was used to track head motion during PET scans. Under the awake condition, emission and head motion-tracking data were acquired for 40-75 min post-injection. Anesthetized monkeys were scanned for 90 min. Cortisol measurements were acquired during awake and anesthetized scans. Equilibrium analysis was used for both the anesthetized (n=4) and awake (n=5) datasets to compute mean BPND images in NHP template space, using the pons as a reference region. Percent change per min (%Δ/min) in radioactivity concentration was calculated in high and low binding regions to assess the quality of equilibrium. Results The monkeys acclimated to procedures in the NHP chair necessary to perform awake PET imaging. Image quality was comparable between awake and anesthetized conditions. The relationship between awake and anesthetized values was BPND(awake)=0.94BPND

  16. New measurements of the astrophysical S factor for {sup 12}C(p,{gamma}){sup 13}N reaction at low energies and the asymptotic normalization coefficient (nuclear vertex constant) for the p+{sup 12}C{yields}{sup 13}N reaction

    SciTech Connect

    Burtebaev, N.; Zazulin, D. M.; Igamov, S. B.; Yarmukhamedov, R.; Peterson, R. J.

    2008-09-15

    New measurements of differential and total cross sections for the {sup 12}C(p,{gamma}){sup 13}N reaction have been made at beam energies of E{sub p}=354,390,460,463,565,750, and 1061 keV. Analysis of the astrophysical S factor S(E) for the {sup 12}C(p,{gamma}){sup 13}N reaction at low energies and of the reaction rates has been carried out within the R-matrix approach by using the previously measured nuclear vertex constant (or the respective asymptotic normalization coefficient) for the virtual decay {sup 13}N{yields}p+{sup 12}C to fix the direct capture part of the amplitude in S(E). It is demonstrated that the R-matrix approach, using the measured asymptotic normalization coefficient, can be employed as an ideal tool, minimizing the uncertainties associated with a calculation of the direct capture cross section of the {sup 12}C(p,{gamma}){sup 13}N reaction at extremely low energies. New information on the proton and {gamma} width for the first excited state of {sup 13}N is obtained.

  17. The combination of 13N-ammonia and 18F-FDG whole-body PET/CT on the same day for diagnosis of advanced prostate cancer

    PubMed Central

    Yi, Chang; Yu, Donglan; Shi, Xinchong; Luo, Ganhua; He, Qiao; Zhang, Xuezhen

    2016-01-01

    Purpose The aim of the study was to evaluate the efficacy of 13N-ammonia and 18F-fluorodeoxyglucose (18F-FDG) PET performed on the same day in the detection of advanced prostate cancer (PC) and its metastases. Patients and methods Twenty-six patients with high-risk PC [Gleason score 8–10 or prostate-specific antigen (PSA)>20 ng/ml or clinical tumor extension≥T2c] were recruited into the study. 13N-Ammonia and 18F-FDG PET/CT were performed on the same day (18F-FDG followed ammonia, with an interval of a minimum of 2 h). Lesions were interpreted as positive, negative, or equivocal. Patient-based and field-based performance characteristics for both imaging techniques were reported. Results There was significant correlation between 13N-ammonia and 18F-FDG PET/CT in the detection of primary PC (κ=0.425, P=0.001) and no significant difference in sensitivity (60.2 vs. 54.5%) and specificity (100 vs. 83.3%). The maximum standard uptake values and corresponding target-to-background ratio values of the concordantly positive lesions in prostate glands in the two studies did not differ significantly (P=0.124 and 0.075, respectively). The sensitivity and specificity of PET imaging using 13N-ammonia for lymph node metastases were 77.5 and 96.3%, respectively, whereas the values were 75 and 44.4% using 18F-FDG. The two modalities were highly correlated with respect to the detection of lymph nodes and bone metastases. Conclusion The concordance between the two imaging modalities suggests a clinical impact of 13N-ammonia PET/CT in advanced PC patients as well as of 18F-FDG. 13N-Ammonia is a useful PET tracer and a complement to 18F-FDG for detecting primary focus and distant metastases in PC. The combination of these two tracers on the same day can accurately detect advanced PC. PMID:26588068

  18. Alterations in CNS Activity Induced by Botulinum Toxin Treatment in Spasmodic Dysphonia: An H[subscript 2][superscript 15]O PET Study

    ERIC Educational Resources Information Center

    Ali, S. Omar; Thomassen, Michael; Schulz, Geralyn M.; Hosey, Lara A.; Varga, Mary; Ludlow, Christy L.; Braun, Allen R.

    2006-01-01

    Speech-related changes in regional cerebral blood flow (rCBF) were measured using H[subscript 2][superscript 15]O positron-emission tomography in 9 adults with adductor spasmodic dysphonia (ADSD) before and after botulinum toxin (BTX) injection and 10 age- and gender-matched volunteers without neurological disorders. Scans were acquired at rest…

  19. An Artificial SEI Enables the Use of A LiNi0.5Mn1.5O4 5 V Cathode with Conventional Electrolytes

    SciTech Connect

    Li, Juchuan ORNL; Baggetto, Loic ORNL; Martha, Surendra K ORNL; Veith, Gabriel M ORNL; Nanda, Jagjit ORNL; Liang, Chengdu ORNL; Dudney, Nancy J ORNL

    2013-01-01

    LiNi0.5Mn1.5O4 spinel is considered one of the most promising cathodes for advanced lithium ion batteries. However, the operation potential of LiNi0.5Mn1.5O4, ~4.75 V, is beyond the high voltage limit of the state-of-art electrolyte, ~4.3 V. Here, using thin films of LiNi0.5Mn1.5O4 as a model material, we show evidence that an artificial solid electrolyte interphase (SEI) enables the use of this 5 V cathode with conventional carbonate electrolytes. A thin coating of Lipon (lithium phosphorus oxynitride) as an artificial SEI on LiNi0.5Mn1.5O4 could remedy the decomposition of the electrolyte. The thickness of the Lipon artificial SEI is optimized by balancing the protection and additional resistance. The strategy of artificial SEI on cathodes is expected to enable the wide application of other high voltage cathodes for lithium ion batteries.

  20. Quantitative agreement between [(15) O]H2 O PET and model free QUASAR MRI-derived cerebral blood flow and arterial blood volume.

    PubMed

    Heijtel, D F R; Petersen, E T; Mutsaerts, H J M M; Bakker, E; Schober, P; Stevens, M F; van Berckel, B N M; Majoie, C B L M; Booij, J; van Osch, M J P; van Bavel, E T; Boellaard, R; Lammertsma, A A; Nederveen, A J

    2016-04-01

    The purpose of this study was to assess whether there was an agreement between quantitative cerebral blood flow (CBF) and arterial cerebral blood volume (CBVA) measurements by [(15) O]H2 O positron emission tomography (PET) and model-free QUASAR MRI. Twelve healthy subjects were scanned within a week in separate MRI and PET imaging sessions, after which quantitative and qualitative agreement between both modalities was assessed for gray matter, white matter and whole brain region of interests (ROI). The correlation between CBF measurements obtained with both modalities was moderate to high (r(2) : 0.28-0.60, P < 0.05), although QUASAR significantly underestimated CBF by 30% (P < 0.001). CBVA was moderately correlated (r(2) : 0.28-0.43, P < 0.05), with QUASAR yielding values that were only 27% of the [(15) O]H2 O-derived values (P < 0.001). Group-wise voxel statistics identified minor areas with significant contrast differences between [(15) O]H2 O PET and QUASAR MRI, indicating similar qualitative CBVA and CBF information by both modalities. In conclusion, the results of this study demonstrate that QUASAR MRI and [(15) O]H2 O PET provide similar CBF and CBVA information, but with systematic quantitative discrepancies. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26876426

  1. Investigation on preparation and performance of spinel LiNi0.5Mn1.5O4 with different microstructures for lithium-ion batteries.

    PubMed

    Xue, Yuan; Wang, Zhenbo; Zheng, Lili; Yu, Fuda; Liu, Baosheng; Zhang, Yin; Ke, Ke

    2015-01-01

    The high voltage spinel LiNi0.5Mn1.5O4 is a promising cathode material in next generation of lithium ion batteries. In this study, LiNi0.5Mn1.5O4 with various particle microstructures are prepared by controlling the microstructures of precursors. LiNi0.5Mn1.5O4 spinel samples with solid, hollow and hierarchical microstructures are prepared with solid MnCO3, hollow MnO2 and hierarchical Mn2O3 as precursor, respectively. The homemade spinel materials are investigated and the results show that the content of Mn(3+) and impurity phase differ much in these three spinel samples obtained under the same calcining and annealing conditions. It is revealed for the first time that an inhomogeneous migration of atoms may introduce Mn(3+) and impurity phase in the spinel. The hierarchical microstructure with the primary particles interconnected is optimal for electrode materials because this microstructure has a higher conductivity between the interconnected primary particles and appropriate specific surface area. LiNi0.5Mn1.5O4 in this microstructure has the best rate capability and also the best long-term cycling stability. PMID:26299774

  2. Investigation on preparation and performance of spinel LiNi0.5Mn1.5O4 with different microstructures for lithium-ion batteries

    NASA Astrophysics Data System (ADS)

    Xue, Yuan; Wang, Zhenbo; Zheng, Lili; Yu, Fuda; Liu, Baosheng; Zhang, Yin; Ke, Ke

    2015-08-01

    The high voltage spinel LiNi0.5Mn1.5O4 is a promising cathode material in next generation of lithium ion batteries. In this study, LiNi0.5Mn1.5O4 with various particle microstructures are prepared by controlling the microstructures of precursors. LiNi0.5Mn1.5O4 spinel samples with solid, hollow and hierarchical microstructures are prepared with solid MnCO3, hollow MnO2 and hierarchical Mn2O3 as precursor, respectively. The homemade spinel materials are investigated and the results show that the content of Mn3+ and impurity phase differ much in these three spinel samples obtained under the same calcining and annealing conditions. It is revealed for the first time that an inhomogeneous migration of atoms may introduce Mn3+ and impurity phase in the spinel. The hierarchical microstructure with the primary particles interconnected is optimal for electrode materials because this microstructure has a higher conductivity between the interconnected primary particles and appropriate specific surface area. LiNi0.5Mn1.5O4 in this microstructure has the best rate capability and also the best long-term cycling stability.

  3. Phase transition kinetics of LiNi0.5Mn1.5O4 analyzed by temperature-controlled operando X-ray absorption spectroscopy.

    PubMed

    Takahashi, Ikuma; Arai, Hajime; Murayama, Haruno; Sato, Kenji; Komatsu, Hideyuki; Tanida, Hajime; Koyama, Yukinori; Uchimoto, Yoshiharu; Ogumi, Zempachi

    2016-01-21

    LiNi0.5Mn1.5O4 (LNMO) is a promising positive electrode material for lithium ion batteries because it shows a high potential of 4.7 V vs. Li/Li(+). Its charge-discharge reaction includes two consecutive phase transitions between LiNi0.5Mn1.5O4 (Li1) ↔ Li0.5Ni0.5Mn1.5O4 (Li0.5) and Li0.5 ↔ Ni0.5Mn1.5O4 (Li0) and the complex transition kinetics that governs the rate capability of LNMO can hardly be analyzed by simple electrochemical techniques. Herein, we apply temperature-controlled operando X-ray absorption spectroscopy to directly capture the reacting phases from -20 °C to 40 °C under potential step (chronoamperometric) conditions and evaluate the phase transition kinetics using the apparent first-order rate constants at various temperatures. The constant for the Li1 ↔ Li0.5 transition (process 1) is larger than that for the Li0.5 ↔ Li0 transition (process 2) at all the measured temperatures, and the corresponding activation energies are 29 and 46 kJ mol(-1) for processes 1 and 2, respectively. The results obtained are discussed to elucidate the limiting factor in this system as well as in other electrode systems. PMID:26686382

  4. First application of the Trojan horse method with a radioactive ion beam: Study of the 18F (p,α ) 15O reaction at astrophysical energies

    NASA Astrophysics Data System (ADS)

    Cherubini, S.; Gulino, M.; Spitaleri, C.; Rapisarda, G. G.; La Cognata, M.; Lamia, L.; Pizzone, R. G.; Romano, S.; Kubono, S.; Yamaguchi, H.; Hayakawa, S.; Wakabayashi, Y.; Iwasa, N.; Kato, S.; Komatsubara, T.; Teranishi, T.; Coc, A.; de Séréville, N.; Hammache, F.; Kiss, G.; Bishop, S.; Binh, D. N.

    2015-07-01

    Measurement of nuclear cross sections at astrophysical energies involving unstable species is one of the most challenging tasks in experimental nuclear physics. The use of indirect methods is often unavoidable in this scenario. In this paper the Trojan horse method is applied for the first time to a radioactive ion beam-induced reaction studying the 18F (p ,α )15O process at low energies relevant to astrophysics via the three-body reaction 2H (18F ,α15O ) n . The knowledge of the 18F (p,α ) 15O reaction rate is crucial to understand the nova explosion phenomena. The cross section of this reaction is characterized by the presence of several resonances in 19Ne and possibly interference effects among them. The results reported in literature are not satisfactory and new investigations of the 18F (p,α ) 15O reaction cross section will be useful. In the present work the spin-parity assignments of relevant levels have been discussed and the astrophysical S factor has been extracted considering also interference effects.

  5. Verification of a semi-automated MRI-guided technique for non-invasive determination of the arterial input function in 15O-labeled gaseous PET

    NASA Astrophysics Data System (ADS)

    Iguchi, Satoshi; Hori, Yuki; Moriguchi, Tetsuaki; Morita, Naomi; Yamamoto, Akihide; Koshino, Kazuhiro; Kawashima, Hidekazu; Zeniya, Tsutomu; Enmi, Jun-ichiro; Iida, Hidehiro

    2013-02-01

    A semi-automated MR-guided technique has been evaluated for non-invasive estimation of cerebral metabolic rate of oxygen (CMRO2) using the sequential administration of 15O oxygen (O2) and 15O carbon dioxide (CO2) during a single PET scan. Two mathematical models, which assess the arterial input function (AIF) from time-activity curves (TAC) in the internal carotid artery region, were tested, namely one with a simple correction for the recovery coefficient (RC) and another with corrections for RC and spillover from surrounding tissues. RC was determined from MRA and black-blood image. RC was also determined from C15O blood volume images as a reference. RC agreed between MR-based and C15O-PET based methods, suggesting validity of MR-based methods. Area-under-the-curve (AUC) of the early portion of estimated AIF agreed with that of measured AIF in both models. AUC of the delayed phase of estimated AIF was largely overestimated in the first model, but was sufficiently improved by the spillover correction implemented in the second model.

  6. Investigation on preparation and performance of spinel LiNi0.5Mn1.5O4 with different microstructures for lithium-ion batteries

    PubMed Central

    Xue, Yuan; Wang, Zhenbo; Zheng, Lili; Yu, Fuda; Liu, Baosheng; Zhang, Yin; Ke, Ke

    2015-01-01

    The high voltage spinel LiNi0.5Mn1.5O4 is a promising cathode material in next generation of lithium ion batteries. In this study, LiNi0.5Mn1.5O4 with various particle microstructures are prepared by controlling the microstructures of precursors. LiNi0.5Mn1.5O4 spinel samples with solid, hollow and hierarchical microstructures are prepared with solid MnCO3, hollow MnO2 and hierarchical Mn2O3 as precursor, respectively. The homemade spinel materials are investigated and the results show that the content of Mn3+ and impurity phase differ much in these three spinel samples obtained under the same calcining and annealing conditions. It is revealed for the first time that an inhomogeneous migration of atoms may introduce Mn3+ and impurity phase in the spinel. The hierarchical microstructure with the primary particles interconnected is optimal for electrode materials because this microstructure has a higher conductivity between the interconnected primary particles and appropriate specific surface area. LiNi0.5Mn1.5O4 in this microstructure has the best rate capability and also the best long-term cycling stability. PMID:26299774

  7. A simple system for remote processing and delivery of H{sub 2}[{sup 15}O] produced from a N{sub 2}/H{sub 2} target

    SciTech Connect

    Ferrieri, R.A.; Alexoff, D.L.; Schlyer, D.L.; Wolf, A.P.

    1993-12-31

    The N{sub 2} + H{sub 2} target can produce more than enough H{sub 2}[{sup 15}O] to meet the demands of any PET imaging facility. We have shown that the radiotracer can be transported across 300 feet of tubing without significant loss of activity, using fast tows of target gas. Thus, there is no need to maintain an extraneous chemical Processing station at the PET imaging facility. A simple remotely operated system is reported that performs the three step operation for H{sub 2}[{sup 15}O] delivery at the PET imaging facility: collection of the radiotracer in water; removal of ammonia from the preparation and delivery of the radiotracer to the injection syringe. The system can process and make available for injection 100 mCi of H{sub 2}[{sup 15}O]. The machine is easily prepped for subsequent deliveries. So that additional doses of radiotracer can be made available within 12 minutes. A general syringe loading device with remote hydraulic injector is that is compatible for use with any H{sub 2}[{sup 15}O] radiotracer processing station. The device allows for direct measurement of syringe dose while filling, and for easy, as well as safe transfer of the injection syringe assembly to a delivery cart that houses the remote hydraulic injector. The injection syringe is never handled directly during transport nor during injection except, to connect it to the intravenous line, thus minimizing radiation exposure to personnel.

  8. BACE0.85Y0.15O3-DELTA Based Materials for Inovative Monolithic Solid Oxide Fuel Cells

    NASA Astrophysics Data System (ADS)

    Krezhov, Kiril; Vladikova, Daria

    2016-07-01

    Solid oxide fuel cells (SOFCs) offer a promising green technology of direct conversion of chemical energy of fuel into electricity. Among the families of metal oxides, which can be successfully used as electrodes (cathodes or anodes) in SOFC, certain members of the large family of transition-metal oxides with perovskite structure ABO _{3} were found very prospective to fulfil most of the features required for preparation of mixed ionic-electronic conductor (MIEC) oxide materials for SOFCs operated in the intermediate temperature range. In this regard Barium cerate with Y-substitution at the B-site (Ce site) is well known for excellent conduction capabilities in the temperature range 400-800 °C as a result from the proton motion in the crystal lattice. Doping with Y ^{3+} is very effective and the proton conductivity in BaCe _{1-x}Y _{x}O _{3-δ} increases with the increasing of the dopant concentration up to x =0.2. However, the phase behaviour of the composition BCY20 (x=0.20) is very complicated. Even at room temperature the crystalline structure remains contradictory because various structures of monoclinic, rhombohedral and orthorhombic symmetry are reported. The characterization of the chemical composition and stability, oxygen stoichiometry and cationic ratios of each synthesized phase is of great importance to understand the defect-chemistry that would govern the transport properties. We report on oxygen-deficient BaCe _{0.85}Y _{0.15}O _{3-δ} (BCY15) perovskites prepared by auto-combustion with following calcination at high temperature. The structural details of powder, dense and porous samples of materials based on BCY15 were investigated from full profile analysis of neutron and x-ray diffraction patterns. The materials were used recently as cathode, anode and central membrane in an innovative monolithic design of SOFC.

  9. Is perivetricular hyperintensity region caused by decreased cerebral blood flow?; assessment by {sup 15}O-PET study

    SciTech Connect

    Kaminaga, T.; Hayashida, K.; Ishida, Y.

    1994-05-01

    The clinical significance of the regional cerebral blood flow (rCBF) and oxygen metabolism has not been established in patients who had periventricular hyperintensity (PVH) by magnetic resonance imaging (MRI). The aim of this study is to correlate the results of rCBF and oxygen metabolism by positron emission tomography (PET) with PVH by MRI. The subjects were 27 patients; 16 patient (group I) (male; 7, female; 9, age; 56.8{plus_minus}18.6) with PVH and age matched 11 patients (group II) (male; 6, female; 5, age; 55.3{plus_minus}13.6) without PVH. {sup 15}O-PET study was carried out by Headtome IV and rCBF, cerebral metabolic rate of oxygen (CMRO{sub 2}), oxygen extraction fraction (OEF) of PVH and cerebellum was calculated. T1- and T2-weighted images were obtained in all patients. Angiography was performed over 11 patients. The mean rCBF of group I in PVH (28.5{plus_minus}7.5 ml/100g/min) was significantly (p<0.01) lower than that of group II (38.6{plus_minus}5.7). The mean rCBF of group I and group II in cerebellum were 49.5{plus_minus}9.9 ml/100g/min and 50.2{plus_minus}8.9 respectively. There was no significant difference on CMRO{sub 2} and OEF between group I and group II. In MRI examination, PVH was detected in all group I patients and multiple high intensities were also detected in 7 patients of group I and 4 patients of group II on T2-weighted images. No significant stenosis (more than 75%) was detected in 11 patients by angiography. These data strongly indicate that PVH might be caused by decreased cerebral blood flow.

  10. Astrophysically Important 19Ne States Studied with the 2H(18F,alpha+15O)n Reaction

    SciTech Connect

    Adekola, Aderemi S; Bardayan, Daniel W; Blackmon, Jeff C; Brune, C.; Chae, K. Y.; Champagne, A. E.; Domizioli, Carlo P; Greife, U.; Heinen, Z.; Hornish, M.; Johnson, Micah; Jones, K. L.; Kapler, R.; Livesay, Jake; Ma, Zhanwen; Massey, T.; Moazen, Brian; Nesaraja, Caroline D; Pain, Steven D; ShrinerJr., J. F.; Thomas, J. S.; Smith, Nathan A; Smith, Michael Scott; Visser, D. W.; Voinov, A.

    2009-01-01

    The nuclear structure of {sup 19}Ne near the proton threshold is of interest for understanding the rates of proton-induced reactions on {sup 18}F in novae. Analogues for several states in the mirror nucleus {sup 19}F have not yet been identified in {sup 19}Ne indicating the level structure of {sup 19}Ne in this region is incomplete. The {sup 18}F(d;n){sup 19}Ne and {sup 18}F(d,p){sup 19}F reactions have been measured simultaneously at E{sub c.m.} = 14.9 MeV. The experiments were performed at the Holifield Radioactive Ion Beam Facility (HRIBF) of Oak Ridge National Laboratory (ORNL) by bombarding a 720-mg/cm{sub 2} CD{sub 2} target with a radioactive {sup 18}F beam. The {sup 19}Ne states of interest near the proton threshold decay by breakup into a and {sup 15}O particles. These decay products were detected in coincidence with position-sensitive E-{Delta}E silicon telescopes. The {alpha} and {sup 15}N particles from the break up of the mirror nucleus {sup 19}F were also measured with these detectors. Particle identification, coincidence, and Q-value requirements enable us to distinguish the reaction of interest from other reactions. The reconstruction of relative energy of the detected particles reveals the excited states of {sup 19}Ne and {sup 19}F which are populated. The neutron (proton) angular distributions for states in {sup 19}Ne ({sup 19}F) were extracted using momentum conservation. The observed states in {sup 19}Ne and {sup 19}F will be presented.

  11. Propofol anaesthesia does not alter regional rates of cerebral protein synthesis measured with L-[1-11C]leucine and PET in healthy male subjects

    PubMed Central

    Bishu, Shrinivas; Schmidt, Kathleen C; Burlin, Thomas; Channing, Michael; Horowitz, Lisa; Huang, Tianjiang; Liu, Zhong-hua; Qin, Mei; Vuong, B-K; Unterman, Aaron; Xia, Zengyan; Zametkin, Alan; Herscovitch, Peter; Quezado, Zenaide; Smith, Carolyn Beebe

    2009-01-01

    We report regional rates of cerebral protein synthesis (rCPS) in ten healthy young males each studied under two conditions: awake and anaesthetized with propofol. We used the quantitative L-[1-11C]leucine PET method to measure rCPS. The method accounts for the fraction (λ) of unlabeled leucine in the precursor pool for protein synthesis that is derived from arterial plasma; the remainder comes from proteolysis of tissue proteins. Across 18 regions and whole brain, mean differences in rCPS between studies ranged from −5 to 5% and were within the variability of rCPS in awake studies (coefficient of variation range: 7–14%). Similarly, differences in λ (range: 1% to 4%) were typically within the variability of λ (coefficient of variation range: 3–6%). Intersubject variances and patterns of regional variation were also similar under both conditions. In propofol anesthetised subjects, rCPS varied regionally from 0.98 ± 0.12 to 2.39 ± 0.23 nmol g−1min−1 in corona radiata and cerebellum, respectively. Our data indicate that the values, variances, and patterns of regional variation in rCPS and λ measured by the L-[1-11C]leucine PET method are not significantly altered by anaesthesia with propofol. PMID:19223912

  12. Histone Deacetylase Inhibitor MS-275 Exhibits Poor Brain Penetration: Pharmacokinetic Studies of [11C]MS-275 using Positron Emission Tomography

    SciTech Connect

    Hooker, J.M.; Hooker, J.M.; Kim, S.W.; Alexoff, D.; Xu, Y.; Shea, C.; Reid, A.; Volkow, N.D.; Fowler, J.S.

    2009-10-01

    MS-275 (entinostat) is a histone deacetylase (HDAC) inhibitor currently in clinical trials for the treatment of several types of cancer. Recent reports have noted that MS-275 can cross the blood-brain barrier (BBB) and cause region-specific changes in rodent brain histone acetylation. To characterize the pharmacokinetics and distribution of MS-275 in the brain using positron emission tomography (PET), we labeled the carbamate carbon of MS-275 with carbon-11. Using PET, we determined that [{sup 11}C]MS-275 has low uptake in brain tissue when administered intravenously to nonhuman primates. In rodent studies, we observed that pharmacokinetics and brain accumulation of [{sup 11}C]MS-275 were not changed by the coadministration of large doses of unlabeled MS-275. These results, which both highlight the poor brain penetration of MS-275, clearly suggest its limitation as a therapeutic agent for the central nervous system (CNS). Moreover, our study demonstrates the effectiveness of PET at providing brain pharmacokinetic data for HDAC inhibitors. These data are important not only for the development of new compounds for peripheral cancer treatment (where CNS exclusion is often advantageous) but also for the treatment of neurological disorders (where CNS penetration is critical).

  13. Imaging endogenous opioid peptide release with [11C]carfentanil and [3H]diprenorphine: influence of agonist-induced internalization

    PubMed Central

    Quelch, Darren R; Katsouri, Loukia; Nutt, David J; Parker, Christine A; Tyacke, Robin J

    2014-01-01

    Understanding the cellular processes underpinning the changes in binding observed during positron emission tomography neurotransmitter release studies may aid translation of these methodologies to other neurotransmitter systems. We compared the sensitivities of opioid receptor radioligands, carfentanil, and diprenorphine, to amphetamine-induced endogenous opioid peptide (EOP) release and methadone administration in the rat. We also investigated whether agonist-induced internalization was involved in reductions in observed binding using subcellular fractionation and confocal microscopy. After radioligand administration, significant reductions in [11C]carfentanil, but not [3H]diprenorphine, uptake were observed after methadone and amphetamine pretreatment. Subcellular fractionation and in vitro radioligand binding studies showed that amphetamine pretreatment only decreased total [11C]carfentanil binding. In vitro saturation binding studies conducted in buffers representative of the internalization pathway suggested that μ-receptors are significantly less able to bind the radioligands in endosomal compared with extracellular compartments. Finally, a significant increase in μ-receptor-early endosome co-localization in the hypothalamus was observed after amphetamine and methadone treatment using double-labeling confocal microscopy, with no changes in δ- or κ-receptor co-localization. These data indicate carfentanil may be superior to diprenorphine when imaging EOP release in vivo, and that alterations in the ability to bind internalized receptors may be a predictor of ligand sensitivity to endogenous neurotransmitter release. PMID:25005876

  14. Arabidopsis PEROXIN11c-e, FISSION1b, and DYNAMIN-RELATED PROTEIN3A Cooperate in Cell Cycle–Associated Replication of Peroxisomes[W

    PubMed Central

    Lingard, Matthew J.; Gidda, Satinder K.; Bingham, Scott; Rothstein, Steven J.; Mullen, Robert T.; Trelease, Richard N.

    2008-01-01

    Although participation of PEROXIN11 (PEX11), FISSION1 (FISl), and DYNAMIN-RELATED PROTEIN (DRP) has been well established during induced peroxisome proliferation in response to external stimuli, their roles in cell cycle–associated constitutive replication/duplication have not been fully explored. Herein, bimolecular fluorescence complementation experiments with Arabidopsis thaliana suspension cells revealed homooligomerization of all five PEX11 isoforms (PEX11a-e) and heterooligomerizations of all five PEX11 isoforms with FIS1b, but not FIS1a nor DRP3A. Intracellular protein targeting experiments demonstrated that FIS1b, but not FIS1a nor DRP3A, targeted to peroxisomes only when coexpressed with PEX11d or PEX11e. Simultaneous silencing of PEX11c-e or individual silencing of DRP3A, but not FIS1a nor FIS1b, resulted in ∼40% reductions in peroxisome number. During G2 in synchronized cell cultures, peroxisomes sequentially enlarged, elongated, and then doubled in number, which correlated with peaks in PEX11, FIS1, and DRP3A expression. Overall, these data support a model for the replication of preexisting peroxisomes wherein PEX11c, PEX11d, and PEX11e act cooperatively during G2 to promote peroxisome elongation and recruitment of FIS1b to the peroxisome membrane, where DRP3A stimulates fission of elongated peroxisomes into daughter peroxisomes, which are then distributed between daughter cells. PMID:18539750

  15. Use of 2-deoxy-D(1-/sup 11/C)glucose for the determination of local cerebral glucose metabolism in humans: variation within and between subjects

    SciTech Connect

    Reivich, M.; Alavi, A.; Wolf, A.; Greenberg, J.H.; Fowler, J.; Christman, D.; MacGregor, R.; Jones, S.C.; London, J.; Shiue, C.; Yonekura, Y.

    1982-09-01

    The deoxyglucose technique for the measurement of local cerebral glucose metabolism (LCMRgl) has been widely applied in animals utilizing /sup 14/C-deoxyglucose and in humans employing /sup 18/F-fluorodeoxyglucose. Repeat studies in humans over a relatively brief period of time have not been possible because of the 110-min half-life of /sup 18/F. With the synthesis of /sup 11/C-deoxyglucose it has now become possible to utilize this short-lived (20 min) tracer for the measurement of LCMRgl and to determine its variability within subjects over a 2-h period. The kinetic rate constants for /sup 11/C-deoxyglucose were determined for gray and white matter and found to be very similar to those for /sup 18/F-fluorodeoxyglucose, suggesting that these two analogues of glucose have similar affinities for the facilitated transport system and are similar substrates for hexokinase in the brain. The coefficient of variation of repeated measurements of LCMRgl in a series of six normal subjects was 5.5% to 8.7% for various gray matter structures and 9.7% and 14.0% for white matter structures. The pattern of cerebral metabolic rates is relatively constant in a given individual when the conditions of the study are unchanged. The ability to make repeat measurements in the same subject reduces the variance due to between-subject differences, allowing smaller changes in LCMRgl to be detected with confidence.

  16. Optimization of supervised cluster analysis for extracting reference tissue input curves in (R)-[11C]PK11195 brain PET studies

    PubMed Central

    Yaqub, Maqsood; van Berckel, Bart NM; Schuitemaker, Alie; Hinz, Rainer; Turkheimer, Federico E; Tomasi, Giampaolo; Lammertsma, Adriaan A; Boellaard, Ronald

    2012-01-01

    Performance of two supervised cluster analysis (SVCA) algorithms for extracting reference tissue curves was evaluated to improve quantification of dynamic (R)-[11C]PK11195 brain positron emission tomography (PET) studies. Reference tissues were extracted from images using both a manually defined cerebellum and SVCA algorithms based on either four (SVCA4) or six (SVCA6) kinetic classes. Data from controls, mild cognitive impairment patients, and patients with Alzheimer's disease were analyzed using various kinetic models including plasma input, the simplified reference tissue model (RPM) and RPM with vascular correction (RPMVb). In all subject groups, SVCA-based reference tissue curves showed lower blood volume fractions (Vb) and volume of distributions than those based on cerebellum time-activity curve. Probably resulting from the presence of specific signal from the vessel walls that contains in normal condition a significant concentration of the 18 kDa translocation protein. Best contrast between subject groups was seen using SVCA4-based reference tissues as the result of a lower number of kinetic classes and the prior removal of extracerebral tissues. In addition, incorporation of Vb in RPM improved both parametric images and binding potential contrast between groups. Incorporation of Vb within RPM, together with SVCA4, appears to be the method of choice for analyzing cerebral (R)-[11C]PK11195 neurodegeneration studies. PMID:22588187

  17. Enhancement in optical and structural properties of Zn0.85Mg0.15O nanorods over thin films synthesized by hydrothermal chemical treatment

    NASA Astrophysics Data System (ADS)

    Murkute, P.; Sehara, N.; Ghadi, H.; Pandey, S. K.; Maity, S.; Chakrabarti, S.

    2016-02-01

    We are reporting an enhancement in optical properties by changing the structure of Zn0.85Mg0.15O thin films through formation of crystalline hexagonal nanorods. Zn0.85Mg0.15O thin films were deposited on Si (100) substrate using dielectric sputter followed by annealing in oxygen ambient at temperatures of 700, 800 and 900° C for 10 seconds to reduce oxygen vacancies defects. Deposited thin film annealed at 900 °C (sample A) measured highest peak intensity and it was subjected to controlled the hydrothermal bath conditioning for forming hexagonal nanorods. Four samples were dipped in 2 different solutions with variable molar ratio of zinc nitrate hexahydrate and hexamethylentetramine for 2 and 3 hours, respectively. Samples processed in solution 1 (1:1) ratio for 2 and 3 hours were named B and C and those in solution 2 (2:1) were D and E, respectively. Photoluminescence measurement at 18K demonstrates exciton near-band-edge (NBE) emission peak at 3.61eV from Zn0.85Mg0.15O sample A whereas other samples exhibited slight blue shift along with bimodal peaks. The other peak observed at lower energy 3.43eV corresponds to transitions due to presence of ZnO phase in Zn0.85Mg0.15O. All samples compared to sample A exhibited more than 10 times increment in peak intensities with sample B producing the highest (~ 20 times). Nanorods formation was confirmed using crosssectional SEM imaging. X-ray diffraction measurements revealed that all Zn0.85Mg0.15O samples had (002) preferred crystal orientation with peak position at 34.7°. All nanorods samples measured lower reflectance compared to sample A, indicating high absorption in nanorods due to high scattering of light at the nanorods surface.

  18. Reduced uptake of 18F-FDG and 15O-H2O in Alzheimer's disease-related regions after glucose loading.

    PubMed

    Ishibashi, Kenji; Kawasaki, Keiichi; Ishiwata, Kiichi; Ishii, Kenji

    2015-08-01

    Increased plasma glucose levels are known to reduce fluorine-18-labeled fluorodeoxyglucose ((18)F-FDG) uptake in Alzheimer's disease (AD)-related regions, resulting in the appearance of an AD-like pattern. However, the relationships of its appearance with cerebral blood flow and insulin levels are uncertain. We performed (18)F-FDG and oxygen-15-labeled water ((15)O-H2O) positron emission tomography in the fasting and glucose-loading conditions on nine young healthy volunteers with no cognitive impairments. Measurement of plasma glucose and insulin levels confirmed that all subjects were free of insulin resistance, and that glucose loading significantly increased plasma glucose and insulin levels. Fluorine-18-labeled fluorodeoxyglucose and (15)O-H2O images were compared between the two conditions, focusing on AD-related regions: precuneus/posterior cingulate (PP), lateral parietal cortex (LPC), and frontal cortex (FC). Volume-of-interest analyses showed significantly lower uptake of both (18)F-FDG and (15)O-H2O in PP, LPC, and FC after glucose loading (P<0.05). Whole-brain voxel-wise analyses also revealed the PP, LPC, and FC areas where uptake of both (18)F-FDG and (15)O-H2O decreased (P<0.05, familywise error rate-corrected). We concluded that increased plasma glucose and insulin levels can cause the appearance of the AD-like pattern in both (18)F-FDG and (15)O-H2O images, and this phenomenon can occur even in subjects without insulin resistance. PMID:26058692

  19. Remote processing, delivery and injection of H2[15O] produced from a N2/H2 gas target using a simple and compact apparatus.

    PubMed

    Ferrieri, R A; Alexoff, D L; Schlyer, D J; Wolf, A P

    1994-12-01

    We report here a simple apparatus for remote trapping and processing of H2[15O] produced from the N2/H2 target. The system performs a three step operation for H2[15O] delivery at the PET imaging facility which includes the following: (i) collecting the radiotracer in sterile water; (ii) adjusting preparation pH through removal of radiolytically produced ammonia, while at the same time adjusting solution isotonicity; and (iii) delivery of the radiotracer preparation to the injection syringe in a sterile and pyrogen-free form suitable for human studies. The processing apparatus is simple, can be remotely operated and fits inside a Capintec Dose Monitoring Chamber for direct measurement of accumulated radioactivity. Using this system, 300 mCi of H2[15O] (15 microA of 8 MeV D+ on target) is transferred from target through 120 m x 3.18 mm o.d. Impolene tubing to yield 100 mCi of H2[15O] which is isotonic, neutral and suitable for human studies. A remote hydraulically driven system for i.v. injection of the H2[15O] is also described. The device allows for direct measurement of syringe dose while filling, and for easy, as well as safe transport of the injection syringe assembly to the patient's bedside via a shielded delivery cart. This cart houses a hydraulic piston that allows the physician to "manually" inject the radiotracer without directly handling the syringe. PMID:7894394

  20. (R)-[11C]verapamil is selectively transported by murine and human P-glycoprotein at the blood–brain barrier, and not by MRP1 and BCRP

    PubMed Central

    Römermann, Kerstin; Wanek, Thomas; Bankstahl, Marion; Bankstahl, Jens P.; Fedrowitz, Maren; Müller, Markus; Löscher, Wolfgang; Kuntner, Claudia; Langer, Oliver

    2013-01-01

    Introduction Positron emission tomography (PET) with [11C]verapamil, either in racemic form or in form of the (R)-enantiomer, has been used to measure the functional activity of the adenosine triphosphate-binding cassette (ABC) transporter P-glycoprotein (Pgp) at the blood–brain barrier (BBB). There is some evidence in literature that verapamil inhibits two other ABC transporters expressed at the BBB, i.e. multidrug resistance protein 1 (MRP1) and breast cancer resistance protein (BCRP). However, previous data were obtained with micromolar concentrations of verapamil and do not necessarily reflect the transporter selectivity of verapamil at nanomolar concentrations, which are relevant for PET experiments. The aim of this study was to assess the selectivity of verapamil, in nanomolar concentrations, for Pgp over MRP1 and BCRP. Methods Concentration equilibrium transport assays were performed with [3H]verapamil (5 nM) in cell lines expressing murine or human Pgp, human MRP1, and murine Bcrp1 or human BCRP. Paired PET scans were performed with (R)-[11C]verapamil in female FVB/N (wild-type), Mrp1(−/−), Mdr1a/b(−/−), Bcrp1(−/−) and Mdr1a/b(−/−)Bcrp1(−/−) mice, before and after Pgp inhibition with 15 mg/kg tariquidar. Results In vitro transport experiments exclusively showed directed transport of [3H]verapamil in Mdr1a- and MDR1-overexpressing cells which could be inhibited by tariquidar (0.5 μM). In PET scans acquired before tariquidar administration, brain-to-blood ratio (Kb,brain) of (R)-[11C]verapamil was low in wild-type (1.3 ± 0.1), Mrp1(−/−) (1.4 ± 0.1) and Bcrp1(−/−) mice (1.8 ± 0.1) and high in Mdr1a/b(−/−) (6.9 ± 0.8) and Mdr1a/b(−/−)Bcrp1(−/−) mice (7.9 ± 0.5). In PET scans after tariquidar administration, Kb,brain was significantly increased in Pgp-expressing mice (wild-type: 5.0 ± 0.3-fold, Mrp1(−/−): 3.2 ± 0.6-fold, Bcrp1(−/−): 4.3 ± 0.1-fold) but not in Pgp knockout mice (Mdr1a

  1. Design a 10 kJ IS Mather Type Plasma Focus for Solid Target Activation to Produce Short-Lived Radioisotopes 12C(d,n)13N

    NASA Astrophysics Data System (ADS)

    Sadat Kiai, S. M.; Adlparvar, S.; Sheibani, S.; Elahi, M.; Safarien, A.; Farhangi, S.; Zirak, A. R.; Alhooie, S.; Mortazavi, B. N.; Khalaj, M. M.; Khanchi, A. R.; Dabirzadeh, A. A.; Kashani, A.; Zahedi, F.

    2010-10-01

    A 10 kJ (15 kV, 88 μF) IS (Iranian Sun) Mather type plasma focus device has been studied to determine the activity of a compound exogenous carbon solid target through 12C(d,n)13N nuclear reaction. The produced 13N is a short-lived radioisotope with a half-life of 9.97 min and threshold energy of 0.28 MeV. The results indicate that energetic deuterons impinging on the solid target can produce yield of = 6.7 × 10-5 with an activity of A = 6.8 × 104 Bq for one plasma focus shut and A ν = 4 × 105 Bq for 6 shut per mint when the projectile maximum deuterons energy is E max = 3 MeV.

  2. Synthesis, crystal structure and NLO property of a nonmetal pentaborate [C 6H 13N 2][B 5O 6(OH) 4

    NASA Astrophysics Data System (ADS)

    Liu, Huan-Xin; Liang, Yun-Xiao; Jiang, Xiao

    2008-12-01

    A nonmetal pentaborate [C 6H 13N 2][B 5O 6(OH) 4] ( 1) has been synthesized by 1,4-diazabicyclo[2.2.2] octane (DABCO) and boric acid, and characterized by single-crystal X-ray diffraction, FTIR, elemental analysis, and thermogravimetric analysis. Compound 1 crystallizes in the monoclinic system with space group Cc (no. 9), a=10.205(2) Å, b=14.143(3) Å, c=11.003(2) Å, β=113.97(3)°, V=1451.1(5) Å 3, Z=4. The anionic units, [B 5O 6(OH) 4] -, are interlinked via hydrogen bonding to form a three-dimensional (3D) supramolecular network containing large channels, in which the protonated [C 6H 13N 2] + cations are located. Second-harmonic generation (SHG) measurements on the powder samples reveal that 1 exhibits SHG efficiency approximately 0.9 times that of potassium dihydrogen phosphate (KDP).

  3. Ketamine decreased striatal [(11)C]raclopride binding with no alterations in static dopamine concentrations in the striatal extracellular fluid in the monkey brain: multiparametric PET studies combined with microdialysis analysis.

    PubMed

    Tsukada, H; Harada, N; Nishiyama, S; Ohba, H; Sato, K; Fukumoto, D; Kakiuchi, T

    2000-08-01

    The effects of ketamine, a noncompetitive antagonist of NMDA receptors, on the striatal dopaminergic system were evaluated multiparametrically in the monkey brain using high-resolution positron emission tomography (PET) in combination with microdialysis. L-[beta-(11)C]DOPA, [(11)C]raclopride, and [(11)C]beta-CFT were used to evaluate dopamine synthesis rate, D(2) receptor binding, and transporter availability, respectively, in conscious and ketamine-anesthetized animals. Dopamine concentrations in the striatal extracellular fluid (ECF) were simultaneously measured by PET. Thirty minutes prior to PET scan, intravenous administration of ketamine was started by continuous infusion at a rate of 3 or 10 mg/kg/h. Ketamine infusion dose-dependently decreased [(11)C]raclopride binding, but induced no significant changes in dopamine concentration in the striatal ECF as measured by microdialysis at any dose used. In contrast, ketamine increased both dopamine synthesis and DAT availability as measured by L-[beta-(11)C]DOPA and [(11)C]beta-CFT, respectively, in a dose-dependent manner. These results suggest that the inhibition of glutamatergic neuronal activity modulates dopamine turnover in the striatum by simultaneous enhancement of the dynamics of dopamine synthesis and DAT availability to the same extent, resulting in no apparent changes in ECF dopamine concentration as measured by microdialysis. It also suggests that the alteration of [(11)C]raclopride binding in vivo as measured by PET might not simply be modulated by the static synaptic concentration of dopamine. PMID:10881030

  4. An open-label, randomized positron emission tomography (PET) study in healthy male volunteers consisiting of Part A and Part B. Part A: Clinical validation of norepinephrine transporter (NET) PET ligand, (S,S)-[11C]O-methylreboxetine ([11C]MRB) using different doses of oral atomoxetine as NET reuptake inhibitor. Part B: Evaluation of NET occupancy, as measured by [11C]MRB, with multiple dosing regimens of orally administered GSK372475.

    SciTech Connect

    Fowler, Joanna

    2007-08-31

    Results from human studies with the PET radiotracer (S,S)-[(11)C]O-methyl reboxetine ([(11)C](S,S)-MRB), a ligand targeting the norepinephrine transporter (NET), are reported. Quantification methods were determined from test/retest studies, and sensitivity to pharmacological blockade was tested with different doses of atomoxetine (ATX), a drug that binds to the NET with high affinity (K(i)=2-5 nM). METHODS: Twenty-four male subjects were divided into different groups for serial 90-min PET studies with [(11)C](S,S)-MRB to assess reproducibility and the effect of blocking with different doses of ATX (25, 50 and 100 mg, po). Region-of-interest uptake data and arterial plasma input were analyzed for the distribution volume (DV). Images were normalized to a template, and average parametric images for each group were formed. RESULTS: [(11)C](S,S)-MRB uptake was highest in the thalamus (THL) and the midbrain (MBR) [containing the locus coeruleus (LC)] and lowest for the caudate nucleus (CDT). The CDT, a region with low NET, showed the smallest change on ATX treatment and was used as a reference region for the DV ratio (DVR). The baseline average DVR was 1.48 for both the THL and MBR with lower values for other regions [cerebellum (CB), 1.09; cingulate gyrus (CNG) 1.07]. However, more accurate information about relative densities came from the blocking studies. MBR exhibited greater blocking than THL, indicating a transporter density approximately 40% greater than THL. No relationship was found between DVR change and plasma ATX level. Although the higher dose tended to induce a greater decrease than the lower dose for MBR (average decrease for 25 mg=24+/-7%; 100 mg=31+/-11%), these differences were not significant. The different blocking between MBR (average decrease=28+/- 10%) and THL (average decrease=17+/-10%) given the same baseline DVR indicates that the CDT is not a good measure for non-NET binding in both regions. Threshold analysis of the difference between the

  5. Method for selective recovery of PET-usable quantities of [.sup.18 F] fluoride and [.sup.13 N] nitrate/nitrite from a single irradiation of low-enriched [.sup.18 O] water

    DOEpatents

    Ferrieri, Richard A.; Schlyer, David J.; Shea, Colleen

    1995-06-13

    A process for simultaneously producing PET-usable quantities of [.sup.13 N]NH.sub.3 and [.sup.18 F]F.sup.- for radiotracer synthesis is disclosed. The process includes producing [.sup.13 N]NO.sub.2.sup.- /NO.sub.3.sup.- and [.sup.18 F]F.sup.- simultaneously by exposing a low-enriched (20%-30%) [.sup.18 O]H.sub.2 O target to proton irradiation, sequentially isolating the [.sup.13 N]NO.sub.2.sup.- /NO.sub.3.sup.- and [.sup.18 F]F.sup.- from the [.sup.18 O]H.sub.2 O target, and reducing the [.sup.13 N]NO.sub.2.sup.- /NO.sub.3.sup.- to [.sup.13 N]NH.sub.3. The [.sup.13 N]NH.sub.3 and [.sup.18 F]F.sup.- products are then conveyed to a laboratory for radiotracer applications. The process employs an anion exchange resin for isolation of the isotopes from the [.sup.18 O]H.sub.2 O, and sequential elution of [.sup.13 N]NO.sub.2.sup.- /NO.sub.3.sup.- and [ .sup.18 F]F.sup.- fractions. Also the apparatus is disclosed for simultaneously producing PET-usable quantities of [.sup.13 N]NH.sub.3 and [.sup.18 F]F.sup.- from a single irradiation of a single low-enriched [.sup.18 O]H.sub.2 O target.

  6. 11C choline PET guided salvage radiotherapy with volumetric modulation arc therapy and hypofractionation for recurrent prostate cancer after HIFU failure: preliminary results of tolerability and acute toxicity.

    PubMed

    Alongi, Filippo; Liardo, Rocco L E; Iftode, Cristina; Lopci, Egesta; Villa, Elisa; Comito, Tiziana; Tozzi, Angelo; Navarria, Pierina; Ascolese, Anna M; Mancosu, Pietro; Tomatis, Stefano; Bellorofonte, Carlo; Arturo, Chiti; Scorsetti, Marta

    2014-10-01

    The purpose of this work was to evaluate tolerance, feasibility and acute toxicity in patients undergoing salvage radiotherapy after high-intensity focused ultrasound (HIFU) failure. From 2005 to 2011 a total of 15 patients were treated with HIFU as primary radical treatment. Between July 2011 and February 2013, all 15 patients presented biochemical relapse after HIFU and 11C choline PET documenting intrapostatic-only failure. Salvage EBRT was performed with moderate hypofractionation schedule in 28 fractions with volumetric modulation arc therapy (VMAT). Genito-urinary (GU) and rectal and bowel toxicity were scored by common terminology criteria for adverse events version 4 (CTCAE V.4) scale. Biochemical response was assessed by ASTRO Phoenix criteria. Median age of patients was 67 years (range: 53-85). The median Gleason score was 7 (range: 6-9). The median prostate specific antigen (PSA) at the time of biochemical relapse after HIFU was 5.2 ng/mL (range: 2-64.2). Seven of the 15 patients received androgen deprivation therapy (ADT) started after HIFU failure, interrupted before 11C choline PET and radiotherapy. Median prescribed dose was 71.4 Gy (range: 71.4-74.2 Gy) in 28 fractions. No radiation related major upper gastrointestinal (GI), rectal and GU toxicity were experienced. GU, acute grade 1 and grade 2 toxicities were recorded in 7/15 and 4/15 respectively; bowel acute grade 1 and grade 2 toxicities in 4/15 and 1/15; rectal acute grade 1 and grade 2 toxicities in 3/15 and 2/15 respectively. No grade 3 or greater acute or late toxicities occurred. Biochemical control was assessed in 12/15 (80%) patients. With a median follow up of 12 months, three out of 15 patients, with biochemical relapse, showed lymph-nodal recurrence. Our early clinical results and biochemical data confirm the feasibility and show a good tolerance of the 11C choline PET guided salvage radiation therapy after HIFU failure. The findings of low acute toxicity is encouraging, but longer

  7. Vibronic valence and Rydberg transitions in geminal chloro-fluoro-ethene (1,1-C2H2FCl): a spectroscopic and quantum chemical investigation

    NASA Astrophysics Data System (ADS)

    Locht, R.; Dehareng, D.; Leyh, B.

    2014-06-01

    The vacuum ultraviolet photoabsorption spectrum of 1,1-C2H2FCl has been examined in detail between 5 and 15 eV photon energy by using synchrotron radiation dispersed by three different monochromators. Quantum chemical calculations are performed to help in the analysis of the valence/Rydberg transition region centred at 7.05 eV including the 3a″(π)→π* and the 3a″(π)→3s Rydberg transitions. Interactions between states involving transitions to the 3s, 4d and σ* orbitals are identified. A vibrational analysis is proposed for the structures belonging to these transitions. For the π(3a″)→π* transition, one vibrational progression is observed with ω3 = 1410 ± 50 cm-1 and its lowest excitation energy is determined at about 6.398 ± 0.003 eV. The π(3a″)→3s Rydberg transition is characterised by a single progression with ω3 = 1410 ± 80 cm-1 likely starting at about 6.45 eV. These vibrations are ascribed to the C=C stretching motion. The abundant structure observed in the spectrum between 7.8 and 10.5 eV has been analysed in terms of vibronic transitions to ns (δ = 0.97), np (δ = 0.63 and 0.40) and nd (δ = 0.13 and -0.11) Rydberg states, which belong to series converging to the 1,1-C2H2FCl+(?) ionic ground state. The analysis of the vibrational structure of the individual Rydberg states has been attempted leading to average values of the wave numbers ω3 = 1420 ± 20 cm-1, ω7 = 720 ± 50 cm-1 and ω9 = 390 ± 50 cm-1. Between 10.5 and 12.5 eV, nine other Rydberg states converging to the 1,1-C2H2FCl+(?) first excited state were analysed by the same way. The vibrational structure of these Rydberg states results from the excitation of one vibrational normal mode ν7 with an average value of ω7 = 520 ± 20 cm-1, which is assigned to the C-Cl stretching vibration as inferred from quantum chemical calculations.

  8. Synthesis of (R)-(-)- and (S)-(+)-4-fluorodeprenyl and (R)-(-)- and (S)-(+)-(N- sup 11 C-methyl)-4-fluorodeprenyl and positron emission tomography studies in baboon brain

    SciTech Connect

    Plenevaux, A.; Dewey, S.L.; Fowler, J.S.; Guillaume, M.; Wolf, A.P. )

    1990-07-01

    (R)-(-)- and (S)-(+)-alpha-methyl-beta-4-(fluorophenyl)-N-methyl-N- propynylethylamine (R)-(-)- and (S)-(+)-4-fluorodeprenyl were synthesized via the reaction of 4-fluorobenzaldehyde with nitroethane followed by reduction with lithium aluminum hydride to produce racemic 4-fluoroamphetamine, which was resolved by recrystallization with L- or D-N-acetylleucine to yield (R)-(-)-4-fluoroamphetamine or (S)-(+)-4-fluoroamphetamine in greater than 96% enantiomeric excesses and in yields of 42 and 39%, respectively. Alkylation with propargyl bromide gave (R)-(-)- or (S)-(+)-4-fluoronordeprenyl which was reductively methylated (Borch conditions) to produce (R)-(-)- or (S)-(+)-4-fluorodeprenyl. Alkylation of (R)-(-)- or (S)-(+)-4-fluoronordeprenyl with carbon-11 labeled methyl iodide gave (R)-(-)- or (S)-(+)-(N-11C-methyl)-4-fluorodeprenyl in a radiochemical yield of 30-40%. Comparative PET studies of the two labeled enantiomers in baboons showed a significantly lower retention of radioactivity in the striatum for the (S)-(+) enantiomer relative to the (R)-(-) enantiomer.

  9. Dopamine D2/3 Receptor Availability in the Striatum of Antipsychotic-Free Older Patients with Schizophrenia - A [11C]-raclopride PET Study

    PubMed Central

    Nakajima, Shinichiro; Caravaggio, Fernando; Mamo, David C.; Mulsant, Benoit H.; Chung, Jun Ku; Plitman, Eric; Iwata, Yusuke; Gerretsen, Philip; Uchida, Hiroyuki; Suzuki, Takefumi; Mar, Wanna; Wilson, Alan A.; Houle, Sylvain; Graff-Guerrero, Ariel

    2015-01-01

    Background No study has examined dopamine D2/3 receptor (D2/3R) availability in antipsychotic-free older patients with schizophrenia. Methods We included patients with schizophrenia 50 years or older who were antipsychotic-free for at least 3 months. We compared non-displaceable binding potential (BPND) of [11C]-raclopride in the caudate, putamen, ventral striatum, and globus pallidus between patients and age- and sex-matched healthy controls. Results Ten patients participated (antipsychotic-naïve=4). No differences in BPND were found between patients and controls in any ROIs (F(1, 72)=.42, p=.52). Conclusion The preliminary results suggest no differences in D2/3R availability between antipsychotic-free older patients with schizophrenia and controls. PMID:25757713

  10. Test–retest reproducibility of cannabinoid-receptor type 1 availability quantified with the PET ligand [11C]MePPEP

    PubMed Central

    Riaño Barros, Daniela A.; McGinnity, Colm J.; Rosso, Lula; Heckemann, Rolf A.; Howes, Oliver D.; Brooks, David J.; Duncan, John S.; Turkheimer, Federico E.; Koepp, Matthias J.; Hammers, Alexander

    2014-01-01

    Background Endocannabinoids are involved in normal cognition, and dysfunction in cannabinoid-receptor-mediated neurotransmission has been suggested in a variety of neurological and psychiatric pathologies. The type 1 cannabinoid receptor (CB1) is widely expressed in the human central nervous system. The objective of this study was to quantify the test–retest reproducibility of measures of the PET ligand [11C]MePPEP in order to assess the stability of CB1-receptor quantification in humans in vivo. Methods Fifteen healthy subjects (eight females; median age 32 years, range 25 to 65 years) had a 90-minute PET scan on two occasions after injection of a median dose of [11C]MePPEP of 364 MBq. Metabolite-corrected arterial plasma input functions were obtained for all scans. Eight ROIs, reflecting different levels of receptor densities/concentrations, were defined automatically: hippocampus, anterior cingulate gyrus, inferior frontal gyrus, caudate nucleus, globus pallidus, nucleus accumbens, thalamus, and pons. We used seven quantification methods: reversible compartmental models with one and two tissue classes, two and four rate constants, and a variable blood volume term (2kbv; 4kbv); model-free (spectral) analyses with and without regularisation, including one with voxel-wise quantification; the simplified reference tissue model (SRTM) with pons as a pseudo-reference region; and modified standard uptake values (mSUVs) calculated for the period of ~ 30–60 min after injection. Percentage test–retest change and between-subject variability were both assessed, and test–retest reliability was quantified by the intraclass correlation coefficient (ICC). The ratio of binding estimates pallidum:pons served as an indicator of a method's ability to reflect binding heterogeneity. Results Neither the SRTM nor the 4kbv model produced reliable measures, with ICCs around zero. Very good (> 0.75) or excellent (> 0.80) ICCs were obtained with the other methods. The most

  11. 15O PET Measurement of Blood Flow and Oxygen Consumption in Cold-Activated Human Brown Fat

    PubMed Central

    Muzik, Otto; Mangner, Thomas J.; Leonard, William R.; Kumar, Ajay; Janisse, James; Granneman, James G.

    2013-01-01

    Although it has been believed that brown adipose tissue (BAT) depots disappear shortly after the perinatal period in humans, PET imaging using the glucose analog 18F-FDG has shown unequivocally the existence of functional BAT in adult humans, suggesting that many humans retain some functional BAT past infancy. The objective of this study was to determine to what extent BAT thermogenesis is activated in adults during cold stress and to establish the relationship between BAT oxidative metabolism and 18F-FDG tracer uptake. Methods Twenty-five healthy adults (15 women and 10 men; mean age ± SD, 30 ± 7 y) underwent triple-oxygen scans (H215O, C15O, and 15O2) as well as measurements of daily energy expenditure (DEE; kcal/d) both at rest and after exposure to mild cold (15.5°C [60°F]) using indirect calorimetry. The subjects were divided into 2 groups (high BAT and low BAT) based on the presence or absence of 18F-FDG tracer uptake (standardized uptake value [SUV] > 2) in cervical–supraclavicular BAT. Blood flow and oxygen extraction fraction (OEF) were calculated from dynamic PET scans at the location of BAT, muscle, and white adipose tissue. Regional blood oxygen saturation was determined by near-infrared spectroscopy. The total energy expenditure during rest and mild cold stress was measured by indirect calorimetry. Tissue-level metabolic rate of oxygen (MRO2) in BAT was determined and used to calculate the contribution of activated BAT to DEE. Results The mass of activated BAT was 59.1 ± 17.5 g (range, 32–85 g) in the high-BAT group (8 women and 1 man; mean age, 29.6 ± 5.5 y) and 2.2 ± 3.6 g (range, 0–9.3 g) in the low-BAT group (9 men and 7 women; mean age, 31.4 ± 10 y). Corresponding maximal SUVs were significantly higher in the high-BAT group than in the low-BAT group (10.7 ± 3.9 vs. 2.1 ± 0.7, P = 0.01). Blood flow values were significantly higher in the high-BAT group than in the low-BAT group for BAT (12.9 ± 4.1 vs. 5.9 ± 2.2 mL/100 g/min, P = 0

  12. In Vivo Evaluation of Blood Based and Reference Tissue Based PET Quantifications of [11C]DASB in the Canine Brain

    PubMed Central

    Polis, Ingeborgh; Neyt, Sara; Kersemans, Ken; Dobbeleir, Andre; Saunders, Jimmy; Goethals, Ingeborg; Peremans, Kathelijne; De Vos, Filip

    2016-01-01

    This first-in-dog study evaluates the use of the PET-radioligand [11C]DASB to image the density and availability of the serotonin transporter (SERT) in the canine brain. Imaging the serotonergic system could improve diagnosis and therapy of multiple canine behavioural disorders. Furthermore, as many similarities are reported between several human neuropsychiatric conditions and naturally occurring canine behavioural disorders, making this tracer available for use in dogs also provide researchers an interesting non-primate animal model to investigate human disorders. Five adult beagles underwent a 90 minutes dynamic PET scan and arterial whole blood was sampled throughout the scan. For each ROI, the distribution volume (VT), obtained via the one- and two- tissue compartment model (1-TC, 2-TC) and the Logan Plot, was calculated and the goodness-of-fit was evaluated by the Akaike Information Criterion (AIC). For the preferred compartmental model BPND values were estimated and compared with those derived by four reference tissue models: 4-parameter RTM, SRTM2, MRTM2 and the Logan reference tissue model. The 2-TC model indicated in 61% of the ROIs a better fit compared to the 1-TC model. The Logan plot produced almost identical VT values and can be used as an alternative. Compared with the 2-TC model, all investigated reference tissue models showed high correlations but small underestimations of the BPND-parameter. The highest correlation was achieved with the Logan reference tissue model (Y = 0.9266 x + 0.0257; R2 = 0.9722). Therefore, this model can be put forward as a non-invasive standard model for future PET-experiments with [11C]DASB in dogs. PMID:26859850

  13. Expression of CD11c+HLA-DR+dendritic cells and related cytokines in the follicular fluid might be related to pathogenesis of ovarian hyperstimulation syndrome

    PubMed Central

    Shi, Sen-Lin; Peng, Zhao-Feng; Yao, Gui-Dong; Jin, Hai-Xia; Song, Wen-Yan; Yang, Hong-Yi; Xue, Ru-Yue; Sun, Ying-Pu

    2015-01-01

    Objective: To explore the expressions of CD11c+HLA-DR+dentritic cells in the follicular fluid of patients with OHSS and their significances. Subjects: 100 individuals. Treatment: embryos were observed. The distribution of dentritic cells in follicular fluid and the levels of IL-10, IL-12, IL-18 and IL-23 in follicular fluid were detected. Methods: There were ovarian hyperstimulation syndrome (OHSS) group and control group in this study. The OHSS group consisted of 50 patients with OHSS and the control group consisted of 50 patients who underwent in vitro fertilization-embryo transfer (IVF-ET) only due to male factors. The statuses of embryos were compared between the two groups. The distribution of dentritic cells in follicular fluid was determined with flow cytometry, and the levels of IL-10, IL-12, IL-18 and IL-23 in follicular fluid were detected with enzyme-linked immunosorbent assay (ELISA) in all patients. Results: The two-pronuclear (2PN) fertility rate, high-quality embryo rate and available embryo rate were all significantly lower in OHSS group than in control group (all P<0.05). The number of CD11c+HLA-DR+dentritic cells (P<0.05) and the levels of IL-10, IL-12, IL-18 and IL-23 were all significantly higher in OHSS group than in control group (all P<0.01). Conclusion: The follicular fluid of the patients with OHSS is in an inflammatory status, the inflammatory status may be involved in OHSS and the microenvironment of follicular fluid may affects oocyte quality and embryo development. PMID:26823856

  14. In vivo markers of inflammatory response in recent-onset schizophrenia: a combined study using [11C]DPA-713 PET and analysis of CSF and plasma

    PubMed Central

    Coughlin, J M; Wang, Y; Ambinder, E B; Ward, R E; Minn, I; Vranesic, M; Kim, P K; Ford, C N; Higgs, C; Hayes, L N; Schretlen, D J; Dannals, R F; Kassiou, M; Sawa, A; Pomper, M G

    2016-01-01

    Several lines of evidence suggest aberrant immune response in schizophrenia, including elevated levels of cytokines. These cytokines are thought to be produced by activated microglia, the innate immune cells of the central nervous system. However, increase in translocator protein 18 kDa (TSPO), a marker of activated glia, has not been found in patients with chronic schizophrenia using second-generation radiotracers and positron emission tomography (PET)-based neuroimaging. In this study we focused on patients with recent onset of schizophrenia (within 5 years of diagnosis). Quantified levels of TSPO in the cortical and subcortical brain regions using the PET-based radiotracer [11C]DPA-713 were compared between the patients and healthy controls. Markers of inflammation, including interleukin 6 (IL-6), were assessed in the plasma and cerebrospinal fluid (CSF) in these participants. We observed no significant change in the binding of [11C]DPA-713 to TSPO in 12 patients with recent onset of schizophrenia compared with 14 controls. Nevertheless, the patients with recent onset of schizophrenia showed a significant increase in IL-6 in both plasma (P<0.001) and CSF (P=0.02). The CSF levels of IL-6 were significantly correlated with the levels of IL-6 in plasma within the total study population (P<0.001) and in patients with recent onset of schizophrenia alone (P=0.03). Our results suggest that increased levels of IL-6 may occur in the absence of changed TSPO PET signal in the brains of medicated patients with recent onset of schizophrenia. Future development of PET-based radiotracers targeting alternative markers of glial activation and immune response may be needed to capture the inflammatory signature present in the brains of patients with early-stage disease. PMID:27070405

  15. Washout rate in rat brain irradiated by a 11C beam after acetazolamide loading using a small single-ring OpenPET prototype

    NASA Astrophysics Data System (ADS)

    Hirano, Yoshiyuki; Takuwa, Hiroyuki; Yoshida, Eiji; Nishikido, Fumihiko; Nakajima, Yasunori; Wakizaka, Hidekatsu; Yamaya, Taiga

    2016-03-01

    In dose verification techniques of particle therapies based on in-beam positron emission tomography (PET), the causes of washout of positron emitters by physiological effects should be clarified to correct washout for accurate verification. As well, the quantitative washout rate has a potential usefulness as a diagnostic index which should be explored. Therefore, we measured washout rates of rat brain after vasodilator acetazolamide loading to investigate the possible effects of blood flow on washout. Six rat brains were irradiated by a radioisotope 11C beam and time activity curves on the whole brains were obtained with a small single-ring OpenPET prototype. Then, washout rates were calculated with the Mizuno model, where two washout rates (k 2m and k 2s ) were assumed, and a two-compartment model including efflux from tissue to blood (k 2) and influx (k 3) and efflux (k 4) between the two tissue compartments. Before the irradiations, we used laser-Doppler flowmetry to confirm that acetazolamide increased cerebral blood flow (CBF) of a rat. We compared means of k 2m , k 2s and k 2, k 3 and k 4 without acetazolamide loading (Rest) and with acetazolamide loading (ACZ). For all k values, ACZ values were lower than Rest values. In other words, though CBF increased, washout rates were decreased. This may be attributed to the implanted 11C reacting to form 11CO2. Because acetazolamide increased the concentration of CO2 in brain, suppressed diffusion of 11CO2 and decomposition of 11CO2 into ions were prevented.

  16. In vivo markers of inflammatory response in recent-onset schizophrenia: a combined study using [(11)C]DPA-713 PET and analysis of CSF and plasma.

    PubMed

    Coughlin, J M; Wang, Y; Ambinder, E B; Ward, R E; Minn, I; Vranesic, M; Kim, P K; Ford, C N; Higgs, C; Hayes, L N; Schretlen, D J; Dannals, R F; Kassiou, M; Sawa, A; Pomper, M G

    2016-01-01

    Several lines of evidence suggest aberrant immune response in schizophrenia, including elevated levels of cytokines. These cytokines are thought to be produced by activated microglia, the innate immune cells of the central nervous system. However, increase in translocator protein 18 kDa (TSPO), a marker of activated glia, has not been found in patients with chronic schizophrenia using second-generation radiotracers and positron emission tomography (PET)-based neuroimaging. In this study we focused on patients with recent onset of schizophrenia (within 5 years of diagnosis). Quantified levels of TSPO in the cortical and subcortical brain regions using the PET-based radiotracer [(11)C]DPA-713 were compared between the patients and healthy controls. Markers of inflammation, including interleukin 6 (IL-6), were assessed in the plasma and cerebrospinal fluid (CSF) in these participants. We observed no significant change in the binding of [(11)C]DPA-713 to TSPO in 12 patients with recent onset of schizophrenia compared with 14 controls. Nevertheless, the patients with recent onset of schizophrenia showed a significant increase in IL-6 in both plasma (P<0.001) and CSF (P=0.02). The CSF levels of IL-6 were significantly correlated with the levels of IL-6 in plasma within the total study population (P<0.001) and in patients with recent onset of schizophrenia alone (P=0.03). Our results suggest that increased levels of IL-6 may occur in the absence of changed TSPO PET signal in the brains of medicated patients with recent onset of schizophrenia. Future development of PET-based radiotracers targeting alternative markers of glial activation and immune response may be needed to capture the inflammatory signature present in the brains of patients with early-stage disease. PMID:27070405

  17. Risky Decision-Making and Ventral Striatal Dopamine Responses to Amphetamine: A Positron Emission Tomography [11C] Raclopride Study in Healthy Adults

    PubMed Central

    Oswald, Lynn M.; Wand, Gary S.; Wong, Dean F.; Brown, Clayton H.; Kuwabara, Hiroto; Brašić, James R.

    2015-01-01

    Recent functional magnetic resonance imaging (fMRI) studies have provided compelling evidence that corticolimbic brain regions are integrally involved in human decision-making. Although much less is known about molecular mechanisms, there is growing evidence that the mesolimbic dopamine (DA) neurotransmitter system may be an important neural substrate. Thus far, direct examination of DA signaling in human risk-taking has centered onl gambling disorder. Findings from several positron emission tomography (PET) studies suggest that dysfunctions in mesolimbic DA circuits may play an important role in gambling behavior. Nevertheless, interpretation of these findings is currently hampered by a need for better understanding of how individual differences in regional DA function influence normative decision-making in humans. To further our understanding of these processes, we used [11C]raclopride PET to examine associations between ventral striatal (VS) DA responses to amphetamine (AMPH) and risky decision-making in a sample of healthy young adults with no history of psychiatric disorder, Forty-five male and female subjects, ages 18–29 years, completed a computerized version of the IOWA Gambling Task. Participants then underwent two 90-minute PET studies with high specific activity [11C]raclopride. The first scan was preceded by intravenous saline; the second, by intravenous AMPH (0.3 mg/kg). Findings of primary analyses showed that less advantageous decision-making was associated with greater right VS DA release; the relationship did not differ as a function of gender. No associations were observed between risk-taking and left VS DA release or baseline D2/D3 receptor availability in either hemisphere. Overall, the results support notions that variability in striatal DA function may mediate inter-individual differences in risky decision-making in healthy adults, further suggesting that hypersensitive DA circuits may represent a risk pathway in this population. PMID

  18. Effect of chronic antipsychotic treatment on striatal phosphodiesterase 10A levels: a [11C]MP-10 PET rodent imaging study with ex vivo confirmation

    PubMed Central

    Natesan, S; Ashworth, S; Nielsen, J; Tang, S-P; Salinas, C; Kealey, S; Lauridsen, J B; Stensbøl, T B; Gunn, R N; Rabiner, E A; Kapur, S

    2014-01-01

    A number of phosphodiesterase 10A (PDE10) inhibitors are about to undergo clinical evaluation for their efficacy in treating schizophrenia. As phosphodiesterases are in the same signalling pathway as dopamine D2 receptors, it is possible that prior antipsychotic treatment could influence these enzyme systems in patients. Chronic, in contrast to acute, antipsychotic treatment has been reported to increase brain PDE10A levels in rodents. The aim of this study was to confirm these findings in a manner that can be translated to human imaging studies to understand its consequences. Positron emission tomography (PET) scanning was used to evaluate PDE10A enzyme availability, after chronic haloperidol administration, using a specific PDE10A ligand ([11C]MP-10). The binding of [11C]MP-10 in the striatum and the cerebellum was measured in rodents and a simplified reference tissue model (SRTM) with cerebellum as the reference region was used to determine the binding potential (BPND). In rats treated chronically with haloperidol (2 mg kg−1 per day), there was no significant difference in PDE10A levels compared with the vehicle-treated group (BPND±s.d.: 3.57±0.64 versus 2.86±0.71). Following PET scans, ex vivo analysis of striatal brain tissue for PDE10A mRNA (Pde10a) and PDE10A enzyme activity showed no significant difference. Similarly, the PDE10A protein content determined by western blot analysis was similar between the two groups, contrary to an earlier finding. The results of the study indicate that prior exposure to antipsychotic medication in rodents does not alter PDE10A levels. PMID:24690597

  19. Wavelet-based resolution recovery using an anatomical prior provides quantitative recovery for human population phantom PET [11C]raclopride data

    NASA Astrophysics Data System (ADS)

    Shidahara, M.; Tsoumpas, C.; McGinnity, C. J.; Kato, T.; Tamura, H.; Hammers, A.; Watabe, H.; Turkheimer, F. E.

    2012-05-01

    The objective of this study was to evaluate a resolution recovery (RR) method using a variety of simulated human brain [11C]raclopride positron emission tomography (PET) images. Simulated datasets of 15 numerical human phantoms were processed by a wavelet-based RR method using an anatomical prior. The anatomical prior was in the form of a hybrid segmented atlas, which combined an atlas for anatomical labelling and a PET image for functional labelling of each anatomical structure. We applied RR to both 60 min static and dynamic PET images. Recovery was quantified in 84 regions, comparing the typical ‘true’ value for the simulation, as obtained in normal subjects, simulated and RR PET images. The radioactivity concentration in the white matter, striatum and other cortical regions was successfully recovered for the 60 min static image of all 15 human phantoms; the dependence of the solution on accurate anatomical information was demonstrated by the difficulty of the technique to retrieve the subthalamic nuclei due to mismatch between the two atlases used for data simulation and recovery. Structural and functional synergy for resolution recovery (SFS-RR) improved quantification in the caudate and putamen, the main regions of interest, from -30.1% and -26.2% to -17.6% and -15.1%, respectively, for the 60 min static image and from -51.4% and -38.3% to -27.6% and -20.3% for the binding potential (BPND) image, respectively. The proposed methodology proved effective in the RR of small structures from brain [11C]raclopride PET images. The improvement is consistent across the anatomical variability of a simulated population as long as accurate anatomical segmentations are provided.

  20. Early Ovariectomy Results in Reduced Numbers of CD11c+/CD11b+ Spleen Cells and Impacts Disease Expression in Murine Lupus

    PubMed Central

    Cunningham, Melissa A.; Wirth, Jena R.; Scott, Jennifer L.; Eudaly, Jackie; Collins, Erin L.; Gilkeson, Gary S.

    2016-01-01

    Ninety percent of those diagnosed with systemic lupus erythematosus are female, with peak incidence between the ages of 15 and 45, when women are most hormonally active. Despite significant research effort, the mechanisms underlying this sex bias remain unclear. We previously showed that a functional knockout of estrogen receptor alpha (ERα) resulted in significantly reduced renal disease and increased survival in murine lupus. Dendritic cell (DC) development, which requires both estrogen and ERα, is impacted, as is activation status and cytokine production. Since both estrogen and testosterone levels have immunomodulating effects, we presently studied the phenotype of NZM2410 lupus-prone mice following post- and prepubertal ovariectomy (OVX) ± estradiol (E2) replacement to determine the impact of hormonal status on disease expression and DC development in these mice. We observed a trend toward survival benefit in addition to decreased proteinuria and improved renal histology in the early OVX, but not late OVX- or E2-repleted WT mice. Interestingly, there was also a significant difference in splenic DC subsets by flow cytometry. Spleens from NZM mice OVX’d early had a significant decrease in proinflammatory CD11c+CD11b+ DCs (vs. unmanipulated WTs, late OVX- and E2-repleted mice). These early OVX’d animals also had a significant increase in tolerogenic CD11c+CD8a+ DCs vs. WT. These data join a growing body of evidence that supports a role for hormone modulation of DCs that likely impacts the penetrance and severity of autoimmune diseases, such as lupus. PMID:26913030

  1. A Comparison of D2 Receptor Specific Binding in Obese and Normal-weight Individuals Using PET with (N-[11C]methyl)benperidol

    PubMed Central

    Eisenstein, Sarah A.; Antenor-Dorsey, Jo Ann V.; Gredysa, Danuta M.; Koller, Jonathan M.; Bihun, Emily C.; Ranck, Samantha A.; Arbeláez, Ana Maria; Klein, Samuel; Perlmutter, Joel S.; Moerlein, Stephen M.; Black, Kevin J.; Hershey, Tamara

    2013-01-01

    Previous PET imaging studies have demonstrated mixed findings regarding dopamine D2/D3 receptor availability in obese relative to non-obese humans. Nonspecific D2/D3 radioligands do not allow for separate estimation of D2 receptor (D2R) and D3 receptor (D3R) subtypes of the D2 receptor family, which may play different roles in behavior and are distributed differently throughout the brain. These radioligands are also displaceable by endogenous dopamine, confounding interpretation of differences in receptor availability with differing levels of dopamine release. The present study used PET imaging with the D2R-selective radioligand (N-[11C] methyl)benperidol ([11C]NMB), which is non-displaceable by endogenous dopamine, to estimate D2R specific binding (BPND) and its relationship to body mass index (BMI) and age in 15 normal-weight (mean BMI = 22.6 kg/m2) and 15 obese (mean BMI = 40.3 kg/m2) men and women. Subjects with illnesses or taking medications that interfere with dopamine signaling were excluded. Striatal D2R BPND was calculated using the Logan graphical method with cerebellum as a reference region. D2R BPND estimates were higher in putamen and caudate relative to nucleus accumbens, but did not differ between normal-weight and obese groups. BMI values did not correlate with D2R BPND. Age was negatively correlated with putamen D2R BPND in both groups. These results suggest that altered D2R specific binding is not involved in the pathogenesis of obesity per se and underscore the need for additional studies evaluating the relationship between D3R, dopamine reuptake, or endogenous dopamine release and human obesity. PMID:23650017

  2. Synthesis of ({sup 11}C) RO 19 6327, a highly selective and reversible monoamine oxidase B inhibitor potentially useful for treatment of Parkinson`s disease

    SciTech Connect

    Ding, Y.S.; Rehder, K.; Vassello, M.

    1994-05-01

    The potential neuroprotective effect of monoamine oxidase B (MAO B) inhibitors has stimulated intense interest in characterizing their modes of action and in developing new MAO B inhibitor drugs with different properties for clinical investigation in Parkinson`s disease and other enurodegenerative diseases. One of these drugs is Ro 19 6327 (N-(2-aminoethyl)-5-chloro-2-pyridine carboxamide {center_dot}HCl). Ro 19 6327 differs from the suicide inhibitor L-deprenyl in that it is more specific, greater than twenty times as potent in inhibiting MAO B, has no amphetamine metabolites, and is reversible. The recovery of MAO B activity 36 hours after Ro19 6327 treatment discontinuation is relevant in clinical studies since treatment can be withdrawn and changed without the complication of long term effects, as is seen with L-deprenyl. We report here a new synthetic approach to the precursor for Ro 19 6327 suitable for subsequent C-11 labeling for PET studies. Homolytic amidation of 3-chloropyridine afforded 5-chlor-2-pyridinecarboxamide which upon treatment with formaldehyde yielded 5-chlor-N-(hydroxymethyl)-2-pyridinecarboxamide. Conversion to the corresponding acetate afforded a substrate for the displacement reaction with ({sup 11}C) cyanide. Finding a highly selective reducing reagent for the following reduction step was crucial due t;o the presence of four reducible functional groups within the molecule, namely chlorine, pyridine ring, amide, and nitrile. Sodium borohydride in the presence of aluminum chloride was by far the most effective reagent. The final product was then purified by HPLC. The pharmacokinetics, regional distribution and metabolism of ({sup 11}C)Ro 19 6317 are currently under investigation with PET.

  3. In Vivo Evaluation of Blood Based and Reference Tissue Based PET Quantifications of [11C]DASB in the Canine Brain.

    PubMed

    Van Laeken, Nick; Taylor, Olivia; Polis, Ingeborgh; Neyt, Sara; Kersemans, Ken; Dobbeleir, Andre; Saunders, Jimmy; Goethals, Ingeborg; Peremans, Kathelijne; De Vos, Filip

    2016-01-01

    This first-in-dog study evaluates the use of the PET-radioligand [11C]DASB to image the density and availability of the serotonin transporter (SERT) in the canine brain. Imaging the serotonergic system could improve diagnosis and therapy of multiple canine behavioural disorders. Furthermore, as many similarities are reported between several human neuropsychiatric conditions and naturally occurring canine behavioural disorders, making this tracer available for use in dogs also provide researchers an interesting non-primate animal model to investigate human disorders. Five adult beagles underwent a 90 minutes dynamic PET scan and arterial whole blood was sampled throughout the scan. For each ROI, the distribution volume (VT), obtained via the one- and two- tissue compartment model (1-TC, 2-TC) and the Logan Plot, was calculated and the goodness-of-fit was evaluated by the Akaike Information Criterion (AIC). For the preferred compartmental model BPND values were estimated and compared with those derived by four reference tissue models: 4-parameter RTM, SRTM2, MRTM2 and the Logan reference tissue model. The 2-TC model indicated in 61% of the ROIs a better fit compared to the 1-TC model. The Logan plot produced almost identical VT values and can be used as an alternative. Compared with the 2-TC model, all investigated reference tissue models showed high correlations but small underestimations of the BPND-parameter. The highest correlation was achieved with the Logan reference tissue model (Y = 0.9266 x + 0.0257; R2 = 0.9722). Therefore, this model can be put forward as a non-invasive standard model for future PET-experiments with [11C]DASB in dogs. PMID:26859850

  4. Dopamine Transporter Correlates and Occupancy by Modafinil in Cocaine-Dependent Patients: A Controlled Study With High-Resolution PET and [(11)C]-PE2I.

    PubMed

    Karila, Laurent; Leroy, Claire; Dubol, Manon; Trichard, Christian; Mabondo, Audrey; Marill, Catherine; Dubois, Albertine; Bordas, Nadège; Martinot, Jean-Luc; Reynaud, Michel; Artiges, Eric

    2016-08-01

    Modafinil is a candidate compound for the treatment of cocaine addiction that binds to the dopamine transporter (DAT) in healthy humans, as observed by positron emission tomography (PET). This mechanism, analogous to that of cocaine, might mediate a putative therapeutic effect of modafinil on cocaine dependence, though the binding of modafinil to DAT has never been assessed in cocaine-dependent patients. We aimed at quantifying the DAT availability during a controlled treatment by modafinil, and its clinical and psychometric correlates in cocaine-dependent patients at the onset of abstinence initiation. Twenty-nine cocaine-dependent male patients were enrolled in a 3-month trial for cocaine abstinence. Modafinil was used in a randomized double-blind placebo-controlled design and was administered as follows: 400 mg/day for 26 days, then 300 mg/day for 30 days, and 200 mg/day for 31 days. Participants were examined twice during a 17-day hospitalization for their DAT availability using PET and [(11)C]-PE2I and for assessments of craving, depressive symptoms, working memory, and decision-making. Cocaine abstinence was further assessed during a 10-week outpatient follow-up period. Baseline [(11)C]-PE2I-binding potential covaried with risk taking and craving index in striatal and extrastriatal regions. A 65.6% decrease of binding potential was detected in patients receiving modafinil for 2 weeks, whereas placebo induced no significant change. During hospitalization, an equivalent improvement in clinical outcomes was observed in both treatment