Science.gov

Sample records for potential pet ligand

  1. Bis(methylpyridine)-EDTA derivative as a potential ligand for PET imaging: synthesis, complexation, and biological evaluation.

    PubMed

    Singh, Pooja; Aggarwal, Swati; Tiwari, Anjani K; Kumar, Vikas; Pratap, Ramendra; Chuttani, Krishna; Mishra, Anil K

    2014-12-01

    A novel transitional metal ligand derivatized from EDTA-conjugated 2-amino-4-methyl pyridine, an acyclic vehicle (EDTA-Mepy2 ) was designed, synthesized, and characterized for PET imaging with ⁶⁸Ga. The drug likeliness and appropriate lipophilicity were first analyzed by molecular docking studies which shows interactive property of ligand with serum albumin protein (HSA: PDB 1E78), at Lys199, Arg257, and His242 residues, which make it more appropriate in transportation as a specific ligand for PET imaging. As a confirmation, binding constant of the ligand with human serum albumin was calculated at λex = 350 nm which was found to be 4.9 × 10³ m⁻¹. The pharmacokinetics of (68) Ga-EDTA-Mepy2 was analyzed by blood kinetics (t(1/2) slow: 3 h 56 min and t(1/2) fast: 32 min) and biodistribution (maximum % ID/g was found in kidney at 1 h). Further the capability of this ligand was analyzed as optical marker also, by recording λex = 380 nm, RFU = 8000; 710 nm, RFU = 1000 units at fixed λem = 280 nm. Additionally, in physiological conditions where its stability was calculated, suggests 15-20 times selectivity over the endogenously present metal ions (KG aL /KZ nL = 14.3, KG aL /KC uL = 18.1).

  2. Radiosynthesis and preclinical evaluation of [11C]prucalopride as a potential agonist PET ligand for the 5-HT4 receptor

    PubMed Central

    2013-01-01

    Background Serotonin 5-HT4 receptor (5-HT4-R) agonists are potential therapeutic agents for enterokinetic and cognitive disorders and are marketed for treatment of constipation. The aim of this study was to develop an agonist positron emission tomography (PET) ligand in order to label the active G-protein coupled 5-HT4-R in peripheral and central tissues. For this purpose prucalopride, a high-affinity selective 5-HT4-R agonist, was selected. Methods [11C]Prucalopride was synthesized from [11C]methyl triflate and desmethyl prucalopride, and its LogDoct,pH7.4 was determined. Three distinct studies were performed with administration of IV [11C]prucalopride in male rats: (1) The biodistribution of radioactivity was measured ex vivo; (2) the kinetics of radioactivity levels in brain regions and peripheral organs was assessed in vivo under baseline conditions and following pre-treatment with tariquidar, a P-glycoprotein efflux pump inhibitor; and (3) in vivo stability of [11C]prucalopride was checked ex vivo in plasma and brain extracts using high-performance liquid chromatography. Results [11C]Prucalopride was synthesized in optimised conditions with a yield of 21% ± 4% (decay corrected) and a radiochemical purity (>99%), its LogDoct,pH7.4 was 0.87. Ex vivo biodistribution studies with [11C]prucalopride in rats showed very low levels of radioactivity in brain (maximal 0.13% ID·g−1) and ten times higher levels in certain peripheral tissues. The PET studies confirmed very low brain levels of radioactivity under baseline conditions; however, it was increased three times after pre-treatment with tariquidar. [11C]Prucalopride was found to be very rapidly metabolised in rats, with no parent compound detectable in plasma and brain extracts at 5 and 30 min following IV administration. Analysis of levels of radioactivity in peripheral tissues revealed a distinct PET signal in the caecum, which was reduced following tariquidar pre-treatment. The latter is in line with the

  3. Development of indazolylpyrimidine derivatives as high-affine EphB4 receptor ligands and potential PET radiotracers.

    PubMed

    Ebert, Kristin; Wiemer, Jens; Caballero, Julio; Köckerling, Martin; Steinbach, Jörg; Pietzsch, Jens; Mamat, Constantin

    2015-09-01

    Due to their essential role in the pathogenesis of cancer, members of the Eph (erythropoietin-producing hepatoma cell line-A2) receptor tyrosine kinase family represent promising candidates for molecular imaging. Thus, the development and preparation of novel radiotracers for the noninvasive imaging of the EphB4 receptor via positron emission tomography (PET) is described. First in silico investigations with the indazolylpyrimidine lead compound which is known to be highly affine to EphB4 were executed to identify favorable labeling positions for an introduction of fluorine-18 to retain the affinity. Based on this, reference compounds as well as precursors were developed and labeled with carbon-11 and fluorine-18, respectively. For this purpose, a protecting group strategy essentially had to be generated to prevent unwanted methylation and to enable the introduction of fluorine-18. Further, a convenient radiolabeling strategy using [(11)C]methyl iodide was established which afforded the isotopically labeled radiotracer in 30-35% RCY (d.c.) which is identical with the original inhibitor molecule. A spiro ammonium precursor was prepared for radiolabeling with fluorine-18. Unfortunately, the labeling did not lead to the desired (18)F-radiotracer under the chosen conditions.

  4. Synthesis, in vitro and in vivo evaluation of [11C]MMTP: A potential PET ligand for mGluR1 receptors

    PubMed Central

    Prabhakaran, Jaya; Majo, Vattoly J.; Milak, Matthew S.; Kassir, Suham A.; Palner, Mikael; Savenkova, Lyudmila; Pratap, Mali; Arango, Victoria; Mann, J. John; Parsey, Ramin V.; Dileep Kumar, J. S.

    2010-01-01

    Synthesis, in vitro and in vivo evaluation of [O-methyl-11C]dimethylamino-3(4-methoxyphenyl)-3H-pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidin-4-one (1), a potential imaging agent for mGluR1 receptors using PET are described. Synthesis of the corresponding desmethyl precursor 2 was achieved by demethylation of the methoxyphenyl compound 1 in 90% yield. Methylation using [11C]MeOTf in presence of NaOH afforded [11C]1 in 30% yield (EOS) with >99 % chemical and radiochemical purities and with a specific activity of 3–5 Ci/μmol (n = 6). The total synthesis time was 30 minutes from EOB. The radiotracer selectively labeled mGluR1 receptors in slide-mounted sections of postmortem human brain containing cerebellum, hippocampus, prefrontal cortex and striatum as demonstrated by in vitro autoradiography using phosphor imaging. PET studies in anesthetized baboon show that [11C]1 penetrates the BBB and accumulates in cerebellum, a region reported to have higher expression of mGluR1. These findings suggest [11C]1 is a promising PET radiotracer candidate for mGluR1. PMID:20494576

  5. Synthesis and evaluation of potent and selective human V1a receptor antagonists as potential ligands for PET or SPECT imaging

    PubMed Central

    Fabio, Karine; Guillon, Christophe; Lacey, Carl J.; Lu, Shi-fang; Heindel, Ned D.; Ferris, Craig F.; Placzek, Michael; Jones, Graham; Brownstein, Michael J.; Simon, Neal G.

    2012-01-01

    SRX246 is a potent, highly selective human vasopressin V1a antagonist that crosses the blood–brain barrier in rats. CNS penetration makes SRX246 an ideal candidate for potential radiolabeling and use in visualization and characterization of the role of the V1a receptor in multiple stress-related disorders. Before radiolabeling studies, cold reference analogs of SRX246 were prepared. This study describes the synthesis and in vitro screening for human V1a receptor binding and permeability of fluoro, iodo, and methyl reference compounds for SRX246 and the preparation of a tin precursor. For each compound, the potential utility of corresponding radiolabeled analogs for PET and SPECT imaging is discussed. PMID:22249122

  6. Preclinical TSPO Ligand PET to Visualize Human Glioma Xenotransplants: A Preliminary Study

    PubMed Central

    Buck, Jason R.; McKinley, Eliot T.; Fu, Allie; Abel, Ty W.; Thompson, Reid C.; Chambless, Lola; Watchmaker, Jennifer M.; Harty, James P.; Cooper, Michael K.; Manning, H. Charles

    2015-01-01

    Current positron emission tomography (PET) imaging biomarkers for detection of infiltrating gliomas are limited. Translocator protein (TSPO) is a novel and promising biomarker for glioma PET imaging. To validate TSPO as a potential target for molecular imaging of glioma, TSPO expression was assayed in a tumor microarray containing 37 high-grade (III, IV) gliomas. TSPO staining was detected in all tumor specimens. Subsequently, PET imaging was performed with an aryloxyanilide-based TSPO ligand, [18F]PBR06, in primary orthotopic xenograft models of WHO grade III and IV gliomas. Selective uptake of [18F]PBR06 in engrafted tumor was measured. Furthermore, PET imaging with [18F]PBR06 demonstrated infiltrative glioma growth that was undetectable by traditional magnetic resonance imaging (MRI). Preliminary PET with [18F]PBR06 demonstrated a preferential tumor-to-normal background ratio in comparison to 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG). These results suggest that TSPO PET imaging with such high-affinity radiotracers may represent a novel strategy to characterize distinct molecular features of glioma growth, as well as better define the extent of glioma infiltration for therapeutic purposes. PMID:26517124

  7. Ligands for SPECT and PET imaging of muscarinic-cholinergic receptors of the heart and brain

    SciTech Connect

    Knapp, F.F. Jr.; McPherson, D.W.; Luo, H.

    1995-06-01

    Interest in the potential use of cerebral SPECT and PET imaging for determination of the density and activity of muscarinic-cholinergic receptors (mAChR) has been stimulated by the changes in these receptors which occur in many neurological diseases. In addition, the important involvement of mAChR in modulating negative inotropic cardiac activity suggests that such receptor ligands may have important applications in evaluation of changes which may occur in cardiac disease. In this paper, the properties of several key muscarinic receptor ligands being developed or which have been used for clinical SPECT and PET are discussed. In addition, the ORNL development of the new iodinated IQNP ligand based on QNB and the results of in vivo biodistribution studies in rats, in vitro competitive binding studies and ex vivo autoradiographic experiments are described. The use of radioiodinated IQNP may offer several advantages in comparison to IQNB because of its easy and high yield preparation and high brain uptake and the potential usefulness of the {open_quotes}partial{close_quotes} subtype selective IONP isomers. We also describe the development of new IQNP-type analogues which offer the opportunity for radiolabeling with positron-emitting radioisotopes (carbon-11, fluorine-18 and bromine-76) for potential use with PET.

  8. Subdomain 2 of the Autotransporter Pet Is the Ligand Site for Recognizing the Pet Receptor on the Epithelial Cell Surface

    PubMed Central

    Chavez-Dueñas, Lucia; Serapio-Palacios, Antonio; Nava-Acosta, Raul

    2016-01-01

    Most autotransporter passenger domains, regardless of their diversity in function, fold or are predicted to fold as right-handed β-helices carrying various loops that are presumed to confer functionality. Our goal here was to identify the subdomain (loop) or amino acid sequence of the Pet passenger domain involved in the receptor binding site on the host cell for Pet endocytosis. Here, we show that d1 and d2 subdomains, as well as the amino acid sequence linking the subdomain d2 and the adjacent β-helix (PDWET), are not required for Pet secretion through the autotransporter system and that none of our deletion mutants altered the predicted long right-handed β-helical structure. Interestingly, Pet lacking the d2 domain (PetΔd2) was unable to bind on the epithelial cell surface, in contrast to Pet lacking d1 (PetΔd1) subdomain or PDWET sequences. Moreover, the purified d1 subdomain, the biggest subdomain (29.8 kDa) containing the serine protease domain, was also unable to bind the cell surface. Thus, d2 sequence (54 residues without the PDWET sequence) was required for Pet binding to eukaryotic cells. In addition, this d2 sequence was also needed for Pet internalization but not for inducing cell damage. In contrast, PetΔd1, which was able to bind and internalize inside the cell, was unable to cause cell damage. Furthermore, unlike Pet, PetΔd2 was unable to bind cytokeratin 8, a Pet receptor. These data indicate that the surface d2 subdomain is essential for the ligand-receptor (Pet-Ck8) interaction for Pet uptake and to start the epithelial cell damage by this toxin. PMID:27113356

  9. Analogs of JHU75528, a PET ligand for imaging of cerebral cannabinoid receptors (CB1): development of ligands with optimized lipophilicity and binding affinity

    PubMed Central

    Fan, Hong; Kotsikorou, Evangelia; Hoffman, Alexander F.; Ravert, Hayden T.; Holt, Daniel; Hurst, Dow P.; Lupica, Carl R.; Reggio, Patricia H.; Dannals, Robert F.; Horti, Andrew G.

    2009-01-01

    Cyano analogs of Rimonabant with high binding affinity for the cerebral cannabinoid receptor (CB1) and with optimized lipophilicity have been synthesized as potential positron emission tomography (PET) ligands. The best ligands of the series are optimal targets for the future radiolabeling with PET isotopes and in vivo evaluation as radioligands with enhanced properties for PET imaging of CB1 receptors in human subjects. Extracellular electrophysiological recordings in rodent brain slices demonstrated that JHU75528, 4, the lead compound of the new series, has functional CB antagonist properties that are consistent with its structural relationship to Rimonabant. Molecular modeling analysis revealed an important role of the binding of the cyano-group with the CB1 binding pocket. PMID:18511157

  10. Early Detection of Bilateral Testicular Metastases From Prostatic Adenocarcinoma Using 68Ga-PSMA Ligand PET/CT.

    PubMed

    Weiberg, Desiree; Radner, Herbert; Derlin, Thorsten; Thon, Walter F

    2017-03-31

    We present the case of a 76-year-old man with biochemical relapse after primary therapy for prostate cancer. Ga prostate-specific membrane antigen (PSMA) ligand PET/CT performed for localization of recurrent disease revealed bilateral metastases to the testes. Histopathologic evaluation after bilateral orchiectomy revealed testicular metastases. Metastases to the testes are rare and usually seen in advanced stages. Ga-PSMA ligand PET/CT is a highly sensitive and specific imaging method for the detection of primary and metastatic prostate cancer and has refined diagnostic approaches. This case highlights the potential of PSMA-targeted PET/CT for detection of prostate cancer metastases, even in very unusual localizations.

  11. Potentially Dangerous Items for Your Pet

    MedlinePlus

    ... Animal & Veterinary Home Animal & Veterinary Resources for ... our homes to keep young children safe, but what about “pet proofing” our homes too? Many edible and non-edible dangers for your pet may exist in or around ...

  12. Radiosynthesis and in vivo evaluation of a novel σ1 selective PET ligand

    PubMed Central

    Jin, Hongjun; Fan, Jinda; Zhang, Xiang; Li, Junfeng; Flores, Hubert P.; Perlmutter, Joel S.; Parsons, Stanley M.; Tu, Zhude

    2014-01-01

    The σ1 receptor is an important target for CNS disorders. We previously identified a σ1 ligand TZ3108 having highly potent (Ki-σ1 = 0.48 nM) and selective affinity for σ1 versus σ2 receptors. TZ3108 was 18F-labeled with F-18 for in vivo evaluation. Biodistribution and blocking studies of [18F]TZ3108 in male Sprague-Dawley rats demonstrated high brain uptake, which was σ1-specific with no in vivo defluorination. MicroPET studies in cynomolgus macaques showed high brain penetration of [18F]TZ3108; the regional brain distribution was consistent with that of the σ1 receptor. Pseudo-equilibrium in the brain was reached ~ 45 min post-injection. Metabolite analysis of [18F]TZ3108 in NHP blood and rodent blood and brain revealed that ~ 70% parent remained in the plasma of NHPs 60 min post-injection and the major radiometabolite did not cross the blood-brain barrier in rats. In summary, the potent, selective and metabolically stable σ1 specific radioligand [18F]TZ3108 represents a potentially useful PET radioligand for quantifying the σ1 receptor in the brain. PMID:25584182

  13. Potential improvements in instrumentation for PET

    SciTech Connect

    Derenzo, S.E.

    1984-09-01

    This paper discusses the potential for improved detectors in Positron Emission Tomography (PET) and explores the ultimate limits that might be achieved in the areas of spatial resolution, sensitivity, and maximum imaging rates. It is shown that if an ultra-fast, high efficiency scintillator and a thin, low-noise, position-sensitive photodetector were available, a multi-layer time-of-flight tomograph would be possible with a 10 cm axial field of view, a 3-dimensional spatial resolution of 2 mm fwhm, and >700,000 prompt unscattered coincidences per sec for 1 ..mu..Ci per cm/sup 3/ in a 20 cm diam cylinder of water. 39 refs., 3 figs., 3 tabs.

  14. Docking study, synthesis, and in vitro evaluation of fluoro-MADAM derivatives as SERT ligands for PET imaging.

    PubMed

    Mavel, Sylvie; Vercouillie, Johnny; Garreau, Lucette; Raguza, Tiziana; Ravna, Aina Westrheim; Chalon, Sylvie; Guilloteau, Denis; Emond, Patrick

    2008-10-01

    In order to predict affinity of new diphenylsulfides for the serotonin transporter (SERT), a molecular modeling model was used to compare potential binding affinity of new compounds with known potent ligands. The aim of this study is to identify a suitable PET radioligand for imaging the SERT, new derivatives, and their precursors for a C-11 or F-18 radiolabeling, were synthesized. Two fluorinated derivatives displayed good in vitro affinity for the SERT (K(i)=14.3+/-1 and 10.1+/-2.7 nM) and good selectivity toward the other monoamine transporters as predicted by the docking study.

  15. [F-18]-(-,-)-FQNPe - an attractive ligand for evaluation of muscarinic-cholinergic neuron activity by PET

    SciTech Connect

    Luo, H.; McPherson, D.W.; Beets, A.L.; Knapp, F.F. Jr.

    1997-05-01

    The stereoisomers of 1-azabicyclo[2.2.2]oct-3-yl {alpha}-{alpha}-(1-fluoropentan-5-yl)-{alpha}-hydroxy-{alpha}-phenylacetate ({open_quotes}FQNPe{close_quotes}) have been resolved. (-,-)- receptors (K{sub i}, nM; ml, 0.3; m2, 0.1). [F-18]-(-,-)-FQNPe demonstrated high cerebral and myocardial uptake in rats in vivo. We now report significant blocking of [F-18]-(-.-)-FQNPe uptake in receptor-rich tissues in rats in vivo after (R)-QNB pretreatment and the absence of any TLC detectable FQNPe metabolites in tissue extracts. Rats were injected with (R)-QNB (3 mg/kg) 1 h prior to [F-18]-FQNPe injection (370-629 KBq). After 1 h, rats were sacrificed and tissues removed and counted. (R)-QNB significantly decreased FQNPe uptake in heart and all receptor-rich regions but not blood (Table; Mean % ID/g, n=5); C, control; Q, (R)-QNB; Hrt, heart; Cer, cerebellum; Pon, pons; Med, medulla; Cor, cortex; Stri, striatum; Hip, hippocampus; Th, thallamus; SuC, superior colliculi; InC, inferior colliculi. Tissues from untreated rats were Folch-extracted and 71-77% of activity was in organic extracts from brain and heart. TLC of organic extracts indicated a single radioactive component with R{sub f} of FQNPe. These combined results demonstrate that [F-18]-(-,-)-FQNPe does not appear to be metabolized in heart and brain, shows good receptor localization and is thus an attractive ligand for evaluation as a potential imaging agent by PET.

  16. A short-scan method for k(3) estimation with moderately reversible PET ligands: application of irreversible model to early-phase PET data.

    PubMed

    Sato, Koichi; Fukushi, Kiyoshi; Shinotoh, Hitoshi; Shimada, Hitoshi; Tanaka, Noriko; Hirano, Shigeki; Irie, Toshiaki

    2012-02-15

    Long dynamic scans (60-120 min) are often required for estimating the k(3) value, an index of receptor density, by positron emission tomography (PET). However, the precision of k(3) is usually low in kinetic analyses for reversible PET ligands compared with irreversible ligands. That is largely due to unstable estimation of the dissociation rate constant, k(4). We propose a novel '3P+' method for estimating k(3) of moderately reversible ligands, where a 3-parameter model without k(4) is applied to early-phase PET data to obtain a good model-fit of k(3) estimation. By using [(11)C] Pittsburgh compound B (PIB) (k(4) = 0.018/min) as an example of a moderately reversible ligand, the 3P+ method simulation with a 28 min PET scan yielded less than 3% k(3) relative bias with a +100% k(3) change. In [(11)C]PIB PET scans of 15 normal controls (NC) and nine patients with Alzheimer's disease (AD), the 3P+ method provided a precise k(3) estimate (mean SE of 13.6% in parietal cortex; covariance matrix method). The results revealed linear correlations (r = 0.964) of parietal k(3) values in 24 subjects between 28minute 3P+ method and conventional 90 minute 4-parameter method. A good separation of k(3) between NC and AD groups (P < 0.001; t-test) was replicated in 28 minute 3P+ method. The short-scan 3P+ method may be a practical alternative method for analyzing reversible ligands.

  17. Synthesis of four stereoisomers of 1-azabiocyclo[2.2.2]OCT-3-YL-{alpha}-fluoroalkyl-{alpha}-hydroxy-{alpha}-phenylacetate (FQNPe): Potential imaging ligands for the muscarinic-cholinergic receptor (m-AChR) by PET

    SciTech Connect

    Luo, H.; McPherson, D.W.; Knapp, F.F. Jr.

    1996-10-01

    Earlier studies with the racemic 1-azabiocyclo[2.2.2]oct-3-yl {alpha}-fluoroalkyl-{alpha}-hydroxy-{alpha}-phenylacetate (FQNPe) mixture had demonstrated high in vitro binding affinity for the muscarinic-cholinergic receptor (m-AChR). Pre-treatment of rats with this new agent significantly blocked receptor localization of subsequently injected [I-131]-Z-(-,-)-IQNP, which is an established high affinity m-AChR ligand. Syntheses and characterization of the four FQNPe stereoisomers: (-)(-) FQNPe, (-)(+) FQNPe, (+)(-) FQNPe, and (+)(+) FQNPe will be presented. The interesting NMR spectra of the diastereomeric salts formed in the resolution of racemic {alpha}-(1-chloropent-5-yl)-{alpha}-hydroxy {alpha}-phenylacetic acid will also be discussed.

  18. Pharmacological characterization of the cannabinoid CB₁ receptor PET ligand ortholog, [³H]MePPEP.

    PubMed

    Suter, Todd M; Chesterfield, Amy K; Bao, Chun; Schaus, John M; Krushinski, Joseph H; Statnick, Michael A; Felder, Christian C

    2010-12-15

    MePPEP ((3R,5R)-5-(3-methoxy-phenyl)-3-((R)-1-phenyl-ethylamino)-1-(4-trifluoromethyl-phenyl)-pyrrolidin-2-one) is an inverse agonist shown to be an effective PET ligand for labeling cannabinoid CB₁ receptors in vivo. [¹¹C]MePPEP and structurally related analogs have been reported to specifically and reversibly label cannabinoid CB₁ receptors in rat and non-human primate brains, and [¹¹C]MePPEP has been used in human subjects as a PET tracer. We have generated [³H]MePPEP, an ortholog of [¹¹C]MePPEP, to characterize the molecular pharmacology of the cannabinoid CB₁ receptor across preclinical and clinical species. [³H]MePPEP demonstrates saturable, reversible, and single-site high affinity binding to cannabinoid CB₁ receptors. In cerebellar membranes purified from brains of rat, non-human primate and human, and cells ectopically expressing recombinant human cannabinoid CB₁ receptor, [³H]MePPEP binds cannabinoid CB₁ receptors with similar affinity with K(d) values of 0.09 nM, 0.19 nM, 0.14 nM and 0.16 nM, respectively. Both agonist and antagonist cannabinoid ligands compete [³H]MePPEP with predicted rank order potency. No specific binding is present in autoradiographic sections from cannabinoid CB₁ receptor knockout mouse brains, demonstrating that [³H]MePPEP selectively binds cannabinoid CB₁ receptors in native mouse tissue. Furthermore, [³H]MePPEP binding to anatomical sites in mouse and rat brain is comparable to the anatomical profiles of [¹¹C]MePPEP in non-human primate and human brain in vivo, as well as the binding profiles of other previously described cannabinoid CB₁ receptor agonist and antagonist radioligands. Therefore, [³H]MePPEP is a promising tool for translation of preclinical cannabinoid CB₁ receptor pharmacology to clinical PET ligand and cannabinoid CB₁ receptor inverse agonist therapeutic development.

  19. Potential applications for sigma receptor ligands in cancer diagnosis and therapy.

    PubMed

    van Waarde, Aren; Rybczynska, Anna A; Ramakrishnan, Nisha K; Ishiwata, Kiichi; Elsinga, Philip H; Dierckx, Rudi A J O

    2015-10-01

    Sigma receptors (sigma-1 and sigma-2) represent two independent classes of proteins. Their endogenous ligands may include the hallucinogen N,N-dimethyltryptamine (DMT) and sphingolipid-derived amines which interact with sigma-1 receptors, besides steroid hormones (e.g., progesterone) which bind to both sigma receptor subpopulations. The sigma-1 receptor is a ligand-regulated molecular chaperone with various ion channels and G-protein-coupled membrane receptors as clients. The sigma-2 receptor was identified as the progesterone receptor membrane component 1 (PGRMC1). Although sigma receptors are over-expressed in tumors and up-regulated in rapidly dividing normal tissue, their ligands induce significant cell death only in tumor tissue. Sigma ligands may therefore be used to selectively eradicate tumors. Multiple mechanisms appear to underlie cell killing after administration of sigma ligands, and the signaling pathways are dependent both on the type of ligand and the type of tumor cell. Recent evidence suggests that the sigma-2 receptor is a potential tumor and serum biomarker for human lung cancer and an important target for inhibiting tumor invasion and cancer progression. Current radiochemical efforts are focused on the development of subtype-selective radioligands for positron emission tomography (PET) imaging. Right now, the mostpromising tracers are [18F]fluspidine and [18F]FTC-146 for sigma-1 receptors and [11C]RHM-1 and [18F]ISO-1 for the sigma-2 subtype. Nanoparticles coupled to sigma ligands have shown considerable potential for targeted delivery of antitumor drugs in animal models of cancer, but clinical studies exploring this strategy in cancer patients have not yet been reported. This article is part of a Special Issue entitled: Membrane channels and transporters in cancers.

  20. Improved PET Imaging of uPAR Expression Using new 64Cu-labeled Cross-Bridged Peptide Ligands: Comparative in vitro and in vivo Studies

    PubMed Central

    Persson, Morten; Hosseini, Masood; Madsen, Jacob; Jørgensen, Thomas J. D.; Jensen, Knud J; Kjaer, Andreas; Ploug, Michael

    2013-01-01

    The correlation between uPAR expression, cancer cell invasion and metastases is now well-established and has prompted the development of a number of uPAR PET imaging agents, which could potentially identify cancer patients with invasive and metastatic lesions. In the present study, we synthesized and characterized two new cross-bridged 64Cu-labeled peptide conjugates for PET imaging of uPAR and performed a head-to-head comparison with the corresponding and more conventionally used DOTA conjugate. Based on in-source laser-induced reduction of chelated Cu(II) to Cu(I), we now demonstrate the following ranking with respect to the chemical inertness of their complexed Cu ions: DOTA-AE105 << CB-TE2A-AE105 < CB-TE2A-PA-AE105, which is correlated to their corresponding demetallation rate. No penalty in the uPAR receptor binding affinity of the targeting peptide was encountered by conjugation to either of the macrobicyclic chelators (IC50 ~ 5-10 nM) and high yields and radiochemical purities (>95%) were achieved in all cases by incubation at 95ºC. In vivo, they display identical tumor uptake after 1h, but differ significantly after 22 hrs, where the DOTA-AE105 uptake remains surprisingly high. Importantly, the more stable of the new uPAR PET tracers, 64Cu-CB-TE2A-PA-AE105, exhibits a significantly reduced liver uptake compared to 64Cu-DOTA-AE105 as well as 64Cu-CB-TE2A-AE105, (p<0.0001), emphasizing that our new in vitro stability measurements by mass spectrometry predicts in vivo stability in mice. Specificity of the best performing ligand, 64Cu-CB-TE2A-PA-AE105 was finally confirmed in vivo using a non-binding 64Cu-labeled peptide as control (64Cu-CB-TE2A-PA-AE105mut). This control PET-tracer revealed significantly reduced tumor uptake (p<0.0001), but identical hepatic uptake compared to its active counterpart (64Cu-CB-TE2A-PA-AE105) after 1h. In conclusion, our new approach using in-source laser-induced reduction of Cu(II)-chelated PET-ligands provides useful

  1. Synthesis, Structure-affinity Relationships and Radiolabeling of Selective High-affinity 5-HT4 Receptor Ligands as Prospective Imaging Probes for PET

    PubMed Central

    Xu, Rong; Hong, Jinsoo; Morse, Cheryl L.; Pike, Victor W.

    2010-01-01

    In a search for high-affinity receptor ligands that might serve for development as radioligands for the imaging of brain 5-HT4 receptors in vivo with positron emission tomography (PET), structural modifications were made to the high-affinity 5-HT4 antagonist, (1-butylpiperidin-4-yl)methyl 8-amino-7-iodo-2,3-dihydrobenzo[b][1,4]dioxine-5-carboxylate (1, SB 207710). These modifications were made mainly on the aryl side of the ester bond to permit possible rapid labeling of the carboxylic acid component with a positron-emitter, either carbon-11 (t1/2 = 20.4 min) or fluorine-18 (t1/2 = 109.7 min), and included, i) replacement of the iodine atom with a small substituent such as nitrile, methyl or fluoro, ii) methylation of the 8-amino group, iii) opening of the dioxan ring, and iv) alteration of the length of the N-alkyl goup. High-affinity ligands were discovered for recombinant human 5-HT4 receptors with amenability to labeling with a positron-emitter and potential for development as imaging probes. The ring-opened radioligand, (([methoxy-11C]1-butylpiperidin-4-yl)methyl 4-amino-3-methoxybenzoate; [11C]13), showed an especially favorable array of properties for future evaluation as a PET radioligand for brain 5-HT4 receptors. PMID:20812727

  2. Islet-selectivity of G-protein coupled receptor ligands evaluated for PET imaging of pancreatic {beta}-cell mass

    SciTech Connect

    Cline, Gary W.; Zhao, Xiaojian; Jakowski, Amy B.; Soeller, Walter C.; Treadway, Judith L.

    2011-09-02

    Highlights: {yields} We screened G-protein coupled receptors for imaging pancreatic. {yields} Database mining and immunohistochemistry identified GPCRs enriched in {beta}-cells. {yields} In vitro and in vivo assays were used to determine exocrine vs endocrine specificity. {yields} GPCR candidates for imaging of {beta}-cell mass are Prokineticin-1R, mGluR5, and GLP-1R. -- Abstract: A critical unmet need exists for methods to quantitatively measure endogenous pancreatic {beta}-cell mass (BCM) for the clinical evaluation of therapies to prevent or reverse loss of BCM and diabetes progression. Our objective was to identify G-protein coupled receptors (GPCRs) that are expressed with a high degree of specificity to islet {beta}-cells for receptor-targeted imaging of BCM. GPCRs enriched in pancreatic islets relative to pancreas acinar and hepatic tissue were identified using a database screen. Islet-specific expression was confirmed by human pancreas immunohistochemistry (IHC). In vitro selectivity assessment was determined from the binding and uptake of radiolabeled ligands to the rat insulinoma INS-1 832/13 cell line and isolated rat islets relative to the exocrine pancreas cell-type, PANC-1. Tail-vein injections of radioligands into rats were used to determine favorable image criteria of in vivo biodistribution to the pancreas relative to other internal organs (i.e., liver, spleen, stomach, and lungs). Database and IHC screening identified four candidate receptors for further in vitro and in vivo evaluation for PET imaging of BCM: prokineticin-1 receptor (PK-1R), metabotropic glutamate receptor type-5 (mGluR5), neuropeptide Y-2 receptor (NPY-2R), and glucagon-like peptide 1 receptor (GLP-1R). In vitro specificity ratios gave the following receptor rank order: PK-1R > GLP-1R > NPY-2R > mGluR5. The biodistribution rank order of selectivity to the pancreas was found to be PK-1R > VMAT2 {approx} GLP-1R > mGluR5. Favorable islet selectivity and biodistribution

  3. [64Cu]XYIMSR-06: A dual-motif CAIX ligand for PET imaging of clear cell renal cell carcinoma

    PubMed Central

    Minn, Il; Koo, Soo Min; Lee, Hye Soo; Brummet, Mary; Rowe, Steven P.; Gorin, Michael A.; Sysa-Shah, Polina; Lewis, William D.; Ahn, Hye-Hyun; Wang, Yuchuan; Banerjee, Sangeeta Ray; Mease, Ronnie C.; Nimmagadda, Sridhar; Allaf, Mohamad E.; Pomper, Martin G.; Yang, Xing

    2016-01-01

    Carbonic anhydrase IX (CAIX) is a cell surface enzyme that is over-expressed in approximately 95% of cases of clear cell renal cell carcinoma (ccRCC), the most common renal cancer. We synthesized and performed in vitro and in vivo evaluation of a dual-motif ligand, [64Cu]XYIMSR-06, for imaging CAIX expression on ccRCC tumors using positron emission tomography (PET). [64Cu]XYIMSR-06 was generated in yields of 51.0 ± 4.5% (n=5) and specific activities of 4.1 – 8.9 GBq/μmol (110-240 Ci/mmol). Tumor was visualized on PET images by 1 h post-injection with high tumor-to-background levels (>100 tumor-to-blood and -muscle) achieved within 24 h. Biodistribution studies demonstrated a maximum tumor uptake of 19.3% injected dose per gram of radioactivity at 4 h. Tumor-to-blood, -muscle and -kidney ratios were 129.6 ± 18.8, 84.3 ± 21.0 and 2.1 ± 0.3, respectively, at 8 h post-injection. At 24 h a tumor-to-kidney ratio of 7.1 ± 2.5 was achieved. These results indicate pharmacokinetics superior to those of previously reported imaging agents binding to CAIX. [64Cu]XYIMSR-06 is a new low-molecular-weight PET ligand targeting CAIX, which can image localized and metastatic ccRCC. PMID:27437764

  4. Sulfonamido tripods: tuning redox potentials via ligand modifications

    PubMed Central

    Lau, Nathanael; Ziller, Joseph W.

    2014-01-01

    A series of FeII–OH2 complexes were synthesized with ligands based on the tetradentate sulfonamido tripod N,N',N"-[2,2',2"-nitrilotris(ethane-2,1-diyl)]-tris-({R-Ph}-sulfonamido). These complexes differ by the substituent on the aryl rings and were fully characterized, including their molecular structures via X-ray diffraction methods. All the complexes were five-coordinate with trigonal bipyramidal geometry. A linear correlation was observed between the electronic effects of each ligand, given by the Hammett constants of the para-substituents, and the potential of the FeII/FeIII redox couple, which were determined using cyclic voltammetry. It was found that the range of redox potentials for the complexes spanned approximately 160 mV. PMID:25419035

  5. Pharmacology and therapeutic potential of sigma(1) receptor ligands.

    PubMed

    Cobos, E J; Entrena, J M; Nieto, F R; Cendán, C M; Del Pozo, E

    2008-12-01

    Sigma (sigma) receptors, initially described as a subtype of opioid receptors, are now considered unique receptors. Pharmacological studies have distinguished two types of sigma receptors, termed sigma(1) and sigma(2). Of these two subtypes, the sigma(1) receptor has been cloned in humans and rodents, and its amino acid sequence shows no homology with other mammalian proteins. Several psychoactive drugs show high to moderate affinity for sigma(1) receptors, including the antipsychotic haloperidol, the antidepressant drugs fluvoxamine and sertraline, and the psychostimulants cocaine and methamphetamine; in addition, the anticonvulsant drug phenytoin allosterically modulates sigma(1) receptors. Certain neurosteroids are known to interact with sigma(1) receptors, and have been proposed to be their endogenous ligands. These receptors are located in the plasma membrane and in subcellular membranes, particularly in the endoplasmic reticulum, where they play a modulatory role in intracellular Ca(2+) signaling. Sigma(1) receptors also play a modulatory role in the activity of some ion channels and in several neurotransmitter systems, mainly in glutamatergic neurotransmission. In accordance with their widespread modulatory role, sigma(1) receptor ligands have been proposed to be useful in several therapeutic fields such as amnesic and cognitive deficits, depression and anxiety, schizophrenia, analgesia, and against some effects of drugs of abuse (such as cocaine and methamphetamine). In this review we provide an overview of the present knowledge of sigma(1) receptors, focussing on sigma(1) ligand neuropharmacology and the role of sigma(1) receptors in behavioral animal studies, which have contributed greatly to the potential therapeutic applications of sigma(1) ligands.

  6. Metabotropic glutamate receptor ligands as potential therapeutics for addiction

    PubMed Central

    Olive, M. F.

    2009-01-01

    There is now compelling evidence that the excitatory amino acid neurotransmitter glutamate plays a pivotal role in drug addiction and alcoholism. As a result, there has been increasing interest in developing glutamate-based therapies for the treatment of addictive disorders. Receptors for glutamate are primarily divided into two classes: ionotropic glutamate receptors (iGluRs) that mediate fast excitatory glutamate transmission, and metabotropic glutamate receptors (mGluRs), which are G-protein coupled receptors that mediate slower, modulatory glutamate transmission. Most iGluR antagonists, while showing some efficacy in animal models of addiction, exhibit serious side effects when tested in humans. mGluR ligands, on the other hand, which have been advanced to testing in clinical trials for various medical conditions, have demonstrated the ability to reduce drug reward, reinforcement, and relapse-like behaviors in animal studies. mGluR ligands that have been shown to be primarily effective are Group I (mGluR1 and mGluR5) negative allosteric modulators and Group II (mGluR2 and mGluR3) orthosteric presynaptic autoreceptor agonists. In this review, we will summarize findings from animal studies suggesting that these mGluR ligands may be of potential benefit in reducing on-going drug self-administration and may aid in the prevention of relapse. The neuroanatomical distribution of mGluR1, mGluR2/3, and mGluR5 receptors and the pharmacological properties of Group I negative allosteric modulators and Group II agonists will also be overviewed. Finally, we will discuss the current status of mGluR ligands in human clinical trials. PMID:19630739

  7. Optimization of Acquisition time of 68Ga-PSMA-Ligand PET/MRI in Patients with Local and Metastatic Prostate Cancer

    PubMed Central

    Lütje, Susanne; Blex, Sebastian; Gomez, Benedikt; Schaarschmidt, Benedikt M.; Umutlu, Lale; Forsting, Michael; Jentzen, Walter; Bockisch, Andreas; Poeppel, Thorsten D.; Wetter, Axel

    2016-01-01

    Objective The aim of this optimization study was to minimize the acquisition time of 68Ga-HBED-CC-PSMA positron emission tomography/magnetic resonance imaging (PET/MRI) in patients with local and metastatic prostate cancer (PCa) to obtain a sufficient image quality and quantification accuracy without any appreciable loss. Methods Twenty patients with PCa were administered intravenously with the 68Ga-HBED-CC-PSMA ligand (mean activity 99 MBq/patient, range 76–148 MBq) and subsequently underwent PET/MRI at, on average, 168 min (range 77–320 min) after injection. PET and MR imaging data were acquired simultaneously. PET acquisition was performed in list mode and PET images were reconstructed at different time intervals (1, 2, 4, 6, 8, and 10 min). Data were analyzed regarding radiotracer uptake in tumors and muscle tissue and PET image quality. Tumor uptake was quantified in terms of the maximum and mean standardized uptake value (SUVmax, SUVmean) within a spherical volume of interest (VOI). Reference VOIs were drawn in the gluteus maximus muscle on the right side. PET image quality was evaluated by experienced nuclear physicians/radiologists using a five-point ordinal scale from 5–1 (excellent—insufficient). Results Lesion detectability linearly increased with increasing acquisition times, reaching its maximum at PET acquisition times of 4 min. At this image acquisition time, tumor lesions in 19/20 (95%) patients were detected. PET image quality showed a positive correlation with increasing acquisition time, reaching a plateau at 4–6 min image acquisition. Both SUVmax and SUVmean correlated inversely with acquisition time and reached a plateau at acquisition times after 4 min. Conclusion In the applied image acquisition settings, the optimal acquisition time of 68Ga-PSMA-ligand PET/MRI in patients with local and metastatic PCa was identified to be 4 min per bed position. At this acquisition time, PET image quality and lesion detectability reach a maximum

  8. Di-macrocyclic terephthalamide ligands as chelators for the PET radionuclide zirconium-89

    DOE PAGES

    Pandya, Darpan N.; Pailloux, Sylvie; Tatum, David; ...

    2014-12-18

    The development of bifunctional chelators (BFCs) which can stably chelate zirconium-89 ((89)Zr) while being conjugated to targeting molecules is an area of active research. Herein we report the first octadentate terephthalamide ligands, which are easily radiolabeled with (89)Zr and are highly stable in vitro. Lastly, they represent a novel class of chelators, which are worthy of further development as BFCs for (89)Zr.

  9. Vertebral Hemangioma Mimicking Bone Metastasis in 68Ga-PSMA Ligand PET/CT.

    PubMed

    Artigas, Carlos; Otte, François-Xavier; Lemort, Marc; van Velthoven, Roland; Flamen, Patrick

    2017-05-01

    Ga-PSMA PET/CT was performed in a 68-year-old man to evaluate recurrent prostate cancer due to elevated serum prostate-specific antigen level. Images showed a focal uptake in the prostatic gland, suggesting local relapse, and an intense uptake in the 12th thoracic vertebra, with no morphological abnormalities in CT slices. In order to confirm extraprostatic disease and before radiotherapy planning, a full-spine MRI was performed, resulting with the morphological pattern of a vertebral hemangioma. Hystological analysis confirmed the local relapse in the prostate. No radiotherapy treatment was given to the vertebra, and after 1 year of follow-up without systemic treatment, prostate-specific antigen is still undetectable.

  10. THE POTENTIAL FOR HUMAN EXPOSURES TO PET-BORNE DIAZINON RESIDUES FOLLOWING RESIDENTIAL LAWN APPLICATIONS

    EPA Science Inventory

    This observational study examined the potential for indoor/outdoor pet dogs to be an important pathway for transporting diazinon residues into homes and onto occupants following residential lawn applications. The primary objective was to investigate the potential exposures of chi...

  11. Evaluating the potential for recycling all PET bottles into new food packaging.

    PubMed

    Begley, T H; McNeal, T P; Biles, J E; Paquette, K E

    2002-01-01

    To evaluate the feasibility of recycling all PET bottles into food packaging, realistic estimates of the maximum concentration of contaminants that might be expected in the polymer are needed. To estimate the maximum concentration of a contaminant that might be in PET from the storage of non-food substances, sorption experiments into two types of PET were performed. These test materials were 0.8mm thick amorphous PET (a relative sink for contaminants) and commercial PET bottle wall. Using a commercial shampoo containing 1% lindane (C6H6Cl6), the test materials were stored in contact with the shampoo at 20 and 40 degrees C for 231 days. This commercial shampoo also represents an extreme case because it contains 7% acetone, a solvent which swells PET, further enhancing sorption of chemicals. Additional sorption experiments into PET were performed by preparing solutions of 10% toluene in Miglyol (a fractionated coconut oil), 10% benzophenone in Miglyol, 5% 2-butoxyethoxy ethanol (2-BE) in 50/50 water/ethanol, and 10% methyl stearate in heptane. Sorption data from the shampoo into PET illustrate Fickian behaviour. Specifically, the amount of sorption at room temperature is approximately40 times less than that at 40 degrees C. The amount of lindane sorbed into PET from the shampoo after 231 days was 0.1 and 3.7 mgdm(-2) at 20 and 40 degrees C respectively. These values correspond to 28 and 765 mg kg(-1) on a mass/mass basis. All sorptions are within the ranges measured and published by other authors using surrogate contamination testing schemes. Additionally, actual bottles from recycle bins were analysed for the amout of contamination. Results are discussed in terms of potential consumer exposure to non-food contaminants in food containers made of recycled PET and in relation to the surrogate testing methods recommended by the Food and Drug Administration (FDA) for determining the compatibility of a PET recycling process to produce containers suitable for food

  12. PSMA Expression in Tumor Neovasculature Endothelial Cells of Follicular Thyroid Adenoma as Identified by Molecular Imaging Using 68Ga-PSMA Ligand PET/CT.

    PubMed

    Derlin, Thorsten; Kreipe, Hans-Heinrich; Schumacher, Udo; Soudah, Bisharah

    2017-03-01

    The prostate-specific membrane antigen (PSMA) is expressed by both prostate cancer and other neoplasms. We report the case of a 65-year-old man with castration-resistant metastatic prostate cancer who underwent Ga-PSMA ligand PET/CT for restaging of disease. Ga-PSMA ligand accumulation was noted in a thyroid lesion, suspicious for thyroid malignancy on complementary ultrasound. Subsequent resection and histopathological analysis showed follicular thyroid adenoma with PSMA expression in tumor neovasculature endothelial cells, but not in thyroid epithelial cells. It is important to be aware that both malignant and benign thyroid neoplasms may show PSMA expression to avoid misinterpretation.

  13. 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.

  14. The degradation potential of PET bottles in the marine environment: An ATR-FTIR based approach

    PubMed Central

    Ioakeimidis, C.; Fotopoulou, K. N.; Karapanagioti, H. K.; Geraga, M.; Zeri, C.; Papathanassiou, E.; Galgani, F.; Papatheodorou, G.

    2016-01-01

    The dominance and persistence of plastic debris in the marine environment are well documented. No information exists in respect to their lifespan in the marine environment. Nevertheless, the degradation potential of plastic litter items remains a critical issue for marine litter research. In the present study, polyethylene terephthalate bottles (PETs) collected from the submarine environment were characterized using ATR-FTIR in respect to their degradation potential attributed to environmental conditions. A temporal indication was used as indicative to the years of presence of the PETs in the environment as debris. PETs seem to remain robust for approximately fifteen years. Afterwards, a significant decrease of the native functional groups was recorded; some even disappear; or new-not typical for PETs-are created. At a later stage, using the PET time series collected from the Saronikos Gulf (Aegean Sea–E. Mediterranean), it was possible to date bottles that were collected from the bottom of the Ionian Sea (W. Greece). It is the first time that such a study has been conducted with samples that were actually degraded in the marine environment. PMID:27000994

  15. The degradation potential of PET bottles in the marine environment: An ATR-FTIR based approach

    NASA Astrophysics Data System (ADS)

    Ioakeimidis, C.; Fotopoulou, K. N.; Karapanagioti, H. K.; Geraga, M.; Zeri, C.; Papathanassiou, E.; Galgani, F.; Papatheodorou, G.

    2016-03-01

    The dominance and persistence of plastic debris in the marine environment are well documented. No information exists in respect to their lifespan in the marine environment. Nevertheless, the degradation potential of plastic litter items remains a critical issue for marine litter research. In the present study, polyethylene terephthalate bottles (PETs) collected from the submarine environment were characterized using ATR-FTIR in respect to their degradation potential attributed to environmental conditions. A temporal indication was used as indicative to the years of presence of the PETs in the environment as debris. PETs seem to remain robust for approximately fifteen years. Afterwards, a significant decrease of the native functional groups was recorded; some even disappear; or new-not typical for PETs-are created. At a later stage, using the PET time series collected from the Saronikos Gulf (Aegean Sea–E. Mediterranean), it was possible to date bottles that were collected from the bottom of the Ionian Sea (W. Greece). It is the first time that such a study has been conducted with samples that were actually degraded in the marine environment.

  16. The degradation potential of PET bottles in the marine environment: An ATR-FTIR based approach.

    PubMed

    Ioakeimidis, C; Fotopoulou, K N; Karapanagioti, H K; Geraga, M; Zeri, C; Papathanassiou, E; Galgani, F; Papatheodorou, G

    2016-03-22

    The dominance and persistence of plastic debris in the marine environment are well documented. No information exists in respect to their lifespan in the marine environment. Nevertheless, the degradation potential of plastic litter items remains a critical issue for marine litter research. In the present study, polyethylene terephthalate bottles (PETs) collected from the submarine environment were characterized using ATR-FTIR in respect to their degradation potential attributed to environmental conditions. A temporal indication was used as indicative to the years of presence of the PETs in the environment as debris. PETs seem to remain robust for approximately fifteen years. Afterwards, a significant decrease of the native functional groups was recorded; some even disappear; or new-not typical for PETs-are created. At a later stage, using the PET time series collected from the Saronikos Gulf (Aegean Sea-E. Mediterranean), it was possible to date bottles that were collected from the bottom of the Ionian Sea (W. Greece). It is the first time that such a study has been conducted with samples that were actually degraded in the marine environment.

  17. PET Neuroimaging: Insights on Dystonia and Tourette Syndrome and Potential Applications

    PubMed Central

    Alongi, Pierpaolo; Iaccarino, Leonardo; Perani, Daniela

    2014-01-01

    Primary dystonia (pD) is a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures, or both. Gilles de la Tourette syndrome (GTS) is a childhood-onset neuropsychiatric developmental disorder characterized by motor and phonic tics, which could progress to behavioral changes. GTS and obsessive–compulsive disorders are often seen in comorbidity, also suggesting that a possible overlap in the pathophysiological bases of these two conditions. PET techniques are of considerable value in detecting functional and molecular abnormalities in vivo, according to the adopted radioligands. For example, PET is the unique technique that allows in vivo investigation of neurotransmitter systems, providing evidence of changes in GTS or pD. For example, presynaptic and post-synaptic dopaminergic studies with PET have shown alterations compatible with dysfunction or loss of D2-receptors bearing neurons, increased synaptic dopamine levels, or both. Measures of cerebral glucose metabolism with 18F-fluorodeoxyglucose PET (18F-FDG PET) are very sensitive in showing brain functional alterations as well. 18F-FDG PET data have shown metabolic changes within the cortico-striato-pallido-thalamo-cortical and cerebello-thalamo-cortical networks, revealing possible involvement of brain circuits not limited to basal ganglia in pD and GTS. The aim of this work is to overview PET consistent neuroimaging literature on pD and GTS that has provided functional and molecular knowledge of the underlying neural dysfunction. Furthermore, we suggest potential applications of these techniques in monitoring treatments. PMID:25295029

  18. Potential of PET-MRI for imaging of non-oncologic musculoskeletal disease

    PubMed Central

    Fan, Audrey P.; Gold, Garry E.

    2016-01-01

    Early detection of musculoskeletal disease leads to improved therapies and patient outcomes, and would benefit greatly from imaging at the cellular and molecular level. As it becomes clear that assessment of multiple tissues and functional processes are often necessary to study the complex pathogenesis of musculoskeletal disorders, the role of multi-modality molecular imaging becomes increasingly important. New positron emission tomography-magnetic resonance imaging (PET-MRI) systems offer to combine high-resolution MRI with simultaneous molecular information from PET to study the multifaceted processes involved in numerous musculoskeletal disorders. In this article, we aim to outline the potential clinical utility of hybrid PET-MRI to these non-oncologic musculoskeletal diseases. We summarize current applications of PET molecular imaging in osteoarthritis (OA), rheumatoid arthritis (RA), metabolic bone diseases and neuropathic peripheral pain. Advanced MRI approaches that reveal biochemical and functional information offer complementary assessment in soft tissues. Additionally, we discuss technical considerations for hybrid PET-MR imaging including MR attenuation correction, workflow, radiation dose, and quantification. PMID:28090451

  19. PET amyloid ligand [11C]PIB uptake shows predominantly striatal increase in variant Alzheimer's disease.

    PubMed

    Koivunen, J; Verkkoniemi, A; Aalto, S; Paetau, A; Ahonen, J-P; Viitanen, M; Någren, K; Rokka, J; Haaparanta, M; Kalimo, H; Rinne, J O

    2008-07-01

    Variant Alzheimer's disease (VarAD) with spastic paraparesis and presenile dementia is associated with certain mutations of the presenilin 1 (PS-1) gene, particularly those leading to deletion of exon 9 (PS-1Delta E9). VarAD is neuropathologically characterized by the presence of unusually large, Abeta42 positive, non-cored 'cotton wool' plaques (CWPs), also devoid of dystrophic neurites. The aim of the present study was to find out whether [(11)C]PIB would show increased uptake and serve as an in vivo biomarker of amyloid accumulation in VarAD. A further aim was to assess the correspondence of the [(11)C]PIB binding to the amount and type of Abeta deposits in another group of deceased VarAD patients' brains. We studied four patients with VarAD and eight healthy controls with PET using [(11)C]PIB as tracer. Parametric images were computed by calculating the region-to-cerebellum and region-to-pons ratio in each voxel over 60-90 min. Group differences in [(11)C]PIB uptake were analysed with automated region-of-interest (ROI) analysis. [(11)C]PIB uptake was compared to the immunohistochemically demonstrated deposition of Abeta in the brains of another group of four deceased VarAD patients. Patients with VarAD had significantly higher [(11)C] PIB uptake than the control group in the striatum (caudate nucleus and putamen), anterior and posterior cingulate gyrus, occipital cortex and thalamus. In the caudate and putamen [(11)C]PIB uptake, expressed as region-to-cerebellum ratio, was on the average 43% greater than the mean of the control group. The increases in the anterior (28%) and posterior (27%) cingulate gyrus, occipital cortex (21%) and thalamus (14%) were smaller. All VarAD patients showed this similar topographical pattern of increased [(11)C]PIB uptake. The results were essentially similar when the uptake was expressed as region-to-pons ratios. [(11)C]PIB imaging shows increased uptake in patients with VarAD especially in the striatum, and it can be used to

  20. 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

  1. Usefulness of a dopamine transporter PET ligand [18F]β-CFT in assessing disability in Parkinson's disease

    PubMed Central

    Rinne, J.; Ruottinen, H.; Bergman, J.; Haaparanta, M.; Sonninen, P.; Solin, O.

    1999-01-01

    OBJECTIVES—The usefulness of a novel dopamine transporter PET ligand, [18F]β-CFT in assessing disability in Parkinson's disease was studied.
METHODS—Twenty seven patients with Parkinson's disease in different disability stages (of which nine were patients with early disease) and nine healthy controls were studied. The regions of interest were drawn on a magnetic resonance image resliced according to the PET image.
RESULTS—There was a significant reduction in [18F]β-CFT uptake in the posterior putamen (to 18% of the control mean, p<0.00001), anterior putamen (28%, p<0.00001), and caudate nucleus (51%, p<0.00001) in the total population of patients with Parkinson's disease. The reduction in [18F]β-CFT uptake was more pronounced with more severe disability of the patients, the correlations between the total motor score of the unified Parkinson's disease rating scale (UPDRS) and [18F]β-CFT uptake being significant in the posterior putamen (r=−0.62 p=0.0005), anterior putamen (r=-0.64, p=0.0003), and the caudate nucleus (r=−0.62, p=0.0006). There was a significant negative correlation with putaminal [18F]β-CFT uptake and the hypokinesia and rigidity scores, but not with the tremor score of the UPDRS motor part. In nine patients with early disease and without any antiparkinsonian medication the reduction in the [18F]β-CFT uptake (average of ipsilateral and contralateral side) was reduced in the total putamen to 34% of the mean control value (p<0.00001). The corresponding figures in the other brain areas were: posterior putamen 21% (p<0.00001), anterior putamen 43% (p<0.00001), and caudate nucleus 76% (p<0.01). The reductions in [18F]β-CFT uptake were more severe in the contralateral than in the ipsilateral side. Individually, [18F]β-CFT uptake in the putamen in all patients was below 3 SD from the control mean. 
CONCLUSIONS—[18F]β-CFT is a sensitive marker of nigrostriatal dopaminergic dysfunction in Parkinson's disease and can be used in the

  2. Structure-selectivity investigations of D2-like receptor ligands by CoMFA and CoMSIA guiding the discovery of D3 selective PET radioligands.

    PubMed

    Salama, Ismail; Hocke, Carsten; Utz, Wolfgang; Prante, Olaf; Boeckler, Frank; Hübner, Harald; Kuwert, Torsten; Gmeiner, Peter

    2007-02-08

    Elucidation of the physiological role of the D3 receptor and its distribution in the brain using positron emission tomography (PET) is hampered by the lack of bioavailable subtype selective tracer ligands. To develop appropriate D3 radioligands, we designed an integrative procedure involving the elucidation of structural features determining D3 selectivity over both congeners D2 and D4 by comparative molecular analysis. Thus, we have successfully generated CoMFA and CoMSIA models based on the affinitiy differences of a series of 79 ligands representing a broad range of selectivities. These models yielded highly significant cross-validations (q2cv(D3/D2) = 0.86; q2cv(D3/D4) = 0.92) and excellent predictions of a 16-ligand test set (r2pred = 0.79-0.93). Exploiting this information, synthesis and receptor binding studies directed us to the fluorinated lead compounds 78 and 79, featuring subnanomolar D3 affinities and considerable selectivities over D2 and D4 and, subsequently, to the subtype selective PET tracers [18F]78 and [18F]79.

  3. Central nicotinic receptors: structure, function, ligands, and therapeutic potential.

    PubMed

    Romanelli, M Novella; Gratteri, Paola; Guandalini, Luca; Martini, Elisabetta; Bonaccini, Claudia; Gualtieri, Fulvio

    2007-06-01

    The growing interest in nicotinic receptors, because of their wide expression in neuronal and non-neuronal tissues and their involvement in several important CNS pathologies, has stimulated the synthesis of a high number of ligands able to modulate their function. These membrane proteins appear to be highly heterogeneous, and still only incomplete information is available on their structure, subunit composition, and stoichiometry. This is due to the lack of selective ligands to study the role of nAChR under physiological or pathological conditions; so far, only compounds showing selectivity between alpha4beta2 and alpha7 receptors have been obtained. The nicotinic receptor ligands have been designed starting from lead compounds from natural sources such as nicotine, cytisine, or epibatidine, and, more recently, through the high-throughput screening of chemical libraries. This review focuses on the structure of the new agonists, antagonists, and allosteric ligands of nicotinic receptors, it highlights the current knowledge on the binding site models as a molecular modeling approach to design new compounds, and it discusses the nAChR modulators which have entered clinical trials.

  4. Identification of inhibitors against the potential ligandable sites in the active cholera toxin.

    PubMed

    Gangopadhyay, Aditi; Datta, Abhijit

    2015-04-01

    The active cholera toxin responsible for the massive loss of water and ions in cholera patients via its ADP ribosylation activity is a heterodimer of the A1 subunit of the bacterial holotoxin and the human cytosolic ARF6 (ADP Ribosylation Factor 6). The active toxin is a potential target for the design of inhibitors against cholera. In this study we identified the potential ligandable sites of the active cholera toxin which can serve as binding sites for drug-like molecules. By employing an energy-based approach to identify ligand binding sites, and comparison with the results of computational solvent mapping, we identified two potential ligandable sites in the active toxin which can be targeted during structure-based drug design against cholera. Based on the probe affinities of the identified ligandable regions, docking-based virtual screening was employed to identify probable inhibitors against these sites. Several indole-based alkaloids and phosphates showed strong interactions to the important residues of the ligandable region at the A1 active site. On the other hand, 26 top scoring hits were identified against the ligandable region at the A1 ARF6 interface which showed strong hydrogen bonding interactions, including guanidines, phosphates, Leucopterin and Aristolochic acid VIa. This study has important implications in the application of hybrid structure-based and ligand-based methods against the identified ligandable sites using the identified inhibitors as reference ligands, for drug design against the active cholera toxin.

  5. Detection efficacy of hybrid (68)Ga-PSMA ligand PET/CT in prostate cancer patients with biochemical recurrence after primary radiation therapy defined by Phoenix criteria.

    PubMed

    Einspieler, Ingo; Rauscher, Isabel; Düwel, Charlotte; Krönke, Markus; Rischpler, Christoph; Habl, Gregor; Dewes, Sabrina; Ott, Armin; Wester, Hans-Jürgen; Schwaiger, Markus; Maurer, Tobias; Eiber, Matthias

    2017-02-16

    The aim of this retrospective study was to evaluate the detection rate of Glu-NH-CO-NH-Lys-(Ahx)-[(68)Ga(HBED-CC)] ((68)Ga-PSMA ligand) positron emission tomography/computed tomography (PET/CT) in patients with biochemical recurrent prostate cancer (PC) defined by Phoenix criteria after external beam radiotherapy (EBRT) or brachytherapy as primary treatment. Methods: 118 patients were finally eligible for this retrospective analysis with a median prostate-specific antigen (PSA) of 6.4 ng/mL (range: 2.2-158.4 ng/mL, IQR: 4.2-10.2 ng/mL). 77 and 41 patients had been treated by EBRT or brachytherapy, respectively. Of the 118 patients, 45 were receiving androgen deprivation therapy (ADT) within at least 6 months prior to the PET/CT. The detection rates were stratified by PSA. The influence of primary Gleason score (GS) and ADT was assessed. Relationships between standardized uptake values (SUV) and clinical as well as pathological features in patients with positive findings were analyzed using univariate and multivariable linear regression models. Results: 90.7% (107/118) patients showed pathological findings indicative for tumor recurrence in (68)Ga-PSMA ligand PET/CT. The detection rates were 81.8% (36/44), 95.3% (41/43) and 96.8% (30/31) for PSA of 2 to <5, 5 to <10 and ≥10 ng/mL, respectively (P = 0.0377). (68)Ga-PSMA ligand PET/CT indicated local recurrence in 68/107 patients (63.5%), only distant lesions in 64/107 patients (59.8%) and local recurrence as well as distant lesions in 25/107 patients (23.4%). The detection rate was significantly higher in patients with ADT (97.7%) vs. without ADT (86.3%, P = 0.0381), but independent from primary GS ≥8 (92.0%) vs. ≤7 (90.2%, P = 0.6346). SUVmax and SUVmean were significantly associated with PSA and ADT (P = 0.018 and 0.004 for SUVmax, respectively; P = 0.025 and 0.007 for SUVmean, respectively) . Conclusion:(68)Ga-PSMA ligand PET/CT demonstrates high detection rates in patients with biochemical recurrence of PC

  6. Evoked Potentials and Neuropsychological Tests Validate Positron Emission Topography (PET) Brain Metabolism in Cognitively Impaired Patients

    PubMed Central

    Braverman, Eric R.; Blum, Kenneth; Damle, Uma J.; Kerner, Mallory; Dushaj, Kristina; Oscar-Berman, Marlene

    2013-01-01

    Fluorodeoxyglucose (FDG) Positron Emission Topography (PET) brain hypometabolism (HM) correlates with diminished cognitive capacity and risk of developing dementia. However, because clinical utility of PET is limited by cost, we sought to determine whether a less costly electrophysiological measure, the P300 evoked potential, in combination with neuropsychological test performance, would validate PET HM in neuropsychiatric patients. We found that patients with amnestic and non-amnestic cognitive impairment and HM (n = 43) evidenced significantly reduced P300 amplitudes, delayed latencies, and neuropsychological deficits, compared to patients with normal brain metabolism (NM; n = 187). Data from patients with missing cognitive test scores (n = 57) were removed from the final sample, and logistic regression modeling was performed on the modified sample (n = 173, p = .000004). The logistic regression modeling, based on P300 and neuropsychological measures, was used to validate membership in the HM vs. NM groups. It showed classification validation in 13/25 HM subjects (52.0%) and in 125/148 NM subjects (84.5%), correlating with total classification accuracy of 79.8%. In this paper, abnormal P300 evoked potentials coupled with cognitive test impairment validates brain metabolism and mild/moderate cognitive impairment (MCI). To this end, we cautiously propose incorporating electrophysiological and neuropsychological assessments as cost-effective brain metabolism and MCI indicators in primary care. Final interpretation of these results must await required additional studies confirming these interesting results. PMID:23526928

  7. Designing and Developing PET-Based Precision Model in Thyroid Carcinoma: The Potential Avenues for a Personalized Clinical Care.

    PubMed

    Basu, Sandip; Parghane, Rahul Vithalrao

    2017-01-01

    This communication enumerates the current uses and potential areas where PET could be clinically utilized for developing "precision medicine" type model in thyroid carcinoma. (1) In routine clinics, PET imaging (with fluorodeoxyglucose [FDG]) is utilized to investigate patients of differentiated thyroid carcinoma (DTC) with high thyroglobulin and negative iodine scintigraphy (TENIS) and in medullary carcinoma thyroid (MCT) when the tumor markers (eg, calcitonin and carcino embryonic antigen [CEA]) are raised postoperatively (PET with FDG, (68)Ga-DOTA-NOC/TATE, FDOPA). Both are examples of management personalization, where PET-computed tomography (CT) has been found substantially useful in detecting sites of metastatic disease and making decision with regard to feasibility and planning of surgery on an individual patient basis. (2) The next important area of management personalization is in patients of TENIS with metastatic disease not amenable to surgery through examining FDG-PET findings in tandem with radio iodine scan and (68)Ga-DOTA-TATE/NOC PET/CT. Heterogeneous behavior of the metastatic lesions is frequently observed clinically: analyzing the findings of three studies aids in sub-segmenting patients into subgroups and thereby deciding upon the best approach (observation with LT4 suppression vs PRRT vs tyrosine kinase inhibitors) that could be individualized in a given case. (3) In metastatic/inoperable MCT, (68)Ga-DOTA-TATE/NOC PET-CT helps in deciding upon feasibility of targeted PRRT in an individual patient and helps in follow-up and response evaluation. (4) Disease prognostification with FDG-PET is evolving both in DTC and MCT, where FDG avidity would indicate an aggressive biology, though the implication of this from treatment viewpoint is unclear at this point. Conversely, a negative FDG-PET in DTC and TENIS would suggest a favorable prognosis in an individual. (5) Iodine-124 PET/CT has the added potential of obtaining lesional dosimetry compared to

  8. Prospects for vaccination against the ticks of pets and the potential impact on pathogen transmission.

    PubMed

    de la Fuente, José; Villar, Margarita; Contreras, Marinela; Moreno-Cid, Juan A; Merino, Octavio; Pérez de la Lastra, José M; de la Fuente, Gabriela; Galindo, Ruth C

    2015-02-28

    Diseases transmitted by arthropod vectors such as ticks greatly impact human and animal health. In particular, many diseases of dogs and cats are potentially transmissible to people by arthropod vectors and therefore their control is important for the eradication of vector-borne diseases (VBD). Vaccination is an environmentally friendly alternative for vector control that allows control of several VBD by targeting their common vector. Recent results have shown that it is possible to use vector protective antigens for the control of arthropod vector infestations and pathogen infection. However, as reviewed in this paper, very little progress has been made for the control of ectoparasite infestations and VBD in pets using vaccination with vector protective antigens. The growing interaction between pets and people underlines the importance of developing new interventions for the monitoring and control of VBD.

  9. Electron capture by the thiyl radical and disulfide bond: ligand effects on the reduction potential.

    PubMed

    Roos, Goedele; De Proft, Frank; Geerlings, Paul

    2013-04-15

    The effect of non-polar and polar ligands and of monovalent cations on the one-electron reduction potential of the thiyl radical and the disulfide bond was evaluated. The reduction potentials E° for the CH3S(.)-nL/CH3S(-)-nL and CH3SSCH3-L/CH3SSCH3(.-)-L redox couples were calculated at the B3LYP, M06-2X and MP2 levels of theory, with n=1, 2 and L=CH4, C2H4, H2O, CH3OH, NH3, CH3COOH, CH3CONH2, NH4(+), Na(+), K(+) and Li(+). Non-polar ligands decrease the E° value of the thiyl radical and disulfide bond, while neutral polar ligands favour electron uptake. Charged polar ligands and cations favour electron capture by the thiyl radical while disfavouring electron uptake by the disulfide bond. Thus, the same type of ligand can have a different effect on E° depending on the redox couple. Therefore, properties of an isolated ligand cannot uniquely determine E°. The ligand effects on E° are discussed in terms of the vertical electron affinity and reorganization energy, as well as molecular orbital theory. For a given redox couple, the ligand type influences the nature of the anion formed upon electron capture and the corresponding reorganization process towards the reduced geometry.

  10. Specific, reversible binding of [18F]benperidol to baboon D2 receptors: PET evaluation of an improved 18F-labeled ligand.

    PubMed

    Moerlein, S M; Perlmutter, J S; Welch, M J

    1995-08-01

    [18F]Benperidol ([18F]BP), a positron-emitting analogue of the dopaminergic D2 antagonist benperidol, was evaluated as a radiopharmaceutical for use with positron emission tomography (PET). PET imaging of baboons after i.v. injection of [18F]BP indicated that the radiofluorinated ligand rapidly localized in vivo within dopaminergic receptor-rich cerebral tissues, and that selective disposition was retained for over 2 h. Pretreatment of an animal with unlabeled receptor-specific antagonists prior to injection of [18F]BP confirmed that the radioligand bound specifically to central D2 receptors in vivo, and not to S2 or D1 receptors. [18F]BP bound to D2 receptors in a reversible manner; unlabeled eticlopride displaced D2 receptor-bound [18F]BP in vivo. The radioligand was metabolized in the periphery to polar metabolites which are not expected to cross the blood-brain barrier. [18F]BP has advantages over other tracers as a radiopharmaceutical for PET study of central D2 receptor activity, and can be applied for noninvasive evaluation of the interaction of unlabeled drugs with central D2 receptor sites.

  11. New multifunctional ligands for potential use in the design therapeutic or diagnostic radiopharmaceutical imaging agents

    DOEpatents

    Katti, Kattesh V.; Volkert, Wynn A.; Ketring, Alan R.; Singh, Prahlad R.

    1997-01-01

    A class of diagnostic and therapeutic compounds derived from phosphinimines that include ligands containing either a single phosphinimine functionality or both a phosphinimine group and a phosphine or arsine group, or an aminato group, or a second phosphinimine moiety. These phosphinimine ligands are complexed to early transition metal radionuclides (e.g. .sup.99m Tc or .sup.186 Re/.sup.188 Re) or late transition metals (e.g., .sup.105 Rh or .sup.109 Pd). The complexes with these metals .sup.186 Re/.sup.188 Re, .sup.99m Tc and .sup.109 Pd exhibit a high in vitro and high in vivo stability. The complexes are formed in high yields and can be neutral or charged. These ligands can also be used to form stable compounds with paramagnetic transition metals (e.g. Fe and Mn) for potential use as MRI contrast agents. Applications for the use of ligands and making the ligands are also disclosed.

  12. Potential ligand-binding residues in rat olfactory receptors identified by correlated mutation analysis

    NASA Technical Reports Server (NTRS)

    Singer, M. S.; Oliveira, L.; Vriend, G.; Shepherd, G. M.

    1995-01-01

    A family of G-protein-coupled receptors is believed to mediate the recognition of odor molecules. In order to identify potential ligand-binding residues, we have applied correlated mutation analysis to receptor sequences from the rat. This method identifies pairs of sequence positions where residues remain conserved or mutate in tandem, thereby suggesting structural or functional importance. The analysis supported molecular modeling studies in suggesting several residues in positions that were consistent with ligand-binding function. Two of these positions, dominated by histidine residues, may play important roles in ligand binding and could confer broad specificity to mammalian odor receptors. The presence of positive (overdominant) selection at some of the identified positions provides additional evidence for roles in ligand binding. Higher-order groups of correlated residues were also observed. Each group may interact with an individual ligand determinant, and combinations of these groups may provide a multi-dimensional mechanism for receptor diversity.

  13. A group of thermodynamic potentials applicable to ligand binding by a polyfunctional macromolecule.

    PubMed Central

    Wyman, J

    1975-01-01

    The binding of ligands by a macromolecule can be well described by a group of potentials derivable from the energy and of which the original binding potential is one. The group is Abelian and is isomorphic with a group of symmetries. Each member corresponds to a particular set of experimental conditions--system open to some, closed to others, of the ligand-and the group as a whole is an immediate source of all possible linkage relations applicable to the macromolecule. Seen in terms of information theory it can be interpreted as a program for the response of the macromolecule to its ligands according to the conditions with which it is faced. The group provides a ready formulation of the effect of a ligand on the equilibrium constant for a reaction involving a set of macromolecules, and it leads to a clear-cut distinction between true and pseudolinkage. PMID:1055419

  14. Assessing potential peptide targeting ligands by quantification of cellular adhesion of model nanoparticles under flow conditions.

    PubMed

    Broda, Ellen; Mickler, Frauke Martina; Lächelt, Ulrich; Morys, Stephan; Wagner, Ernst; Bräuchle, Christoph

    2015-09-10

    Sophisticated drug delivery systems are coated with targeting ligands to improve the specific adhesion to surface receptors on diseased cells. In our study, we developed a method with which we assessed the potential of peptide ligands to specifically bind to receptor overexpressing target cells. Therefore, a microfluidic setup was used where the cellular adhesion of nanoparticles with ligand and of control nanoparticles was observed in parallel under the same experimental conditions. The effect of the ligand on cellular binding was quantified by counting the number of adhered nanoparticles with ligand and differently labeled control nanoparticles on single cells after incubation under flow conditions. To provide easy-to-synthesize, stable and reproducible nanoparticles which mimic the surface characteristics of drug delivery systems and meet the requirements for quantitative analysis, latex beads based on amine-modified polystyrene were used as model nanoparticles. Two short peptides were tested to serve as targeting ligand on the beads by increasing the specific binding to HuH7 cells. The c-Met binding peptide cMBP2 was used for hepatocyte growth factor receptor (c-Met) targeting and the peptide B6 for transferrin receptor (TfR) targeting. The impact of the targeting peptide on binding was investigated by comparing the beads with ligand to different internal control beads: 1) without ligand and tailored surface charge (electrostatic control) and 2) with scrambled peptide and similar surface charge, but a different amino acid sequence (specificity control). Our results demonstrate that the method is very useful to select suitable targeting ligands for specific nanoparticle binding to receptor overexpressing tumor cells. We show that the cMBP2 ligand specifically enhances nanoparticle adhesion to target cells, whereas the B6 peptide mediates binding to tumor cells mainly by nonspecific interactions. All together, we suggest that cMBP2 is a suitable choice for

  15. Exploring the potential of protein-based pharmacophore models in ligand pose prediction and ranking

    PubMed Central

    Hu, Bingjie; Lill, Markus A.

    2013-01-01

    Protein-based pharmacophore models derived from the protein binding site atoms without the inclusion of any ligand information have become more popular in virtual screening studies. However, the accuracy of protein-based pharmacophore models for reproducing the critical protein-ligand interactions has never been explicitly assessed. In this study, we used known protein-ligand contacts from a large set of experimentally determined protein-ligand complexes to assess the quality of the protein-based pharmacophores in reproducing these critical contacts. We demonstrate how these contacts can be used to optimize the pharmacophore generation procedure to produce pharmacophore models that optimally cover the known protein-ligand interactions. Finally, we explored the potential of the optimized protein-based pharmacophore models for pose prediction and pose rankings. Our results demonstrate that there are significant variations in the success of protein-based pharmacophore models to reproduce native contacts and consequently native ligand poses dependent on the details of the pharmacophore-generation process. We show that the generation of optimized protein-based pharmacophore models is a promising approach for ligand pose prediction and pose rankings. PMID:23621564

  16. Tunable and noncytotoxic PET/SPECT-MRI multimodality imaging probes using colloidally stable ligand-free superparamagnetic iron oxide nanoparticles

    PubMed Central

    Pham, TH Nguyen; Lengkeek, Nigel A; Greguric, Ivan; Kim, Byung J; Pellegrini, Paul A; Bickley, Stephanie A; Tanudji, Marcel R; Jones, Stephen K; Hawkett, Brian S; Pham, Binh TT

    2017-01-01

    Physiologically stable multimodality imaging probes for positron emission tomography/single-photon emission computed tomography (PET/SPECT)-magnetic resonance imaging (MRI) were synthesized using the superparamagnetic maghemite iron oxide (γ-Fe2O3) nanoparticles (SPIONs). The SPIONs were sterically stabilized with a finely tuned mixture of diblock copolymers with either methoxypolyethylene glycol (MPEG) or primary amine NH2 end groups. The radioisotope for PET or SPECT imaging was incorporated with the SPIONs at high temperature. 57Co2+ ions with a long half-life of 270.9 days were used as a model for the radiotracer to study the kinetics of radiolabeling, characterization, and the stability of the radiolabeled SPIONs. Radioactive 67Ga3+ and Cu2+-labeled SPIONs were also produced successfully using the optimized conditions from the 57Co2+-labeling process. No free radioisotopes were detected in the aqueous phase for the radiolabeled SPIONs 1 week after dispersion in phosphate-buffered saline (PBS). All labeled SPIONs were not only well dispersed and stable under physiological conditions but also noncytotoxic in vitro. The ability to design and produce physiologically stable radiolabeled magnetic nanoparticles with a finely controlled number of functionalizable end groups on the SPIONs enables the generation of a desirable and biologically compatible multimodality PET/SPECT-MRI agent on a single T2 contrast MRI probe. PMID:28184160

  17. Analysis of plasma metabolites during human PET-studies with three receptor ligands, [11C]YM-09151-2, [11C]doxepin and [11C]pyrilamine.

    PubMed

    Ishiwata, K; Yanai, K; Iwata, R; Takahashi, T; Hatazawa, J; Itoh, M; Watabe, K; Watanabe, T; Ido, T

    1996-02-01

    Carbon-11 labeled metabolites in human plasma were analyzed by high-performance liquid chromatography during positron emission tomography (PET) studies using the dopamine D2 ligand [11C]YM-09151-2 as well as the histamine H1 ligands [11C]doxepin and [11C]pyrilamine. For all the three tracers, blood clearance of the radioactivity was extremely rapid after an i.v. injection. The plasma protein-binding of [11C]YM-09151-2 and [11C]doxepin had protective effects upon the metabolic alteration of the ligands, whereas [11C]pyrilamine was free from the protein-binding and immediately degraded. The degradation of [11C]doxepin was more rapid in epileptic patients on medication than in normal subjects. These results indicate that analysis of metabolites in the plasma is necessary to determine the accurate arterial input function for quantitative PET measurement.

  18. PILOT STUDY OF THE POTENTIAL FOR HUMAN EXPOSURES TO PET-BORNE DIAZINON RESIDUES FOLLOWING LAWN APPLICATIONS IN NORTH CAROLINA

    EPA Science Inventory

    This study examined the potential for indoor/outdoor pet dogs to be an important pathway for transporting diazinon residues into homes and onto occupants following residential lawn applications. The primary objective was to investigate the potential exposures of children and thei...

  19. Potential Toxicity of Up-Converting Nanoparticles Encapsulated with a Bilayer Formed by Ligand Attraction

    PubMed Central

    2015-01-01

    The cellular toxicity of nanoparticles that were capped with a bilayered ligand was studied using an up-converting (UC) phosphor material as a representative nanoparticle (NP). The results indicate that although UC NPs are known to be nontoxic, the toxicity of the NPs depends strongly on ligand coordination conditions, in addition to the other commonly known parameters such as size, structure, surface charge etc. Oleate-capped hydrophobic NaYF4:Yb,Er NPs were surface modified to yield three extreme conditions: bare particles that were stripped of the oleate ligands; particles with covalently bound poly(ethylene glycol) (PEG) ligands; and particles with an bilayer of PEG-oleate ligands using the oleate surface group that was remained after synthesis. It was found that the bare particles and the covalent PEG NPs induced little toxicity. However, particles that were rendered biocompatible by forming a bilayer with an amphiphilic ligand (i.e., PEG-oleate) resulted in significant cell toxicity. These findings strongly suggest that the PEG-oleate group dissociated from the bilayered oleate-capped NPs, resulting in significant toxicity by exposing the hydrophobic oleate-capped NPs to the cell. Based on results with bare particles, the NaLnF4:Yb,Er (Ln = Y, Gd) up-converting phosphors are essentially less-toxic. Capping and functionalizing these particles with ligand intercalation may, however, not be a suitable method for rendering the NPs suitable for bioapplication as the ligand can potentially dissociate upon cellular interaction, leading to significant toxicity. PMID:24971524

  20. Phthalocyanines: a new class of G-quadruplex-ligands with many potential applications.

    PubMed

    Yaku, Hidenobu; Fujimoto, Takeshi; Murashima, Takashi; Miyoshi, Daisuke; Sugimoto, Naoki

    2012-06-25

    A G-quadruplex is a four-stranded DNA structure featuring stacked guanine tetrads, G-quartets. Formation of a G-quadruplex in telomere DNA can inhibit telomerase activity; therefore, development of G-quadruplex-ligands, which induce and/or stabilize G-quadruplexes, has become an area of great interest. Phthalocyanine derivatives have substantial potential as high-affinity G-quadruplex-ligands because these planar chromophores are similar in size and shape to the G-quartets. Here, we focus on the latest findings on phthalocyanine derivatives as G-quadruplex-ligands, and discuss the mechanisms by which phthalocyanines bind to G-quadruplexes with high affinity and selectivity. We also discuss potential biomedical and organic electronic applications of phthalocyanines that are dependent on their photophysical properties.

  1. Identification of mangiferin as a potential Glucokinase activator by structure-based virtual ligand screening

    PubMed Central

    Min, Qiuxia; Cai, Xinpei; Sun, Weiguang; gao, Fei; Li, Zhimei; Zhang, Qian; Wan, Luo-Sheng; Li, Hua; Chen, Jiachun

    2017-01-01

    The natural product mangiferin (compound 7) has been identified as a potential glucokinase activator by structure-based virtual ligand screening. It was proved by enzyme activation experiment and cell-based assays in vitro, with potency in micromolar range. Meanwhile, this compound showed good antihyperglycemic activity in db/db mice without obvious side effects such as excessive hypoglycaemia. PMID:28317897

  2. Emerging clinical applications of PET based molecular imaging in oncology: the promising future potential for evolving personalized cancer care

    PubMed Central

    Dhingra, Vandana K; Mahajan, Abhishek; Basu, Sandip

    2015-01-01

    This review focuses on the potential of advanced applications of functional molecular imaging in assessing tumor biology and cellular characteristics with emphasis on positron emission tomography (PET) applications with both 18-fluorodeoxyglucose (FDG) and non-FDG tracers. The inherent heterogeneity of cancer cells with their varied cellular biology and metabolic and receptor phenotypic expression in each individual patient and also intra-and inter-lesionally in the same individual mandates for transitioning from a generalized “same-size-fits-all” approach to personalized medicine in oncology. The past two decades have witnessed improvement of oncological imaging through CT, MR imaging, PET, subsequent movement through hybrid or fusion imaging with PET/CT and single-photon emission computerized tomography (SPECT-CT), and now toward the evolving PET/MR imaging. These recent developments have proven invaluable in enhancing oncology care and have the potential to help image the tumor biology at the cellular level, followed by providing a tailored treatment. Molecular imaging, integrated diagnostics or Radiomics, biology-driven interventional radiology and theranostics, all hold immense potential to serve as a guide to give “start and stop” treatment for a patient on an individual basis. This will likely have substantial impact on both treatment costs and outcomes. In this review, we bring forth the current trends in molecular imaging with established techniques (PET/CT), with particular emphasis on newer molecules (such as amino acid metabolism and hypoxia imaging, somatostatin receptor based imaging, and hormone receptor imaging) and further potential for FDG. An introductory discussion on the novel hybrid imaging techniques such as PET/MR is also made to understand the futuristic trends. PMID:26752813

  3. New multifunctional ligands for potential use in the design therapeutic or diagnostic radiopharmaceutical imaging agents

    DOEpatents

    Katti, K.V.; Volkert, W.A.; Ketring, A.R.; Singh, P.R.

    1997-02-11

    A class of diagnostic and therapeutic compounds are derived from phosphinimines that include ligands containing either a single phosphinimine functionality or both a phosphinimine group and a phosphine or arsine group, or an aminato group, or a second phosphinimine moiety. These phosphinimine ligands are complexed to early transition metal radionuclides (e.g., {sup 99m}Tc or {sup 186}Re/{sup 188}Re) or late transition metals (e.g., {sup 105}Rh or {sup 109}Pd). The complexes with these metals {sup 186}Re/{sup 188}Re, {sup 99m}Tc and {sup 109}Pd exhibit a high in vitro and high in vivo stability. The complexes are formed in high yields and can be neutral or charged. These ligands can also be used to form stable compounds with paramagnetic transition metals (e.g., Fe and Mn) for potential use as MRI contrast agents. Applications for the use of ligands and making the ligands are also disclosed.

  4. A FEASIBILITY STUDY EXAMINING THE POTENTIAL FOR HUMAN HEALTH EXPOSURE TO PET-BORNE DIAZINON RESIDUES FOLLOWING RESIDENTIAL TURF APPLICATIONS

    EPA Science Inventory

    The domestic dog may be a vehicle for translocation of pesticide residues following residential applications to turf. In addition, human occupants may be exposed to residues deposited inside homes by pets or by intimate contacts with them. This study examines the potential of a...

  5. A FEASIBILITY STUDY EXAMINING THE POTENTIAL FOR HUMAN EXPOSURE TO PET-BORNE DIAZINON RESIDUES FOLLOWING RESIDENTIAL TURF APPLICATIONS

    EPA Science Inventory

    The domestic dog may be a vehicle for translocation of pesticide residues following residential applications to turf. In addition, human occupants may be exposed to residues deposited inside homes by pets or by intimate contacts with them. This study examines the potential of ...

  6. Leptospirosis and Pets

    MedlinePlus

    ... Bacterial Special Pathogens Branch (BSPB) BSPB Laboratory Submissions Pets Recommend on Facebook Tweet Share Compartir Leptospirosis is ... that can affect human and animals, including your pets. All animals can potentially become infected with Leptospirosis. ...

  7. Tumor escape mechanisms: Potential role of soluble HLA antigens and NK cells activating ligands

    PubMed Central

    Campoli, Michael; Ferrone, Soldano

    2009-01-01

    The crucial role played by HLA antigens and natural killer (NK) cell activating ligands in the interactions of malignant cells with components of the host's immune system has stimulated interest in the characterization of their expression by malignant cells. Convincing evidence generated by the immunohistochemical staining of surgically removed malignant lesions with monoclonal antibodies (mAb) recognizing HLA antigens and NK cell activating ligands indicates that the surface expression of these molecules is frequently altered on malignant cells. These changes appear to have clinical significance, since in some types of malignant disease they are associated with the histopathological characteristics of the lesions as well as with disease free interval and survival. These associations have been suggested to reflect the effect of HLA antigen and NK cell activating ligand abnormalities on the interactions of tumor cells with antigen-specific cytotoxic T lymphocytes (CTL) and with NK cells. Nevertheless, there are examples in which disease progresses in the face of appropriate HLA antigen and/or NK cell activating ligand as well as tumor antigen expression by malignant cells and of functional antigen-specific CTL in the investigated patient. In such scenarios, it is likely that the tumor microenvironment is unfavorable for CTL and NK cell activity and contributes to tumor immune escape. Many distinct escape mechanisms have been shown to protect malignant cells from immune recognition and destruction in the tumor microenvironment. In this paper, following the description of the structural and functional characteristics of soluble HLA antigens and NK cell activating ligands, we will review changes in their serum level in malignant disease and discuss their potential role in the escape mechanisms utilized by tumor cells to avoid recognition and destruction. PMID:18700879

  8. (18)F-fluoromisonidazole (FMISO) PET may have the potential to detect cardiac sarcoidosis.

    PubMed

    Manabe, Osamu; Hirata, Kenji; Shozo, Okamoto; Shiga, Tohru; Uchiyama, Yuko; Kobayashi, Kentaro; Watanabe, Shiro; Toyonaga, Takuya; Kikuchi, Hisaya; Oyama-Manabe, Noriko; Tamaki, Nagara

    2017-02-01

    (18)F-fluoromisonidazole (FMISO) is a positron emission tomography (PET) tracer that accumulates in hypoxic tissues. We here present a case of suspected cardiac sarcoidosis which was detected with increased FMISO uptake.

  9. Antibody-based PET imaging of amyloid beta in mouse models of Alzheimer's disease

    PubMed Central

    Sehlin, Dag; Fang, Xiaotian T.; Cato, Linda; Antoni, Gunnar; Lannfelt, Lars; Syvänen, Stina

    2016-01-01

    Owing to their specificity and high-affinity binding, monoclonal antibodies have potential as positron emission tomography (PET) radioligands and are currently used to image various targets in peripheral organs. However, in the central nervous system, antibody uptake is limited by the blood–brain barrier (BBB). Here we present a PET ligand to be used for diagnosis and evaluation of treatment effects in Alzheimer's disease. The amyloid β (Aβ) antibody mAb158 is radiolabelled and conjugated to a transferrin receptor antibody to enable receptor-mediated transcytosis across the BBB. PET imaging of two different mouse models with Aβ pathology clearly visualize Aβ in the brain. The PET signal increases with age and correlates closely with brain Aβ levels. Thus, we demonstrate that antibody-based PET ligands can be successfully used for brain imaging. PMID:26892305

  10. Potential medical applications of the plasma focus in the radioisotope production for PET imaging

    NASA Astrophysics Data System (ADS)

    Roshan, M. V.; Razaghi, S.; Asghari, F.; Rawat, R. S.; Springham, S. V.; Lee, P.; Lee, S.; Tan, T. L.

    2014-06-01

    Devices other than the accelerators are desired to be investigated for generating high energy particles to induce nuclear reaction and positron emission tomography (PET) producing radioisotopes. The experimental data of plasma focus devices (PF) are studied and the activity scaling law for External Solid Target (EST) activation is established. Based on the scaling law and the techniques to enhance the radioisotopes production, the feasibility of generating the required activity for PET imaging is studied.

  11. Multilocus genotyping of potentially zoonotic Giardia duodenalis in pet chinchillas (Chinchilla lanigera) in China.

    PubMed

    Qi, Meng; Yu, Fuchang; Li, Shouyi; Wang, Haiyan; Luo, Nannan; Huang, Jianying; Zhang, Longxian

    2015-03-15

    Giardia duodenalis is a common protozoan that colonizes and reproduces in the small intestine, causing giardiasis. This parasite infects a wide range of vertebrate hosts, including humans, domestic animals and wildlife. It has been suggested that chinchillas (Chinchilla lanigera) kept as domestic pets are potential reservoirs for the zoonotic transmission of G. duodenalis. In this study, 140 chinchilla samples from four cities in China were examined to determine the prevalence of G. duodenalis. Thirty-eight (27.1%) chinchillas were found to be positive for G. duodenalis. The prevalence of infection was analyzed in relation to collection site, age and sex. Molecular characterization was also carried out on the 38 chinchilla samples to determine common genotypes. G. duodenalis assemblages A and B were identified in the chinchilla samples by analysis of the small subunit ribosomal RNA (ssur RNA) gene. Genotyping at the subtype level using multiple genes (glutamate dehydrogenase (gdh), triose phosphate isomerase (tpi) and β-giardin (bg) genes) determined that the majority of assemblage A isolate sequences were identical to subtype AI. Assemblage B isolates showed variability among the nucleotide sequences belonging to subtype BIV. This is the first report of G. duodenalis in chinchillas from China. As subtype AI and BIV are associated with human infection, G. duodenalis in chinchillas should be regarded as zoonotic.

  12. Induced Long-Range Attractive Potentials of Human Serum Albumin by Ligand Binding

    SciTech Connect

    Sato, Takaaki; Komatsu, Teruyuki; Nakagawa, Akito; Tsuchida, Eishun

    2007-05-18

    Small-angle x-ray scattering and dielectric spectroscopy investigation on the solutions of recombinant human serum albumin and its heme hybrid revealed that heme incorporation induces a specific long-range attractive potential between protein molecules. This is evidenced by the enhanced forward intensity upon heme binding, despite no hindrance to rotatory Brownian motion, unbiased colloid osmotic pressure, and discontiguous nearest-neighbor distance, confirming monodispersity of the proteins. The heme-induced potential may play a trigger role in recognition of the ligand-filled human serum albumins in the circulatory system.

  13. Pannexin-1 as a potentiator of ligand-gated receptor signaling.

    PubMed

    Isakson, Brant E; Thompson, Roger J

    2014-01-01

    Pannexins are a class of plasma membrane spanning proteins that presumably form a hexameric, non-selective ion channel. Although similar in secondary structure to the connexins, pannexins notably do not form endogenous gap junctions and act as bona fide ion channels. The pannexins have been primarily studied as ATP-release channels, but the overall diversity of their functions is still being elucidated. There is an intriguing theme with pannexins that has begun to develop. In this review we analyze several recent reports that converge on the idea that pannexin channels (namely Panx1) can potentiate ligand-gated receptor signaling. Although the literature remains sparse, this emerging concept appears consistent between both ionotropic and metabotropic receptors of several ligand families.

  14. Sigma-1 receptor ligands: potential in the treatment of neuropsychiatric disorders.

    PubMed

    Hayashi, Teruo; Su, Tsung-Ping

    2004-01-01

    The sigma receptor was originally proposed to be a subtype of the opioid receptor. However, it is now clear that sigma receptors are unique non-opioid, non-phencyclidine brain proteins. Two types of sigma receptor exist, the sigma-1 receptor and the sigma-2 receptor. sigma-1 receptors have been cloned and their distribution, physiological functions and roles in signal transduction were recently characterised. Certain sex hormones in the brain (neurosteroids) are known to interact with sigma-1 receptors. sigma-1 receptors regulate glutamate NMDA receptor function and the release of neurotransmitters such as dopamine. They are thus proposed to be involved in learning and memory as well as in certain neuropsychiatric disorders. Selective sigma-1 receptor ligands have been suggested to represent a new class of therapeutic agents for neuropsychiatric disorders, although none have yet been introduced into therapeutic use. Early studies showed that psychotomimetic benzomorphans, as well as several antipsychotics, can bind to sigma-1 receptors. As a result of these findings, sigma-1 receptor ligands have been proposed as being of potential use in the treatment of schizophrenia. Nevertheless, the relationship of sigma-1 receptors to the underlying pathogenesis of schizophrenia is still unclear. sigma-1 receptor ligands have failed to improve acute psychotic symptoms of schizophrenia in clinical trials, but, interestingly, a few studies have shown an improvement in negative symptoms in schizophrenic patients. A number of preclinical studies have shown that selective agonists of sigma-1 receptors affect higher-ordered brain functions such as learning and memory, cognition and mood. These studies indicate that sigma-1 receptor agonists may exert therapeutic effects in depression and senile dementia. Indeed, the sigma-1 receptor agonist igmesine, has been shown to improve depression in a clinical trial. The most distinctive feature of the action of sigma-1 receptor ligands is

  15. Distinct binding of PET ligands PBB3 and AV-1451 to tau fibril strains in neurodegenerative tauopathies.

    PubMed

    Ono, Maiko; Sahara, Naruhiko; Kumata, Katsushi; Ji, Bin; Ni, Ruiqing; Koga, Shunsuke; Dickson, Dennis W; Trojanowski, John Q; Lee, Virginia M-Y; Yoshida, Mari; Hozumi, Isao; Yoshiyama, Yasumasa; van Swieten, John C; Nordberg, Agneta; Suhara, Tetsuya; Zhang, Ming-Rong; Higuchi, Makoto

    2017-03-01

    Diverse neurodegenerative disorders are characterized by deposition of tau fibrils composed of conformers (i.e. strains) unique to each illness. The development of tau imaging agents has enabled visualization of tau lesions in tauopathy patients, but the modes of their binding to different tau strains remain elusive. Here we compared binding of tau positron emission tomography ligands, PBB3 and AV-1451, by fluorescence, autoradiography and homogenate binding assays with homologous and heterologous blockades using tauopathy brain samples. Fluorescence microscopy demonstrated intense labelling of non-ghost and ghost tangles with PBB3 and AV-1451, while dystrophic neurites were more clearly detected by PBB3 in brains of Alzheimer's disease and diffuse neurofibrillary tangles with calcification, characterized by accumulation of all six tau isoforms. Correspondingly, partially distinct distributions of autoradiographic labelling of Alzheimer's disease slices with 11C-PBB3 and 18F-AV-1451 were noted. Neuronal and glial tau lesions comprised of 4-repeat isoforms in brains of progressive supranuclear palsy, corticobasal degeneration and familial tauopathy due to N279K tau mutation and 3-repeat isoforms in brains of Pick's disease and familial tauopathy due to G272V tau mutation were sensitively detected by PBB3 fluorescence in contrast to very weak AV-1451 signals. This was in line with moderate 11C-PBB3 versus faint 18F-AV-1451 autoradiographic labelling of these tissues. Radioligand binding to brain homogenates revealed multiple binding components with differential affinities for 11C-PBB3 and 18F-AV-1451, and higher availability of binding sites on progressive supranuclear palsy tau deposits for 11C-PBB3 than 18F-AV-1451. Our data indicate distinct selectivity of PBB3 compared to AV-1451 for diverse tau fibril strains. This highlights the more robust ability of PBB3 to capture wide-range tau pathologies.

  16. Design of vanadium mixed-ligand complexes as potential anti-protozoa agents.

    PubMed

    Benítez, Julio; Guggeri, Lucía; Tomaz, Isabel; Arrambide, Gabriel; Navarro, Maribel; Pessoa, João Costa; Garat, Beatriz; Gambino, Dinorah

    2009-04-01

    In the search for new therapeutic tools against Chagas' disease (American Trypanosomiasis) four novel mixed-ligand vanadyl complexes, [V(IV)O(L(2)-2H)(L(1))], including a bidentate polypyridyl DNA intercalator (L(1)) and a tridentate salycylaldehyde semicarbazone derivative (L(2)) as ligands were synthesized, characterized by a combination of techniques, and in vitro evaluated. EPR suggest a distorted octahedral geometry with the tridentate semicarbazone occupying three equatorial positions and the polypyridyl ligand coordinated in an equatorial/axial mode. Both complexes including dipyrido[3,2-a: 2',3'-c]phenazine (dppz) as polypyridyl coligand showed IC(50) values in the muM range against Dm28c strain (epimastigotes) of Trypanosoma cruzi, causative agent of the disease, being as active as the anti-trypanosomal reference drug Nifurtimox. To get an insight into the trypanocidal mechanism of action of these compounds, DNA was evaluated as a potential parasite target and EPR, and (51)V NMR experiments were also carried out upon aging aerated solutions of the complexes. Data obtained by electrophoretic analysis suggest that the mechanism of action of these complexes could include DNA interactions.

  17. An observational study of the potential for human exposures to pet-borne diazinon residues following lawn applications

    SciTech Connect

    Morgan, Marsha K. Stout, Daniel M.; Jones, Paul A.; Barr, Dana B.

    2008-07-15

    This study examined the potential for pet dogs to be an important pathway for transporting diazinon residues into homes and onto its occupants following residential lawn applications. The primary objectives were to investigate the potential exposures of occupants and their pet dogs to diazinon after an application to turf at their residences and to determine if personal contacts between occupants and their pet dogs resulted in measurable exposures. It was conducted from April to August 2001 before the Agency phased out all residential uses of diazinon in December 2004. Six families and their pet dogs were recruited into the study. Monitoring was conducted at pre-, 1, 2, 4, and 8 days post-application of a commercial, granular formulation of diazinon to the lawn by the homeowner. Environmental samples collected included soil, indoor air, carpet dust, and transferable residues from lawns and floors. Samples collected from the pet dogs consisted of paw wipes, fur clippings, and transferable residues from the fur by a technician or child wearing a cotton glove(s). First morning void (FMV) urine samples were collected from each child and his/her parent on each sampling day. Diazinon was analyzed in all samples, except urine, by GC-MS. The metabolite 2-isopropyl-4-methyl-6-hydroxypyrimidine (IMPy) was analyzed in the urine samples by HPLC-MS/MS. Mean airborne residues of diazinon on day 1 post-application were at least six times higher in both the living rooms (235{+-}267 ng/m{sup 3}) and children's bedrooms (179{+-}246 ng/m{sup 3}) than at pre-application. Mean loadings of diazinon in carpet dust samples were at least 20 times greater on days 2, 4, and 8 post-application than mean loadings (0.03{+-}0.04 ng/cm{sup 2}) at pre-application. The pet dogs had over 900 times higher mean loadings of diazinon residues on their paws on day 1 post-application (88.1{+-}100.1 ng/cm{sup 2}) compared to mean loadings (<0.09 ng/cm{sup 2}) at pre-application. The mean diazinon loadings

  18. Structural basis for potentiation by alcohols and anaesthetics in a ligand-gated ion channel

    PubMed Central

    Sauguet, Ludovic; Howard, Rebecca J.; Malherbe, Laurie; Lee, Ui S.; Corringer, Pierre-Jean; Harris, R. Adron; Delarue, Marc

    2014-01-01

    Ethanol alters nerve signalling by interacting with proteins in the central nervous system, particularly pentameric ligand-gated ion channels. A recent series of mutagenesis experiments on Gloeobacter violaceus ligand-gated ion channel, a prokaryotic member of this family, identified a single-site variant that is potentiated by pharmacologically relevant concentrations of ethanol. Here we determine crystal structures of the ethanol-sensitized variant in the absence and presence of ethanol and related modulators, which bind in a transmembrane cavity between channel subunits and may stabilize the open form of the channel. Structural and mutagenesis studies defined overlapping mechanisms of potentiation by alcohols and anaesthetics via the inter-subunit cavity. Furthermore, homology modelling show this cavity to be conserved in human ethanol-sensitive glycine and GABA(A) receptors, and to involve residues previously shown to influence alcohol and anaesthetic action on these proteins. These results suggest a common structural basis for ethanol potentiation of an important class of targets for neurological actions of ethanol. PMID:23591864

  19. Radiosynthesis and evaluation of [11C]EMPA as a potential PET tracer for orexin 2 receptors.

    PubMed

    Wang, Changning; Moseley, Christian K; Carlin, Stephen M; Wilson, Colin M; Neelamegam, Ramesh; Hooker, Jacob M

    2013-06-01

    EMPA is a selective antagonist of orexin 2 (OX2) receptors. Previous literature with [(3)H]-EMPA suggest that it may be used as an imaging agent for OX2 receptors; however, brain penetration is known to be modest. To evaluate the potential of EMPA as a PET radiotracer in non-human primate (as a step to imaging in man), we radiolabeled EMPA with carbon-11. Radiosynthesis of [(11)C]N-ethyl-2-(N-(6-methoxypyridin-3-yl)-2-methylphenylsulfonamido)-N-(pyridin-3-ylmethyl)acetamide ([(11)C]EMPA), and evaluation as a potential PET tracer for OX2 receptors is described. Synthesis of an appropriate non-radioactive O-desmethyl precursor was achieved from EMPA with sodium iodide and chlorotrimethylsilane. Selective O-methylation using [(11)C]CH3I in the presence of cesium carbonate in DMSO at room temp afforded [(11)C]EMPA in 1.5-2.5% yield (non-decay corrected relative to trapped [(11)C]CH3I at EOS) with ≥95% chemical and radiochemical purities. The total synthesis time was 34-36min from EOB. Studies in rodent suggested that uptake in tissue was dominated by nonspecific binding. However, [(11)C]EMPA also showed poor uptake in both rats and baboon as measured with PET imaging.

  20. The Pearl of FDG PET/CT in Preoperative Assessment of Patients with Potentially Operable Non-Small-Cell Lung Cancer and its Clinical Impact.

    PubMed

    Kung, Boom Ting; Yong, Ting Kun Au; Tong, Cheuk Man

    2017-01-01

    The aim of this retrospective study is to evaluate the clinical impact and efficacy of fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT) on management decisions for patients suffering from clinically operable non-small-cell lung cancer (NSCLC). A retrospective review of 186 potentially operable NSCLC patients who underwent whole-body PET/CT examination in 2012 was performed. The patients were further analyzed via the electronic patient record (ePR) system for relevant findings. Overall change in management was assigned if a patient avoided unnecessary surgery due to disease upstaging or if a patient underwent further neoadjuvant treatment or investigation before the curative surgery. Of all 186 subjects, 65 (34.9%) became inoperable after PET/CT due to disease upstaging. The remaining 121 (65.1%) of patients remained operable after PET/CT examination. Nineteen out of 121 potentially operable patients did not receive curative surgery eventually, as 11 patients had poor clinical condition and 8 patients refused surgery. One hundred two out of 186 (54.8%) patients received curative operation following PET/CT. Among these 102 individuals, 97 patients (95%) proceeded to surgery without further neoadjuvant treatment or other investigatory procedures. Of the remaining 5 patients, 4 (3.9%) received neoadjuvant treatment and 1 (1.0%) had further investigation after PET/CT. Seventy of the 186 (37.6%) patients underwent changes in management plans after PET/CT study. Out of the 186 individuals, a subgroup of 141 (75.8%) patients underwent dedicated CT thorax before PET/CT examination. Forty-seven (33.3%) patients had avoided futile surgery due to disease upstaging. Fifty-one of the 141 (36.2%) patients underwent changes in management plans after PET/CT. PET/CT had great clinical impact, with significant reduction of futile curative surgery.

  1. Visualization of early infarction in rat brain after ischemia using a translocator protein (18 kDa) PET ligand [11C]DAC with ultra-high specific activity.

    PubMed

    Yui, Joji; Hatori, Akiko; Kawamura, Kazunori; Yanamoto, Kazuhiko; Yamasaki, Tomoteru; Ogawa, Masanao; Yoshida, Yuichiro; Kumata, Katsushi; Fujinaga, Masayuki; Nengaki, Nobuki; Fukumura, Toshimitsu; Suzuki, Kazutoshi; Zhang, Ming-Rong

    2011-01-01

    The aim of this study was to visualize early infarction in the rat brain after ischemia using a translocator protein (TSPO) (18 kDa) PET ligand [(11)C]DAC with ultra-high specific activity (SA) of 3670-4450 GBq/μmol. An infarction model of rat brain was prepared by ischemic surgery and evaluated 2 days after ischemia using small-animal PET and in vitro autoradiography. Early infarction with a small increase of TSPO expression in the brain was visualized using PET with high SA [(11)C]DAC (average 4060 GBq/μmol), but was not distinguished clearly with usually reported SA [(11)C]DAC (37 GBq/μmol). Infarction in the rat brain 4 days after ischemia was visualized using high and usually reported SAs [(11)C]DAC. Displacement experiments with unlabeled TSPO-selective AC-5216 or PK11195 diminished the difference in radioactivity between ipsilateral and contralateral sides, confirming that the increased uptake on the infracted brain was specific to TSPO. In vitro autoradiography with high SA [(11)C]DAC showed that the TSPO expression increased on early infarction in the rat brain. High SA [(11)C]DAC is a useful and sensitive biomarker for the visualization of early infarction and the characterization of TSPO expression which was slightly elevated in the infarcted brain using PET.

  2. [C-11]{beta}CNT: A new monoamine uptake ligand for studying serotonin and dopamine transporter sites in the living brain with PET

    SciTech Connect

    Mulholland, G.K.; Zheng, Q.H.; Zhou, F.C.

    1996-05-01

    There is considerable interest in measuring serotonin (5HT) and dopamine (DA) function in the human brain. Altered levels of 5HT and DA are recognized in drug abuse, neurotoxicities, psychiatric disorders, and neurodegenerative conditions including Alzheimer`s and Parkinson`s disease. Several phenyltropane analogs of cocaine bind tightly to both DA and 5HT uptake proteins. We have made a new agent from this class called {beta}CNT, 2{beta}-carboxymethyl-3{beta}-(2-naphthyl)-tropane, the isosteric O-for-CH{sub 2} analog of a compound reported to have among the highest measured affinities for DA and 5HT transporters and studied its in vivo brain distributions in animals for the first time. Optically pure {beta}CNT was made from cocaine, and labeled at the O-methyl position by esterification of {beta}CNT-acid with [C-11]CH{sub 3}OTfl under conditions similar to Wilson`s. HPLC-purified (99+%) final products (15-50% eob yield from CO{sub 2}, 40 min synth) had specific activities 0.1-1.2 Ci/{mu}mol at the time of injection. Preliminary [C-11]{beta}{beta}CNT rodent distribution showed very high brain uptake (3% ID at 60 min) and localization (striat: fr cort: hypo: cer: blood, 11: 5: 4: 1: 06). {beta}CNT-PET studies in juvenile pigs (5-20 mCi, 20-35 kg) found rapid brain uptake, and prominent retention (85 min) in midbrain, anterior brainstem and striatum, followed by cortex and olfactory bulb. Paroxetine pretreatment (5HT uptake blocker, 2mg/kg), diminished retention in most brain areas; nomifensine (DA/NE uptake blocker, 6 mg/kg) reduced striatum selectively. Direct comparisons of [C-11]{beta}CNT with other PET transporter radioligands {beta}CFT, {beta}CIT, and {beta}CTT (RTI-32) in the same pig found {beta}CNT had highest overall brain uptake among the agents. These initial results suggest {beta}CNT has favorable properties for imaging both 5HT and DA transporters in vivo, and further evaluation of its potential as a human PET agent is warranted.

  3. Evaluation of Potential PET Imaging Probes for the Orexin 2 Receptors

    PubMed Central

    Wang, Changning; Wilson, Colin M.; Moseley, Christian K.; Carlin, Stephen M.; Hsu, Shirley; Arabasz, Grae; Schroeder, Frederick A.; Sander, Christin Y.; Hooker, Jacob M.

    2013-01-01

    A wide range of central nervous system (CNS) disorders, particularly those related to sleep, are associated with the abnormal function of orexin (OX) receptors. Several orexin receptor antagonists have been reported in recent years, but currently there are no imaging tools to probe the density and function of orexin receptors in vivo. To date there are no published data on the pharmacokinetics (PK) and accumulation of some lead orexin receptor antagonists. Evaluation of CNS pharmacokinetics in the pursuit of positron emission tomography (PET) radiotracer development could be used to elucidate the association of orexin receptors with diseases and to facilitate the drug discovery and development. To this end, we designed and evaluated carbon-11 labeled compounds based on diazepane orexin receptor antagonists previously described. One of the synthesized compounds, [11C]CW4 showed high brain uptake in rats and further evaluated in non-human primate (NHP) using PET-MR imaging. PET scans performed in a baboon showed appropriate early brain uptake for consideration as a radiotracer. However, [11C]CW4 exhibited fast kinetics and high nonspecific binding, as determined after co-administration of [11C]CW4 and unlabeled CW4. These properties indicate that [11C]CW4 has excellent brain penetrance and could be used as a lead compound for developing new CNS-penetrant PET imaging probes of orexin receptors. PMID:23953751

  4. Health effects in family pets and 2,3,7,8-TCDD contamination in Missouri: a look at potential animal sentinels

    SciTech Connect

    Schilling, R.J.; Stehr-Green, P.A.

    1987-05-01

    In 1971, waste oils containing 2,3,7,8:tetrachlorodibenzodioxin (TCDD) were sprayed in Missouri for dust control. To determine if pets could serve as sentinels of human health risks associated with this contamination, we asked pet owners in a pilot study of exposed human populations about their pets' illnesses. Of 13 pets with owner-reported illnesses, 8 had potential TCDD exposures and 5 did not (p less than .05 by Mantel-Haenzel chi-square analysis stratified by age). Owner-reported illnesses in 2 of 8 illness categories were associated with TCDD contamination after adjusting for age. Although these findings suggest that pets in TCDD-contaminated areas may have greater health risks, the small sample size, unlikely pathologic groupings, and unconfirmed nature of the data fail to support a relationship between pet illnesses and possible TCDD exposure and thus make extrapolation to human populations inappropriate. The limited validity found for owner-reported pet illnesses should caution against using such data in future environmental health studies.

  5. Benign fibrous dysplasia on [(11)C]choline PET: a potential mimicker of disease in patients with biochemical recurrence of prostate cancer.

    PubMed

    Gu, Chris N; Hunt, Christopher H; Lehman, Vance T; Johnson, Geoffrey B; Diehn, Felix E; Schwartz, Kara M; Eckel, Laurence J

    2012-08-01

    We present the case of a 74-year-old male with biochemical recurrence of prostate cancer who underwent [(11)C]choline PET/CT. The PET/CT demonstrated an intense focus of uptake within the skull base that was initially felt to potentially represent metastatic disease. Subsequent evaluation with MRI and dedicated thin-section CT revealed this area to be benign fibrous dysplasia of the bone. The focal uptake on PET/CT with [(11)C]choline in benign fibrous dysplasia represents a potential mimicker of metastatic disease. Due to recognizing this benign process, our patient was able to avoid systemic treatment and/or focal radiation and was treated with cryotherapy for biopsy-proven local recurrence within the prostate bed. While benign fibrous dysplasia can demonstrate increased radiotracer uptake on other modalities (i.e., bone scintigraphy, FDG PET/CT), its appearance on [(11)C]choline PET/CT has been largely overlooked in the literature. With the increasing use of [(11)C]choline PET/CT for biochemical recurrent prostate cancer evaluation, it is important to understand this potential mimicker of disease.

  6. Potential of F-18 PET/CT in the Detection of Leptomeningeal Metastasis.

    PubMed

    Short, Ryan G; Bal, Susan; German, John P; Poelstra, Raymond J; Kardan, Arash

    2014-12-01

    Leptomeningeal metastasis (LM) is a rare but increasingly common condition in which malignant cells migrate to the meninges. The gold standard for diagnosing LM is detection of cancer cells in the cerebrospinal fluid (CSF). Contrast enhanced-magnetic resonance imaging (CE-MRI) is also used to diagnose LM. We describe a case of LM in which CE-MRI of the neuroaxis was initially negative for meningeal enhancement but F-18 fluorodeoxyglucose positron-emission tomography/computed tomography (F-18 FDG PET/CT) revealed hypermetabolism within the lumbar spinal canal. Positive F-18 FDG PET findings have rarely been reported in LM and, to our knowledge, have never been reported in the context of initially negative CE-MRI scanning of the neuroaxis. F-18 FDG PET/CT may represent an alternative modality for diagnosing LM in patients who are unable to undergo CE-MRI and/or LP or in patients for whom initial CE-MRI and/or LP are negative for LM.

  7. Iodine-122-labeled amphetamine derivative with potential for PET brain blood-flow studies

    SciTech Connect

    Mathis, C.A.; Sargent, T. 3d.; Shulgin, A.T.

    1985-11-01

    The positron emitter SSI (t1/2 3.6 min) was collected from a xenon- SS/iodine- SS ( SSXe/ SSI) generator and incorporated into an amphetamine analog, 2,4-dimethoxy-N,N-dimethyl-5-( SSI)iodophenylisopropylamine (5-( SSI)-2,4-DNNA). The remote synthesis was achieved in 3 min with a 50% radioincorporation yield and a product radiopurity of greater than 98%. 5-( SSI)-2,4-DNNA was injected into a beagle dog and a brain section imaged with positron emission tomography (PET). The uptake and retention of 5-( SSI)-2,4-DNNA was compared to that of YSRb in the same animal. Dynamic PET activity data were obtained 0-20 min postinjection of 5-( SSI)-2,4-DNNA and showed rapid uptake by brain and good cerebral/extracerebral tissue distinction. A whole-body scan of a dog was also obtained with 5-123I-2,4-DNNA showing uptake in brain, lung, and other body organs. The feasibility of incorporating SSI into an extracted brain perfusion agent for use with PET is demonstrated.

  8. New organoruthenium complexes with bioactive thiosemicarbazones as co-ligands: potential anti-trypanosomal agents†

    PubMed Central

    Demoro, Bruno; Sarniguet, Cynthia; Sánchez-Delgado, Roberto; Rossi, Miriam; Liebowitz, Daniel; Caruso, Francesco; Olea-Azar, Claudio; Moreno, Virtudes; Medeiros, Andrea; Comini, Marcelo A.; Otero, Lucía; Gambino, Dinorah

    2012-01-01

    In the search for new therapeutic tools against neglected diseases produced by trypanosomatid parasites, and particularly against African Trypanosomiasis, whose etiological agent is Trypanosoma brucei, organoruthenium compounds with bioactive nitrofuran containing thiosemicarbazones (L) as co-ligands were obtained. Four ruthenium(ii) complexes with the formula [Ru2(p-cymene)2(L)2]X2, where X = Cl or PF6, were synthesized and the crystal structures of two of them were solved by X-ray diffraction methods. Two of the complexes show significant in vitro growth inhibition activity against Trypanosoma brucei brucei and are highly selective towards trypanosomal cells with respect to mammalian cells (J774 murine macrophages). These promising results make the title organoruthenium compounds good lead candidates for further developments towards potential antitrypanosomal organometallic drugs. PMID:22138896

  9. Comparison of first pass bolus AIFs extracted from sequential 18F-FDG PET and DSC-MRI of mice

    NASA Astrophysics Data System (ADS)

    Evans, Eleanor; Sawiak, Stephen J.; Ward, Alexander O.; Buonincontri, Guido; Hawkes, Robert C.; Adrian Carpenter, T.

    2014-01-01

    Accurate kinetic modelling of in vivo physiological function using positron emission tomography (PET) requires determination of the tracer time-activity curve in plasma, known as the arterial input function (AIF). The AIF is usually determined by invasive blood sampling methods, which are prohibitive in murine studies due to low total blood volumes. Extracting AIFs from PET images is also challenging due to large partial volume effects (PVE). We hypothesise that in combined PET with magnetic resonance imaging (PET/MR), a co-injected bolus of MR contrast agent and PET ligand can be tracked using fast MR acquisitions. This protocol would allow extraction of a MR AIF from MR contrast agent concentration-time curves, at higher spatial and temporal resolution than an image-derived PET AIF. A conversion factor could then be applied to the MR AIF for use in PET kinetic analysis. This work has compared AIFs obtained from sequential DSC-MRI and PET with separate injections of gadolinium contrast agent and 18F-FDG respectively to ascertain the technique‧s validity. An automated voxel selection algorithm was employed to improve MR AIF reproducibility. We found that MR and PET AIFs displayed similar character in the first pass, confirmed by gamma variate fits (p<0.02). MR AIFs displayed reduced PVE compared to PET AIFs, indicating their potential use in PET/MR studies.

  10. Organometallic Palladium Complexes with a Water-Soluble Iminophosphorane Ligand as Potential Anticancer Agents

    PubMed Central

    Carreira, Monica; Calvo-Sanjuán, Rubén; Sanaú, Mercedes; Marzo, Isabel; Contel, María

    2012-01-01

    The synthesis and characterization of a new water-soluble iminophosphorane ligand TPA=N-C(O)-2BrC6H4 (C,N-IM; TPA = 1,3,5-triaza-7-phosphaadamantane) 1 is reported. Oxidative addition of 1 to Pd2(dba)3 affords the orthopalladated dimer [Pd(μ-Br){C6H4(C(O)N=TPA-kC,N)-2}]2 (2) as a mixture of cis and trans isomers (1:1 molar ratio) where the iminophosphorane moeity behaves as a C,N-pincer ligand. By addition of different neutral or monoanionic ligands to 2, the bridging bromide can be cleaved and a variety of hydrophilic or water-soluble mononuclear organometallic palladium(II) complexes of the type [Pd{C6H4(C(O)N=TPA-kC,N)-2}(L-L)] (L-L = acac (3); S2CNMe2 (4); 4,7-Diphenyl-1,10-phenanthrolinedisulfonic acid disodium salt C12H6N2(C6H4SO3Na)2 (5)); [Pd{C6H4(C(O)N=TPA-kC,N)-2}(L)Br] (L = P(mC6H4SO3Na)3 (6); P(3-Pyridyl)3 (7)) and, [Pd(C6H4(C(O)N=TPA)-2}(TPA)2Br] (8) are obtained as single isomers. All new complexes were tested as potential anticancer agents and their cytotoxicity properties were evaluated in vitro against human Jurkat-T acute lymphoblastic leukemia cells, normal T-lymphocytes (PBMC) and DU-145 human prostate cancer cells. Compounds [Pd(μ-Br){C6H4(C(O)N=TPA-kC,N)-2}]2 (2) and [Pd{C6H4(C(O)N=TPA-kC,N)-2}(acac)] 3 (which has been crystallographically characterized) display the higher cytotoxicity against the above mentioned cancer cell lines while being less toxic to normal T-lymphocytes (peripheral blood mononuclear cells: PBMC). In addition, 3 is very toxic to cisplatin resistant Jurkat shBak indicating a cell death pathway that may be different to that of cisplatin. The interaction of 2 and 3 with plasmid (pBR322) DNA is much weaker than that of cisplatin pointing to an alternative biomolecular target for these cytotoxic compounds. All the compounds show an interaction with human serum albumin (HSA) faster than that of cisplatin. PMID:23066172

  11. Paget Disease: A Potential Pitfall in PSMA PET for Prostate Cancer.

    PubMed

    Blazak, John Kenneth; Thomas, Paul

    2016-09-01

    We present a case of an 81-year-old man with multifocal Paget disease found on bone scan that was performed for incidentally diagnosed prostate cancer. The subsequent Ga-PSMA (HBED-CC) PET scan also displayed increased uptake in the same distribution. Multiple known tumors display increased Ga-PSMA uptake due to neovasculature. We postulate that increased Ga-PSMA uptake within the pagetoid bone relates to neovascularity known to occur in Paget disease. Such pagetic uptake could result in false-positive studies for bone metastases, particularly in the setting of less typical Paget disease.

  12. SiOx layer as functional barrier in polyethylene terephthalate (PET) bottles against potential contaminants from post-consumer recycled PET.

    PubMed

    Welle, Frank; Franz, Roland

    2008-06-01

    The barrier effect of a silicon oxide (SiOx) coating on the inner surface of PET bottles, in terms of the ability to reduce the migration of post-consumer compounds from the PET bottle wall into food simulants (3% acetic acid and 10% ethanol), was investigated. The barrier effect was examined by artificially introducing model substances (surrogates) into the PET bottle wall to represent a worst-case scenario. Test bottles with three different spiking levels up to approximately 1000 mg kg(-1) per surrogate were blown and coated on the inner surface. The SiOx-coated bottles and the non-coated reference bottles were filled with food simulants. From the specific migration of the surrogates with different bottles wall concentrations, the maximum surrogate concentrations in the bottle wall corresponding to migration of 10 microg l(-1) were determined. It was shown that the SiOx coating layer is an efficient barrier to post-consumer compounds. The maximum bottle wall concentrations of the surrogates corresponding to migration of 10 microg l(-1) were in the range of 200 mg kg(-1) for toluene and approximately 900 mg kg(-1) for benzophenone. Consequently, the SiOx coating allows use of conventionally recycled post-consumer PET flakes (without a super-clean recycling process) for packaging aqueous and low alcoholic foodstuffs (under cold-fill conditions) and protects food from migration of unwanted contaminants from post-consumer PET.

  13. Macrophage Membrane Potential Changes Associated with γ 2b/γ 1 Fc Receptor-Ligand Binding

    NASA Astrophysics Data System (ADS)

    Young, John Ding-E; Unkeless, Jay C.; Kaback, H. Ronald; Cohn, Zanvil A.

    1983-03-01

    We have studied the effects of specific ligands of the receptor for the IgG Fc fragment (FcR) on the membrane potential (Δ Psi ) of the macrophage cell line J774 by the [3H]tetraphenylphosphonium ion equilibration technique. We observe a membrane depolarization with binding of FcR ligands that is dependent on the degree of receptor crosslinking. Binding of the FcR by monovalent ligands is not sufficient to induce a significant drop in Δ Psi , but a sustained depolarization lasting ≈ 20 min occurs with insoluble multivalent ligands. This FcR-mediated depolarization can be inhibited by substitution of Na+ from the cell incubation medium with monovalent choline cation, indicating that depolarization is due to Na+ influx into the cell. The extracellular Ca2+ does not play a significant role in membrane depolarization. The depolarization response is not triggered by monoclonal antibodies directed against three other major macrophage surface antigens. The cell depolarization mediated by FcR ligands is followed by a prolonged hyperpolarization that can be partially blocked by ouabain and quinine, indicating that the hyperpolarization response is a result of a combination of a Na+, K+-ATPase activity and a Ca2+-activated K+ conductance. These data support our hypothesis that the mouse macrophage IgG FcR is a ligand-dependent ion channel.

  14. Radiobrominated m-tyrosine analog as potential CNS L-dopa PET tracer

    SciTech Connect

    De Jesus, O.T.; Mukherjee, J.

    1988-02-15

    Radiobrominated 6-bromo-m-tyrosine (6-BMT) was prepared and the time course of its localization in selected cerebral and peripheral organs in the mouse was determined. Since m-tyrosine is known to have L-dopa-like properties in vivo, our goal was to assess the utility of a radiolabeled analog as a tracer for cerebral L-dopa. Our preliminary results showed that substantial amounts of 6-BMT is extracted by the mouse brain and that the regional distribution and time course of the radiotracer is consistent with uptake in regions rich in dopamine neurons. Although a more thorough biochemical characterization of 6-BMT is necessary, this or other positron emitting analogs of m-tyrosine, such as an /sup 18/F labelled analog, may be useful PET tracers for the non-invasive study of dopamine turnover in humans.

  15. Latest advances in novel cannabinoid CB(2) ligands for drug abuse and their therapeutic potential.

    PubMed

    Yang, Peng; Wang, Lirong; Xie, Xiang-Qun

    2012-02-01

    The field of cannabinoid (CB) drug research is experiencing a challenge as the CB(1) antagonist Rimonabant, launched in 2006 as an anorectic/anti-obesity drug, was withdrawn from the European market due to the complications of suicide and depression as side effects. There is interest in developing CB(2) drugs without CB(1) psychotropic side effects for drug-abuse treatment and therapeutic medication. The CB(1) receptor was discovered predominantly in the brain, whereas the CB(2) is mainly expressed in peripheral cells and tissues, and is involved in immune signal transduction. Conversely, the CB(2) receptor was recently detected in the CNS, for example, in the microglial cells and the neurons. While the CB(2) neurons activity remains controversial, the CB(2) receptor is an attractive therapeutic target for neuropathic pain, immune system, cancer and osteoporosis without psychoactivity. This review addresses CB drug abuse and therapeutic potential with a focus on the most recent advances on new CB(2) ligands from the literature as well as patents.

  16. A graphical method to compare the in vivo binding potential of PET radioligands in the absence of a reference region: application to [11C]PBR28 and [18F]PBR111 for TSPO imaging

    PubMed Central

    Guo, Qi; Owen, David R; Rabiner, Eugenii A; Turkheimer, Federico E; Gunn, Roger N

    2014-01-01

    Positron emission tomography (PET) radioligands for a reversible central nervous system (CNS) demand a high specific to nonspecific signal characterized by the binding potential (BPND). The quantification of BPND requires the determination of the nondisplaceable binding usually derived from a reference region devoid of the target of interest. However, for many CNS targets, there is no valid reference region available. In such cases, the total volume of distribution (VT) is often used as the outcome measure, which includes both the specific and nonspecific binding signals. Here we present a graphical method that allows for direct comparison of the binding potential of ligands using the regional VT data alone via linear regression. The method was first validated using literature data for five serotonin transporter ligands, for which a reference region exists, and then applied to two second generation 18 kDa translocator protein radioligands, namely [11C]PBR28 and [18F]PBR111. The analysis determined that [11C]PBR28 had a higher BPND than [18F]PBR111. PMID:24736889

  17. Trypsin-Ligand Binding Free Energies from Explicit and Implicit Solvent Simulations with Polarizable Potential

    PubMed Central

    Jiao, Dian; Zhang, Jiajing; Duke, Robert E.; Li, Guohui; Ren, Pengyu

    2009-01-01

    We have calculated the binding free energies of a series of benzamidine-like inhibitors to trypsin with a polarizable force field using both explicit and implicit solvent approaches. Free energy perturbation has been performed for the ligands in bulk water and in protein complex with molecular dynamics simulations. The calculated binding free energies are well within the accuracy of experimental measurement and the direction of change is predicted correctly in call cases. We analyzed the molecular dipole moments of the ligands in gas, water and protein environments. Neither binding affinity nor ligand solvation free energy in bulk water shows much dependence on the molecular dipole moments of the ligands. Substitution of the aromatic or the charged group in the ligand results in considerable change in the solvation energy in bulk water and protein whereas the binding affinity varies insignificantly due to cancellation. The effect of chemical modification on ligand charge distribution is mostly local. Replacing benzene with diazine has minimal impact on the atomic multipoles at the amidinium group. We have also utilized an implicit solvent based end-state approach to evaluate the binding free energies of these inhibitors. In this approach, the polarizable multipole model combined with Poisson-Boltzmann/surface area (PMPB/SA) provides the electrostatic interaction energy and the polar solvation free energy. Overall the relative binding free energies obtained from the PMPB/SA model are in good agreement with the experimental data. PMID:19399779

  18. Effect of temperature on the release of intentionally and non-intentionally added substances from polyethylene terephthalate (PET) bottles into water: chemical analysis and potential toxicity.

    PubMed

    Bach, Cristina; Dauchy, Xavier; Severin, Isabelle; Munoz, Jean-François; Etienne, Serge; Chagnon, Marie-Christine

    2013-08-15

    The purpose of this study was to investigate the impact of temperature on the release of PET-bottle constituents into water and to assess the potential health hazard using in vitro bioassays with bacteria and human cell lines. Aldehydes, trace metals and other compounds found in plastic packaging were analysed in PET-bottled water stored at different temperatures: 40, 50, and 60°C. In this study, temperature and the presence of CO2 increased the release of formaldehyde, acetaldehyde and antimony (Sb). In parallel, genotoxicity assays (Ames and micronucleus assays) and transcriptional-reporter gene assays for estrogenic and anti-androgenic activity were performed on bottled water extracts at relevant consumer exposure levels. As expected, and in accordance with the chemical formulations specified for PET bottles, neither phthalates nor UV stabilisers were present in the water extracts. However, 2,4-di-tert-butylphenol, a degradation compound of phenolic antioxidants, was detected. In addition, an intermediary monomer, bis(2-hydroxyethyl)terephthalate, was found but only in PET-bottled waters. None of the compounds are on the positive list of EU Regulation No. 10/2011. However, the PET-bottled water extracts did not induce any cytotoxic, genotoxic or endocrine-disruption activity in the bioassays after exposure.

  19. Multitracer Molecular Imaging of Paget Disease Targeting Bone Remodeling, Fatty Acid Metabolism, and PSMA Expression on PET/CT.

    PubMed

    Derlin, Thorsten; Weiberg, Desiree; Sohns, Jan M

    2016-12-01

    Paget disease is a chronic disorder resulting in enlarged and misshapen bones, and is caused by disorganized bone remodeling. We present the case of an 85-year-old man with prostatic adenocarcinoma and known Paget disease of the right iliac bone who underwent Ga-prostate-specific membrane antigen ligand, C-acetate, and F-fluoride PET/CT for restaging of cancer. On all PET scans, increased tracer accumulation was observed in Paget disease of bone. Besides that Paget disease may mimic metastases on PET/CT using various radiotracers, including Ga-prostate-specific membrane antigen ligands and C-acetate, this case highlights the potential of multiparametric disease characterization on PET.

  20. [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.

  1. The scope and potentials of functional radionuclide imaging towards advancing personalized medicine in oncology: emphasis on PET-CT.

    PubMed

    Basu, Sandip

    2012-01-01

    Behavioral heterogeneity within a given patient cohort has been a major challenge in clinical practice and is probably most prominently observed in the field of oncology. This has been the prime impetus of the cutting-edge preclinical and clinical research studies over recent times, many of which seek to further stratify patients based on patients' genetic, proteomic, and metabolic profile (the three key components of "-omics" research), in order to select the appropriate therapy according to an individual's best-fit. Data from functional radionuclide imaging particularly that obtained from PET-CT, with regard to characterization of an individual's tumor phenotype, can play a very important role in answering some of the critical decision-making questions on an individual basis. The role of molecular imaging with PET, SPECT, and planar radionuclide technologies is not confined to early response assessment of administered therapeutics (which is its major benefit compared to conventional methods), rather it has a much broader perspective and encompasses multiple steps in decision making steps of patient management. The immense impact of the radionuclide-based molecular imaging techniques on the selection of an appropriate treatment (at initial diagnosis, during therapy, or after therapy) or in defining the tumor biology has been documented and increasingly recognized through both large and small-scale studies. However, there has been relatively less systematic effort towards the development of a successful and definitive clinical model of "personalized cancer medicine" (based on accurate disease triaging on an individual basis) by the medical community that would be suitable for routine adoption. In this paper, an endeavor has been made to explore the potential of this approach and underscore the areas that would require further critical evaluation to make this a reality.

  2. Detecting a dexmedetomidine-evoked reduction of noradrenaline release in the human brain with the alpha2C-adrenoceptor PET ligand [11C]ORM-13070.

    PubMed

    Lehto, Jussi; Scheinin, Annalotta; Johansson, Jarkko; Marjamäki, Päivi; Arponen, Eveliina; Scheinin, Harry; Scheinin, Mika

    2016-02-01

    PET imaging can for some neurotransmitters be used to measure synaptic neurotransmitter concentrations. The objective of this study was to test whether the receptor binding of the α2C -AR antagonist PET tracer [(11)C]ORM-13070 would increase in response to reductions in synaptic noradrenaline, evoked by dexmedetomidine as a sympatholytic drug challenge. Six subjects underwent a control PET scan and two dexmedetomidine PET scans. Dexmedetomidine was infused with target plasma concentrations of 0.6 and 0.2 ng/ml. Tracer binding was measured by voxel-based analysis of bound per free (B/F) images. ROI-based analysis was performed in the dorsal striatum and in the thalamus. Vital signs and drug concentrations in plasma were measured and the sedative effect was estimated with the visual analog scale. In the voxel-based analysis, dexmedetomidine administration was associated with a tendency to increased B/F tracer in the right thalamus (mean, +17%, P = 0.14, and +19%, P = 0.05, with the low and high dose, respectively). Tracer binding in the dorsal striatum was unaffected by dexmedetomidine. A cluster with significantly increased B/F tracer (+42%, P = 0.01) was seen in the right superior temporal gyrus with low-dose dexmedetomidine, but not after the high dose. Brain uptake of [(11)C]ORM-13070 has previously been shown to be reduced in conditions of increased synaptic noradrenaline concentrations. In this study, tracer binding in the thalamus tended to increase in accordance with reduced activity of noradrenergic projections from the locus coeruleus, but statistical significance was not reached.

  3. Accelerated flexible protein-ligand docking using Hamiltonian replica exchange with a repulsive biasing potential

    PubMed Central

    Ostermeir, Katja; Zacharias, Martin

    2017-01-01

    A molecular dynamics replica exchange based method has been developed that allows rapid identification of putative ligand binding sites on the surface of biomolecules. The approach employs a set of ambiguity restraints in replica simulations between receptor and ligand that allow close contacts in the reference replica but promotes transient dissociation in higher replicas. This avoids long-lived trapping of the ligand or partner proteins at nonspecific, sticky, sites on the receptor molecule and results in accelerated exploration of the possible binding regions. In contrast to common docking methods that require knowledge of the binding site, exclude solvent and often keep parts of receptor and ligand rigid the approach allows for full flexibility of binding partners. Application to peptide-protein, protein-protein and a drug-receptor system indicate rapid sampling of near-native binding regions even in case of starting far away from the native binding site outperforming continuous MD simulations. An application on a DNA minor groove binding ligand in complex with DNA demonstrates that it can also be used in explicit solvent simulations. PMID:28207811

  4. PSMA PET and Radionuclide Therapy in Prostate Cancer.

    PubMed

    Bouchelouche, Kirsten; Turkbey, Baris; Choyke, Peter L

    2016-11-01

    Prostate cancer (PCa) is the most common malignancy in men and a major cause of cancer death. Accurate imaging plays an important role in diagnosis, staging, restaging, detection of biochemical recurrence, and for therapy of patients with PCa. Because no effective treatment is available for advanced PCa, there is an urgent need to develop new and more effective therapeutic strategies. To optimize treatment outcome, especially in high-risk patients with PCa, therapy for PCa is moving rapidly toward personalization. Medical imaging, including positron emission tomography (PET)/computed tomography (CT), plays an important role in personalized medicine in oncology. In the recent years, much focus has been on prostate-specific membrane antigen (PSMA) as a promising target for imaging and therapy with radionuclides, as it is upregulated in most PCa. In the prostate, one potential role for PSMA PET imaging is to help guide focal therapy. Several studies have shown great potential of PSMA PET/CT for initial staging, lymph node staging, and detection of recurrence of PCa, even at very low prostate-specific antigen values after primary therapy. Furthermore, studies have shown that PSMA PET/CT has a higher detection rate than choline PET/CT. Radiolabeled PSMA ligands for therapy show promise in several studies with metastatic PCa and is an area of active investigation. The "image and treat" strategy, with radiolabeled PSMA ligands, has the potential to improve the treatment outcome of patients with PCa and is paving the way for precision medicine in PCa. The aim of this review is to give an overview of recent advancement in PSMA PET and radionuclide therapy for PCa.

  5. Potential role of pet animals in household transmission of methicillin-resistant Staphylococcus aureus: a narrative review.

    PubMed

    Bramble, Manuel; Morris, Daniel; Tolomeo, Pam; Lautenbach, Ebbing

    2011-06-01

    In this narrative review, we found numerous reports suggesting that dogs and cats may play a role in household methicillin-resistant Staphylococcus aureus (MRSA) transmission and recurrent MRSA infection in human contacts. Future work should emphasize elucidating more clearly the prevalence of MRSA in household pets and characterize transmission dynamics of MRSA humans and pet animals.

  6. Bivalent peptidomimetic ligands of TrkC are biased agonists, selectively induce neuritogenesis, or potentiate neurotrophin-3 trophic signals

    PubMed Central

    Chen, Dianjun; Brahimi, Fouad; Angell, Yu; Li, Yu-Chin; Moscowicz, Jennifer; Saragovi, H. Uri; Burgess, Kevin

    2009-01-01

    This study was initiated to find small molecule ligands that would induce a functional response when docked with neurotrophin Trk receptors. “Minimalist” mimics of β-turns were designed for this purpose. These mimics are: (i) rigid, yet easily folded into turn-like conformations, and (ii) readily accessible from amino acids bearing most of the natural side chains. Gram quantities of sixteen of these turn mimics were prepared, then assembled into 152 fluorescein-labeled bivalent peptidomimetics via a solution-phase combinatorial method. Fluorescence-based screening of these molecules using cells transfected with the Trk receptors identified 10 potential ligands of TrkC, the receptor for neurotrophin-3 (NT-3). Analogs of these bivalent peptidomimetics with biotin replacing the fluorescein label were then prepared and tested to confirm that binding was not due to the fluorescein. Several assays were conducted to find the mode of action of these biotinylated compounds. Thus, direct binding, survival and neuritogenic, and biochemical signal transduction assays showed 8 of the original 10 hits were agonistic ligands binding to the ectodomain of TrkC. Remarkably, some peptidomimetics afford discrete signals leading to either cell survival or neuritogenic differentiation. The significance of this work is three fold. First, we succeeded in finding small, selective, proteolytically stable ligands for the TrkC receptor; there are very few of these in the literature. Second, we show that it is possible to activate distinct and biased signaling pathways with ligands binding at the ectodomain of wild type receptors. Third, the discovery that some peptidomimetics initiate different modes of cell signaling increases their potential as pharmacological probes and therapeutic leads. PMID:19735123

  7. Potential for pet animals to harbour methicillin-resistant Staphylococcus aureus when residing with human MRSA patients.

    PubMed

    Morris, D O; Lautenbach, E; Zaoutis, T; Leckerman, K; Edelstein, P H; Rankin, S C

    2012-06-01

    Colonization by methicillin-resistant Staphylococcus aureus (MRSA) may be persistent in people and is horizontally transmissible. The scientific literature suggests that domestic pets may also participate in cross-transmission of MRSA within households. The objectives of this study were to evaluate the prevalence of and risk factors for MRSA carriage by pets residing in households with an MRSA-infected person. From 66 households in which an MRSA-infected patient resided, we screened 47 dogs and 52 cats using a swab protocol. Isolates from pets and humans were genotyped using two techniques and compared for concordance. Human participants completed a 22-question survey of demographic and epidemiologic data relevant to staphylococcal transmission. Eleven of 99 pets (11.5%) representing 9 (13.6%) of households were MRSA-positive, but in only six of these households were the human and animal-source strains genetically concordant. Human infection by strain USA 100 was significantly associated with pet carriage [OR = 11.4 (95% CI 1.7, 76.9); P = 0.013]. Yet, for each day of delay in sampling the pet after the person's MRSA diagnosis, the odds of isolating any type of MRSA from the pet decreased by 13.9% [(95% CI 2.6, 23.8); P = 0.017)]. It may be concluded that pets can harbour pandemic strains of MRSA while residing in a household with an infected person. However, the source of MRSA to the pet cannot always be attributed to the human patient. Moreover, the rapid attrition of the odds of obtaining a positive culture from pets over time suggests that MRSA carriage may be fleeting.

  8. CpG oligodeoxynucleotide ligand potentiates the activity of the pVAX1-Sj26GST

    PubMed Central

    LU, JUN; JIANG, SHAN; YE, SONG; DENG, YUN; MA, SHUAI; LI, CHAO-PIN

    2013-01-01

    Schistosomiasis is considered one of the most important neglected tropical diseases and remains a major public health problem in endemic countries. Toll-like receptor (TLR) ligands have been investigated as potential vaccine adjuvants for tumor and virus immunotherapy. However, few TLR ligands affecting schistosoma vaccines have been characterized. In this study, we evaluated a TLR9 ligand (CpG oligodeoxynucleotide 1826, CpG) as an adjuvant for a partially protective DNA vaccine encoding a 26-kDa glutathione S-transferase of Schistosoma japonicum (pVAX1-Sj26GST). Vaccination with pVAX1-Sj26GST in combination with CpG inhibited Treg immunosuppressive function, upregulated the production of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-4, IL-10, IL-2 and IL-6, and decreased CD4+CD8+Foxp3+ expression in vitro, which may contribute to the escape from Treg-mediated suppression during vaccination, allowing expansion of antigen-specific T cells against pathogens. In conclusion, our data demonstrated that selective TLR ligand combination may increase protective efficacy against schistosomiasis, which may synergistically antagonize Treg-mediated suppression. PMID:24648995

  9. Biological redundancy of endogenous GPCR ligands in the gut and the potential for endogenous functional selectivity

    PubMed Central

    Thompson, Georgina L.; Canals, Meritxell; Poole, Daniel P.

    2014-01-01

    This review focuses on the existence and function of multiple endogenous agonists of the somatostatin and opioid receptors with an emphasis on their expression in the gastrointestinal tract. These agonists generally arise from the proteolytic cleavage of prepropeptides during peptide maturation or from degradation of peptides by extracellular or intracellular endopeptidases. In other examples, endogenous peptide agonists for the same G protein-coupled receptors can be products of distinct genes but contain high sequence homology. This apparent biological redundancy has recently been challenged by the realization that different ligands may engender distinct receptor conformations linked to different intracellular signaling profiles and, as such the existence of distinct ligands may underlie mechanisms to finely tune physiological responses. We propose that further characterization of signaling pathways activated by these endogenous ligands will provide invaluable insight into the mechanisms governing biased agonism. Moreover, these ligands may prove useful in the design of novel therapeutic tools to target distinct signaling pathways, thereby favoring desirable effects and limiting detrimental on-target effects. Finally we will discuss the limitations of this area of research and we will highlight the difficulties that need to be addressed when examining endogenous bias in tissues and in animals. PMID:25506328

  10. Combined TLR7/8 and TLR9 Ligands Potentiate the Activity of a Schistosoma japonicum DNA Vaccine

    PubMed Central

    Wang, Xuefeng; Dong, Liyang; Ni, Hongchang; Zhou, Sha; Xu, Zhipeng; Hoellwarth, Jason Shih; Chen, Xiaojun; Zhang, Rongbo; Chen, Qiaoyun; Liu, Feng; Wang, Jun; Su, Chuan

    2013-01-01

    Background Toll-like receptor (TLR) ligands have been explored as vaccine adjuvants for tumor and virus immunotherapy, but few TLR ligands affecting schistosoma vaccines have been characterized. Previously, we developed a partially protective DNA vaccine encoding the 26-kDa glutathione S-transferase of Schistosoma japonicum (pVAX1-Sj26GST). Methodology/Principal Findings In this study, we evaluated a TLR7/8 ligand (R848) and a TLR9 ligand (CpG oligodeoxynucleotides, or CpG) as adjuvants for pVAX1-Sj26GST and assessed their effects on the immune system and protection against S. japonicum. We show that combining CpG and R848 with pVAX1-Sj26GST immunization significantly increases splenocyte proliferation and IgG and IgG2a levels, decreases CD4+CD25+Foxp3+ regulatory T cells (Treg) frequency in vivo, and enhances protection against S. japonicum. CpG and R848 inhibited Treg-mediated immunosuppression, upregulated the production of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-4, IL-10, IL-2, and IL-6, and decreased Foxp3 expression in vitro, which may contribute to prevent Treg suppression and conversion during vaccination and allow expansion of antigen-specific T cells against pathogens. Conclusions Our data shows that selective TLR ligands can increase the protective efficacy of DNA vaccines against schistosomiasis, potentially through combined antagonism of Treg-mediated immunosuppression and conversion. PMID:23593527

  11. Herbo-mineral based Schiff base ligand and its metal complexes: Synthesis, characterization, catalytic potential and biological applications.

    PubMed

    Kareem, Abdul; Laxmi; Arshad, Mohammad; Nami, Shahab A A; Nishat, Nahid

    2016-07-01

    Schiff base ligand, (L), derived from condensation reaction of 1,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione, (curcumin), with pyridine-3-carboxamide, (nicotinamide), and its complexes of Co(II), Ni(II) and Cu(II) ions, containing 1,10-phenanthroline as auxiliary ligand were synthesized and characterized by various physico-chemical techniques. From the micro analytical data, the stoichiometry of the complexes 1:1 (metal: ligand) was ascertained. The Co(II) and Cu(II) forms octahedral complexes, while the geometric structure around Ni(II) atom can be described as square planar. The catalytic potential of the metal complexes have been evaluated by recording the rate of decomposition of hydrogen peroxide. The results reveal that the percent decomposition of H2O2increases with time and the highest value (50.50%) was recorded for Co(II) complex. The ligand and its complexes were also screened for their in vitro antibacterial activity against Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pyogenes and Pseudomonas aeruginosa. The relative order of antibacterial activity against S. Pyogenes, S. aureus and E. coli is Cu(II)>Ni(II)>Co(II)>(L); while with P. aeruginosa, K. pneumoniae the order of activity is Cu(II)>Co(II)>Ni(II)>(L). The anthelmintic screening was performed using Pheretima posthuma. The order of anthelmintic activity of ligand and its complexes is [(Phen)CuLCl2]>[(Phen)CoLCl2]>[(Phen)NiL]Cl2>(L).

  12. Synthesis, characterisation, spectral, thermal, XRD, molecular modelling and potential antibacterial study of metal complexes containing octadentate azodye ligands

    NASA Astrophysics Data System (ADS)

    Mahapatra, Bipin Bihari; Chaulia, Satyanarayan; Sarangi, Ashish Kumar; Dehury, Satyanarayan; Panda, Jnyanaranjan

    2015-05-01

    Twelve tetrametallic complexes of Co(II), Ni(II), Cu(II), Zn(II), Cd(II) and Hg(II) with two new octadentate azodye ligands, 4,4‧-bis(2‧,4‧-dihydroxy-5‧carboxyphenylazo) diphenylether (LH6) and 4,4‧-bis(2‧,4‧-dihydroxy-5‧-acylphenylazo) diphenylether (L‧H4) have been synthesised. The structural elucidation of the complexes was made basing upon analytical, conductance, magnetic susceptibility, IR, electronic spectra, ESR, NMR, ESI-MS, TG, DTG, DTA and X-ray diffraction (powder pattern) data. The cobalt (II) and nickel (II) complexes are found to be octahedral, copper (II) complexes are distorted octahedral and a tetrahedral stereochemistry has been suggested to zinc (II), cadmium (II) and mercury (II) complexes. The thermal analysis data provided the kinetic parameters as order of decomposition reaction, activation energy and frequency factor. The geometry of the ligands and their Co(II), Ni(II), Cu(II) and Zn(II) complexes were optimised and their physicochemical properties were calculated by using molecular modelling procedure. The ESI-MS determination supports the molecular formula and molecular weight of the ligands and the complexes. The Ni(II) complex is found to have a triclinic crystal system. The potential antibacterial study of the two ligands and eight metal complexes was made by cup-plate method against one gram positive and one gram negative bacteria. The results showed increase in the activity of some metal complexes as compare with azodye ligands.

  13. Pet Health

    MedlinePlus

    ... Before getting a pet, think carefully about which animal is best for your family. What is each ... Does anyone have pet allergies? What type of animal suits your lifestyle and budget? Once you own ...

  14. Select corn coproducts from the ethanol industry and their potential as ingredients in pet foods.

    PubMed

    de Godoy, M R C; Bauer, L L; Parsons, C M; Fahey, G C

    2009-01-01

    The objectives of this study were to determine the chemical composition and nutritive value of corn protein product 1 (CPP 1), corn protein product 2 (CPP 2), and corn fiber (CF), novel coproducts of the ethanol industry, and compare these feed ingredients with standard plant protein ingredients [soybean meal (SBM), distillers dried grains with solubles (DDGS), corn gluten meal (CGlM), and corn germ meal (CGeM)], and to compare CF sources (CF control 1 and control 2) with standard fiber sources (peanut hulls, Solka-Floc, and beet pulp) commonly used in pet foods. Corn fiber, CPP 1, and CPP 2 were produced at a pilot-scale modified dry-grind plant, with CPP 2 having a greater degree of purification than CPP 1. Crude protein values for CPP 2 and CPP 1 were 57.3 and 49.7%, respectively. Total dietary fiber concentration was 29% for CPP 2 and 23.5% for CPP 1. Acid-hydrolyzed fat and GE concentrations were similar for these ingredients. In a protein efficiency ratio assay, no differences (P > 0.05) in feed intake, BW gain, or CP intake were noted for CPP 2, CPP 1, or CGlM. However, feeding CPP 2 resulted in a greater (P < 0.05) G:F ratio and protein efficiency ratio than CPP 1 and CGlM. In a cecectomized rooster assay, CGlM had numerically the greatest standardized total AA, total essential AA, and total nonessential AA digestibilities, but they were not different (P > 0.05) from CPP 1 or SBM values. Corn germ meal resulted in the least values, but they were not different from those for DDGS and CPP 1. The greatest values for true nitrogen-corrected ME were obtained with CGlM, followed by CPP 2, DDGS, CPP 1, SBM, and CGeM. Distillers dried grains with solubles and CPP 1 had similar true nitrogen-corrected ME values, and they were not different from values for CPP 2 and SBM. In vitro CP disappearance was greatest (P < 0.05) for CGlM (94.1%), intermediate for DDGS (76.8%) and CPP 1 (77.5%), and least for CPP 2 (74.1%) and CGeM (67.7%). Corn fibers contained predominantly

  15. Synthesis and Characterization of a Tetramethyl Furanone Functionalized Diiminedioxime, A Potential Ligand for 64Cu Radiopharmaceuticals, and its Copper(II) and Nickel(II) Complexes

    PubMed Central

    Kiani, Salma; Staples, Richard J.; Treves, S. Ted; Packard, Alan B.

    2009-01-01

    As part of our on-going effort to develop 64Cu-based radiopharmaceuticals for PET (positron emission tomography) imaging of multidrug resistance in cancer, we prepared a tetramethylfuranone-functionalized diiminedioxime ligand, TMFPreH (TMFPreH = 4-[3-(4-Hydroxyimino-2,2,5,5-dimethyl-dihydro-furan-3-ylideneamino)-propylimino]-2,2,5,5-tetramethyl-dihydro-furan-3-one oxime) and its Cu(II) and Ni(II) complexes. When the copper(II) complex was prepared from Cu(ClO4)2 in ethanol, it was isolated as a Cu(II)-bridged dimer, but when it was prepared from Cu(OAc)2 and heated in acetone, an unusual example of an acetone adduct of the ligand is formed by reduction of one of the imine double bonds by the solvent. The Ni(II) complex is square pyramidal with the perchlorate counterion at the apex. PMID:20161333

  16. Four-body atomic potential for modeling protein-ligand binding affinity: application to enzyme-inhibitor binding energy prediction

    PubMed Central

    2013-01-01

    Background Models that are capable of reliably predicting binding affinities for protein-ligand complexes play an important role the field of structure-guided drug design. Methods Here, we begin by applying the computational geometry technique of Delaunay tessellation to each set of atomic coordinates for over 1400 diverse macromolecular structures, for the purpose of deriving a four-body statistical potential that serves as a topological scoring function. Next, we identify a second, independent set of three hundred protein-ligand complexes, having both high-resolution structures and known dissociation constants. Two-thirds of these complexes are randomly selected to train a predictive model of binding affinity as follows: two tessellations are generated in each case, one for the entire complex and another strictly for the isolated protein without its bound ligand, and a topological score is computed for each tessellation with the four-body potential. Predicted protein-ligand binding affinity is then based on an empirically derived linear function of the difference between both topological scores, one that appropriately scales the value of this difference. Results A comparison between experimental and calculated binding affinity values over the two hundred complexes reveals a Pearson's correlation coefficient of r = 0.79 with a standard error of SE = 1.98 kcal/mol. To validate the method, we similarly generated two tessellations for each of the remaining protein-ligand complexes, computed their topological scores and the difference between the two scores for each complex, and applied the previously derived linear transformation of this topological score difference to predict binding affinities. For these one hundred complexes, we again observe a correlation of r = 0.79 (SE = 1.93 kcal/mol) between known and calculated binding affinities. Applying our model to an independent test set of high-resolution structures for three hundred diverse enzyme-inhibitor complexes

  17. Selective fluorescence sensing of Cu(II) and Zn(II) using a simple Schiff base ligand: Naked eye detection and elucidation of photoinduced electron transfer (PET) mechanism

    NASA Astrophysics Data System (ADS)

    Ganguly, Aniruddha; Ghosh, Soumen; Kar, Samiran; Guchhait, Nikhil

    2015-05-01

    A simple Schiff base compound 2-((cyclohexylmethylimino)-methyl)-naphthalen-1-ol (2CMIMN1O) has been synthesized and characterized by 1H NMR, 13C NMR and FT-IR spectroscopic techniques. A significantly low emission yield of the compound has been rationalized in anticipation with photo-induced electron transfer (PET) from the imine receptor moiety to the naphthalene fluorophore unit. Consequently, an evaluation of the transition metal ion-induced modification of the fluorophore-receptor communication reveals the promising prospect of the title compound to function as a chemosensor for Cu2+ and Zn2+ ions selectively, through remarkable fluorescence enhancement as well as visual changes. While perturbation of the PET process has been argued to be the plausible mechanism behind the fluorescence enhancement, the selectivity for these two metal ions has been interpreted on the grounds of an appreciably strong binding interaction. Particularly notable aspects regarding the chemosensory activity of the compound is its ability to detect the aforesaid transition metal ions down to the level of micromolar concentration (detection limit being 2.74 and 2.27 ppm respectively), along with a simple and efficient synthetic procedure.

  18. RutheniumII complexes bearing fused polycyclic ligands: from fundamental aspects to potential applications.

    PubMed

    Troian-Gautier, Ludovic; Moucheron, Cécile

    2014-04-22

    In this review, we first discuss the photophysics reported in the literature for mononuclear ruthenium complexes bearing ligands with extended aromaticity such as dipyrido[3,2-a:2',3'-c]phenazine (DPPZ), tetrapyrido[3,2-a:2',3'-c:3'',2''-h:2''',3'''-j]-phenazine (TPPHZ),  tetrapyrido[3,2-a:2',3'-c:3'',2''-h:2''',3'''-j]acridine (TPAC), 1,10-phenanthrolino[5,6-b]1,4,5,8,9,12-hexaazatriphenylene (PHEHAT) 9,11,20,22-tetraaza- tetrapyrido[3,2-a:2',3'-c:3'',2''-l:2''',3'''-n]pentacene (TATPP), etc. Photophysical properties of binuclear and polynuclear complexes based on these extended ligands are then reported. We finally develop the use of binuclear complexes with extended π-systems for applications such as photocatalysis.

  19. Targeting programmed cell death ligand 1 in osteosarcoma: an auto-commentary on therapeutic potential.

    PubMed

    Shen, Jacson K; Cote, Gregory M; Choy, Edwin; Hornicek, Francis J; Duan, Zhenfeng

    Programmed cell death ligand 1 (PDL1) expression was recently shown to correlate with tumor-infiltrating lymphocytes (TILs) in a subset of osteosarcoma patients. Among clinical factors evaluated across human osteosarcoma samples, a pulmonary origin of metastases correlated with high PDL1 expression and prominent TILs. Considering that multiple agents targeting PD-1/PDL1 are under development, targeting this immune checkpoint may be a novel immunotherapeutic route for osteosarcoma in future clinical trials.

  20. Pharmacologic perturbation as a potential tool to increase the sensitivity of FDG-PET in the evaluation of brain tumors

    SciTech Connect

    Wong, F.C.L.; Kim, E.E.; Yung, W.K.A.

    1994-05-01

    The usefulness of F-18 FDG PET in the study of brain tumors is limited by the high baseline cortical uptake which decreases the contrast of the tumor. Two alternatives to increase the tumor/background contrast have been reported: barbiturate-induced coma and postprandial state. This project evaluates the effects of sedation with diazepam or of oral glucose intake on the brain tumor/background contrast during F-18 FDG PET studies.

  1. PET with radiolabeled aminoacid.

    PubMed

    Crippa, F; Alessi, A; Serafini, G L

    2012-04-01

    Since the clinical introduction of FDG, neuroimaging has been the first area of PET application in oncology. Later, while FDG-PET became progressively a key imaging modality in the management of the majority of malignancies outside the brain, its neuro-oncologic indications faced some limitations because of the unfavourable characteristics of FDG as brain tumor-seeking agent. PET applications in neuro-oncology have received new effectiveness by the advent of positron-emission labelled amino acids, so that it has been coined the term "Amino acid PET" to differentiate this imaging tool from FDG-PET. Radiolabeled amino acids are a very interesting class of PET tracers with great diagnostic potential in neuro-oncology because of their low uptake in normal brain and, conversely, high uptake in most brain tumors including low-grade gliomas. The present article surveys the results obtained using L-[methyl-11C]Methionine (MET), that has been the ancestor of PET amino acid tracers and is still the most popular amino acid imaging modality in oncology, and stresses the important role that this diagnostic modality can play in the evaluation of brain tumors. However, the use of MET is restricted to PET centers with an in-house cyclotron and radiochemistry facility, because of the short half-life (20 min) of 11C. The promising results of MET have stimulated the development of 18F-labelled aminoacid tracers, particularly O-(2-18F-fluoeoethyl1)-L-tyrosine (FET), that has the same properties of MET and, thanks to the longer half-life of 18F (about 110 min), allows a distribution strategy from a production tracer site to user satellite PET centers. Considering a more widespread use of Amino acid PET, together with the recent development of integrated PET-MRI imaging systems, and the oncoming clinical validation of other interesting PET tracers, i.e. FMISO or 18F-FAZA for hypoxia imaging and FLT for tumor proliferation imaging, it can be reasonably expected that metabolic imaging

  2. Activation of gene transcription via CIM0216, a synthetic ligand of transient receptor potential melastatin-3 (TRPM3) channels.

    PubMed

    Rubil, Sandra; Thiel, Gerald

    2017-01-02

    Several compounds have been proposed to stimulate TRPM3 Ca(2+) channels. We recently showed that stimulation of TRPM3 channels with pregnenolone sulfate activated the transcription factor AP-1, while other proposed TRPM3 ligands (nifedipine, D-erythro-sphingosine) exhibited either no or TRPM3-independent effects on gene transcription. Here, we have analyzed the transcriptional activity of CIM0216, a synthetic TRPM3 ligand proposed to have a higher potency and affinity for TRPM3 than pregnenolone sulfate. The results show that CIM0216 treatment of HEK293 cells expressing TRPM3 channels activated AP-1 and stimulated the transcriptional activation potential of c-Jun and c-Fos, 2 basic region leucine zipper transcription factors that constitute AP-1. CIM0216-induced gene transcription was attenuated by knock-down of TRPM3 or treatment with mefenamic acid, a TRPM3 inhibitor. CIM0216 was similarly or less capable in activating TRPM3-mediated gene transcription, suggesting that pregnenolone sulfate is still the ligand of choice for changing the gene expression pattern via TRPM3.

  3. Evaluation of a potential generator-produced PET tracer for cerebral perfusion imaging: single-pass cerebral extraction measurements and imaging with radiolabeled Cu-PTSM.

    PubMed

    Mathias, C J; Welch, M J; Raichle, M E; Mintun, M A; Lich, L L; McGuire, A H; Zinn, K R; John, E K; Green, M A

    1990-03-01

    Copper(II) pyruvaldehyde bis(N4-methylthiosemicarbazone) (Cu-PTSM), copper(II) pyruvaldehyde bis(N4-dimethylthiosemicarbazone) (Cu-PTSM2), and copper(II) ethylglyoxal bis(N4-methylthiosemicarbazone) (Cu-ETSM), have been proposed as PET tracers for cerebral blood flow (CBF) when labeled with generator-produced 62Cu (t1/2 = 9.7 min). To evaluate the potential of Cu-PTSM for CBF PET studies, baboon single-pass cerebral extraction measurements and PET imaging were carried out with the use of 67Cu (t1/2 = 2.6 days) and 64Cu (t1/2 = 12.7 hr), respectively. All three chelates were extracted into the brain with high efficiency. There was some clearance of all chelates in the 10-50-sec time frame and Cu-PTSM2 continued to clear. Cu-PTSM and Cu-ETSM have high residual brain activity. PET imaging of baboon brain was carried out with the use of [64Cu]-Cu-PTSM. For comparison with the 64Cu brain image, a CBF (15O-labeled water) image (40 sec) was first obtained. Qualitatively, the H2(15)O and [64Cu]-Cu-PTSM images were very similar; for example, a comparison of gray to white matter uptake resulted in ratios of 2.42 for H2(15)O and 2.67 for Cu-PTSM. No redistribution of 64Cu was observed in 2 hr of imaging, as was predicted from the single-pass study results. Quantitative determination of blood flow using Cu-PTSM showed good agreement with blood flow determined with H2(15)O. This data suggests that [62Cu]-Cu-PTSM may be a useful generator-produced radiopharmaceutical for blood flow studies with PET.

  4. New lithium borates with bistetrazolato(2-) and pyrazinediolato(2-) ligands - potentially interesting lithium electrolyte additives.

    PubMed

    Finger, Lars H; Venker, Alexander; Schröder, Fabian G; Sundermeyer, Jörg

    2017-02-28

    We present a convenient synthesis of the first silylated bistetrazole via a catalyzed twin [2 + 3] cycloaddition of TMS-azide at cyanogen and its application to access bistetrazolatoborates, structurally characterized by a unique unsaturated ten-membered B2N4C4 heterocyclic system. Furthermore, new borate anions with two pyrazine-2,3-diolato ligands were synthesized from tetrafluoroborate salts and structurally characterized. Their organic cation can be exchanged for Li(+)via cation exchange. The conceptual relation of these new salts to lithium ion battery bisoxalalatoborate additive LiBOB, a prominent solid electrolyte interface (SEI) generator, is discussed.

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

    PubMed

    Huang, Yiyun; Narendran, Raj; Bae, Sung-A; Erritzoe, David; Guo, Ningning; Zhu, Zhihong; Hwang, Dah-Ren; Laruelle, Marc

    2004-08-01

    A new serotonin transporter (SERT) ligand, [11C]2-[2-(dimethylaminomethylphenylthio)]-5-fluorophenylamine (10, [11C]AFA), was synthesized and evaluated as a candidate PET radioligand in pharmacological and pharmacokinetic studies. As a PET radioligand, AFA (8) can be labeled with either C-11 or F-18. In vitro, AFA displayed high affinity for SERT (Ki 1.46 +/- 0.15 nM) and lower affinity for norepinephrine transporter (NET, Ki 141.7 +/- 47.4 nM) or dopamine transporter (DAT, Ki > 10,000 nM). [11C]AFA (10) was prepared from its monomethylamino precursor 9 by reaction with high specific activity [11C]methyl iodide. Radiochemical yield was 43 +/- 20% based on [11C]methyl iodide at end of bombardment (EOB, n = 10) and specific activity was 2,129 +/- 1,369 Ci/mmol at end of synthesis (EOS, n = 10). Biodistribution studies in rats indicated that [11C]AFA accumulated in brain regions known to contain high concentrations of SERT. Binding in SERT-rich brain regions was reduced significantly by pretreatment with either the cold compound 8 or with the selective serotonin reuptake inhibitor (SSRI) citalopram, but not by the selective norepinephrine reuptake inhibitor nisoxetine, thus underlining its in vivo binding selectivity and specificity for SERT. Imaging experiments in baboons demonstrated that the uptake pattern of [11C]AFA in the baboon brain is consistent with the known distribution of SERT, with highest activity levels in the midbrain and thalamus, followed by striatum, hippocampus, and cortical regions. Activity levels in the baboon brain peaked at 15-40 min after radioligand injection, indicating a fast uptake kinetics for [11C]AFA. Pretreatment of the baboon with citalopram (4 mg/kg) significantly reduced the specific binding of [11C]AFA in all SERT-containing brain regions. Kinetic analysis revealed that the regional equilibrium specific to non-specific partition coefficients (V3") of [11C]AFA are similar to those of [11C]McN5652, but lower than those of [11C

  6. Potential New Ligand Systems for Binding Uranyl Ions in Seawater Environments

    SciTech Connect

    Arnold, John

    2014-12-13

    Work began this quarter on a new project involving a combined computational and biosynthetic approach to selective recognition of uranyl ion in aqueous solution. This project exploits the results of computational studies to discover new ligand classes. Synthetic studies will follow to generate target systems for uranyl binding and determination of binding constants. The process will be iterative, with results from computation informing synthesis, and vice versa. The theme of the ligand classes to be examined initially will be biologically based. New phosphonate-containing α-amino acid N-carboxyanhydride (NCA) monomers were used recently to prepare well-defined phosphonate-containing poly-peptides and block copolypeptides. Our first approach is to utilize these phosphate- and phosphonate-containing NCAs for the coordination of uranyl. The work includes the laboratory-scale preparation of a series of NCAs and the full thermodynamic and spectroscopic characterization of the resulting uranyl complexes. We are also evaluating the sequestering activity in different physiological and environmental conditions of these copolymers as well as their biodegradability.

  7. Future laser-accelerated proton beams at ELI-Beamlines as potential source of positron emitters for PET

    NASA Astrophysics Data System (ADS)

    Amato, E.; Italiano, A.; Margarone, D.; Pagano, B.; Baldari, S.; Korn, G.

    2016-04-01

    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 novel, fast and efficient, radiopharmaceutical methods of labeling. We studied the feasibility to produce clinically-relevant amounts of PET isotopes by means of laser-accelerated proton sources expected at the ELI-Beamlines facility where a PW, 30 fs, 10 Hz laser system will be available. The production yields of several positron emitters were calculated through the TALYS software, by taking into account three possible scenarios of broad proton spectra expected, with maximum energies ranging from about 8 MeV to 100 MeV. With the hypothesized proton fluencies, clinically-relevant amounts of radionuclides can be obtained, suitable to prepare single doses of radiopharmaceuticals exploiting modern fast and efficient labeling systems.

  8. Pseudo-Mannosylated DC-SIGN Ligands as Potential Adjuvants for HIV Vaccines

    PubMed Central

    Berzi, Angela; Varga, Norbert; Sattin, Sara; Antonazzo, Patrizio; Biasin, Mara; Cetin, Irene; Trabattoni, Daria; Bernardi, Anna; Clerici, Mario

    2014-01-01

    The development of new and effective adjuvants may play a fundamental role in improving HIV vaccine efficacy. New classes of vaccine adjuvants activate innate immunity receptors, notably toll like receptors (TLRs). Adjuvants targeting the C-Type lectin receptor DC-SIGN may be alternative or complementary to adjuvants based on TRL activation. Herein we evaluate the ability of the glycomimetic DC-SIGN ligand Polyman 19 (PM 19) to modulate innate immune responses. Results showed that PM 19 alone, or in combination with TLR agonists, induces the expression of cytokines, β chemokines and co-stimulatory molecules that may, in turn, modulate adaptive immunity and exert anti-viral effects. These results indicate that the suitability of this compound as a vaccine adjuvant should be further evaluated. PMID:24473338

  9. Dual time-point imaging for post-dose binding potential estimation applied to a [(11)C]raclopride PET dose occupancy study.

    PubMed

    Alves, Isadora L; Willemsen, Antoon Tm; Dierckx, Rudi A; da Silva, Ana Maria M; Koole, Michel

    2017-03-01

    Receptor occupancy studies performed with PET often require time-consuming dynamic imaging for baseline and post-dose scans. Shorter protocol approximations based on standard uptake value ratios have been proposed. However, such methods depend on the time-point chosen for the quantification and often lead to overestimation and bias. The aim of this study was to develop a shorter protocol for the quantification of post-dose scans using a dual time-point approximation, which employs kinetic parameters from the baseline scan. Dual time-point was evaluated for a [(11)C]raclopride PET dose occupancy study with the D2 antagonist JNJ-37822681, obtaining estimates for binding potential and receptor occupancy. Results were compared to standard simplified reference tissue model and standard uptake value ratios-based estimates. Linear regression and Bland-Altman analysis demonstrated excellent correlation and agreement between dual time-point and the standard simplified reference tissue model approach. Moreover, the stability of dual time-point-based estimates is shown to be independent of the time-point chosen for quantification. Therefore, a dual time-point imaging protocol can be applied to post-dose [(11)C]raclopride PET scans, resulting in a significant reduction in total acquisition time while maintaining accuracy in the quantification of both the binding potential and the receptor occupancy.

  10. Distribution Atlas of Proliferating Bone Marrow in Non-Small Cell Lung Cancer Patients Measured by FLT-PET/CT Imaging, With Potential Applicability in Radiation Therapy Planning

    SciTech Connect

    Campbell, Belinda A.; Callahan, Jason; Bressel, Mathias; Simoens, Nathalie; Everitt, Sarah; Hofman, Michael S.; Hicks, Rodney J.; Burbury, Kate; MacManus, Michael

    2015-08-01

    Purpose: Proliferating bone marrow is exquisitely sensitive to ionizing radiation. Knowledge of its distribution could improve radiation therapy planning to minimize unnecessary marrow exposure and avoid consequential prolonged myelosuppression. [18F]-Fluoro-3-deoxy-3-L-fluorothymidine (FLT)–positron emission tomography (PET) is a novel imaging modality that provides detailed quantitative images of proliferating tissues, including bone marrow. We used FLT-PET imaging in cancer patients to produce an atlas of marrow distribution with potential clinical utility. Methods and Materials: The FLT-PET and fused CT scans of eligible patients with non-small cell lung cancer (no distant metastases, no prior cytotoxic exposure, no hematologic disorders) were reviewed. The proportions of skeletal FLT activity in 10 predefined bony regions were determined and compared according to age, sex, and recent smoking status. Results: Fifty-one patients were studied: 67% male; median age 68 (range, 31-87) years; 8% never smokers; 70% no smoking in the preceding 3 months. Significant differences in marrow distribution occurred between sex and age groups. No effect was detected from smoking in the preceding 3 months. Using the mean percentages of FLT uptake per body region, we created an atlas of the distribution of functional bone marrow in 4 subgroups defined by sex and age. Conclusions: This atlas has potential utility for estimating the distribution of active marrow in adult cancer patients to guide radiation therapy planning. However, because of interindividual variation it should be used with caution when radiation therapy risks ablating large proportions of active marrow; in such cases, individual FLT-PET scans may be required.

  11. Evaluation of Several Two-Step Scoring Functions Based on Linear Interaction Energy, Effective Ligand Size, and Empirical Pair Potentials for Prediction of Protein-Ligand Binding Geometry and Free Energy

    PubMed Central

    Rahaman, Obaidur; Estrada, Trilce P.; Doren, Douglas J.; Taufer, Michela; Brooks, Charles L.; Armen, Roger S.

    2011-01-01

    The performance of several two-step scoring approaches for molecular docking were assessed for their ability to predict binding geometries and free energies. Two new scoring functions designed for “step 2 discrimination” were proposed and compared to our CHARMM implementation of the linear interaction energy (LIE) approach using the Generalized-Born with Molecular Volume (GBMV) implicit solvation model. A scoring function S1 was proposed by considering only “interacting” ligand atoms as the “effective size” of the ligand, and extended to an empirical regression-based pair potential S2. The S1 and S2 scoring schemes were trained and five-fold cross validated on a diverse set of 259 protein-ligand complexes from the Ligand Protein Database (LPDB). The regression-based parameters for S1 and S2 also demonstrated reasonable transferability in the CSARdock 2010 benchmark using a new dataset (NRC HiQ) of diverse protein-ligand complexes. The ability of the scoring functions to accurately predict ligand geometry was evaluated by calculating the discriminative power (DP) of the scoring functions to identify native poses. The parameters for the LIE scoring function with the optimal discriminative power (DP) for geometry (step 1 discrimination) were found to be very similar to the best-fit parameters for binding free energy over a large number of protein-ligand complexes (step 2 discrimination). Reasonable performance of the scoring functions in enrichment of active compounds in four different protein target classes established that the parameters for S1 and S2 provided reasonable accuracy and transferability. Additional analysis was performed to definitively separate scoring function performance from molecular weight effects. This analysis included the prediction of ligand binding efficiencies for a subset of the CSARdock NRC HiQ dataset where the number of ligand heavy atoms ranged from 17 to 35. This range of ligand heavy atoms is where improved accuracy of

  12. Evaluation of several two-step scoring functions based on linear interaction energy, effective ligand size, and empirical pair potentials for prediction of protein-ligand binding geometry and free energy.

    PubMed

    Rahaman, Obaidur; Estrada, Trilce P; Doren, Douglas J; Taufer, Michela; Brooks, Charles L; Armen, Roger S

    2011-09-26

    The performances of several two-step scoring approaches for molecular docking were assessed for their ability to predict binding geometries and free energies. Two new scoring functions designed for "step 2 discrimination" were proposed and compared to our CHARMM implementation of the linear interaction energy (LIE) approach using the Generalized-Born with Molecular Volume (GBMV) implicit solvation model. A scoring function S1 was proposed by considering only "interacting" ligand atoms as the "effective size" of the ligand and extended to an empirical regression-based pair potential S2. The S1 and S2 scoring schemes were trained and 5-fold cross-validated on a diverse set of 259 protein-ligand complexes from the Ligand Protein Database (LPDB). The regression-based parameters for S1 and S2 also demonstrated reasonable transferability in the CSARdock 2010 benchmark using a new data set (NRC HiQ) of diverse protein-ligand complexes. The ability of the scoring functions to accurately predict ligand geometry was evaluated by calculating the discriminative power (DP) of the scoring functions to identify native poses. The parameters for the LIE scoring function with the optimal discriminative power (DP) for geometry (step 1 discrimination) were found to be very similar to the best-fit parameters for binding free energy over a large number of protein-ligand complexes (step 2 discrimination). Reasonable performance of the scoring functions in enrichment of active compounds in four different protein target classes established that the parameters for S1 and S2 provided reasonable accuracy and transferability. Additional analysis was performed to definitively separate scoring function performance from molecular weight effects. This analysis included the prediction of ligand binding efficiencies for a subset of the CSARdock NRC HiQ data set where the number of ligand heavy atoms ranged from 17 to 35. This range of ligand heavy atoms is where improved accuracy of predicted ligand

  13. Synthesis and pharmacological evaluation of dual acting ligands targeting the adenosine A2A and dopamine D2 receptors for the potential treatment of Parkinson's disease.

    PubMed

    Jörg, Manuela; May, Lauren T; Mak, Frankie S; Lee, Kiew Ching K; Miller, Neil D; Scammells, Peter J; Capuano, Ben

    2015-01-22

    A relatively new strategy in drug discovery is the development of dual acting ligands. These molecules are potentially able to interact at two orthosteric binding sites of a heterodimer simultaneously, possibly resulting in enhanced subtype selectivity, higher affinity, enhanced or modified physiological response, and reduced reliance on multiple drug administration regimens. In this study, we have successfully synthesized a series of classical heterobivalent ligands as well as a series of more integrated and "drug-like" dual acting molecules, incorporating ropinirole as a dopamine D2 receptor agonist and ZM 241385 as an adenosine A2A receptor antagonist. The best compounds of our series maintained the potency of the original pharmacophores at both receptors (adenosine A2A and dopamine D2). In addition, the integrated dual acting ligands also showed promising results in preliminary blood-brain barrier permeability tests, whereas the classical heterobivalent ligands are potentially more suited as pharmacological tools.

  14. Kinetics of protein-ligand unbinding via smoothed potential molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Mollica, Luca; Decherchi, Sergio; Zia, Syeda Rehana; Gaspari, Roberto; Cavalli, Andrea; Rocchia, Walter

    2015-06-01

    Drug discovery is expensive and high-risk. Its main reasons of failure are lack of efficacy and toxicity of a drug candidate. Binding affinity for the biological target has been usually considered one of the most relevant figures of merit to judge a drug candidate along with bioavailability, selectivity and metabolic properties, which could depend on off-target interactions. Nevertheless, affinity does not always satisfactorily correlate with in vivo drug efficacy. It is indeed becoming increasingly evident that the time a drug spends in contact with its target (aka residence time) can be a more reliable figure of merit. Experimental kinetic measurements are operatively limited by the cost and the time needed to synthesize compounds to be tested, to express and purify the target, and to setup the assays. We present here a simple and efficient molecular-dynamics-based computational approach to prioritize compounds according to their residence time. We devised a multiple-replica scaled molecular dynamics protocol with suitably defined harmonic restraints to accelerate the unbinding events while preserving the native fold. Ligands are ranked according to the mean observed scaled unbinding time. The approach, trivially parallel and easily implementable, was validated against experimental information available on biological systems of pharmacological relevance.

  15. A novel ligand of calcitonin receptor reveals a potential new sensor that modulates programmed cell death

    PubMed Central

    Furness, SGB; Hare, DL; Kourakis, A; Turnley, AM; Wookey, PJ

    2016-01-01

    We have discovered that the accumulation of an anti-calcitonin receptor (anti-CTR) antibody conjugated to a fluorophore (mAb2C4:AF568) provides a robust signal for cells undergoing apoptotic programmed cell death (PCD). PCD is an absolute requirement for normal development of metazoan organisms. PCD is a hallmark of common diseases such as cardiovascular disease and tissue rejection in graft versus host pathologies, and chemotherapeutics work by increasing PCD. This robust signal or high fluorescent events were verified by confocal microscopy and flow cytometry in several cell lines and a primary culture in which PCD had been induced. In Jurkat cells, GBM-L2 and MG63 cells, the percentage undergoing PCD that were positive for both mAb2C4:AF568 and annexin V ranged between 70 and >90%. In MG63 cells induced for the preapoptotic cell stress response (PACSR), the normal expression of α-tubulin, a key structural component of the cytoskeleton, and accumulation of mAb2C4:AF568 were mutually exclusive. Our data support a model in which CTR is upregulated during PACSR and recycles to the plasma membrane with apoptosis. In cells committed to apoptosis (α-tubulin negative), there is accumulation of the CTR-ligand mAb2C4:AF568 generating a high fluorescent event. The reagent mAb2C4:AF568 effectively identifies a novel event linked to apoptosis. PMID:27777788

  16. Evaluation of N-Phenyl Homopiperazine Analogs as Potential Dopamine D3 Receptor Selective Ligands

    PubMed Central

    Li, Aixiao; Mishra, Yogesh; Malik, Maninder; Wang, Qi; Li, Shihong; Taylor, Michelle; Reichert, David E.; Luedtke, Robert R.; Mach, Robert H.

    2013-01-01

    A series of N-(2-methoxyphenyl)homopiperazine analogs was prepared and their affinities for dopamine D2, D3, and D4 receptors were measured using competitive radioligand binding assays. Several ligands exhibited high binding affinity and selectivity for the D3 dopamine receptor compared to the D2 receptor subtype. Compounds 11a, 11b, 11c, 11f, 11j and 11k had Ki values ranging from 0.7–3.9 nM for the D3 receptor with 30- to 170-fold selectivity for the D3 vs. D2 receptor. Calculated log P values (log P = 2.6–3.6) are within the desired range for passive transport across the blood brain barrier. When the binding and the intrinsic efficacy of these phenylhomopiperazines was compared to those of previously published phenylpiperazine analogues, it was found that a) affinity at D2 and D3 dopamine receptors generally decreased, b) the D3 receptor binding selectivity (D2:D3 Ki value ratio) decreased and, c) the intrinsic efficacy, measured using a forskolin-dependent adenylyl cyclase inhibition assay, generally increased. PMID:23618707

  17. Early-Phase 11C-PiB PET in Amyloid Angiopathy-Related Symptomatic Cerebral Hemorrhage: Potential Diagnostic Value?

    PubMed

    Farid, Karim; Hong, Young T; Aigbirhio, Franklin I; Fryer, Tim D; Menon, David K; Warburton, Elizabeth A; Baron, Jean-Claude

    2015-01-01

    Although late-phase (>35min post-administration) 11C-PiB-PET has good sensitivity in cerebral amyloid angiopathy (CAA), its specificity is poor due to frequently high uptake in healthy aged subjects. By detecting perfusion-like abnormalities, early-phase 11C-PiB-PET might add diagnostic value. Early-frame (1-6min) 11C-PiB-PET was obtained in 11 non-demented patients with probable CAA-related symptomatic lobar intracerebral haemorrhage (70±7yrs), 9 age-matched healthy controls (HCs) and 10 HCs <55yrs. There was a significant decrease in early-phase atrophy-corrected whole-cortex SUV relative to cerebellar vermis (SUVR) in the CAA vs age-matched HC group. None of the age-matched controls fell below the lower 95% confidence limit derived from the young HCs, while 6/11 CAA patients did (sensitivity = 55%, specificity = 100%). Combining both early- and late-phase 11C-PiB data did not change the sensitivity and specificity of late-phase PiB, but combined early- and late-phase positivity entails a very high suspicion of underlying Aβ-related clinical disorder, i.e., CAA or Alzheimer disease (AD). In order to clarify this ambiguity, we then show that the occipital/posterior cingulate ratio is markedly lower in CAA than in AD (N = 7). These pilot data suggest that early-phase 11C-PiB-PET may not only add to late-phase PiB-PET with respect to the unclear situation of late-phase positivity, but also help differentiate CAA from AD.

  18. Use of concatemers of ligand-gated ion channel subunits to study mechanisms of steroid potentiation.

    PubMed

    Steinbach, Joe Henry; Akk, Gustav

    2011-12-01

    Synaptic receptors of the nicotinic receptor gene family are pentamers of subunits. This modular structure creates problems in studies of drug actions, related to the number of copies of a subunit that are present and their position. A separate issue concerns the mechanism of action of many anesthetics, which involves potentiation of responses to neurotransmitters. Potentiation requires an interaction between a transmitter and a potentiator, mediated through the target receptor. We have studied the mechanism by which neurosteroids potentiate transmitter responses, using concatemers of covalently linked subunits to control the number and position of subunits in the assembled receptor and to selectively introduce mutations into positionally defined copies of a subunit. We found that the steroid needs to interact with only one site to produce potentiation, that the native sites for steroid interaction have indistinguishable properties, and that steroid potentiation appears to result from a global effect on receptor function.

  19. PET/CT in radiation oncology

    SciTech Connect

    Pan, Tinsu; Mawlawi, Osama

    2008-11-15

    PET/CT is an effective tool for the diagnosis, staging and restaging of cancer patients. It combines the complementary information of functional PET images and anatomical CT images in one imaging session. Conventional stand-alone PET has been replaced by PET/CT for improved patient comfort, patient throughput, and most importantly the proven clinical outcome of PET/CT over that of PET and that of separate PET and CT. There are over two thousand PET/CT scanners installed worldwide since 2001. Oncology is the main application for PET/CT. Fluorine-18 deoxyglucose is the choice of radiopharmaceutical in PET for imaging the glucose uptake in tissues, correlated with an increased rate of glycolysis in many tumor cells. New molecular targeted agents are being developed to improve the accuracy of targeting different disease states and assessing therapeutic response. Over 50% of cancer patients receive radiation therapy (RT) in the course of their disease treatment. Clinical data have demonstrated that the information provided by PET/CT often changes patient management of the patient and/or modifies the RT plan from conventional CT simulation. The application of PET/CT in RT is growing and will become increasingly important. Continuing improvement of PET/CT instrumentation will also make it easier for radiation oncologists to integrate PET/CT in RT. The purpose of this article is to provide a review of the current PET/CT technology, to project the future development of PET and CT for PET/CT, and to discuss some issues in adopting PET/CT in RT and potential improvements in PET/CT simulation of the thorax in radiation therapy.

  20. SU-D-9A-01: Listmode-Driven Optimal Gating (OG) Respiratory Motion Management: Potential Impact On Quantitative PET Imaging

    SciTech Connect

    Lee, K; Hristov, D

    2014-06-01

    Purpose: To evaluate the potential impact of listmode-driven amplitude based optimal gating (OG) respiratory motion management technique on quantitative PET imaging. Methods: During the PET acquisitions, an optical camera tracked and recorded the motion of a tool placed on top of patients' torso. PET event data were utilized to detect and derive a motion signal that is directly coupled with a specific internal organ. A radioactivity-trace was generated from listmode data by accumulating all prompt counts in temporal bins matching the sampling rate of the external tracking device. Decay correction for 18F was performed. The image reconstructions using OG respiratory motion management technique that uses 35% of total radioactivity counts within limited motion amplitudes were performed with external motion and radioactivity traces separately with ordered subset expectation maximization (OSEM) with 2 iterations and 21 subsets. Standard uptake values (SUVs) in a tumor region were calculated to measure the effect of using radioactivity trace for motion compensation. Motion-blurred 3D static PET image was also reconstructed with all counts and the SUVs derived from OG images were compared with SUVs from 3D images. Results: A 5.7 % increase of the maximum SUV in the lesion was found for optimal gating image reconstruction with radioactivity trace when compared to a static 3D image. The mean and maximum SUVs on the image that was reconstructed with radioactivity trace were found comparable (0.4 % and 4.5 % increase, respectively) to the values derived from the image that was reconstructed with external trace. Conclusion: The image reconstructed using radioactivity trace showed that the blurring due to the motion was reduced with impact on derived SUVs. The resolution and contrast of the images reconstructed with radioactivity trace were comparable to the resolution and contrast of the images reconstructed with external respiratory traces. Research supported by Siemens.

  1. Negative electrostatic surface potential of protein sites specific for anionic ligands.

    PubMed Central

    Ledvina, P S; Yao, N; Choudhary, A; Quiocho, F A

    1996-01-01

    Determination of the crystal structure of an "open" unliganded active mutant (T141D) form of the Escherichia coli phosphate receptor for active transport has allowed calculation of the electrostatic surface potential for it and two other comparably modeled receptor structures (wild type and D137N). A discovery of considerable implication is the intensely negative potential of the phosphate-binding cleft. We report similar findings for a sulfate transport receptor, a DNA-binding protein, and, even more dramatically, redox proteins. Evidently, for proteins such as these, which rely almost exclusively on hydrogen bonding for anion interactions and electrostatic balance, a noncomplementary surface potential is not a barrier to binding. Moreover, experimental results show that the exquisite specificity and high affinity of the phosphate and sulfate receptors for unions are insensitive to modulations of charge potential, but extremely sensitive to conditions that leave a hydrogen bond donor or acceptor unpaired. Images Fig. 1 Fig. 2 Fig. 3 PMID:8692896

  2. Negative electrostatic surface potential of protein sites specific for anionic ligands.

    PubMed

    Ledvina, P S; Yao, N; Choudhary, A; Quiocho, F A

    1996-06-25

    Determination of the crystal structure of an "open" unliganded active mutant (T141D) form of the Escherichia coli phosphate receptor for active transport has allowed calculation of the electrostatic surface potential for it and two other comparably modeled receptor structures (wild type and D137N). A discovery of considerable implication is the intensely negative potential of the phosphate-binding cleft. We report similar findings for a sulfate transport receptor, a DNA-binding protein, and, even more dramatically, redox proteins. Evidently, for proteins such as these, which rely almost exclusively on hydrogen bonding for anion interactions and electrostatic balance, a noncomplementary surface potential is not a barrier to binding. Moreover, experimental results show that the exquisite specificity and high affinity of the phosphate and sulfate receptors for unions are insensitive to modulations of charge potential, but extremely sensitive to conditions that leave a hydrogen bond donor or acceptor unpaired.

  3. Recycled-PET fibre based panels for building thermal insulation: environmental impact and improvement potential assessment for a greener production.

    PubMed

    Ingrao, Carlo; Lo Giudice, Agata; Tricase, Caterina; Rana, Roberto; Mbohwa, Charles; Siracusa, Valentina

    2014-09-15

    A screening of Life Cycle Assessment for the evaluation of the damage arising from the production of 1 kg of recycled Polyethylene Terephthalate (RPET) fibre-based panel for building heat insulation was carried out according to the ISO 14040:2006 and 14044:2006. All data used were collected on site based on observations during site visits, review of documents and interviews with technical personnel and management. These data were processed by using SimaPro 7.3.3, accessing the Ecoinvent v.2.2 database and using the Impact 2002+ method. The study showed damage to be equal to 0.000299 points mostly due to the: 1) PET thermo-bonding fibre supply from China by means of a freight-equipped intercontinental aircraft; 2) production of bottle-grade granulate PET; 3) medium voltage electricity consumption during the manufacturing of RPET fibre panel. It was also highlighted that there were environmental benefits due to recycling through mainly avoiding significant emissions and reduced resource consumption. An improvement assessment was carried out to find solutions aimed at reducing the damage coming from the most impacting phases. Furthermore, the environmental impacts due to the production of the analysed RPET fibre-based panel were compared to other materials with the same insulating function, such as polystyrene foam, rock wool and cork slab. Finally, the environmental benefits of the recycling of PET bottles for flake production were highlighted compared to other treatment scenarios such as landfill and municipal incineration.

  4. Reproducibility of quantitative measures of binding potential in rat striatum: A test re-test study using DTBZ dynamic PET studies

    SciTech Connect

    Avendaño-Estrada, A. Lara-Camacho, V. M. Ávila-García, M. C. Ávila- Rodríguez, M. A.

    2014-11-07

    There is great interest in the study of dopamine (DA) pathways due to the increasing number of patients with illnesses related to the dopaminergic system and molecular imaging based in Positron Emission Tomography (PET) has been proven helpful for this task. Among the different radiopharmaceuticals available to study DA interaction, [{sup 11}C]Dihydrotetrabenazine (DTBZ) has a high affinity for the vesicular monoamine transporter type 2 (VMAT2) and its binding potential (BP) is a marker of DA terminal integrity. This paper reports on the intersubject reproducibility of BP measurements in rat striatum with [11C]DTBZ using the Logańs method.

  5. A 3-D QSAR-BASED IDENTIFICATION ALGORITHM FOR POTENTIAL ESTROGEN RECEPTOR LIGANDS

    EPA Science Inventory

    Recent reports concerning the lethal effects of solar ultraviolet-B (UV-B) radiation on amphibians suggest that this stressor has the potential to impact some amphibian populations. In this study embryos and larvae of three anuran species, Rana pipiens, R. clamitans, and R. septe...

  6. Development of PET and SPECT Probes for Glutamate Receptors

    PubMed Central

    Nakayama, Morio

    2015-01-01

    l-Glutamate and its receptors (GluRs) play a key role in excitatory neurotransmission within the mammalian central nervous system (CNS). Impaired regulation of GluRs has also been implicated in various neurological disorders. GluRs are classified into two major groups: ionotropic GluRs (iGluRs), which are ligand-gated ion channels, and metabotropic GluRs (mGluRs), which are coupled to heterotrimeric guanosine nucleotide binding proteins (G-proteins). Positron emission tomography (PET) and single photon emission computed tomography (SPECT) imaging of GluRs could provide a novel view of CNS function and of a range of brain disorders, potentially leading to the development of new drug therapies. Although no satisfactory imaging agents have yet been developed for iGluRs, several PET ligands for mGluRs have been successfully employed in clinical studies. This paper reviews current progress towards the development of PET and SPECT probes for GluRs. PMID:25874256

  7. Senior Pets

    MedlinePlus

    ... Health Awareness Events About AVMA Who We Are Governance AVMA Careers AVMF Student AVMA (SAVMA) Allied Organizations ... Although senior pets may develop age-related problems, good care allows them to live happy, healthy and ...

  8. Giardia & Pets

    MedlinePlus

    ... items (for example, bedding and cloth toys) and linens (sheets and towels) can be washed in the ... and food bowls, pet bedding, floors, dog crates, linens, towels, litter box, etc.) regularly for as long ...

  9. PET scan

    MedlinePlus

    ... may have an allergic reaction to the tracer material. Some people have pain, redness, or swelling at ... with diabetes. Most PET scans are now performed along with a CT scan. This combination scan ...

  10. Estrogen Receptors Alpha (ERα) and Beta (ERβ): Subtype-Selective Ligands and Clinical Potential

    PubMed Central

    Paterni, Ilaria; Granchi, Carlotta; Katzenellenbogen, John A.; Minutolo, Filippo

    2014-01-01

    Estrogen receptors alpha (ERα) and beta (ERβ) are nuclear transcription factors that are involved in the regulation of many complex physiological processes in humans. Modulation of these receptors by prospective therapeutic agents is currently being considered for prevention and treatment of a wide variety of pathological conditions, such as, cancer, metabolic and cardiovascular diseases, neurodegeneration, inflammation, and osteoporosis. This review provides an overview and update of compounds that have been recently reported as modulators of ERs, with a particular focus on their potential clinical applications. PMID:24971815

  11. P2Y Receptors in the Mammalian Nervous System: Pharmacology, Ligands and Therapeutic Potential

    PubMed Central

    Weisman, Gary A.; Woods, Lucas T.; Erb, Laurie; Seye, Cheikh I.

    2015-01-01

    P2Y receptors for extracellular nucleotides are coupled to activation of a variety of G proteins and stimulate diverse intracellular signaling pathways that regulate functions of cell types that comprise the central nervous system (CNS). There are 8 different subtypes of P2Y receptor expressed in cells of the CNS that are activated by a select group of nucleotide agonists. Here, the agonist selectivity of these 8 P2Y receptor subtypes is reviewed with an emphasis on synthetic agonists with high potency and resistance to degradation by extracellular nucleotidases that have potential applications as therapeutic agents. In addition, the recent identification of a wide variety of subtype-selective antagonists is discussed, since these compounds are critical for discerning cellular responses mediated by activation of individual P2Y receptor subtypes. The functional expression of P2Y receptor subtypes in cells that comprise the CNS is also reviewed and the role of each subtype in the regulation of physiological and pathophysiological responses is considered. Other topics include the role of P2Y receptors in the regulation of blood-brain barrier integrity and potential interactions between different P2Y receptor subtypes that likely impact tissue responses to extracellular nucleotides in the CNS. Overall, current research suggests that P2Y receptors in the CNS regulate repair mechanisms that are triggered by tissue damage, inflammation and disease and thus P2Y receptors represent promising targets for the treatment of neurodegenerative diseases. PMID:22963441

  12. Early-Late Heterobimetallic Complexes Linked by Phosphinoamide Ligands. Tuning Redox Potentials and Small Molecule Activation

    SciTech Connect

    Thomas, Christine M.

    2015-08-01

    Recent attention in the chemical community has been focused on the energy efficient and environmentally benign conversion of abundant small molecules (CO2, H2O, etc.) to useful liquid fuels. This project addresses these goals by examining fundamental aspects of catalyst design to ultimately access small molecule activation processes under mild conditions. Specifically, Thomas and coworkers have targetted heterobimetallic complexes that feature metal centers with vastly different electronic properties, dictated both by their respective positions on the periodic table and their coordination environment. Unlike homobimetallic complexes featuring identical or similar metals, the bonds between metals in early/late heterobimetallics are more polarized, with the more electron-rich late metal center donating electron density to the more electron-deficient early metal center. While metal-metal bonds pose an interesting strategy for storing redox equivalents and stabilizing reactive metal fragments, the polar character of metal-metal bonds in heterobimetallic complexes renders these molecules ideally poised to react with small molecule substrates via cleavage of energy-rich single and double bonds. In addition, metal-metal interactions have been shown to dramatically affect redox potentials and promote multielectron redox activity, suggesting that metal-metal interactions may provide a mechanism to tune redox potentials and access substrate reduction/activation at mild overpotentials. This research project has provided a better fundamental understanding of how interactions between transition metals can be used as a strategy to promote and/or control chemical transformations related to the clean production of fuels. While this project focused on the study of homogeneous systems, it is anticipated that the broad conclusions drawn from these investigations will be applicable to heterogeneous catalysis as well, particularly on heterogeneous processes that occur at interfaces in

  13. A study of DNA/BSA interaction and catalytic potential of oxidovanadium(v) complexes with ONO donor ligands.

    PubMed

    Dash, Subhashree P; Panda, Alok K; Dhaka, Sarita; Pasayat, Sagarika; Biswas, Ashis; Maurya, Mannar R; Majhi, Paresh Kumar; Crochet, Aurélien; Dinda, Rupam

    2016-11-15

    The study of DNA/BSA interaction and the catalytic potential of four mononuclear oxidoalkoxido vanadium(v) [V(V)O(L(1-4))OEt] (1-4) and one dinuclear oxidoalkoxido mixed-ligand vanadium(v) [{VO(L(2))OEt}2(Q)]{Q = 4,4'-bipyridine}(5) complexes, with tridentate binegative aroylazine ligands are reported [where H2L(1) = anthranylhydrazone of 2-hydroxy-1-napthaldehyde, H2L(2) = salicylhydrazone of 2-hydroxy-1-napthaldehyde, H2L(3) = benzoylhydrazone of 2-hydroxy-1-acetonaphthone, H2L(4) = anthranylhydrazone of 2-hydroxy-1-acetonaphthone]. All the complexes are characterized by elemental analysis as well as various spectroscopic techniques. Single crystal X-ray diffraction crystallography of 2 reveals that the metal centre is in distorted square pyramidal geometry with O4N coordination spheres, whereas 5 exhibits a distorted octahedral geometry around the metal center. In addition, all the complexes (1-5) show moderate DNA binding propensity which is investigated using UV-vis absorption titration, circular dichroism, thermal denaturation and fluorescence spectral studies. The experimental results show that the complexes effectively interact with CT-DNA through both minor and major groove binding modes, with binding constants ranging from 10(4)-10(5) M(-1). Among 1-5, complexes 3 and 4 show higher binding affinity towards CT-DNA than others and at the same time also exhibit negative ΔTm values of about ∼1.5 and 1.0 °C which resembles the properties shown by cisplatin. All complexes show moderate photo-induced cleavage of pUC19 supercoiled plasmid DNA with complex 3 showing the highest photo induced DNA cleavage activity of ∼48%. In coherence with the DNA interaction studies, 3 and 4 also exhibit good binding affinity towards BSA in the range of 10(10)-10(11) M(-1), which is also supported by their ability to quench the tryptophan fluorescence emission spectra of BSA. All the complexes show remarkable photo-induced BSA cleavage activity (>90%) at a complex

  14. Positron Emission Tomography (PET)

    DOE R&D Accomplishments Database

    Welch, M. J.

    1990-01-01

    Positron emission tomography (PET) assesses biochemical processes in the living subject, producing images of function rather than form. Using PET, physicians are able to obtain not the anatomical information provided by other medical imaging techniques, but pictures of physiological activity. In metaphoric terms, traditional imaging methods supply a map of the body's roadways, its, anatomy; PET shows the traffic along those paths, its biochemistry. This document discusses the principles of PET, the radiopharmaceuticals in PET, PET research, clinical applications of PET, the cost of PET, training of individuals for PET, the role of the United States Department of Energy in PET, and the futures of PET.

  15. Positron Emission Tomography (PET)

    SciTech Connect

    Welch, M.J.

    1990-01-01

    Positron emission tomography (PET) assesses biochemical processes in the living subject, producing images of function rather than form. Using PET, physicians are able to obtain not the anatomical information provided by other medical imaging techniques, but pictures of physiological activity. In metaphoric terms, traditional imaging methods supply a map of the body's roadways, its, anatomy; PET shows the traffic along those paths, its biochemistry. This document discusses the principles of PET, the radiopharmaceuticals in PET, PET research, clinical applications of PET, the cost of PET, training of individuals for PET, the role of the United States Department of Energy in PET, and the futures of PET. 22 figs.

  16. Progress in developing cholecystokinin (CCK)/gastrin receptor ligands which have therapeutic potential

    PubMed Central

    Berna, Marc J.; Tapia, Jose A.; Sancho, Veronica; Jensen, Robert T.

    2007-01-01

    Summary Gastrin and CCK are two of the oldest hormones and within the last 15 years there has been an exponential increase in knowledge of their pharmacology, cell biology, receptors (CCK1R, CCK2R) and roles in physiology and pathological conditions. Despite these advances there is no approved disease indication for CCK receptor antagonists and only minor use of agonists. In this review the important factors determining this slow therapeutic development are reviewed. To assess this it is necessary to briefly review what is known about the roles of CCK receptors (CCK1R, CCK2R) in normal human physiology, their role in pathologic conditions, the selectivity of available potent CCKR agonists/antagonists as well as review their use in human conditions to date and the results. Despite extensive studies in animals and some in humans, recent studies suggest that monotherapy with CCK1R agonists will not be effective in obesity, nor CCK2R antagonists in panic disorders or CCK2R antagonists to inhibit growth of pancreatic cancer. Areas that require more study include the use of CCK2R agonists for imaging tumors and radiotherapy, CCK2R antagonists in hypergastrinemic states especially with long term PPI use and for potentiation of analgesia as well as use of CCK1R antagonists for a number of gastrointestinal disorders [motility disorders (irritable bowel syndrome, dyspepsia, constipation) and pancreatitis (acute, chronic)]. PMID:17997137

  17. APRIL, a proliferation-inducing ligand, as a potential marker of lupus nephritis

    PubMed Central

    2012-01-01

    Introduction BLyS and APRIL are cytokines from the tumor necrosis factor family which play an important role in systemic lupus erythematosus (SLE). Previous works suggested an association between both molecules and SLE disease activity although their correlation with lupus nephritis is not known. We therefore assessed serum BLyS and APRIL in active lupus nephritis patients. Methods Serum samples from active lupus nephritis and at 6 months post-treatment were obtained. Serum levels of BLyS and APRIL (n = 47) as well as renal mRNA expression were measured. Serum levels of both molecules and clinical data (n = 27) were available at 6 months follow-up. All biopsy-proven lupus nephritis patients were treated with similar immunosuppressive drugs. Results Serum levels of APRIL were associated with proteinuria (Rs = 0.44, P value < 0.01) and degree of histological activity (Rs = 0.34; P value < 0.05) whereas BLyS levels were associated with complement levels (Rs = 0.46; P value < 0.01) and dosage of immunosuppressant. Interestingly, serum APRIL as well as its intrarenal mRNA levels were associated with resistance to treatment. From the receiver operating characteristic (ROC) analysis, high levels (> 4 ng/mL) of serum APRIL predicted treatment failure with a positive predictive value of 93 percent. Conclusion APRIL could be a potential biomarker for predicting difficult-to-treat cases of lupus nephritis. PMID:23171638

  18. Competitive advantage of PET/MRI.

    PubMed

    Jadvar, Hossein; Colletti, Patrick M

    2014-01-01

    Multimodality imaging has made great strides in the imaging evaluation of patients with a variety of diseases. Positron emission tomography/computed tomography (PET/CT) is now established as the imaging modality of choice in many clinical conditions, particularly in oncology. While the initial development of combined PET/magnetic resonance imaging (PET/MRI) was in the preclinical arena, hybrid PET/MR scanners are now available for clinical use. PET/MRI combines the unique features of MRI including excellent soft tissue contrast, diffusion-weighted imaging, dynamic contrast-enhanced imaging, fMRI and other specialized sequences as well as MR spectroscopy with the quantitative physiologic information that is provided by PET. Most evidence for the potential clinical utility of PET/MRI is based on studies performed with side-by-side comparison or software-fused MRI and PET images. Data on distinctive utility of hybrid PET/MRI are rapidly emerging. There are potential competitive advantages of PET/MRI over PET/CT. In general, PET/MRI may be preferred over PET/CT where the unique features of MRI provide more robust imaging evaluation in certain clinical settings. The exact role and potential utility of simultaneous data acquisition in specific research and clinical settings will need to be defined. It may be that simultaneous PET/MRI will be best suited for clinical situations that are disease-specific, organ-specific, related to diseases of the children or in those patients undergoing repeated imaging for whom cumulative radiation dose must be kept as low as reasonably achievable. PET/MRI also offers interesting opportunities for use of dual modality probes. Upon clear definition of clinical utility, other important and practical issues related to business operational model, clinical workflow and reimbursement will also be resolved.

  19. Encapsulation of Nod1 and Nod2 receptor ligands into poly(lactic acid) nanoparticles potentiates their immune properties.

    PubMed

    Pavot, Vincent; Rochereau, Nicolas; Primard, Charlotte; Genin, Christian; Perouzel, Eric; Lioux, Thierry; Paul, Stéphane; Verrier, Bernard

    2013-04-10

    Most successful vaccines are able to induce persistent antibody responses that can last a lifetime. Emerging evidences indicate that activation of immune cells through pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs) or Nod-like receptors (NLRs) may be critical mechanisms. Among PRRs, the use of TLR ligands as adjuvants is already largely described whereas the use of NLRs ligands remains largely unexplored. As activation of intracytoplasmic NLRs is able to induce proinflammatory molecules, the added value of encapsulation of Nod1 and Nod2 receptor ligands into Poly(Lactic Acid) (PLA) biodegradable nanocarriers to modulate their immune properties on human dendritic cells (DCs) maturation has been evaluated. Their ability to induce systemic immune responses in mice was also measured and compared to free ligands and the Alum adjuvant. Nod ligands encapsulated into PLA NPs were efficiently taken up by DCs and subsequently induced a strong up-regulation of maturation markers and the enhancement of proinflammatory cytokine secretion by DCs. Furthermore, co-injection of encapsulated Nod-ligands with PLA particles carrying Gag p24 HIV-1 antigen allowed a 100 fold increase in antibody responses in comparison to Alum. These results suggest that encapsulation of Nod ligands into PLA-NPs could be an effective way to improve vaccine efficiency.

  20. Crystal structure and dynamics of a lipid-induced potential desensitized-state of a pentameric ligand-gated channel

    PubMed Central

    Basak, Sandip; Schmandt, Nicolaus; Gicheru, Yvonne; Chakrapani, Sudha

    2017-01-01

    Desensitization in pentameric ligand-gated ion channels plays an important role in regulating neuronal excitability. Here, we show that docosahexaenoic acid (DHA), a key ω−3 polyunsaturated fatty acid in synaptic membranes, enhances the agonist-induced transition to the desensitized state in the prokaryotic channel GLIC. We determined a 3.25 Å crystal structure of the GLIC-DHA complex in a potentially desensitized conformation. The DHA molecule is bound at the channel-periphery near the M4 helix and exerts a long-range allosteric effect on the pore across domain-interfaces. In this previously unobserved conformation, the extracellular-half of the pore-lining M2 is splayed open, reminiscent of the open conformation, while the intracellular-half is constricted, leading to a loss of both water and permeant ions. These findings, in combination with spin-labeling/EPR spectroscopic measurements in reconstituted-membranes, provide novel mechanistic details of desensitization in pentameric channels. DOI: http://dx.doi.org/10.7554/eLife.23886.001 PMID:28262093

  1. Symposium on research advances in clinical PET. Final performance report

    SciTech Connect

    J. Michael McGehee

    1992-01-01

    The Institute for Clinical PET and the U.S. Department of Energy (DOE) co-sponsored a symposium entitled 'Research in PET: International and Institutional Perspectives' that highlighted the activities of many leading investigators in the U.S. and throughout the world. Research programs at the DOE were discussed as were potential directions of PET research. International as well as institutional perspectives on PET research were presented. This symposium was successful in reaching those interested in research advances of clinical PET.

  2. System with potential dual modes of metal-ligand cooperation: highly catalytically active pyridine-based PNNH-Ru pincer complexes.

    PubMed

    Fogler, Eran; Garg, Jai Anand; Hu, Peng; Leitus, Gregory; Shimon, Linda J W; Milstein, David

    2014-11-24

    Metal-ligand cooperation (MLC) plays an important role in catalysis. Systems reported so far are generally based on a single mode of MLC. We report here a system with potential for MLC by both amine-amide and aromatization-dearomatization ligand transformations, based on a new class of phosphino-pyridyl ruthenium pincer complexes, bearing sec-amine coordination. These pincer complexes are effective catalysts under unprecedented mild conditions for acceptorless dehydrogenative coupling of alcohols to esters at 35 °C and hydrogenation of esters at room temperature and 5 atm H2. The likely actual catalyst, a novel, crystallographically characterized monoanionic de-aromatized enamido-Ru(II) complex, was obtained by deprotonation of both the N-H and the methylene proton of the N-arm of the pincer ligand.

  3. Glutamate receptor ligands attenuate allodynia and hyperalgesia and potentiate morphine effects in a mouse model of neuropathic pain.

    PubMed

    Osikowicz, Maria; Mika, Joanna; Makuch, Wioletta; Przewlocka, Barbara

    2008-09-30

    Recent studies have indicated that metabotropic glutamate receptors mGluR5, mGluR2/3 and mGluR7 are present in the regions of central nervous system important for nociceptive transmission, but their involvement in neuropathic pain has not been well established. We demonstrated that acute and chronic administration of MPEP (mGluR5 antagonist), LY379268 (mGluR2/3 agonist), and AMN082 (mGluR7 agonist) attenuated allodynia (von Frey test) and hyperalgesia (cold plate test) as measured in Swiss albino mice on day seven after chronic constriction injury (CCI) to the sciatic nerve. Moreover, single administration of MPEP (30 mg/kg; i.p.) or LY379268 (10mg/kg; i.p.) injected 30 min before morphine potentiated morphine's effects (20mg/kg; i.p.) in the mouse CCI model, as measured by both the tests mentioned above. However, a single administration of AMN082 (3mg/kg; i.p.) potentiated the effects of a single morphine injection (20mg/kg; i.p.) in the von Frey test only. Chronic administration (7 days) of low doses of MPEP, LY379268 or AMN082 (all drugs at 3mg/kg; i.p.) potentiated the effects of single doses of morphine (3, 10, and 20mg/kg; i.p.) administered on day seven; however, AMN082 only potentiated the effect in the cold plate test. Additionally, the same doses of MPEP and LY379268 (but not AMN082) chronically co-administered with morphine (40 mg/kg; i.p.) attenuated the development of morphine tolerance in CCI-exposed mice. Our data suggest that mGluR5, mGluR2/3, and mGluR7 are involved in injury-induced plastic changes in nociceptive pathways and that the mGluR5 and mGluR2/3 ligands enhanced morphine's effectiveness in neuropathy, which could have therapeutic implications.

  4. Recent Developments in PET Instrumentation

    PubMed Central

    Peng, Hao; Levin, Craig S.

    2013-01-01

    Positron emission tomography (PET) is used in the clinic and in vivo small animal research to study molecular processes associated with diseases such as cancer, heart disease, and neurological disorders, and to guide the discovery and development of new treatments. This paper reviews current challenges of advancing PET technology and some of newly developed PET detectors and systems. The paper focuses on four aspects of PET instrumentation: high photon detection sensitivity; improved spatial resolution; depth-of-interaction (DOI) resolution and time-of-flight (TOF). Improved system geometry, novel non-scintillator based detectors, and tapered scintillation crystal arrays are able to enhance the photon detection sensitivity of a PET system. Several challenges for achieving high resolution with standard scintillator-based PET detectors are discussed. Novel detectors with 3-D positioning capability have great potential to be deployed in PET for achieving spatial resolution better than 1 mm, such as cadmium-zinc-telluride (CZT) and position-sensitive avalanche photodiodes (PSAPDs). DOI capability enables a PET system to mitigate parallax error and achieve uniform spatial resolution across the field-of-view (FOV). Six common DOI designs, as well as advantages and limitations of each design, are discussed. The availability of fast scintillation crystals such as LaBr3, and the silicon photomultiplier (SiPM) greatly advances TOF-PET development. Recent instrumentation and initial results of clinical trials are briefly presented. If successful, these technology advances, together with new probe molecules, will substantially enhance the molecular sensitivity of PET and thus increase its role in preclinical and clinical research as well as evaluating and managing disease in the clinic. PMID:20497121

  5. Radiofluorination and biological evaluation of N-aryl-oxadiazolyl-propionamides as potential radioligands for PET imaging of cannabinoid CB2 receptors

    PubMed Central

    2013-01-01

    Background The level of expression of cannabinoid receptor type 2 (CB2R) in healthy and diseased brain has not been fully elucidated. Therefore, there is a growing interest to assess the regional expression of CB2R in the brain. Positron emission tomography (PET) is an imaging technique, which allows quantitative monitoring of very low amounts of radiolabelled compounds in living organisms at high temporal and spatial resolution and, thus, has been widely used as a diagnostic tool in nuclear medicine. Here, we report on the radiofluorination of N-aryl-oxadiazolyl-propionamides at two different positions in the lead structure and on the biological evaluation of the potential of the two tracers [18F]1 and [18F]2 as CB2 receptor PET imaging agents. Results High binding affinity and specificity towards CB2 receptors of the lead structure remained unaffected by the structural changes such as the insertion of the aliphatic and aromatic fluorine in the selected labelling sites of 1 and 2. Aliphatic and aromatic radiofluorinations were optimized, and [18F]1 and [18F]2 were achieved in radiochemical yields of ≥30% with radiochemical purities of ≥98% and specific activities of 250 to 450 GBq/μmol. Organ distribution studies in female CD1 mice revealed that both radiotracers cross the blood–brain barrier (BBB) but undergo strong peripheral metabolism. At 30 min after injection, unmetabolized [18F]1 and [18F]2 accounted for 60% and 2% as well as 68% and 88% of the total activity in the plasma and brain, respectively. The main radiometabolite of [18F]2 could be identified as the free acid [18F]10, which has no affinity towards the CB1 and CB2 receptors but can cross the BBB. Conclusions N-aryl-oxadiazolyl-propionamides can successfully be radiolabelled with 18F at different positions. Fluorine substitution at these positions did not affect affinity and specificity towards CB2R. Despite a promising in vitro behavior, a rather rapid peripheral metabolism of [18F]1 and [18F

  6. Pet Therapy.

    ERIC Educational Resources Information Center

    Kavanagh, Kim

    1994-01-01

    This resource guide presents information on a variety of ways that animals can be used as a therapeutic modality with people having disabilities. Aspects addressed include: pet ownership and selection criteria; dogs (including service dogs, hearing/signal dogs, seeing leader dogs, and social/specialty dogs); horseriding for both therapy and fun;…

  7. High performance polyester concrete using recycled PET

    SciTech Connect

    Rebeiz, K.S.

    1995-10-01

    Recycled polyethylene terephthalate (PET) plastic wastes could be used in production of unsaturated polyester resins. In turn, these resins could be mixed with inorganic aggregates to produce polymer concrete (PC). Unsaturated polyesters based on recycled PET might be a potentially lower source cost of resins for producing useful PC based-products. The advantage of recycling PET in PC is that the PET materials do not have to be purified, including removal of colors, to the same extent as other PET recycling applications, which should facilitate the recycling operation and minimize its cost. The recycling of PET in PC could also help save energy and allow the long term disposal of the PET waste, an important advantage in recycling applications.

  8. Structure of a potentially open state of a proton-activated pentameric ligand-gated ion channel.

    PubMed

    Hilf, Ricarda J C; Dutzler, Raimund

    2009-01-01

    The X-ray structure of a pentameric ligand-gated ion channel from Erwinia chrysanthemi (ELIC) has recently provided structural insight into this family of ion channels at high resolution. The structure shows a homo-pentameric protein with a barrel-stave architecture that defines an ion-conduction pore located on the fivefold axis of symmetry. In this structure, the wide aqueous vestibule that is encircled by the extracellular ligand-binding domains of the five subunits narrows to a discontinuous pore that spans the lipid bilayer. The pore is constricted by bulky hydrophobic residues towards the extracellular side, which probably serve as barriers that prevent the diffusion of ions. This interrupted pore architecture in ELIC thus depicts a non-conducting conformation of a pentameric ligand-gated ion channel, the thermodynamically stable state in the absence of bound ligand. As ligand binding promotes pore opening in these ion channels and the specific ligand for ELIC has not yet been identified, we have turned our attention towards a homologous protein from the cyanobacterium Gloebacter violaceus (GLIC). GLIC was shown to form proton-gated channels that are activated by a pH decrease on the extracellular side and that do not desensitize after activation. Both prokaryotic proteins, ELIC and GLIC form ion channels that are selective for cations over anions with poor discrimination among monovalent cations, characteristics that resemble the conduction properties of the cation-selective branch of the family that includes acetylcholine and serotonin receptors. Here we present the X-ray structure of GLIC at 3.1 A resolution. The structure reveals a conformation of the channel that is distinct from ELIC and that probably resembles the open state. In combination, both structures suggest a novel gating mechanism for pentameric ligand-gated ion channels where channel opening proceeds by a change in the tilt of the pore-forming helices.

  9. Epileptic Activity Increases Cerebral Amino Acid Transport Assessed by 18F-Fluoroethyl-l-Tyrosine Amino Acid PET: A Potential Brain Tumor Mimic.

    PubMed

    Hutterer, Markus; Ebner, Yvonne; Riemenschneider, Markus J; Willuweit, Antje; McCoy, Mark; Egger, Barbara; Schröder, Michael; Wendl, Christina; Hellwig, Dirk; Grosse, Jirka; Menhart, Karin; Proescholdt, Martin; Fritsch, Brita; Urbach, Horst; Stockhammer, Guenther; Roelcke, Ulrich; Galldiks, Norbert; Meyer, Philipp T; Langen, Karl-Josef; Hau, Peter; Trinka, Eugen

    2017-01-01

    O-(2-(18)F-fluoroethyl)-l-tyrosine ((18)F-FET) PET is a well-established method increasingly used for diagnosis, treatment planning, and monitoring in gliomas. Epileptic activity, frequently occurring in glioma patients, can influence MRI findings. Whether seizures also affect (18)F-FET PET imaging is currently unknown. The aim of this retrospective analysis was to investigate the brain amino acid metabolism during epileptic seizures by (18)F-FET PET and to elucidate the pathophysiologic background.

  10. ADN-1184 a monoaminergic ligand with 5-HT6/7 receptor antagonist activity: pharmacological profile and potential therapeutic utility

    PubMed Central

    Kołaczkowski, M; Mierzejewski, P; Bieńkowski, P; Wesołowska, A; Newman-Tancredi, A

    2014-01-01

    Background and Purpose Many dementia patients exhibit behavioural and psychological symptoms (BPSD) that include psychosis, aggressivity, depression and anxiety. Antipsychotic drugs are frequently prescribed but fail to significantly attenuate mood deficits, may interfere with cognitive function and are associated with motor and cardiac side effects, which are problematic in elderly patients. A need therefore exists for drugs that are better suited for the treatment of BPSD. Experimental Approach We used in vitro cellular and in vivo behavioural tests to characterize ADN-1184, a novel arylsulfonamide ligand with potential utility for treatment of BPSD. Key Results ADN-1184 exhibits substantial 5-HT6/5-HT7/5-HT2A/D2 receptor affinity and antagonist properties in vitro. In tests of antipsychotic-like activity, it reversed MK-801-induced hyperactivity and stereotypies and inhibited conditioned avoidance response (MED = 3 mg·kg−1 i.p.). Remarkably, ADN-1184 also reduced immobility time in the forced swim test at low doses (0.3 and 1 mg·kg−1 i.p.; higher doses were not significantly active). Notably, up to 30 mg·kg−1 ADN-1184 did not impair memory performance in the passive avoidance test or elicit significant catalepsy and only modestly inhibited spontaneous locomotor activity (MED = 30 mg·kg−1 i.p.). Conclusions and Implications ADN-1184 combines antipsychotic-like with antidepressant-like properties without interfering with memory function or locomotion. This profile is better than that of commonly used atypical antipsychotics tested under the same conditions and suggests that it is feasible to identify drugs that improve BPSD, without exacerbating cognitive deficit or movement impairment, which are of particular concern in patients with dementia. PMID:24199650

  11. Characterizing the Peroxisome Proliferator-Activated Receptor (PPARγ) Ligand Binding Potential of Several Major Flame Retardants, Their Metabolites, and Chemical Mixtures in House Dust

    PubMed Central

    Fang, Mingliang; Webster, Thomas F.; Ferguson, P. Lee

    2014-01-01

    Background: Accumulating evidence has shown that some environmental contaminants can alter adipogenesis and act as obesogens. Many of these contaminants act via the activation of the peroxisome proliferator-activated receptor γ (PPARγ) nuclear receptor. Objectives: Our goal was to determine the PPARγ ligand binding potency of several major flame retardants, including polybrominated diphenyl ethers (PBDEs), halogenated phenols and bisphenols, and their metabolites. Ligand binding activity of indoor dust and its bioactivated extracts were also investigated. Methods: We used a commercially available fluorescence polarization ligand binding assay to investigate the binding potency of flame retardants and dust extracts to human PPARγ ligand-binding domain. Rosiglitazone was used as a positive control. Results: Most of the tested compounds exhibited dose-dependent binding to PPARγ. Mono(2-ethylhexyl) tetrabromophthalate, halogenated bisphenols and phenols, and hydroxylated PBDEs were found to be potent PPARγ ligands. The most potent compound was 3-OH-BDE-47, with an IC50 (concentration required to reduce effect by 50%) of 0.24 μM. The extent of halogenation and the position of the hydroxyl group strongly affected binding. In the dust samples, 21 of the 24 samples tested showed significant binding potency at a concentration of 3 mg dust equivalent (DEQ)/mL. A 3–16% increase in PPARγ binding potency was observed following bioactivation of the dust using rat hepatic S9 fractions. Conclusion: Our results suggest that several flame retardants are potential PPARγ ligands and that metabolism may lead to increased binding affinity. The PPARγ binding activity of house dust extracts at levels comparable to human exposure warrants further studies into agonistic or antagonistic activities and their potential health effects. Citation: Fang M, Webster TF, Ferguson PL, Stapleton HM. 2015. Characterizing the peroxisome proliferator-activated receptor (PPARγ) ligand binding

  12. Competitive antagonism between the nicotinic allosteric potentiating ligand galantamine and kynurenic acid at alpha7* nicotinic receptors.

    PubMed

    Lopes, Cristiane; Pereira, Edna F R; Wu, Hui-Qiu; Purushottamachar, Puranik; Njar, Vincent; Schwarcz, Robert; Albuquerque, Edson X

    2007-07-01

    Galantamine, a drug used to treat Alzheimer's disease, is a nicotinic allosteric potentiating ligand, and kynurenic acid (KYNA), a neuroactive metabolite of the kynurenine pathway, is an endogenous noncompetitive inhibitor of alpha7* nicotinic receptors (nAChRs) [the asterisk next to the nAChR subunit is intended to indicate that the exact subunit composition of the receptor is not known (Pharmacol Rev 51:397-401, 1999)]. Here, possible interactions between KYNA and galantamine at alpha7* nAChRs were examined in vitro and in vivo. In the presence of tetrodotoxin (TTX), approximately 85% of cultured hippocampal neurons responded to choline (0.3-30 mM) with alpha7* nAChR-subserved whole-cell (type IA) currents. In the absence of TTX and in the presence of glutamate receptor antagonists, choline triggered inhibitory postsynaptic currents (IPSCs) by activating alpha7* nAChRs on GABAergic neurons synapsing onto the neurons under study. Galantamine (1-10 microM) potentiated, whereas KYNA (10 nM-1 mM) inhibited, choline-triggered responses. Galantamine (1 microM), applied before KYNA, shifted to the right the concentration-response relationship for KYNA to inhibit type IA currents, increasing the IC(50) of KYNA from 13.9 +/- 8.3 to 271 +/- 131 microM. Galantamine, applied before or after KYNA, antagonized inhibition of choline-triggered IPSCs by KYNA. Local infusion of KYNA (100 nM) in the rat striatum reduced extracellular dopamine levels in vivo. This effect resulted from alpha7* nAChR inhibition and was blocked by coapplied galantamine (1-5 microM). It is concluded that galantamine competitively antagonizes the actions of KYNA on alpha7* nAChRs. Reducing alpha7* nAChR inhibition by endogenous KYNA may be an important determinant of the effectiveness of galantamine in neurological and psychiatric disorders associated with decreased alpha7* nAChR activity in the brain.

  13. Design, synthesis, characterisation and chemical reactivity of mixed-ligand platinum(II) oxadiazoline complexes with potential cytotoxic properties.

    PubMed

    Wagner, Gabriele; Marchant, Anthony; Sayer, James

    2010-09-07

    A series of mixed ligand platinum(II) oxadiazoline complexes bearing 7-nitro-1,3,5-triazaadamantane (7-NO(2)TAA) as a labile and reactive nitrogen ligand has been synthesised from easily accessible starting materials. [2+3] cycloaddition of nitrones R(1)R(2)C-N(+)(Me)O(-) to only one of the nitrile ligands in trans-[PtX(2)(PhCN)(2)] (X = Cl, Br) results in the selective formation of mono-oxadiazoline complexes trans-[PtX(2)(PhCN){N=C(Ph)-O-N(Me)-CR(1)R(2)}] from which the remaining nitrile can be replaced by 7-NO(2)TAA. The resulting complexes trans-[PtX(2)(7-NO(2)TAA) {N=C(Ph)-O-N(Me)-CR(1)R(2)}] and their precursors were characterised by elemental analysis, IR and multinuclear NMR spectroscopy.The suitability of the target complexes as anticancer agents was extrapolated from their general chemical reactivity. They are stable in DMSO, but react with thiols and undergo aquation of a chloro ligand. In the absence of a competing ligand, the coordinated 7-NO(2)TAA ligand slowly hydrolyses in an aqueous medium under release of formaldehyde, and this could induce bioactivity independent of the one typically found with platinum compounds. With nitrogen heterocycles such as pyridine a slow exchange of the 7-NO(2)TAA ligand occurs. A combined DFT/AIM study confirms the reaction observed in the experiment and predicts that other nitrogen heterocycles such as DNA nucleobases should react in the same way. Moreover, the 7-NO(2)TAA should be even more labile in an aqueous medium where protonation of the remaining amines can occur. A PM6 molecular modelling study suggests that the PtCl(oxadiazoline) fragment formed after release of one chloro and the labile 7-NO(2)TAA ligand fits well into the DNA groove and is able to form d(GpG) intrastrand crosslinks similar to the ones observed with cisplatin.

  14. Higher Pre-treatment 5-HT1A Receptor Binding Potential in Bipolar Disorder Depression is Associated with Treatment Remission: A Naturalistic Treatment Pilot PET Study

    PubMed Central

    Lan, Martin J; Hesselgrave, Natalie; Ciarleglio, Adam; Ogden, R Todd; Sullivan, Gregory M; Mann, J John; Parsey, Ramin V

    2013-01-01

    Bipolar Disorder is a major cause of disability and a high risk for suicide. The pathophysiology of the disorder remains largely unknown. Medication choice for bipolar depression patients involves trial and error. Our group reported previously that brain serotonin 1A (5HT1A) receptor binding measured by positron emission tomography (PET) is higher in bipolar depression. We now investigated whether pretreatment 5HT1A levels correlates with antidepressant medication outcome. 41 medication-free DSM-IV diagnosed, bipolar patients in a major depressive episode (MDE) had brain PET scans performed using [11C]WAY-100635 and a metabolite corrected arterial input function. The patients then received naturalistic psychopharmacologic treatment as outpatients and a follow up Hamilton Depression Rating Scale (HDRS) after 3 months of treatment. Patients with 24 item HDRS scores less than 10 were considered to have remitted. A linear mixed effects model was used to compare BPF (binding potential, proportional to the total number of available receptors) in 13 brain regions of interest between remitters and non-remitters. 34 patients completed 3 months of treatment and ratings; 9 had remitted. Remitters and non-remitters did not differ in age, sex or recent medication history with serotonergic medications. Remitters had higher [11C]WAY-100635 BPF across all brain regions compared with non-remitters (p=0.02). Higher pre-treatment brain 5HT1A receptor binding was associated with remission after 3 months of pharmacological treatment in bipolar depression. Prospective treatment studies are warranted to determine whether this test predicts outcome of specific types of treatment. PMID:23720414

  15. Higher pretreatment 5-HT1A receptor binding potential in bipolar disorder depression is associated with treatment remission: a naturalistic treatment pilot PET study.

    PubMed

    Lan, Martin J; Hesselgrave, Natalie; Ciarleglio, Adam; Ogden, R Todd; Sullivan, Gregory M; Mann, J John; Parsey, Ramin V

    2013-11-01

    Bipolar disorder is a major cause of disability and a high risk for suicide. The pathophysiology of the disorder remains largely unknown. Medication choice for bipolar depression patients involves trial and error. Our group reported previously that brain serotonin 1A (5-HT(1A)) receptor binding measured by positron emission tomography (PET) is higher in bipolar depression. We now investigated whether pretreatment 5-HT(1A) levels correlates with antidepressant medication outcome. Forty-one medication-free DSM-IV diagnosed, bipolar patients in a major depressive episode had brain PET scans performed using [(11)C]WAY-100635 and a metabolite corrected arterial input function. The patients then received naturalistic psychopharmacologic treatment as outpatients and a follow up Hamilton Depression Rating Scale (HDRS) after 3 months of treatment. Patients with 24 item HDRS scores less than 10 were considered to have remitted. A linear mixed effects model was used to compare BP(F) (binding potential, proportional to the total number of available receptors) in 13 brain regions of interest between remitters and nonremitters. Thirty-four patients completed 3 months of treatment and ratings; 9 had remitted. Remitters and nonremitters did not differ in age, sex, or recent medication history with serotonergic medications. Remitters had higher [(11)C]WAY-100635 BP(F) across all brain regions compared with nonremitters (P = 0.02). Higher pretreatment brain 5-HT(1A) receptor binding was associated with remission after 3 months of pharmacological treatment in bipolar depression. Prospective treatment studies are warranted to determine whether this test predicts outcome of specific types of treatment.

  16. PET-positive fibrous dysplasia--a potentially misleading incidental finding in a patient with intimal sarcoma of the pulmonary artery.

    PubMed

    Strobel, Klaus; Bode, Beata; Lardinois, Didier; Exner, Ulrich

    2007-06-01

    Benign bone tumors can show an increased FDG uptake in FDG-PET/CT investigations. In the presented case, an incidentally detected PET-positive asymptomatic fibrous dysplasia was initially misinterpreted as a metastasis in a patient with intimal sarcoma of the pulmonary artery.

  17. Birds Kept as Pets

    MedlinePlus

    ... Pets Pets Birds Cats Dogs Farm Animals Backyard Poultry Ferrets Fish Horses Reptiles and Amphibians Turtles Kept ... as pets can be found on the backyard poultry page. Overview Diseases Prevention More Information Boy admiring ...

  18. Mixed-metal supramolecular complexes coupling phosphine-containing Ru(II) light absorbers to a reactive Pt(II) through polyazine bridging ligands.

    PubMed

    Swavey, Shawn; Fang, Zhenglai; Brewer, Karen J

    2002-05-06

    Supramolecular bimetallic Ru(II)/Pt(II) complexes [(tpy)Ru(PEt(2)Ph)(BL)PtCl(2)](2+) and their synthons [(tpy)Ru(L)(BL)](n)()(+) (where L = Cl(-), CH(3)CN, or PEt(2)Ph; tpy = 2,2':6',2''-terpyridine; and BL = 2,2'-bipyrimidine (bpm) or 2,3-bis(2-pyridyl)pyrazine (dpp)) have been synthesized and studied by cyclic voltammetry, electronic absorption spectroscopy, mass spectral analysis, and (31)P NMR. The mixed-metal bimetallic complexes couple phosphine-containing Ru chromophores to a reactive Pt site. These complexes show how substitution of the monodentate ligand on the [(tpy)RuCl(BL)](+) synthons can tune the properties of these light absorbers (LA) and incorporate a (31)P NMR tag by addition of the PEt(2)Ph ligand. The redox potentials for the Ru(III/II) couples occur at values greater than 1.00 V versus the Ag/AgCl reference electrode and can be tuned to more positive potentials on going from Cl(-) to CH(3)CN or PEt(2)Ph (E(1/2) = 1.01, 1.55, and 1.56 V, respectively, for BL = bpm). The BL(0/-) couple at -1.03 (bpm) and -1.05 V (dpp) for [(tpy)Ru(PEt(2)Ph)(BL)](2+) shifts dramatically to more positive potentials upon the addition of the PtCl(2) moiety to -0.34 (bpm) and -0.50 V (dpp) for the [(tpy)Ru(PEt(2)Ph)(BL)PtCl(2)](2+) bridged complex. The lowest energy electronic absorption for these complexes is assigned as the Ru(d pi) --> BL(pi*) metal-to-ligand charge transfer (MLCT) transition. These MLCT transitions are tuned to higher energy in the monometallic synthons when Cl(-) is replaced by CH(3)CN or PEt(2)Ph (516, 452, and 450 nm, for BL = bpm, respectively) and to lower energy when Pt(II)Cl(2) is coordinated to the bridging ligand (560 and 506 nm for BL = bpm or dpp). This MLCT state displays a broad emission at room temperature for all the dpp systems with the [(tpy)Ru(PEt(2)Ph)(dpp)PtCl(2)](2+) system exhibiting an emission centered at 750 nm with a lifetime of 56 ns. These supramolecular complexes [(tpy)Ru(PEt(2)Ph)(BL)PtCl(2)](2+) represent the

  19. Efficiency gains in tracer identification for nuclear imaging: can in vivo LC-MS/MS evaluation of small molecules screen for successful PET tracers?

    PubMed

    Joshi, Elizabeth M; Need, Anne; Schaus, John; Chen, Zhaogen; Benesh, Dana; Mitch, Charles; Morton, Stuart; Raub, Thomas J; Phebus, Lee; Barth, Vanessa

    2014-12-17

    Positron emission tomography (PET) imaging has become a useful noninvasive technique to explore molecular biology within living systems; however, the utility of this method is limited by the availability of suitable radiotracers to probe specific targets and disease biology. Methods to identify potential areas of improvement in the ability to predict small molecule performance as tracers prior to radiolabeling would speed the discovery of novel tracers. In this retrospective analysis, we characterized the brain penetration or peak SUV (standardized uptake value), binding potential (BP), and brain exposure kinetics across a series of known, nonradiolabeled PET ligands using in vivo LC-MS/MS (liquid chromatography coupled to mass spectrometry) and correlated these parameters with the reported PET ligand performance in nonhuman primates and humans available in the literature. The PET tracers studied included those reported to label G protein-coupled receptors (GPCRs), intracellular enzymes, and transporters. Additionally, data for each tracer was obtained from a mouse brain uptake assay (MBUA), previously published, where blood-brain barrier (BBB) penetration and clearance parameters were assessed and compared against similar data collected on a broad compound set of central nervous system (CNS) therapeutic compounds. The BP and SUV identified via nonradiolabeled LC-MS/MS, while different from the published values observed in the literature PET tracer data, allowed for an identification of initial criteria values we sought to facilitate increased potential for success from our early discovery screening paradigm. Our analysis showed that successful, as well as novel, clinical PET tracers exhibited BP of greater than 1.5 and peak SUVs greater than approximately 150% at 5 min post dose in rodents. The brain kinetics appeared similar between both techniques despite differences in tracer dose, suggesting linearity across these dose ranges. The assessment of tracers in a

  20. Some metal complexes of three new potentially heptadentate (N4O3) tripodal Schiff base ligands; synthesis, characterizatin and X-ray crystal structure of a novel eight coordinate Gd(III) complex

    NASA Astrophysics Data System (ADS)

    Golbedaghi, Reza; Moradi, Somaeyh; Salehzadeh, Sadegh; Blackman, Allan G.

    2016-03-01

    The symmetrical and asymmetrical potentially heptadentate (N4O3) tripodal Schiff base ligands (H3L1-H3L3) were synthesized from the condensation reaction of three tripodal tetraamine ligands tpt (trpn), tris (3-aminopropyl) amine; ppe (abap), (2-aminoethyl)bis(3-aminopropyl)amine, and tren, tris(2-aminoethyl)amine, with 5-methoxysalicylaldehyde. Then, the reaction of Ln(III) (Ln = Gd, La and Sm), Al(III), and Fe(III) metal ions with the above ligands was investigated. The resulting compounds were characterized by IR, mass spectrometry and elemental analysis in all cases and NMR spectroscopy in the case of the Schiff base ligands. The X-ray crystal structure of the Gd complex of H3L3 ligand showed that in addition to all donor atoms of the ligand one molecule of H2O is also coordinated to the metal ion and a neutral eight-coordinate complex is formed.

  1. Synthesis of new C-25 and C-26 steroidal acids as potential ligands of the nuclear receptors DAF-12, LXR and GR.

    PubMed

    Dansey, María V; Del Fueyo, María C; Veleiro, Adriana S; Di Chenna, Pablo H

    2017-05-01

    A new methodology to obtain C-25 and C-26 steroidal acids starting from pregnenolone is described. Construction of the side chain was achieved by applying the Mukaiyama aldol reaction with a non-hydrolytic work-up to isolate the trapped silyl enol ether with higher yields. Using this methodology we synthesized three new steroidal acids as potential ligands of DAF-12, Liver X and Glucocorticoid nuclear receptors and studied their activity in reporter gene assays. Our results show that replacement of the 21-CH3 by a 20-keto group in the side chains of the cholestane scaffold of DAF-12 or Liver X receptors ligands causes the loss of the activity.

  2. Pet Problems at Home: Pet Problems in the Community.

    ERIC Educational Resources Information Center

    Soltow, Willow

    1984-01-01

    Discusses problems of pets in the community, examining the community's role related to disruptive pets and pet overpopulation. Also discusses pet problems at home, offering advice on selecting a pet, meeting a pet's needs, and disciplining pets. Includes a list of books, films/filmstrips, teaching materials, and various instructional strategies.…

  3. Functional selectivity in CB(2) cannabinoid receptor signaling and regulation: implications for the therapeutic potential of CB(2) ligands.

    PubMed

    Atwood, Brady K; Wager-Miller, James; Haskins, Christopher; Straiker, Alex; Mackie, Ken

    2012-02-01

    Receptor internalization increases the flexibility and scope of G protein-coupled receptor (GPCR) signaling. CB(1) and CB(2) cannabinoid receptors undergo internalization after sustained exposure to agonists. However, it is not known whether different agonists internalize CB(2) to different extents. Because CB(2) is a promising therapeutic target, understanding its trafficking in response to different agonists is necessary for a complete understanding of its biology. Here we profile a number of cannabinoid receptor ligands and provide evidence for marked functional selectivity of cannabinoid receptor internalization. Classic, aminoalkylindole, bicyclic, cannabilactone, iminothiazole cannabinoid, and endocannabinoid ligands varied greatly in their effects on CB(1) and CB(2) trafficking. Our most striking finding was that (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl) pyrrolo-[1,2,3-d,e]-1,4-benzoxazin-6-yl]-1-naphthalenyl-methanone (WIN55,212-2) (and other aminoalkylindoles) failed to promote CB(2) receptor internalization, whereas 5-(1,1-dimethylheptyl)-2-(5-hydroxy-2-(3-hydroxypropyl)cyclohexyl)phenol (CP55,940) robustly internalized CB(2) receptors. Furthermore, WIN55,212-2 competitively antagonized CP55,940-induced CB(2) internalization. Despite these differences in internalization, both compounds activated CB(2) receptors as measured by extracellular signal-regulated kinase 1/2 phosphorylation and recruitment of β-arrestin(2) to the membrane. In contrast, whereas CP55,940 inhibited voltage-gated calcium channels via CB(2) receptor activation, WIN55,212-2 was ineffective on its own and antagonized the effects of CP55,940. On the basis of the differences we found between these two ligands, we also tested the effects of other cannabinoids on these signaling pathways and found additional evidence for functional selectivity of CB(2) ligands. These novel data highlight that WIN55,212-2 and other cannabinoids show strong functional selectivity at CB(2

  4. The effects of sigma ligands on protein release from lacrimal acinar cells: a potential agonist/antagonist assay.

    PubMed

    Schoenwald, R D; Barfknecht, C F; Shirolkar, S; Xia, E

    1995-03-03

    Sigma receptor antagonists have been proposed as leading clinical candidates for use in various psychotic disorders. Prior to clinical testing, it is imperative that a new agent be correctly identified as an antagonist and not an agonist since the latter may worsen the psychosis. For sigma-ligands many behavioral and pharmacological assays have been developed in an attempt to classify agonist/antagonist activity. These assays evaluate a response or a behavior in an animal model that can be related to clinical efficacy. However, is the action by the presumed antagonist a consequence of sigma-receptor activity? Previously we have identified sigma-receptors in acinar cells of the main lacrimal gland of the New Zealand white rabbit and have measured protein release after the addition of various N,N-disubstituted phenylalkylamine derivatives known to be sigma-ligands by receptor binding studies. Although protein release from acinar cells has been attributed to either muscarinic or alpha-adrenergic stimulation, protein release from sigma-receptor stimulation was also confirmed. In the reported studies here, we isolated and incubated acinar cells with varying concentrations of known sigma-ligands and measured protein concentration. A knowledge of the receptor profile for the disubstituted phenylalkylamines permitted experiments to be designed in which various alpha, muscarinic, serotonergic, and dopaminergic antagonists could be added in equimolar concentrations. Under the conditions of these experiments, statistically significant increases in protein release for sigma-ligands could be attributed to stimulation of sigma-receptors. Haloperidol, an apparent sigma-antagonist, caused a statistically significant decrease in protein release and also inhibited protein release when tested with a known sigma-ligand, AF2975 [N,N-dimethyl-2-phenylethylamine]. In this system, stimulation and inhibition of protein release were defined as agonist and antagonist behavior, respectively

  5. Advances in time-of-flight PET

    PubMed Central

    Surti, Suleman; Karp, Joel S.

    2016-01-01

    This paper provides a review and an update on time-of-flight PET imaging with a focus on PET instrumentation, ranging from hardware design to software algorithms. We first present a short introduction to PET, followed by a description of TOF PET imaging and its history from the early days. Next, we introduce the current state-of-art in TOF PET technology and briefly summarize the benefits of TOF PET imaging. This is followed by a discussion of the various technological advancements in hardware (scintillators, photo-sensors, electronics) and software (image reconstruction) that have led to the current widespread use of TOF PET technology, and future developments that have the potential for further improvements in the TOF imaging performance. We conclude with a discussion of some new research areas that have opened up in PET imaging as a result of having good system timing resolution, ranging from new algorithms for attenuation correction, through efficient system calibration techniques, to potential for new PET system designs. PMID:26778577

  6. Pet allergy: how important for Turkey where there is a low pet ownership rate.

    PubMed

    Mungan, Dilşad; Celik, Gülfem; Bavbek, Sevim; Misirligil, Zeynep

    2003-01-01

    have the potential to become an important source of indoor allergens in our population. Our findings also suggest that current pet ownership--but not childhood pet keeping--seems to be a risk for the development of sensitization to pets.

  7. Pets for Handicapped Children.

    ERIC Educational Resources Information Center

    Frith, Greg H.

    1982-01-01

    Pets can provide valuable learning for handicapped children, but selection of a type of pet should consider cost, availability and care, parents' attitudes, locality, the animal's susceptibility to training, pet's life expectancy, and the child's handicap and emotional maturity. Suggested pet-related activities are listed. (CL)

  8. POTENTIAL CROSS-CONTAMINATION OF SIMILAR Giardia duodenalis ASSEMBLAGE IN CHILDREN AND PET DOGS IN SOUTHERN BRAZIL, AS DETERMINED BY PCR-RFLP.

    PubMed

    Quadros, Rosiléia Marinho de; Weiss, Paulo Henrique Exterchoter; Marques, Sandra Marcia Tietz; Miletti, Luiz Claudio

    2016-09-22

    Giardia duodenalis is an enteric parasite that has distinct genetic groups. Human infections are mainly caused by assemblages A and B, although sporadic infections by assemblages C and D have also been reported. Animals can be infected by a wide range of assemblages (A to H). The aim of this study is to identify the assemblages and sub-assemblages of G. duodenalis with zoonotic features in fecal samples of school-aged children, and in dogs that coexist in the same households in Lages, Santa Catarina, Brazil. Fecal samples of 91 children and 108 dogs were obtained and G. duodenalis cysts were detected in samples from 11 (12.08%) children and 10 (9.25%) dogs. DNA extracted from the 21 positive samples was analyzed by PCR-RFLP, using the gdh gene. Results showed the presence of sub-assemblages AI (2/11), AII (4/11), BIII (2/11), and BIV(3/11) among children and AI (5/10) and BIV(3/10) in dogs, with zoonotic characteristics, and the carnivore specific assemblage C (2/10). G. duodenalis was found to infect both children and dogs living in the same household, with the same sub-assemblage (BIV) indicating that pet dogs are a potential risk of transmission of G. duodenalis to humans.

  9. POTENTIAL CROSS-CONTAMINATION OF SIMILAR Giardia duodenalis ASSEMBLAGE IN CHILDREN AND PET DOGS IN SOUTHERN BRAZIL, AS DETERMINED BY PCR-RFLP

    PubMed Central

    de QUADROS, Rosiléia Marinho; WEISS, Paulo Henrique Exterchoter; MARQUES, Sandra Marcia Tietz; MILETTI, Luiz Claudio

    2016-01-01

    SUMMARY Giardia duodenalis is an enteric parasite that has distinct genetic groups. Human infections are mainly caused by assemblages A and B, although sporadic infections by assemblages C and D have also been reported. Animals can be infected by a wide range of assemblages (A to H). The aim of this study is to identify the assemblages and sub-assemblages of G. duodenalis with zoonotic features in fecal samples of school-aged children, and in dogs that coexist in the same households in Lages, Santa Catarina, Brazil. Fecal samples of 91 children and 108 dogs were obtained and G. duodenalis cysts were detected in samples from 11 (12.08%) children and 10 (9.25%) dogs. DNA extracted from the 21 positive samples was analyzed by PCR-RFLP, using the gdh gene. Results showed the presence of sub-assemblages AI (2/11), AII (4/11), BIII (2/11), and BIV(3/11) among children and AI (5/10) and BIV(3/10) in dogs, with zoonotic characteristics, and the carnivore specific assemblage C (2/10). G. duodenalis was found to infect both children and dogs living in the same household, with the same sub-assemblage (BIV) indicating that pet dogs are a potential risk of transmission of G. duodenalis to humans. PMID:27680171

  10. Synthesis and characterisation of new 4-oxo-N-(substituted-thiazol-2-yl)-4H-chromene-2-carboxamides as potential adenosine receptor ligands

    NASA Astrophysics Data System (ADS)

    Cagide, Fernando; Borges, Fernanda; Gomes, Ligia R.; Low, John Nicolson

    2015-06-01

    Chromones are 4H-benzopyran-4-one heterocycles that have been thoroughly studied due to their interesting biological activities. Thiazole based compounds have been used in therapeutics as antimicrobial, antiviral and as antifungal agents for a long time but, in the past decades, they have been identified as potent and selective ligands for adenosine receptor. In continuation of our project related to the syntheses of pharmacologically important heterocycles, a new series of chromone-thiazole hybrids have been designed as potential ligands for human adenosine receptors. In this context, new 4-oxo-N-(substituted-thiazol-2-yl)-4H-chromene-2-carboxamides were synthesized from chromone-2-carboxylic acid by two different amidation methods. The development of dissimilar synthetic approaches provided the possibility of working with diverse reaction conditions, namely with conventional heating and/or microwave irradiation. The structure of the compounds has been established on the basis of NMR and MS spectroscopy and X-ray crystallography. Relevant data related to the molecular geometry and conformation of the chromone-thiazole hybrids has been acquired which can be of the utmost importance to understand ligand-receptor binding.

  11. A comparative study of zwitterionic ligands-mediated mineralization and the potential of mineralized zwitterionic matrices for bone tissue engineering

    PubMed Central

    Liu, Pingsheng; Emmons, Erin

    2014-01-01

    Cationic and anionic residues of the extracellular matrices (ECM) of bone play synergistic roles in recruiting precursor ions and templating the nucleation, growth and crystalline transformations of calcium apatite in natural biomineralization. We previously reported that zwitterionic sulfobetaine ligands can template extensive 3-dimensional (3-D) hydroxyapaptite (HA)-mineralization of photo-crosslinked polymethacrylatehydrogels. Here, we compared the potency of two other major zwitterionic ligands, phosphobetaine and carboxybetaine, with that of the sulfobetaine in mediating 3-D mineralization using the crosslinked polymethacrylate hydrogel platform. We confirmed that all three zwitterionic hydrogels were able to effectively template 3-D mineralization, supporting the general ability of zwitterions to mediate templated mineralization. Among them, however, sulfobetaine and phosphobetaine hydrogels templated denser 3-D mineralizationthan the carboxybetaine hydrogel, likely due to their higher free water fractions and better maintenance of zwitterionic nature throughout the pH-changes during the in vitro mineralization process. We further demonstrated that the extensively mineralized zwitterionic hydrogels could be exploited for efficient retention (e.g. 99% retention after 24-h incubation in PBS) of osteogenic growth factor recombinant bone morphogenetic protein-2 (rhBMP-2) and subsequent sustained local release with retained bioactivity. Combined with the excellent cytocompatibility of all three zwitterionic hydrogels and the significantly improved cell adhesive properties of their mineralized matrices, these materials could find promising applications in bone tissue engineering. PMID:25558374

  12. Positron emission tomography study on pancreatic somatostatin receptors in normal and diabetic rats with {sup 68}Ga-DOTA-octreotide: A potential PET tracer for beta cell mass measurement

    SciTech Connect

    Sako, Takeo; Hasegawa, Koki; Nishimura, Mie; Kanayama, Yousuke; Wada, Yasuhiro; Hayashinaka, Emi; Cui, Yilong; Kataoka, Yosky; Senda, Michio; Watanabe, Yasuyoshi

    2013-12-06

    Highlights: •PET images showed high uptake of {sup 68}Ga-DOTA-octreotide in the normal pancreas. •{sup 68}Ga-DOTA-octreotide specifically binds to somatostatin receptors in the pancreas. •The pancreatic uptake of {sup 68}Ga-DOTA-octreotide was decreased in the diabetic rats. •{sup 68}Ga-DOTA-octreotide could be a candidate PET probe to measure the beta cell mass. -- Abstract: Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia, and the loss or dysfunction of pancreatic beta cells has been reported before the appearance of clinical symptoms and hyperglycemia. To evaluate beta cell mass (BCM) for improving the detection and treatment of DM at earlier stages, we focused on somatostatin receptors that are highly expressed in the pancreatic beta cells, and developed a positron emission tomography (PET) probe derived from octreotide, a metabolically stable somatostatin analog. Octreotide was conjugated with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), a chelating agent, and labeled with {sup 68}Gallium ({sup 68}Ga). After intravenous injection of {sup 68}Ga-DOTA-octreotide, a 90-min emission scan of the abdomen was performed in normal and DM model rats. The PET studies showed that {sup 68}Ga-DOTA-octreotide radioactivity was highly accumulated in the pancreas of normal rats and that the pancreatic accumulation was significantly reduced in the rats administered with an excess amount of unlabeled octreotide or after treatment with streptozotocin, which was used for the chemical induction of DM in rats. These results were in good agreement with the ex vivo biodistribution data. These results indicated that the pancreatic accumulation of {sup 68}Ga-DOTA-octreotide represented specific binding to the somatostatin receptors and reflected BCM. Therefore, PET imaging with {sup 68}Ga-DOTA-octreotide could be a potential tool for evaluating BCM.

  13. A potential role for the midbrain in integrating fat-free mass determined energy needs: An H2 (15) O PET study.

    PubMed

    Weise, Christopher M; Thiyyagura, Pradeep; Reiman, Eric M; Chen, Kewei; Krakoff, Jonathan

    2015-06-01

    Little is known on how sensing of energy needs is centrally represented, integrated, and translated into the behavioral aspects of energy homeostasis. Fat free mass (FFM) is the major determinant of energy expenditure. We investigated how interindividual variances in FFM relate to neuronal activity in humans. Healthy adults (n = 64, 21F/43M; age 31.3 ± 9.1y; percentage of body fat [PFAT] 25.6 ± 10.7%; BMI 30.4 ± 9) underwent a 36h fast and subsequent H(2) (15) O positron emission tomographic (PET) measurement of regional cerebral blood flow (rCBF). Multiple variable regression analysis revealed significant associations of FFM with rCBF within the midbrain [including parts of the periaqueductal gray (PAG), ventral tegmental area (VTA), thalamic and hypothalamic regions], the bilateral parahippocampal region, left anterior cingulate, left insular cortex, right cerebellum, and distinct regions within the temporal and occipital cortex. In contrast, no significant associations were found for fat mass (FM). We investigated the potential functional-anatomical link between FFM and central regulation of food intake by performing a conjunction analysis of FFM and the perceived hunger feelings. This showed a significant overlap within the midbrain PAG. Mediation analysis demonstrated a significant indirect effect of FFM on hunger with PAG rCBF as mediator. Most regions we found to be associated with FFM form part in ascending homeostatic pathways and cortical circuitries implicated in the regulation of basic bodily functions indicating a potential role of these central networks in the integration of FFM determined energy needs.

  14. A fast, open source implementation of adaptive biasing potentials uncovers a ligand design strategy for the chromatin regulator BRD4

    NASA Astrophysics Data System (ADS)

    Dickson, Bradley M.; de Waal, Parker W.; Ramjan, Zachary H.; Xu, H. Eric; Rothbart, Scott B.

    2016-10-01

    In this communication we introduce an efficient implementation of adaptive biasing that greatly improves the speed of free energy computation in molecular dynamics simulations. We investigated the use of accelerated simulations to inform on compound design using a recently reported and clinically relevant inhibitor of the chromatin regulator BRD4 (bromodomain-containing protein 4). Benchmarking on our local compute cluster, our implementation achieves up to 2.5 times more force calls per day than plumed2. Results of five 1 μs-long simulations are presented, which reveal a conformational switch in the BRD4 inhibitor between a binding competent and incompetent state. Stabilization of the switch led to a -3 kcal/mol improvement of absolute binding free energy. These studies suggest an unexplored ligand design principle and offer new actionable hypotheses for medicinal chemistry efforts against this druggable epigenetic target class.

  15. A fast, open source implementation of adaptive biasing potentials uncovers a ligand design strategy for the chromatin regulator BRD4.

    PubMed

    Dickson, Bradley M; de Waal, Parker W; Ramjan, Zachary H; Xu, H Eric; Rothbart, Scott B

    2016-10-21

    In this communication we introduce an efficient implementation of adaptive biasing that greatly improves the speed of free energy computation in molecular dynamics simulations. We investigated the use of accelerated simulations to inform on compound design using a recently reported and clinically relevant inhibitor of the chromatin regulator BRD4 (bromodomain-containing protein 4). Benchmarking on our local compute cluster, our implementation achieves up to 2.5 times more force calls per day than plumed2. Results of five 1 μs-long simulations are presented, which reveal a conformational switch in the BRD4 inhibitor between a binding competent and incompetent state. Stabilization of the switch led to a -3 kcal/mol improvement of absolute binding free energy. These studies suggest an unexplored ligand design principle and offer new actionable hypotheses for medicinal chemistry efforts against this druggable epigenetic target class.

  16. [Innovation and Future Technologies for PET Scanners].

    PubMed

    Yamaya, Taiga

    2015-01-01

    Positron emission tomography (PET) plays important roles in cancer diagnosis, neuroimaging and molecular imaging research; but potential points remain for which big improvements could be made, including spatial resolution, sensitivity and manufacturing costs. Higher spatial resolution is essential to enable earlier diagnosis, and improved sensitivity results in reduced radiation exposure and shortened measurement time. Therefore, research on next generation PET technologies remains a hot topic worldwide. In this paper, innovation and future technologies for the next generation PET scanners, such as time-of-flight measurement and simultaneous PET/MRI measurement, are described. Among them, depth-of-interaction (DOI) measurement in the radiation sensor will be a key technology to get any significant improvement in sensitivity while maintaining high spatial resolution. DOI measurement also has a potential to expand PET application fields because it allows for more flexible detector arrangement. As an example, the world's first, open-type PET geometry "OpenPET", which is expected to lead to PET imaging during treatment, is under development. The DOI detector itself continues to evolve with the help of recently developed semiconductor photodetectors, often referred to as silicon photomultipliers.

  17. LigandRNA: computational predictor of RNA-ligand interactions.

    PubMed

    Philips, Anna; Milanowska, Kaja; Lach, Grzegorz; Bujnicki, Janusz M

    2013-12-01

    RNA molecules have recently become attractive as potential drug targets due to the increased awareness of their importance in key biological processes. The increase of the number of experimentally determined RNA 3D structures enabled structure-based searches for small molecules that can specifically bind to defined sites in RNA molecules, thereby blocking or otherwise modulating their function. However, as of yet, computational methods for structure-based docking of small molecule ligands to RNA molecules are not as well established as analogous methods for protein-ligand docking. This motivated us to create LigandRNA, a scoring function for the prediction of RNA-small molecule interactions. Our method employs a grid-based algorithm and a knowledge-based potential derived from ligand-binding sites in the experimentally solved RNA-ligand complexes. As an input, LigandRNA takes an RNA receptor file and a file with ligand poses. As an output, it returns a ranking of the poses according to their score. The predictive power of LigandRNA favorably compares to five other publicly available methods. We found that the combination of LigandRNA and Dock6 into a "meta-predictor" leads to further improvement in the identification of near-native ligand poses. The LigandRNA program is available free of charge as a web server at http://ligandrna.genesilico.pl.

  18. Potentiation of the teratogenic effects induced by coadministration of retinoic acid or phytanic acid/phytol with synthetic retinoid receptor ligands.

    PubMed

    Elmazar, M M A; Nau, H

    2004-11-01

    Previous studies in our laboratory identified retinoid-induced defects that are mediated by RAR-RXR heterodimerization using interaction of synthetic ligands selective for the retinoid receptors RAR and RXR in mice (Elmazar et al. 1997, Toxicol Appl Pharmacol 146:21-28; Elmazar et al. 2001, Toxicol Appl Pharmacol 170:2-9; Nau and Elmazar 1999, Handbook of experimental pharmacology, vol 139, Retinoids, Springer-Verlag, pp 465-487). The present study was designed to investigate whether these RAR-RXR heterodimer-mediated defects can be also induced by interactions of natural and synthetic ligands for retinoid receptors. A non-teratogenic dose of the natural RXR agonist phytanic acid (100 mg/kg orally) or its precursor phytol (500 mg/kg orally) was coadministered with a synthetic RARalpha-agonist (Am580; 5 mg/kg orally) to NMRI mice on day 8.25 of gestation (GD8.25). Furthermore, a non-teratogenic dose of the synthetic RXR agonist LGD1069 (20 mg/kg orally) was also coadministered with the natural RAR agonist, all- trans-retinoic acid (atRA, 20 mg/kg orally) or its precursor retinol (ROH, 50 mg/kg orally) to NMRI mice on GD8.25. The teratogenic outcome was scored in day-18 fetuses. The incidence of Am580-induced resorptions, spina bifida aperta, micrognathia, anotia, kidney hypoplasia, dilated bladder, undescended testis, atresia ani, short and absent tail, fused ribs and fetal weight retardation were potentiated by coadministration of phytanic acid or its precursor phytol. Am580-induced exencephaly and cleft palate, which were not potentiated by coadministration with the synthetic RXR agonists, were also not potentiated by coadministration with either phytanic acid or its precursor phytol. LGD1069 potentiated atRA- and ROH-induced resorption, exencephaly, spina bifida, aperta, ear anotia and microtia, macroglossia, kidney hypoplasia, undescended testis, atresia ani, tail defects and fetal weight retardation, but not cleft palate. These results suggest that synergistic

  19. Association between the use of surveillance PET/CT and the detection of potentially salvageable occult recurrences among patients with resected high-risk melanoma.

    PubMed

    Leon-Ferre, Roberto A; Kottschade, Lisa A; Block, Matthew S; McWilliams, Robert R; Dronca, Roxana S; Creagan, Edward T; Allred, Jacob B; Lowe, Val J; Markovic, Svetomir N

    2017-03-14

    The optimal surveillance for patients with resected high-risk melanoma is controversial. Select locoregional or oligometastatic recurrences can be cured with salvage resection. Data on the ability of PET/CT to detect such recurrences are sparse. We evaluated whether surveillance PET/CT in patients with resected stage III-IV melanoma led to detection of clinically occult recurrences amenable to curative-intent salvage treatment. We retrospectively identified 1429 melanoma patients who underwent PET/CT between January 2008 and October 2012 at Mayo Clinic (Rochester, Minnesota). A total of 1130 were excluded because of stage I-II, ocular or mucosal melanoma, incomplete resection, PET/CT not performed for surveillance or performed at a different institution, and records not available. A total of 299 patients were eligible. Overall, 162 (52%) patients developed recurrence [locoregional: 77 (48%), distant: 85 (52%)]. The first recurrence was clinically occult in 98 (60%) and clinically evident in 64 (40%). Clinically evident recurrences were more often superficial (skin, subcutaneous, or nodal) or in the brain, whereas clinically occult recurrences more often visceral. Overall, 90% of all recurrences were detected by 2.8 years. In all, 70% of patients with recurrence underwent curative-intent salvage treatment (locoregional: 94%, distant: 48%), with similar rates for clinically occult versus clinically evident recurrences (66 vs. 75%, P=0.240). Overall survival was superior among those who underwent curative-intent salvage treatment [5.9 vs. 1.2 years; hazard ratio=4.27, 95% confidence interval (CI)=2.68-6.80; P<0.001], despite 79% developing recurrence again. PET/CT had high sensitivity (88%, 95% CI=79.94-93.31%), specificity (90%, 95% CI=88.56-91.56%), and negative predictive value (99%, 95% CI=98.46-99.52%). However, the positive predictive value was only 37% (95% CI=31.32-43.68%). In patients with resected stage III-IV melanoma, surveillance PET/CT detected a large

  20. DNA detection and genotypic identification of potentially human-pathogenic microsporidia from asymptomatic pet parrots in South Korea as a risk factor for zoonotic emergence.

    PubMed

    Lee, So-Young; Lee, Sung-Seok; Lyoo, Young S; Park, Hee-Myung

    2011-12-01

    We detected and identified genotypes of human-pathogenic microsporidia in fecal samples from 51 asymptomatic captive-bred pet parrots in South Korea. Microsporidia were identified in 8 samples (15.7%); 7 parrots tested positive for Encephalitozoon hellem, and 1 parrot tested positive for both E. hellem and Encephalitozoon cuniculi. In genotypic identifications, E. hellem was present in genotypes 1A and 2B and E. cuniculi was present in genotype II. Pet parrots might be a source of human microsporidian infection.

  1. DNA Detection and Genotypic Identification of Potentially Human-Pathogenic Microsporidia from Asymptomatic Pet Parrots in South Korea as a Risk Factor for Zoonotic Emergence ▿

    PubMed Central

    Lee, So-Young; Lee, Sung-Seok; Lyoo, Young S.; Park, Hee-Myung

    2011-01-01

    We detected and identified genotypes of human-pathogenic microsporidia in fecal samples from 51 asymptomatic captive-bred pet parrots in South Korea. Microsporidia were identified in 8 samples (15.7%); 7 parrots tested positive for Encephalitozoon hellem, and 1 parrot tested positive for both E. hellem and Encephalitozoon cuniculi. In genotypic identifications, E. hellem was present in genotypes 1A and 2B and E. cuniculi was present in genotype II. Pet parrots might be a source of human microsporidian infection. PMID:21965400

  2. Pet RX: Implications for Good Health.

    ERIC Educational Resources Information Center

    Wilkes, C. Newton; And Others

    1989-01-01

    Studies reveal that potential health values exist in use of pets in the rehabilitation process. Animal therapy can be a salutary form of rehabilitation if the program is organized, supervised, and implemented in a professional manner. (JD)

  3. PET/MRI – Technical Review

    PubMed Central

    Muzic, Raymond F.; DiFilippo, Frank P.

    2015-01-01

    PET/MR is a hybrid imaging technology with the potential to combine the molecular and functional information of PET with the soft-tissue contrast of MR. Herein we review the technical features and challenges of putting these different technologies together. We emphasize the conceptual to make the material accessible to a wide audience. We begin by reviewing PET/CT, a more mature multi-modality imaging technology, to provide a basis for comparison to the history of PET/MR development. We discuss the motivation and challenges of PET/MR and different approaches that have been used to meet the challenges. We conclude with a speculation about the future of this exciting imaging method. PMID:25497909

  4. Autocrine regulation of stomatal differentiation potential by EPF1 and ERECTA-LIKE1 ligand-receptor signaling

    PubMed Central

    Qi, Xingyun; Han, Soon-Ki; Dang, Jonathan H; Garrick, Jacqueline M; Ito, Masaki; Hofstetter, Alex K; Torii, Keiko U

    2017-01-01

    Development of stomata, valves on the plant epidermis for optimal gas exchange and water control, is fine-tuned by multiple signaling peptides with unique, overlapping, or antagonistic activities. EPIDERMAL PATTERNING FACTOR1 (EPF1) is a founding member of the secreted peptide ligands enforcing stomatal patterning. Yet, its exact role remains unclear. Here, we report that EPF1 and its primary receptor ERECTA-LIKE1 (ERL1) target MUTE, a transcription factor specifying the proliferation-to-differentiation switch within the stomatal cell lineages. In turn, MUTE directly induces ERL1. The absolute co-expression of ERL1 and MUTE, with the co-presence of EPF1, triggers autocrine inhibition of stomatal fate. During normal stomatal development, this autocrine inhibition prevents extra symmetric divisions of stomatal precursors likely owing to excessive MUTE activity. Our study reveals the unexpected role of self-inhibition as a mechanism for ensuring proper stomatal development and suggests an intricate signal buffering mechanism underlying plant tissue patterning. DOI: http://dx.doi.org/10.7554/eLife.24102.001 PMID:28266915

  5. Analogs of LDL Receptor Ligand Motifs in Dengue Envelope and Capsid Proteins as Potential Codes for Cell Entry.

    PubMed

    Guevara, Juan; Romo, Jamie; McWhorter, Troy; Guevara, Natalia Valentinova

    It is established that cell entry of low density lipoprotein particles (LLPs) containing Apo B100 and Apo E is mediated by receptors and GAGs. Receptor ligand motifs, XBBBXXBX, XBBXBX, and ΨBΨXB, and mono- and bipartite NLS sequences are abundant in Apo E and Apo B100 as well as in envelope and capsid proteins of Dengue viruses 1-4 (DENV1-4). Synthetic, fluorescence-labeled peptides of sequences in DENV2 envelope protein, and DENV3 capsid that include these motifs were used to conduct a qualitative assessment of cell binding and entry capacity using HeLa cells. DENV2 envelope peptide, Dsp2EP, (0564)Gly-Gly(0595), was shown to bind and remain at the cell surface. In contrast, DENV3 capsid protein peptide, Dsp3CP, (0002)Asn-Gln(0028), readily enters HeLa cells and accumulates at discrete loci in the nucleus. FITC-labeled dengue synthetic peptides colocalize with Low Density Lipoprotein-CM-DiI and Apo E-CM-DiI to a degree that suggests that Dengue viruses may utilize cell entry pathways used by LLPs.

  6. Analogs of LDL Receptor Ligand Motifs in Dengue Envelope and Capsid Proteins as Potential Codes for Cell Entry

    PubMed Central

    Guevara, Juan; Romo, Jamie; McWhorter, Troy; Guevara, Natalia Valentinova

    2016-01-01

    It is established that cell entry of low density lipoprotein particles (LLPs) containing Apo B100 and Apo E is mediated by receptors and GAGs. Receptor ligand motifs, XBBBXXBX, XBBXBX, and ΨBΨXB, and mono- and bipartite NLS sequences are abundant in Apo E and Apo B100 as well as in envelope and capsid proteins of Dengue viruses 1–4 (DENV1–4). Synthetic, fluorescence-labeled peptides of sequences in DENV2 envelope protein, and DENV3 capsid that include these motifs were used to conduct a qualitative assessment of cell binding and entry capacity using HeLa cells. DENV2 envelope peptide, Dsp2EP, 0564Gly-Gly0595, was shown to bind and remain at the cell surface. In contrast, DENV3 capsid protein peptide, Dsp3CP, 0002Asn-Gln0028, readily enters HeLa cells and accumulates at discrete loci in the nucleus. FITC-labeled dengue synthetic peptides colocalize with Low Density Lipoprotein-CM-DiI and Apo E-CM-DiI to a degree that suggests that Dengue viruses may utilize cell entry pathways used by LLPs. PMID:27123468

  7. PET/MRI and PET/MRI/SISCOM coregistration in the presurgical evaluation of refractory focal epilepsy.

    PubMed

    Fernández, S; Donaire, A; Serès, E; Setoain, X; Bargalló, N; Falcón, C; Sanmartí, F; Maestro, I; Rumià, J; Pintor, L; Boget, T; Aparicio, J; Carreño, M

    2015-03-01

    We aimed to investigate the usefulness of coregistration of positron emission tomography (PET) and magnetic resonance imaging (MRI) findings (PET/MRI) and of coregistration of PET/MRI with subtraction ictal single-photon emission computed tomography (SPECT) coregistered to MRI (SISCOM) (PET/MRI/SISCOM) in localizing the potential epileptogenic zone in patients with drug-resistant epilepsy. We prospectively included 35 consecutive patients with refractory focal epilepsy whose presurgical evaluation included a PET study. Separately acquired PET and structural MRI images were coregistered for each patient. When possible, ictal SPECT and SISCOM were obtained and coregistered with PET/MRI. The potential location of the epileptogenic zone determined by neuroimaging was compared with the seizure onset zone determined by long-term video-EEG monitoring and with invasive EEG studies in patients who were implanted. Structural MRI showed no lesions in 15 patients. In these patients, PET/MRI coregistration showed a hypometabolic area in 12 (80%) patients that was concordant with seizure onset zone on EEG in 9. In 7 patients without MRI lesions, PET/MRI detected a hypometabolism that was undetected on PET alone. SISCOM, obtained in 25 patients, showed an area of hyperperfusion concordant with the seizure onset zone on EEG in 7 (58%) of the 12 of these patients who had normal MRI findings. SISCOM hyperperfusion was less extensive than PET hypometabolism. A total of 19 patients underwent surgery; 11 of these underwent invasive-EEG monitoring and the seizure onset zone was concordant with PET/MRI in all cases. PET/MRI/SISCOM coregistration, performed in 4 of these patients, was concordant in 3 (75%). After epilepsy surgery, 13 (68%) patients are seizure-free after a mean follow-up of 4.5 years. PET/MRI and PET/MRI/SISCOM coregistration are useful for determining the potential epileptogenic zone and thus for planning invasive EEG studies and surgery more precisely, especially in

  8. Synthesis, Characterization, and Biological Studies of a Piperidinyl Appended Dipicolylamine Ligand and Its Rhenium Tricarbonyl Complex as Potential Therapeutic Agents for Human Breast Cancer

    PubMed Central

    Subasinghe, Amali; Perera, Inoka C.; Pakhomova, Svetlana

    2016-01-01

    A novel ligand bearing a central piperidinyl sulfonamide group, N(SO2pip)dpa, and its corresponding Re tricarbonyl complex, [Re(CO)3(N(SO2pip)dpa)]+, have been synthesized in good yield. The methylene CH2 signal seen as a singlet (4.54 ppm) in a 1H NMR spectrum of the ligand in DMSO-d6 appears as two doublets (5.39, 5.01 ppm) in a spectrum of the [Re(CO)3(N(SO2pip)dpa)]+ complex and confirms the presence of magnetically nonequivalent protons upon coordination to Re. Structural results revealed that the Re–N bond lengths fall within the normal range establishing coordination of ligand to metal. The presence of intraligand π → π⁎ and n → π⁎ transitions is indicated by the absorption peaks around 200–250 nm in UV-visible spectra. Absorption peaks in UV-visible spectra around 300 nm for metal complexes were identified as MLCT transitions. The S–N stretch observed as a strong peak at 923 cm−1 for N(SO2pip)dpa appeared at a shorter frequency, at 830 cm−1 in an FTIR spectrum of the [Re(CO)3(N(SO2pip)dpa)]+. The intense fluorescence displayed by the N(SO2pip)dpa ligand has quenched upon coordination to Re. Relatively low IC50 values given by human breast cancer cells, MCF-7, (N(SO2pip)dpa = 139 μM, [Re(CO)3(N(SO2pip)dpa)]+ = 360 μM) indicate that N(SO2pip)dpa and [Re(CO)3(N(SO2pip)dpa)]+ are promising novel compounds that can be further investigated on their usage as potential anticancer agents. PMID:27847444

  9. PET Radiotracers of the Cardiovascular System.

    PubMed

    Gropler, Robert J

    2009-01-01

    Cardiovascular PET provides exquisite measurements of key aspects of the cardiovascular system and as a consequence it plays central role in cardiovascular investigation. Moreover, PET is now playing an ever increasing role in the management of the cardiac patient. Central to the success of PET is the development and use of novel radiotracers that permit measurements of key aspects of cardiovascular health such as myocardial perfusion, metabolism, and neuronal function. Moreover, the development of molecular imaging radiotracers is now permitting the interrogation of cellular and sub cellular processes. This article highlights these various radiotracers and their role in both cardiovascular research and potential clinical applications.

  10. α-Tocopherols modify the membrane dipole potential leading to modulation of ligand binding by P-glycoprotein.

    PubMed

    Davis, Sterenn; Davis, Benjamin M; Richens, Joanna L; Vere, Kelly-Ann; Petrov, Peter G; Winlove, C Peter; O'Shea, Paul

    2015-08-01

    α-Tocopherol (vitamin E) has attracted considerable attention as a potential protective or palliative agent. In vitro, its free radical-scavenging antioxidant action has been widely demonstrated. In vivo, however, vitamin E treatment exhibits negligible benefits against oxidative stress. α-Tocopherol influences lipid ordering within biological membranes and its derivatives have been suggested to inhibit the multi-drug efflux pump, P-glycoprotein (P-gp). This study employs the fluorescent membrane probe, 1-(3-sulfonatopropyl)-4-[β[2-(di-n-octylamino)-6-naphthyl]vinyl] pyridinium betaine, to investigate whether these effects are connected via influences on the membrane dipole potential (MDP), an intrinsic property of biological membranes previously demonstrated to modulate P-gp activity. α-Tocopherol and its non-free radical-scavenging succinate analog induced similar decreases in the MDP of phosphatidylcholine vesicles. α-Tocopherol succinate also reduced the MDP of T-lymphocytes, subsequently decreasing the binding affinity of saquinavir for P-gp. Additionally, α-tocopherol succinate demonstrated a preference for cholesterol-treated (membrane microdomain enriched) cells over membrane cholesterol-depleted cells. Microdomain disruption via cholesterol depletion decreased saquinavir's affinity for P-gp, potentially implicating these structures in the influence of α-tocopherol succinate on P-gp. This study provides evidence of a microdomain dipole potential-dependent mechanism by which α-tocopherol analogs influence P-gp activity. These findings have implications for the use of α-tocopherol derivatives for drug delivery across biological barriers.

  11. Measurements and Modeling To Determine the Reduction Potential of Uncomplexed Bi(III) in Nitrate Solutions for Application in Bi(III)-Ligand Equilibria Studies by Voltammetry.

    PubMed

    Billing, Caren; Cukrowski, Ignacy

    2016-05-12

    The free metal ion potential, E(M), is a critical parameter in the calculation of formation constants when using voltammetry. When studying complex formation of Bi(III), however, E(Bi) cannot be directly measured. In this work a nitrate background electrolyte was employed to obtain reversible reduction waves. To determine E(Bi), measurements have to be made below pH ∼ 2 before the bismuth-oxy-nitrate species precipitates and thus corrections for the diffusion junction potential (monitored using Tl(I) as an internal reference ion) must be made. Additionally shifts in potential due to both Bi(III) hydrolysis and Bi(III) nitrate formation must also be compensated for before E(Bi) can be evaluated. The value of E(Bi) was determined relative to E(Tl) so that in an experiments where ligand is added to determine formation constants, E(Bi) can be determined as accurately as possible (since E(Tl) can generally still be measured). The value of E(Bi) - E(Tl) was found to be 495.6 ± 1.4 mV for the conditions employed.

  12. Pet-Related Infections.

    PubMed

    Day, Michael J

    2016-11-15

    Physicians and veterinarians have many opportunities to partner in promoting the well-being of people and their pets, especially by addressing zoonotic diseases that may be transmitted between a pet and a human family member. Common cutaneous pet-acquired zoonoses are dermatophytosis (ringworm) and sarcoptic mange (scabies), which are both readily treated. Toxoplasmosis can be acquired from exposure to cat feces, but appropriate hygienic measures can minimize the risk to pregnant women. Persons who work with animals are at increased risk of acquiring bartonellosis (e.g., cat-scratch disease); control of cat fleas is essential to minimize the risk of these infections. People and their pets share a range of tick-borne diseases, and exposure risk can be minimized with use of tick repellent, prompt tick removal, and appropriate tick control measures for pets. Pets such as reptiles, amphibians, and backyard poultry pose a risk of transmitting Salmonella species and are becoming more popular. Personal hygiene after interacting with these pets is crucial to prevent Salmonella infections. Leptospirosis is more often acquired from wildlife than infected dogs, but at-risk dogs can be protected with vaccination. The clinical history in the primary care office should routinely include questions about pets and occupational or other exposure to pet animals. Control and prevention of zoonoses are best achieved by enhancing communication between physicians and veterinarians to ensure patients know the risks of and how to prevent zoonoses in themselves, their pets, and other people.

  13. Clinical Utility and Future Applications of PET/CT and PET/CMR in Cardiology

    PubMed Central

    Pan, Jonathan A.; Salerno, Michael

    2016-01-01

    Over the past several years, there have been major advances in cardiovascular positron emission tomography (PET) in combination with either computed tomography (CT) or, more recently, cardiovascular magnetic resonance (CMR). These multi-modality approaches have significant potential to leverage the strengths of each modality to improve the characterization of a variety of cardiovascular diseases and to predict clinical outcomes. This review will discuss current developments and potential future uses of PET/CT and PET/CMR for cardiovascular applications, which promise to add significant incremental benefits to the data provided by each modality alone. PMID:27598207

  14. Potential therapeutic application of dendrimer/cyclodextrin conjugates with targeting ligands as advanced carriers for gene and oligonucleotide drugs.

    PubMed

    Arima, Hidetoshi; Motoyama, Keiichi; Higashi, Taishi

    2017-04-01

    Despite the recent approval of some gene medicines and nucleic acid drugs, further improvement of delivery techniques for these drugs is strongly required. Several delivery technologies for these drugs have been developed, in other words, viral and two types of nonviral (lipofection and polyfection) vectors. Among the polyfection system, the potential use of various cyclodextrin (CyD) derivatives and CyD-appended polymers as carriers for gene and nucleic acid drugs has been demonstrated. The polyamidoamine dendrimer (G3) conjugates with α-CyD (α-CDE (G3)) have been reported to possess noteworthy properties as DNA and nucleic acid drugs carriers. This review will focus on the attempts to develop such cell-specific drug carriers by preparing polyethylene glycol, galactose, lactose, mannose, fucose and folic acid-appended α-CDEs as tissue and cell-selective carriers of gene and nucleic acid drugs.

  15. Personalizing NSCLC therapy by characterizing tumors using TKI-PET and immuno-PET.

    PubMed

    Bahce, I; Yaqub, M; Smit, E F; Lammertsma, A A; van Dongen, G A M S; Hendrikse, N H

    2016-05-31

    Non-small cell lung cancer (NSCLC) therapy has entered a rapidly advancing era of precision medicine with an ever increasing number of drugs directed against a variety of specific tumor targets. Amongst these new agents, tyrosine kinase inhibitors (TKIs) and monoclonal antibodies (mAbs) are most frequently used. However, as only a sensitive subgroup of patients benefits from targeting drugs, predictive biomarkers are needed. Positron emission tomography (PET) may offer such a biomarker for predicting therapy efficacy. Some of the TKIs and mAbs that are in clinical use can be radioactively labeled and used as tracers. PET can visualize and quantify tumor specific uptake of radiolabeled targeting drugs, allowing for characterization of their pharmacokinetic behavior. In this review, the clinical potential of PET using radiolabeled TKIs (TKI-PET) and mAbs (immuno-PET) in NSCLC is discussed, and an overview is provided of the most relevant preclinical and clinical studies.

  16. Synthesis of high affinity fluorine-substituted ligands for the androgen receptor. Potential agents for imaging prostatic cancer by positron emission tomography.

    PubMed

    Liu, A; Carlson, K E; Katzenellenbogen, J A

    1992-05-29

    We have prepared nine androgens substituted with fluorine at C-16 or C-20 to evaluate their potential, as positron emission tomographic (PET) imaging agents for prostatic cancer when labeled with the positron emitting radionuclide fluorine-18 (t1/2 = 110 min). These compounds represent members from the following classes of androgens: testosterone (T), 5 alpha-dihydrotestosterone (DHT), 7 alpha-methyl-19-nortestosterone (MNT), mibolerone (Mib), and metribolone (R1881). All of these compounds were prepared by functionalization of suitable androgen precursors, and the synthetic routes were developed to allow the introduction of fluorine by a fluoride ion displacement reaction late in the synthesis, as is required for the preparation of these compounds in fluorine-18 labeled form. We have also prepared four androgens in which the C-3 carbonyl or 17 beta-hydroxyl groups are replaced by fluorine. Most of the fluorine-substituted androgens show high affinity for the androgen receptor (AR), although fluorine substitution lowers their affinity by a small factor. None of the androgens where fluorine replaces oxygen functions at C-3 or C-17 have substantial affinity for AR. Derivatives of the natural androgens (T and DHT) as well as MNT have little affinity for other steroid hormone receptors (progesterone and mineralocorticoid receptors), whereas the Mib and R1881 derivatives have somewhat greater heterologous binding. With sex steroid binding protein, a human serum binding protein, the pattern of binding affinities is nearly the reverse, with derivatives of Mib, R1881 and MNT having low affinity, and DHT and T, high affinity. From these fluorine-substituted compounds, we can select several whose preparation in fluorine-18 labeled form for further tissue distribution studies is merited.

  17. Down-regulation of protein kinase Ceta potentiates the cytotoxic effects of exogenous tumor necrosis factor-related apoptosis-inducing ligand in PC-3 prostate cancer cells.

    PubMed

    Sonnemann, Jürgen; Gekeler, Volker; Sagrauske, Antje; Müller, Cornelia; Hofmann, Hans-Peter; Beck, James F

    2004-07-01

    Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a highly promising candidate for the treatment of cancer because it elicits cell death in the majority of tumor cells while sparing most normal cells. Some cancers, however, display resistance to TRAIL, suggesting that treatment with TRAIL alone may be insufficient for cancer therapy. In the present study, we explored whether the apoptotic responsiveness of PC-3 prostate cancer cells to TRAIL could be enhanced by targeting the novel protein kinase C (PKC) isoform eta. Transfection of PC-3 cells with second-generation chimeric antisense oligonucleotides against PKCeta caused a time- and dose-dependent knockdown of PKCeta, as revealed by real-time RT-PCR and Western blot analyses. Knockdown of PKCeta resulted in a marked amplification of TRAIL's cytotoxic activity. Cell killing could be substantially prevented by the pan-caspase inhibitor z-VAD-fmk. In addition, PKCeta knockdown and administration of TRAIL significantly synergized in activation of caspase-3 and internucleosomal DNA fragmentation. Knockdown of PKCeta augmented TRAIL-induced dissipation of the mitochondrial transmembrane potential and release of cytochrome c from mitochondria into the cytosol, indicating that PKCeta acts upstream of mitochondria. We conclude that PKCeta represents a considerable resistance factor with respect to TRAIL and a promising target to exploit the therapeutic potential of TRAIL.

  18. In vitro and ex vivo evaluation of cyclic aminoalkyl benzilates as potential emission tomography ligands for the muscarinic receptor.

    PubMed

    Otto, C A; Mulholland, G K; Perry, S E; Combs, R; Sherman, P S; Fisher, S J

    1989-01-01

    A series of muscarinic antagonists were screened as potential receptor imaging agents. (+)2 alpha-tropanyl benzilate (TRB), N-methyl-4-piperidyl benzilate (NMPB) and several analogs amenable to labeling with positron emitting isotopes were evaluated for muscarinic binding to mouse brain tissue in vitro and ex vivo using [3H]quinuclidinyl benzilate as the probe. The in vitro assay directly compared the innate binding affinities of the compounds. The rank order of binding (IC50) was TRB (0.7 nm), QNB (0.8 nm), scopolamine (1.3 nm) and NMPB (1.6 nm). The ex vivo assay was used to gain information regarding the pharmacokinetics and brain penetration of the compounds in live animals. Ex vivo results demonstrated that TRB was rapidly taken up into the brain and was equipotent with QNB in occupying muscarinic binding sites at early time points, but TRB binding decreased twice as fast over time as QNB binding. The results suggest TRB would be a good candidate for radiolabeling and further study.

  19. Gold Nanorods Conjugated with Doxorubicin and cRGD for Combined Anticancer Drug Delivery and PET Imaging

    PubMed Central

    Xiao, Yuling; Hong, Hao; Matson, Vyara Z.; Javadi, Alireza; Xu, Wenjin; Yang, Yunan; Zhang, Yin; Engle, Jonathan W.; Nickles, Robert J.; Cai, Weibo; Steeber, Douglas A.; Gong, Shaoqin

    2012-01-01

    A multifunctional gold nanorod (GNR)-based nanoplatform for targeted anticancer drug delivery and positron emission tomography (PET) imaging of tumors was developed and characterized. An anti-cancer drug (i.e., doxorubicin (DOX)) was covalently conjugated onto PEGylated (PEG: polyethylene glycol) GNR nanocarriers via a hydrazone bond to achieve pH-sensitive controlled drug release. Tumor-targeting ligands (i.e., the cyclo(Arg-Gly-Asp-D-Phe-Cys) peptides, cRGD) and 64Cu-chelators (i.e., 1,4,7-triazacyclononane-N, N', N''-triacetic acid (NOTA)) were conjugated onto the distal ends of the PEG arms to achieve active tumor-targeting and PET imaging, respectively. Based on flow cytometry analysis, cRGD-conjugated nanocarriers (i.e., GNR-DOX-cRGD) exhibited a higher cellular uptake and cytotoxicity than non-targeted ones (i.e., GNR-DOX) in vitro. However, GNR-DOX-cRGD and GNR-DOX nanocarriers had similar in vivo biodistribution according to in vivo PET imaging and biodistribution studies. Due to the unique optical properties of GNRs, this multifunctional GNR-based nanoplatform can potentially be optimized for combined cancer therapies (chemotherapy and photothermal therapy) and multimodality imaging (PET, optical, X-ray computed tomography (CT), etc.). PMID:22916075

  20. The Role of Non-Standard PET Radionuclides in the Development of New Radiopharmaceuticals

    SciTech Connect

    Avila-Rodriguez, M. A.; McQuarrie, S. A.

    2008-08-11

    This paper discusses the production methods of the most commonly used non-standard PET radionuclides, their decay characteristics and importance in the development of novel radiopharmaceuticals for PET-based molecular imaging and potential applications in therapy.

  1. Synthesis, 68Ga-Radiolabeling, and Preliminary In Vivo Assessment of a Depsipeptide-Derived Compound as a Potential PET/CT Infection Imaging Agent

    PubMed Central

    Mokaleng, Botshelo B.; Ebenhan, Thomas; Ramesh, Suhas; Govender, Thavendran; Kruger, Hendrik G.; Hazari, Puja P.; Mishra, Anil K.; Marjanovic-Painter, Biljana; Zeevaart, Jan R.; Sathekge, Mike M.

    2015-01-01

    Noninvasive imaging is a powerful tool for early diagnosis and monitoring of various disease processes, such as infections. An alarming shortage of infection-selective radiopharmaceuticals exists for overcoming the diagnostic limitations with unspecific tracers such as 67/68Ga-citrate or 18F-FDG. We report here TBIA101, an antimicrobial peptide derivative that was conjugated to DOTA and radiolabeled with 68Ga for a subsequent in vitro assessment and in vivo infection imaging using Escherichia coli-bearing mice by targeting bacterial lipopolysaccharides with PET/CT. Following DOTA-conjugation, the compound was verified for its cytotoxic and bacterial binding behaviour and compound stability, followed by 68Gallium-radiolabeling. µPET/CT using 68Ga-DOTA-TBIA101 was employed to detect muscular E. coli-infection in BALB/c mice, as warranted by the in vitro results. 68Ga-DOTA-TBIA101-PET detected E. coli-infected muscle tissue (SUV = 1.3–2.4) > noninfected thighs (P = 0.322) > forearm muscles (P = 0.092) > background (P = 0.021) in the same animal. Normalization of the infected thigh muscle to reference tissue showed a ratio of 3.0 ± 0.8 and a ratio of 2.3 ± 0.6 compared to the identical healthy tissue. The majority of the activity was cleared by renal excretion. The latter findings warrant further preclinical imaging studies of greater depth, as the DOTA-conjugation did not compromise the TBIA101's capacity as targeting vector. PMID:25699267

  2. Sensory analysis of pet foods.

    PubMed

    Koppel, Kadri

    2014-08-01

    Pet food palatability depends first and foremost on the pet and is related to the pet food sensory properties such as aroma, texture and flavor. Sensory analysis of pet foods may be conducted by humans via descriptive or hedonic analysis, pets via acceptance or preference tests, and through a number of instrumental analysis methods. Sensory analysis of pet foods provides additional information on reasons behind palatable and unpalatable foods as pets lack linguistic capabilities. Furthermore, sensory analysis may be combined with other types of information such as personality and environment factors to increase understanding of acceptable pet foods. Most pet food flavor research is proprietary and, thus, there are a limited number of publications available. Funding opportunities for pet food studies would increase research and publications and this would help raise public awareness of pet food related issues. This mini-review addresses current pet food sensory analysis literature and discusses future challenges and possibilities.

  3. Specificity of 68Ga-PSMA PET/CT for Prostate Cancer - Myths and Reality

    PubMed Central

    Sasikumar, Arun

    2017-01-01

    68Ga-PSMA ligand PET/CT for imaging prostate cancer is a novel imaging technique, which is rapidly gaining popularity. Sufficient evidence has been accumulated in literature regarding the usefulness of 68Ga-PSMA PET/CT in prostate cancer. Recently literature regarding the localization of 68Ga-PSMA PET/CT imaging in non-prostatic malignancies is also published, thus questioning the specificity of the tracer with regards to prostate cancer. This commentary tries to address the issue of specificity of 68Ga-PSMA PET/CT and its relevance in imaging prostate cancer. PMID:28242976

  4. Specificity of (68)Ga-PSMA PET/CT for Prostate Cancer - Myths and Reality.

    PubMed

    Sasikumar, Arun

    2017-01-01

    68Ga-PSMA ligand PET/CT for imaging prostate cancer is a novel imaging technique, which is rapidly gaining popularity. Sufficient evidence has been accumulated in literature regarding the usefulness of (68)Ga-PSMA PET/CT in prostate cancer. Recently literature regarding the localization of (68)Ga-PSMA PET/CT imaging in non-prostatic malignancies is also published, thus questioning the specificity of the tracer with regards to prostate cancer. This commentary tries to address the issue of specificity of 68Ga-PSMA PET/CT and its relevance in imaging prostate cancer.

  5. PSMA Ligands for Radionuclide Imaging and Therapy of Prostate Cancer: Clinical Status.

    PubMed

    Lütje, Susanne; Heskamp, Sandra; Cornelissen, Alexander S; Poeppel, Thorsten D; van den Broek, Sebastiaan A M W; Rosenbaum-Krumme, Sandra; Bockisch, Andreas; Gotthardt, Martin; Rijpkema, Mark; Boerman, Otto C

    2015-01-01

    Prostate cancer (PCa) is the most common malignancy in men worldwide, leading to substantial morbidity and mortality. At present, imaging of PCa has become increasingly important for staging, restaging, and treatment selection. Until recently, choline-based positron emission tomography/computed tomography (PET/CT) represented the state-of-the-art radionuclide imaging technique for these purposes. However, its application is limited to patients with high PSA levels and Gleason scores. Prostate-specific membrane antigen (PSMA) is a promising new target for specific imaging of PCa, because it is upregulated in the majority of PCa. Moreover, PSMA can serve as a target for therapeutic applications. Currently, several small-molecule PSMA ligands with excellent in vivo tumor targeting characteristics are being investigated for their potential in theranostic applications in PCa. Here, a review of the recent developments in PSMA-based diagnostic imaging and therapy in patients with PCa with radiolabeled PSMA ligands is provided.

  6. 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

  7. Tau Positron Emission Tomography (PET) Imaging: Past, Present, and Future.

    PubMed

    Ariza, Manuela; Kolb, Hartmuth C; Moechars, Dieder; Rombouts, Frederik; Andrés, José Ignacio

    2015-06-11

    Alzheimer's disease (AD) is a chronic neurodegenerative disorder and the most common cause of dementia among the elderly population. The good correlation of the density and neocortical spread of neurofibrillary tangles (NFTs) with clinical AD disease progression offers an opportunity for the early diagnosis and staging using a noninvasive imaging technique such as positron emission tomography (PET). Thus, PET imaging of NFTs not only holds promise as a diagnostic tool but also may enable the development of disease modifying therapeutics for AD. In this review, we focus on the structural diversity of tau PET tracers, the challenges related to the identification of high affinity and highly selective NFT ligands, and recent progress in the clinical development of tau PET radioligands.

  8. A Small-Animal Pharmacokinetic/Pharmacodynamic PET Study of Central Serotonin 1A Receptor Occupancy by a Potential Therapeutic Agent for Overactive Bladder

    PubMed Central

    Nakatani, Yosuke; Suzuki, Michiyuki; Tokunaga, Masaki; Maeda, Jun; Sakai, Miyuki; Ishihara, Hiroki; Yoshinaga, Takashi; Takenaka, Osamu; Zhang, Ming-Rong; Suhara, Tetsuya; Higuchi, Makoto

    2013-01-01

    Serotonin 1A (5-HT1A) receptors have been mechanistically implicated in micturition control, and there has been a need for an appropriate biomarker surrogating the potency of a provisional drug acting on this receptor system for developing a new therapeutic approach to overactive bladder (OAB). Here, we analyzed the occupancy of 5-HT1A receptors in living Sprague-Dawley rat brains by a novel candidate drug for OAB, E2110, using positron emission tomography (PET) imaging, and assessed the utility of a receptor occupancy (RO) assay to establish a pharmacodynamic index translatable between animals and humans. The plasma concentrations inducing 50% RO (EC50) estimated by both direct and effect compartment models were in good agreement. Dose-dependent therapeutic effects of E2110 on dysregulated micturition in different rat models of pollakiuria were also consistently explained by achievement of 5-HT1A RO by E2110 in a certain range (≥ 60%). Plasma drug concentrations inducing this RO range and EC50 would accordingly be objective indices in comparing pharmacokinetics-RO relationships between rats and humans. These findings support the utility of PET RO and plasma pharmacokinetic assays with the aid of adequate mathematical models in determining the in vivo characteristics of a drug acting on 5-HT1A receptors and thereby counteracting OAB. PMID:24086433

  9. Endothelial targeting of polymeric nanoparticles stably labeled with the PET imaging radioisotope iodine-124.

    PubMed

    Simone, Eric A; Zern, Blaine J; Chacko, Ann-Marie; Mikitsh, John L; Blankemeyer, Eric R; Muro, Silvia; Stan, Radu V; Muzykantov, Vladimir R

    2012-07-01

    Targeting of therapeutics or imaging agents to the endothelium has the potential to improve specificity and effectiveness of treatment for many diseases. One strategy to achieve this goal is the use of nanoparticles (NPs) targeted to the endothelium by ligands of protein determinants present on this tissue, including cell adhesion molecules, peptidases, and cell receptors. However, detachment of the radiolabel probes from NPs poses a significant problem. In this study, we devised polymeric NPs directly labeled with radioiodine isotopes including the positron emission tomography (PET) isotope (124)I, and characterized their targeting to specific endothelial determinants. This approach provided sizable, targetable probes for specific detection of endothelial surface determinants non-invasively in live animals. Direct conjugation of radiolabel to NPs allowed for stable longitudinal tracking of tissue distribution without label detachment even in an aggressive proteolytic environment. Further, this approach permits tracking of NP pharmacokinetics in real-time and non-invasive imaging of the lung in mice using micro-PET imaging. The use of this strategy will considerably improve investigation of NP interactions with target cells and PET imaging in small animals, which ultimately can aid in the optimization of targeted drug delivery.

  10. Potential of the Biotic Ligand Model (BLM) to Predict Copper Toxicity in the White-Water of the Solimões-Amazon River.

    PubMed

    Pont, Giorgi Dal; Domingos, Fabíola Xochilt Valdez; Fernandes-de-Castilho, Marisa; Val, Adalberto Luis

    2017-01-01

    In this study, we evaluated the capacity of the Biotic Ligand Model (BLM) to predict copper toxicity in white-waters of the Solimões-Amazon River. LC50 tests using the species Otocinclus vittatus (Regan, 1904) were performed with Solimões-Amazon river water (100%) at 20%, 40%, 60%, and 80% dilutions. A sevenfold decrease in both dissolved and total Cu toxicity was observed in the experiment conducted with 100% when compared to 20% white-water, indicating that physicochemical characteristics of white-water attenuate Cu toxicity. There was agreement between the observed LC50 and the LC50 predicted by the BLM after the adjustment of critical accumulation concentration (LA50) for O. vittatus. BLM modeling indicated that dissolved organic carbon (DOC) and pH were the most important water parameters influencing Cu toxicity, followed by Ca(2+). Our results highlight the first evidence that the BLM presents potential to predict Cu toxicity to aquatic organisms in the white-water of the Solimões-Amazon River.

  11. Two-ligand priming mechanism for potentiated phosphoinositide synthesis is an evolutionarily conserved feature of Sec14-like phosphatidylinositol and phosphatidylcholine exchange proteins

    PubMed Central

    Huang, Jin; Ghosh, Ratna; Tripathi, Ashutosh; Lönnfors, Max; Somerharju, Pentti; Bankaitis, Vytas A.

    2016-01-01

    Lipid signaling, particularly phosphoinositide signaling, plays a key role in regulating the extreme polarized membrane growth that drives root hair development in plants. The Arabidopsis AtSFH1 gene encodes a two-domain protein with an amino-terminal Sec14-like phosphatidylinositol transfer protein (PITP) domain linked to a carboxy-terminal nodulin domain. AtSfh1 is critical for promoting the spatially highly organized phosphatidylinositol-4,5-bisphosphate signaling program required for establishment and maintenance of polarized root hair growth. Here we demonstrate that, like the yeast Sec14, the AtSfh1 PITP domain requires both its phosphatidylinositol (PtdIns)- and phosphatidylcholine (PtdCho)-binding properties to stimulate PtdIns-4-phosphate [PtdIns(4)P] synthesis. Moreover, we show that both phospholipid-binding activities are essential for AtSfh1 activity in supporting polarized root hair growth. Finally, we report genetic and biochemical evidence that the two-ligand mechanism for potentiation of PtdIns 4-OH kinase activity is a broadly conserved feature of plant Sec14-nodulin proteins, and that this strategy appeared only late in plant evolution. Taken together, the data indicate that the PtdIns/PtdCho-exchange mechanism for stimulated PtdIns(4)P synthesis either arose independently during evolution in yeast and in higher plants, or a suitable genetic module was introduced to higher plants from a fungal source and subsequently exploited by them. PMID:27193303

  12. Complexes of a Zn-metalloenzyme binding site with hydroxamate-containing ligands. A case for detailed benchmarkings of polarizable molecular mechanics/dynamics potentials when the experimental binding structure is unknown.

    PubMed

    Gresh, Nohad; Perahia, David; de Courcy, Benoit; Foret, Johanna; Roux, Céline; El-Khoury, Lea; Piquemal, Jean-Philip; Salmon, Laurent

    2016-12-15

    Zn-metalloproteins are a major class of targets for drug design. They constitute a demanding testing ground for polarizable molecular mechanics/dynamics aimed at extending the realm of quantum chemistry (QC) to very long-duration molecular dynamics (MD). The reliability of such procedures needs to be demonstrated upon comparing the relative stabilities of competing candidate complexes of inhibitors with the recognition site stabilized in the course of MD. This could be necessary when no information is available regarding the experimental structure of the inhibitor-protein complex. Thus, this study bears on the phosphomannose isomerase (PMI) enzyme, considered as a potential therapeutic target for the treatment of several bacterial and parasitic diseases. We consider its complexes with 5-phospho-d-arabinonohydroxamate and three analog ligands differing by the number and location of their hydroxyl groups. We evaluate the energy accuracy expectable from a polarizable molecular mechanics procedure, SIBFA. This is done by comparisons with ab initio quantum-chemistry (QC) calculations in the following cases: (a) the complexes of the four ligands in three distinct structures extracted from the entire PMI-ligand energy-minimized structures, and totaling up to 264 atoms; (b) the solvation energies of several energy-minimized complexes of each ligand with a shell of 64 water molecules; (c) the conformational energy differences of each ligand in different conformations characterized in the course of energy-minimizations; and (d) the continuum solvation energies of the ligands in different conformations. The agreements with the QC results appear convincing. On these bases, we discuss the prospects of applying the procedure to ligand-macromolecule recognition problems. © 2016 Wiley Periodicals, Inc.

  13. Phenyl 1,2,3-Triazole-Thymidine Ligands Stabilize G-Quadruplex DNA, Inhibit DNA Synthesis and Potentially Reduce Tumor Cell Proliferation over 3′-Azido Deoxythymidine

    PubMed Central

    Mahesh Kumar, Jerald; Idris, Mohammed M.; Srinivas, Gunda; Vinay Kumar, Pallerla; Meghah, Vuppalapaty; Kavitha, Mitta; Reddy, Chada Raji; Mainkar, Prathama S.; Pal, Biswajit; Chandrasekar, Srivari; Nagesh, Narayana

    2013-01-01

    Triazoles are known for their non-toxicity, higher stability and therapeutic activity. Few nucleoside (L1, L2 and L3) and non-nucleoside 1,2,3-triazoles (L4–L14) were synthesised using click chemistry and they were screened for tumor cell cytotoxicity and proliferation. Among these triazole ligands studied, nucleoside ligands exhibited higher potential than non-nucleoside ligands. The nucleoside triazole analogues, 3′-Phenyl-1,2,3- triazole-thymidine (L2) and 3′-4-Chlorophenyl-1,2,3-triazole-thymidine (L3), demonstrated higher cytotoxicity in tumor cells than in normal cells. The IC50 value for L3 was lowest (50 µM) among the ligands studied. L3 terminated cell cycle at S, G2/M phases and enhanced sub-G1 populations, manifesting induction of apoptosis in tumor cells. Confocal studies indicated that nucleoside triazole ligands (L2/L3) cause higher DNA fragmentation than other ligands. Preclinical experiments with tumor-induced mice showed greater reduction in tumor size with L3. In vitro DNA synthesis reaction with L3 exhibited higher DNA synthesis inhibition with quadruplex forming DNA (QF DNA) than non quadruplex forming DNA (NQF DNA). Tm of quadruplex DNA increased in the presence of L3, indicating its ability to enhance stability of quadruplex DNA at elevated temperature and the results indicate that it had higher affinity towards quadruplex DNA than the other forms of DNA (like dsDNA and ssDNA). From western blot experiment, it was noticed that telomerase expression levels in the tissues of tumor-induced mice were found to be reduced on L3 treatment. Microcalorimetry results emphasise that two nucleoside triazole ligands (L2/L3) interact with quadruplex DNA with significantly higher affinity (Kd≈10−7 M). Interestingly the addition of an electronegative moiety to the phenyl group of L2 enhanced its anti-proliferative activity. Though IC50 values are not significantly low with L3, the studies on series of synthetic 1,2,3-triazole ligands are useful for

  14. Expression of a P-selectin ligand in zona pellucida of porcine oocytes and P-selectin on acrosomal membrane of porcine sperm cells. Potential implications for their involvement in sperm-egg interactions.

    PubMed

    Geng, J G; Raub, T J; Baker, C A; Sawada, G A; Ma, L; Elhammer, A P

    1997-05-05

    The selectin family of cell adhesion molecules mediates initial leukocyte adhesion to vascular endothelial cells at sites of inflammation. O-glycan structural similarities between oligosaccharides from human leukocyte P-selectin glycoprotein ligand-1 (PSGL-1) and from zona pellucida glycoproteins of porcine oocytes indicate the possible existence of a P-selectin ligand in the zona pellucida. Here, using biochemical as well as morphological approaches, we demonstrate that a P-selectin ligand is expressed in the porcine zona pellucida. In addition, a search for a specific receptor for this ligand leads to the identification of P-selectin on the acrosomal membrane of porcine sperm cells. In vitro binding of porcine acrosome-reacted sperm cells to oocytes was found to be Ca2+ dependent and inhibitable with either P-selectin, P-selectin receptor-globulin, or leukocyte adhesion blocking antibodies against P-selectin and PSGL-1. Moreover, porcine sperm cells were found to be capable of binding to human promyeloid cell line HL-60. Taken together, our findings implicate a potential role for the oocyte P-selectin ligand and the sperm P-selectin in porcine sperm-egg interactions.

  15. My Pet Rock

    ERIC Educational Resources Information Center

    Lark, Adam; Kramp, Robyne; Nurnberger-Haag, Julie

    2008-01-01

    Many teachers and students have experienced the classic pet rock experiment in conjunction with a geology unit. A teacher has students bring in a "pet" rock found outside of school, and the students run geologic tests on the rock. The tests include determining relative hardness using Mohs scale, checking for magnetization, and assessing luster.…

  16. Improving Instruction through PET.

    ERIC Educational Resources Information Center

    Evans, Pamela Roland

    1982-01-01

    Outlines the content and training methods used in the Program for Effective Teaching (PET), the successful staff development program of Newport News (Virginia). PET promotes application of five instructional skills: selecting learning objectives, teaching to the objectives, establishing learner focus, monitoring learner progress, and enhancing…

  17. Mobile PET Center Project

    NASA Astrophysics Data System (ADS)

    Ryzhikova, O.; Naumov, N.; Sergienko, V.; Kostylev, V.

    2017-01-01

    Positron emission tomography is the most promising technology to monitor cancer and heart disease treatment. Stationary PET center requires substantial financial resources and time for construction and equipping. The developed mobile solution will allow introducing PET technology quickly without major investments.

  18. Allosteric Modulation of Related Ligand-Gated Ion Channels Synergistically Induces Long-Term Potentiation in the Hippocampus and Enhances Cognition

    PubMed Central

    Gu, Zhenglin; Yoshimura, Ryan F.; Villegier, Anne-Sophie; Hogenkamp, Derk J.; Whittemore, Edward R.; Huang, Jin-Cheng; Tran, Minhtam B.; Belluzzi, James D.; Yakel, Jerrel L.; Gee, Kelvin W.

    2011-01-01

    α5 Subunit-containing GABAA receptors (GABAARs) and α7 neuronal nicotinic-acetylcholine receptors (nAChRs) are members of the Cys-loop family of ligand-gated ion channels (LGICs) that mediate cognitive and attentional processes in the hippocampus. α5 GABAARs alter network activity by tonic inhibition of CA1/CA3 pyramidal cells of the hippocampus. Postsynaptic α7 nAChRs in the hippocampus regulate inhibitory GABAergic interneuron activity required for synchronization of pyramidal neurons in the CA1, whereas presynaptic α7 nAChRs regulate glutamate release. Can simultaneous allosteric modulation of these LGICs produce synergistic effects on cognition? We show that combined transient application of two allosteric modulators that individually 1) inhibit α5 GABAARs and 2) enhance α7 nAChRs causes long-term potentiation (LTP) of mossy fiber stimulation-induced excitatory postsynaptic currents (EPSC) from CA1 pyramidal neurons of rat hippocampal slices. The LTP effect evoked by two compounds is replicated by 3-(2,5-difluorophenyl)-6-(N-ethylindol-5-yl)-1,2,4-triazolo[4,3-b]pyridazine (522-054), a compound we designed to simultaneously inhibit α5 GABAARs and enhance α7 nAChRs. Selective antagonists for either receptor block sustained EPSC potentiation produced by 522-054. In vivo, 522-054 enhances performance in the radial arm maze and facilitates attentional states in the five-choice serial reaction time trial with similar receptor antagonist sensitivity. These observations may translate into therapeutic utility of dual action compounds in diseases of hippocampal-based cognitive impairment. PMID:21159751

  19. Potential of PEGylated Toll-Like Receptor 7 Ligands for Controlling Inflammation and Functional Changes in Mouse Models of Asthma and Silicosis

    PubMed Central

    Ferreira, Tatiana Paula Teixeira; Mariano, Lívia Lacerda; Ghilosso-Bortolini, Roberta; de Arantes, Ana Carolina Santos; Fernandes, Andrey Junior; Berni, Michelle; Cecchinato, Valentina; Uguccioni, Mariagrazia; Maj, Roberto; Barberis, Alcide; Silva, Patricia Machado Rodrigues e; Martins, Marco Aurélio

    2016-01-01

    Prior investigations show that signaling activation through pattern recognition receptors can directly impact a number of inflammatory lung diseases. While toll-like receptor (TLR) 7 agonists have raised interest for their ability to inhibit allergen-induced pathological changes in experimental asthma conditions, the putative benefit of this treatment is limited by adverse effects. Our aim was to evaluate the therapeutic potential of two PEGylated purine-like compounds, TMX-302 and TMX-306, characterized by TLR7 partial agonistic activity; therefore, the compounds are expected to induce lower local and systemic adverse reactions. In vitro approaches and translation to murine models of obstructive and restrictive lung diseases were explored. In vitro studies with human PBMCs showed that both TMX-302 and TMX-306 marginally affects cytokine production as compared with equivalent concentrations of the TLR7 full agonist, TMX-202. The PEGylated compounds did not induce monocyte-derived DC maturation or B cell proliferation, differently from what observed after stimulation with TMX-202. Impact of PEGylated ligands on lung function and inflammatory changes was studied in animal models of acute lung injury, asthma, and silicosis following Lipopolysaccharide (LPS), allergen (ovalbumin), and silica inhalation, respectively. Subcutaneous injection of TMX-302 prevented LPS- and allergen-induced airway hyper-reactivity (AHR), leukocyte infiltration, and production of pro-inflammatory cytokines in the lung. However, intranasal instillation of TMX-302 led to neutrophil infiltration and failed to prevent allergen-induced AHR, despite inhibiting leukocyte counts in the BAL. Aerosolized TMX-306 given prophylactically, but not therapeutically, inhibited pivotal asthma features. Interventional treatment with intranasal instillation of TMX-306 significantly reduced the pulmonary fibrogranulomatous response and the number of silica particles in lung interstitial space in silicotic mice

  20. Does pet arrival trigger prosocial behaviors in individuals with autism?

    PubMed

    Grandgeorge, Marine; Tordjman, Sylvie; Lazartigues, Alain; Lemonnier, Eric; Deleau, Michel; Hausberger, Martine

    2012-01-01

    Alteration of social interactions especially prosocial behaviors--an important aspect of development--is one of the characteristics of autistic disorders. Numerous strategies or therapies are used to improve communication skills or at least to reduce social impairments. Animal-assisted therapies are used widely but their relevant benefits have never been scientifically evaluated. In the present study, we evaluated the association between the presence or the arrival of pets in families with an individual with autism and the changes in his or her prosocial behaviors. Of 260 individuals with autism--on the basis of presence or absence of pets--two groups of 12 individuals and two groups of 8 individuals were assigned to: study 1 (pet arrival after age of 5 versus no pet) and study 2 (pet versus no pet), respectively. Evaluation of social impairment was assessed at two time periods using the 36-items ADI-R algorithm and a parental questionnaire about their child-pet relationships. The results showed that 2 of the 36 items changed positively between the age of 4 to 5 (t(0)) and time of assessment (t(1)) in the pet arrival group (study 1): "offering to share" and "offering comfort". Interestingly, these two items reflect prosocial behaviors. There seemed to be no significant changes in any item for the three other groups. The interactions between individuals with autism and their pets were more--qualitatively and quantitatively--reported in the situation of pet arrival than pet presence since birth. These findings open further lines of research on the impact of pet's presence or arrival in families with an individual with autism. Given the potential ability of individuals with autism to develop prosocial behaviors, related studies are needed to better understand the mechanisms involved in the development of such child-pet relationship.

  1. PET/CT: underlying physics, instrumentation, and advances.

    PubMed

    Torres Espallardo, I

    2017-01-12

    Since it was first introduced, the main goal of PET/CT has been to provide both PET and CT images with high clinical quality and to present them to radiologists and specialists in nuclear medicine as a fused, perfectly aligned image. The use of fused PET and CT images quickly became routine in clinical practice, showing the great potential of these hybrid scanners. Thanks to this success, manufacturers have gone beyond considering CT as a mere attenuation corrector for PET, concentrating instead on design high performance PET and CT scanners with more interesting features. Since the first commercial PET/CT scanner became available in 2001, both the PET component and the CT component have improved immensely. In the case of PET, faster scintillation crystals with high stopping power such as LYSO crystals have enabled more sensitive devices to be built, making it possible to reduce the number of undesired coincidence events and to use time of flight (TOF) techniques. All these advances have improved lesion detection, especially in situations with very noisy backgrounds. Iterative reconstruction methods, together with the corrections carried out during the reconstruction and the use of the point-spread function, have improved image quality. In parallel, CT instrumentation has also improved significantly, and 64- and 128-row detectors have been incorporated into the most modern PET/CT scanners. This makes it possible to obtain high quality diagnostic anatomic images in a few seconds that both enable the correction of PET attenuation and provide information for diagnosis. Furthermore, nowadays nearly all PET/CT scanners have a system that modulates the dose of radiation that the patient is exposed to in the CT study in function of the region scanned. This article reviews the underlying physics of PET and CT imaging separately, describes the changes in the instrumentation and standard protocols in a combined PET/CT system, and finally points out the most important

  2. Preclinical Evaluation of a Potential GSH Ester Based PET/SPECT Imaging Probe DT(GSHMe)2 to Detect Gamma Glutamyl Transferase Over Expressing Tumors

    PubMed Central

    Khurana, Harleen; Meena, Virendra Kumar; Prakash, Surbhi; Chuttani, Krishna; Chadha, Nidhi; Jaswal, Ambika; Dhawan, Devinder Kumar; Mishra, Anil Kumar; Hazari, Puja Panwar

    2015-01-01

    Gamma Glutamyl Transferase (GGT) is an important biomarker in malignant cancers. The redox processes ensuing from GGT-mediated metabolism of extracellular GSH are implicated in critical aspects of tumor cell biology. Reportedly, Glutathione monoethyl ester (GSHMe) is a substrate of GGT, which has been used for its rapid transport over glutathione. Exploring GGT to be an important target, a homobivalent peptide system, DT(GSHMe)2 was designed to target GGT-over expressing tumors for diagnostic purposes. DT(GSHMe)2 was synthesized, characterized and preclinically evaluated in vitro using toxicity, cell binding assays and time dependent experiments. Stable and defined radiochemistry with 99mTc and 68Ga was optimized for high radiochemical yield. In vivo biodistribution studies were conducted for different time points along with scintigraphic studies of radiolabeled DT(GSHMe)2 on xenografted tumor models. For further validation, in silico docking studies were performed on GGT (hGGT1, P19440). Preclinical in vitro evaluations on cell lines suggested minimal toxicity of DT(GSHMe)2 at 100 μM concentration. Kinetic analysis revealed transport of 99mTc-DT(GSHMe)2 occurs via a saturable high-affinity carrier with Michaelis constant (Km) of 2.25 μM and maximal transport rate velocity (Vmax) of 0.478 μM/min. Quantitative estimation of GGT expression from western blot experiments showed substantial expression with 41.6 ± 7.07 % IDV for tumor. Small animal micro PET (Positron Emission Tomography)/CT(Computed Tomography) coregistered images depicted significantly high uptake of DT(GSHMe)2 at the BMG-1 tumor site. ROI analysis showed high tumor to contra lateral muscle ratio of 9.33 in PET imaging studies. Avid accumulation of radiotracer was observed at tumor versus inflammation site at 2 h post i.v. injection in an Ehrlich Ascites tumor (EAT) mice model, showing evident specificity for tumor. We propose DT(GSHMe)2 to be an excellent candidate for prognostication and tumor

  3. Integrated Whole Body MR/PET: Where Are We?

    PubMed Central

    Yoo, Hye Jin; Lee, Jae Sung

    2015-01-01

    Whole body integrated magnetic resonance imaging (MR)/positron emission tomography (PET) imaging systems have recently become available for clinical use and are currently being used to explore whether the combined anatomic and functional capabilities of MR imaging and the metabolic information of PET provide new insight into disease phenotypes and biology, and provide a better assessment of oncologic diseases at a lower radiation dose than a CT. This review provides an overview of the technical background of combined MR/PET systems, a discussion of the potential advantages and technical challenges of hybrid MR/PET instrumentation, as well as collection of possible solutions. Various early clinical applications of integrated MR/PET are also addressed. Finally, the workflow issues of integrated MR/PET, including maximizing diagnostic information while minimizing acquisition time are discussed. PMID:25598673

  4. Microfluidics for synthesis of peptide-based PET tracers.

    PubMed

    Liu, Yang; Tian, Mei; Zhang, Hong

    2013-01-01

    Positron emission tomography (PET) is a powerful noninvasive tool for acquisition of the physiological parameters in human and animals with the help of PET tracers. Among all the PET tracers, radiolabeled peptides have been widely explored for cancer-related receptor imaging due to their high affinity and specificity to receptors. But radiochemistry procedures for production of peptide-based PET tracers are usually complex, which makes large-scale clinical studies relatively challenging. New radiolabeling technologies which could simplify synthesis and purification procedures, are extremely needed. Over the last decade, microfluidics and lab-on-a-chip (LOC) technology have boomed as powerful tools in the field of organic chemistry, which potentially provide significant help to the PET chemistry. In this minireview, microfluidic radiolabeling technology is described and its application for synthesis of peptide-based PET tracers is summarized and discussed.

  5. PET and SPECT imaging in veterinary medicine.

    PubMed

    LeBlanc, Amy K; Peremans, Kathelijne

    2014-01-01

    Veterinarians have gained increasing access to positron emission tomography (PET and PET/CT) imaging facilities, allowing them to use this powerful molecular imaging technique for clinical and research applications. SPECT is currently being used more in Europe than in the United States and has been shown to be useful in veterinary oncology and in the evaluation of orthopedic diseases. SPECT brain perfusion and receptor imaging is used to investigate behavioral disorders in animals that have interesting similarities to human psychiatric disorders. This article provides an overview of the potential applications of PET and SPECT. The use of commercially available and investigational PET radiopharmaceuticals in the management of veterinary disease has been discussed. To date, most of the work in this field has utilized the commercially available PET tracer, (18)F-fluorodeoxyglucose for oncologic imaging. Normal biodistribution studies in several companion animal species (cats, dogs, and birds) have been published to assist in lesion detection and interpretation for veterinary radiologists and clinicians. Studies evaluating other (18)F-labeled tracers for research applications are underway at several institutions and companion animal models of human diseases are being increasingly recognized for their value in biomarker and therapy development. Although PET and SPECT technologies are in their infancy for clinical veterinary medicine, increasing access to and interest in these applications and other molecular imaging techniques has led to a greater knowledge and collective body of expertise for veterinarians worldwide. Initiation and fostering of physician-veterinarian collaborations are key components to the forward movement of this field.

  6. PET as a tool in the clinical evaluation of pituitary adenomas

    SciTech Connect

    Bergstroem, M.M.; Muhr, C.; Lundberg, P.O.; Langstroem B4 )

    1991-04-01

    Positron emission tomography (PET) was used in over 400 examinations in patients with pituitary adenoma. It was demonstrated that PET with carbon-11-methionine can give valuable complementary information in the diagnosis of this tumor due to PET's ability to adequately depict viable tumor tissue in contrast to fibrosis, cysts and necrosis. Furthermore, PET with dopamine D2 receptor ligands can characterize the degree of receptor binding and thus give information as to the prerequisites for dopamine agonist treatment. Most important is the very high sensitivity given by PET with carbon-11-methionine in the evaluation of treatment effects. It is concluded that when properly used PET can be fully justified in the clinical handling of patients with pituitary adenomas and other intracranial tumors.

  7. Clinical oncologic applications of PET/MRI: a new horizon

    PubMed Central

    Partovi, Sasan; Kohan, Andres; Rubbert, Christian; Vercher-Conejero, Jose Luis; Gaeta, Chiara; Yuh, Roger; Zipp, Lisa; Herrmann, Karin A; Robbin, Mark R; Lee, Zhenghong; Muzic, Raymond F; Faulhaber, Peter; Ros, Pablo R

    2014-01-01

    Positron emission tomography/magnetic resonance imaging (PET/MRI) leverages the high soft-tissue contrast and the functional sequences of MR with the molecular information of PET in one single, hybrid imaging technology. This technology, which was recently introduced into the clinical arena in a few medical centers worldwide, provides information about tumor biology and microenvironment. Studies on indirect PET/MRI (use of positron emission tomography/computed tomography (PET/CT) images software fused with MRI images) have already generated interesting preliminary data to pave the ground for potential applications of PET/MRI. These initial data convey that PET/MRI is promising in neuro-oncology and head & neck cancer applications as well as neoplasms in the abdomen and pelvis. The pediatric and young adult oncology population requiring frequent follow-up studies as well as pregnant woman might benefit from PET/MRI due to its lower ionizing radiation dose. The indication and planning of therapeutic interventions and specifically radiation therapy in individual patients could be and to a certain extent are already facilitated by performing PET/MRI. The objective of this article is to discuss potential clinical oncology indications of PET/MRI. PMID:24753986

  8. Preparation and characterization of vanadyl complexes with bidentate maltol-type ligands; in vivo comparisons of anti-diabetic therapeutic potential.

    PubMed

    Thompson, Katherine H; Liboiron, Barry D; Sun, Yan; Bellman, Karycia D D; Setyawati, Ika A; Patrick, Brian O; Karunaratne, Veranja; Rawji, Gulnar; Wheeler, Jeffrey; Sutton, Kymberley; Bhanot, Sanjay; Cassidy, Carrie; McNeill, John H; Yuen, Violet G; Orvig, Chris

    2003-01-01

    A series of 2-alkyl-3-hydroxy-4-pyrone oxovanadium(IV) compounds has been synthesized, characterized, and tested for bioactivity as potential insulin-enhancing agents. The vanadyl complexes, bis(maltolato)oxovanadium(IV), BMOV, bis(ethylmaltolato)oxovanadium(IV), BEOV, and bis(isopropylmaltolato)oxovanadium(IV), BIOV, were compared against vanadyl sulfate for glucose-lowering ability, when administered i.p. to STZ-diabetic rats, at a one-time dose of 0.1 mmol kg(-1)body weight. Blood levels of vanadium were determined at regular intervals, to 72 h, following i.p. injection. All complexes tested exceeded vanadyl sulfate in glucose-lowering ability; this effect was not correlated, however, with blood vanadium levels. Analysis of the pharmacokinetics of the disappearance of [ethyl-1-(14)C]BEOV after an oral gavage dose (50 mg kg(-1), 0.144 mmol kg(-1), in a 10 mL kg(-1) volume of 1% CMC solution) indicated clearly that metal ion-ligand dissociation took place relatively soon after oral ingestion of the complex. Half-lives of fast phase uptake and slow phase disappearance for (14)C and V were calculated from a two-compartment model for whole blood, plasma, liver, kidney, bone, small intestine, and lung, ranging from 17 min ( t(1/2)alpha for (14)C, liver) to 30 days ( t(1/2)beta for V, bone). Curves of disappearance of plasma and whole blood (14)C and V diverged dramatically within the first hour after administration of the vanadium complex.

  9. Flutriciclamide (18F-GE180) PET: First-in-Human PET Study of Novel Third-Generation In Vivo Marker of Human Translocator Protein.

    PubMed

    Fan, Zhen; Calsolaro, Valeria; Atkinson, Rebecca A; Femminella, Grazia D; Waldman, Adam; Buckley, Christopher; Trigg, William; Brooks, David J; Hinz, Rainer; Edison, Paul

    2016-11-01

    Neuroinflammation is associated with neurodegenerative disease. PET radioligands targeting the 18-kDa translocator protein (TSPO) have been used as in vivo markers of neuroinflammation, but there is an urgent need for novel probes with improved signal-to-noise ratio. Flutriciclamide ((18)F-GE180) is a recently developed third-generation TSPO ligand. In this first study, we evaluated the optimum scan duration and kinetic modeling strategies for (18)F-GE180 PET in (older) healthy controls.

  10. Does Pet Arrival Trigger Prosocial Behaviors in Individuals with Autism?

    PubMed Central

    Grandgeorge, Marine; Tordjman, Sylvie; Lazartigues, Alain; Lemonnier, Eric; Deleau, Michel; Hausberger, Martine

    2012-01-01

    Alteration of social interactions especially prosocial behaviors – an important aspect of development – is one of the characteristics of autistic disorders. Numerous strategies or therapies are used to improve communication skills or at least to reduce social impairments. Animal-assisted therapies are used widely but their relevant benefits have never been scientifically evaluated. In the present study, we evaluated the association between the presence or the arrival of pets in families with an individual with autism and the changes in his or her prosocial behaviors. Of 260 individuals with autism - on the basis of presence or absence of pets - two groups of 12 individuals and two groups of 8 individuals were assigned to: study 1 (pet arrival after age of 5 versus no pet) and study 2 (pet versus no pet), respectively. Evaluation of social impairment was assessed at two time periods using the 36-items ADI-R algorithm and a parental questionnaire about their child-pet relationships. The results showed that 2 of the 36 items changed positively between the age of 4 to 5 (t0) and time of assessment (t1) in the pet arrival group (study 1): “offering to share” and “offering comfort”. Interestingly, these two items reflect prosocial behaviors. There seemed to be no significant changes in any item for the three other groups. The interactions between individuals with autism and their pets were more – qualitatively and quantitatively - reported in the situation of pet arrival than pet presence since birth. These findings open further lines of research on the impact of pet’s presence or arrival in families with an individual with autism. Given the potential ability of individuals with autism to develop prosocial behaviors, related studies are needed to better understand the mechanisms involved in the development of such child-pet relationship. PMID:22870246

  11. Sigma receptor ligands: possible application as therapeutic drugs and as radiopharmaceuticals.

    PubMed

    Hashimoto, Kenji; Ishiwata, Kiichi

    2006-01-01

    Sigma receptors are classified into sigma(1) and sigma(2) subtypes. These subtypes display a different tissue distribution and a distinct physiological and pharmacological profile in the central and peripheral nervous system. The characterization of these subtypes and the discovery of new specific sigma receptor ligands demonstrated that sigma receptors are novel targets for the therapeutic treatment of neuropsychiatric diseases (schizophrenia, depression, and cognition), brain ischemia, and cocaine addiction. Furthermore, imaging of sigma(1) receptors in the human brain using specific PET radioligands has started. In addition, the two sigma receptor subtypes are also expressed on tumor cells, where they could be of prognostic relevance. The ability of sigma(2) receptor agonists to inhibit tumor cell proliferation through mechanisms that might involve apoptosis, intracellular Ca(2+), and sphingolipids has promoted the development of sigma(2) receptor agonists as novel therapeutic drugs for treating cancer. Consequently, sigma(2) receptor ligands have been demonstrated to be potentially useful tumor imaging ligands. In this article, we focus on the sigma receptor ligands as therapeutic agents and as radiopharmaceuticals.

  12. The pyrokinin/ pheromone biosynthesis-activating neuropeptide (PBAN) family of peptides and their receptors in Insecta: evolutionary trace indicates potential receptor ligand-binding domains.

    PubMed

    Jurenka, R; Nusawardani, T

    2011-06-01

    The pyrokinin/pheromone biosynthesis-activating neuropeptide (PBAN) family of G-protein-coupled receptors and their ligands have been identified in various insects. Physiological functions of pyrokinin peptides include muscle contraction, whereas PBAN regulates, among other functions, pheromone production in moths which indicates the pleiotropic nature of these peptides. Based on the alignment of annotated genomic sequences, the pyrokinin/PBAN family of receptors have similarity with the corresponding structures of the capa or periviscerokinin receptors of insects and the neuromedin U receptors of vertebrates. In our study, evolutionary trace (ET) analysis on the insect receptor sequences was conducted to predict the putative ligand recognition and binding sites. The ET analysis of four class-specific receptors indicated several amino acid residues that are conserved in the transmembrane domains. The receptor extracellular domains exhibit several class-specific amino acid residues, which could indicate putative domains for activation of these receptors by ligand recognition and binding.

  13. Synthesis, F-18 Radiolabeling, and MicroPET Evaluation of 3-(2,4-Dichlorophenyl)-N-alkyl-N-fluoroalkyl-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-amines as Ligands of the Corticotropin-Releasing Factor Type-1 (CRF1) Receptor

    PubMed Central

    Stehouwer, Jeffrey S.; Birnbaum, Matthew S.; Voll, Ronald J.; Owens, Michael J.; Plott, Susan J.; Bourke, Chase H.; Wassef, Michael A.; Kilts, Clinton D.; Goodman, Mark M.

    2015-01-01

    A series of 3-(2,4-dichlorophenyl)-N-alkyl-N-fluoroalkyl-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-amines were synthesized and evaluated as potential positron emission tomography (PET) tracers for the corticotropin-releasing factor type-1 (CRF1) receptor. Compounds 27,28,29, and 30 all displayed high binding affinity (≤ 1.2 nM) to the CRF1 receptor when assessed by in vitro competition binding assays at 23 °C, whereas a decrease in affinity (≥ 10-fold) was observed with compound 26. The logP7.4 values of [18F]26 – [18F]29 were in the range of ~2.2 – 2.8 and microPET evaluation of [18F]26 – [18F]29 in an anesthetized male cynomolgus monkey demonstrated brain penetrance, but specific binding was not sufficient enough to differentiate regions of high CRF1 receptor density from regions of low CRF1 receptor density. Radioactivity uptake in the skull, and sphenoid bone and/or sphenoid sinus during studies with [18F]28, [18F]28-d8, and [18F]29 was attributed to a combination of [18F]fluoride generated by metabolic defluorination of the radiotracer and binding of intact radiotracer to CRF1 receptors expressed on mast cells in the bone marrow. Uptake of [18F]26 and [18F]27 in the skull and sphenoid region was rapid but then steadily washed out which suggests that this behavior was the result of binding to CRF1 receptors expressed on mast cells in the bone marrow with no contribution from [18F]fluoride. PMID:26145817

  14. Heart PET scan

    MedlinePlus

    Heart nuclear medicine scan; Heart positron emission tomography; Myocardial PET scan ... Udelson JE, Dilsizian V, Bonow RO. Nuclear cardiology. In: Mann DL, ... A Textbook of Cardiovascular Medicine . 10th ed. Philadelphia, ...

  15. Pets and Pasteurella Infections

    MedlinePlus

    ... Ear Nose & Throat Emotional Problems Eyes Fever From Insects or Animals Genitals and Urinary Tract Glands & Growth ... Preventable Diseases Healthy Children > Health Issues > Conditions > From Insects or Animals > Pets and Pasteurella Infections Health Issues ...

  16. Appropriate and Inappropriate Pets.

    ERIC Educational Resources Information Center

    Soltow, Willow

    1985-01-01

    Presents an 11-lesson mini unit overview on wild and domestic pets. Lessons contain teacher preparation information and student activities. Skills, discipline orientation, and the humane concept associated with each lesson are also outlined. (ML)

  17. Brain PET scan

    MedlinePlus

    ... Tell the difference between Parkinson disease and other movement disorders Several PET scans may be taken to determine ... identify where the seizures start in your brain Movement disorders (such as Parkinson disease )

  18. Healthy Pets and People

    MedlinePlus

    ... Pregnant women should avoid adopting or handling stray cats, especially kittens. They particularly should not clean litter ... may be sick. Many pets, such as dogs, cats, reptiles, rodents, and birds, carry germs that can ...

  19. PET studies in epilepsy

    PubMed Central

    Sarikaya, Ismet

    2015-01-01

    Various PET studies, such as measurements of glucose, serotonin and oxygen metabolism, cerebral blood flow and receptor bindings are availabe for epilepsy. 18Fluoro-2-deoxyglucose (18F-FDG) PET imaging of brain glucose metabolism is a well established and widely available technique. Studies have demonstrated that the sensitivity of interictal FDG-PET is higher than interictal SPECT and similar to ictal SPECT for the lateralization and localization of epileptogenic foci in presurgical patients refractory to medical treatments who have noncontributory EEG and MRI. In addition to localizing epileptogenic focus, FDG-PET provide additional important information on the functional status of the rest of the brain. The main limitation of interictal FDG-PET is that it cannot precisely define the surgical margin as the area of hypometabolism usually extends beyond the epileptogenic zone. Various neurotransmitters (GABA, glutamate, opiates, serotonin, dopamine, acethylcholine, and adenosine) and receptor subtypes are involved in epilepsy. PET receptor imaging studies performed in limited centers help to understand the role of neurotransmitters in epileptogenesis, identify epileptic foci and investigate new treatment approaches. PET receptor imaging studies have demonstrated reduced 11C-flumazenil (GABAA-cBDZ) and 18F-MPPF (5-HT1A serotonin) and increased 11C-cerfentanil (mu opiate) and 11C-MeNTI (delta opiate) bindings in the area of seizure. 11C-flumazenil has been reported to be more sensitive than FDG-PET for identifying epileptic foci. The area of abnormality on GABAAcBDZ and opiate receptor images is usually smaller and more circumscribed than the area of hypometabolism on FDG images. Studies have demonstrated that 11C-alpha-methyl-L-tryptophan PET (to study synthesis of serotonin) can detect the epileptic focus within malformations of cortical development and helps in differentiating epileptogenic from non-epileptogenic tubers in patients with tuberous sclerosis complex

  20. PET studies in epilepsy.

    PubMed

    Sarikaya, Ismet

    2015-01-01

    Various PET studies, such as measurements of glucose, serotonin and oxygen metabolism, cerebral blood flow and receptor bindings are availabe for epilepsy. (18)Fluoro-2-deoxyglucose ((18)F-FDG) PET imaging of brain glucose metabolism is a well established and widely available technique. Studies have demonstrated that the sensitivity of interictal FDG-PET is higher than interictal SPECT and similar to ictal SPECT for the lateralization and localization of epileptogenic foci in presurgical patients refractory to medical treatments who have noncontributory EEG and MRI. In addition to localizing epileptogenic focus, FDG-PET provide additional important information on the functional status of the rest of the brain. The main limitation of interictal FDG-PET is that it cannot precisely define the surgical margin as the area of hypometabolism usually extends beyond the epileptogenic zone. Various neurotransmitters (GABA, glutamate, opiates, serotonin, dopamine, acethylcholine, and adenosine) and receptor subtypes are involved in epilepsy. PET receptor imaging studies performed in limited centers help to understand the role of neurotransmitters in epileptogenesis, identify epileptic foci and investigate new treatment approaches. PET receptor imaging studies have demonstrated reduced (11)C-flumazenil (GABAA-cBDZ) and (18)F-MPPF (5-HT1A serotonin) and increased (11)C-cerfentanil (mu opiate) and (11)C-MeNTI (delta opiate) bindings in the area of seizure. (11)C-flumazenil has been reported to be more sensitive than FDG-PET for identifying epileptic foci. The area of abnormality on GABAAcBDZ and opiate receptor images is usually smaller and more circumscribed than the area of hypometabolism on FDG images. Studies have demonstrated that (11)C-alpha-methyl-L-tryptophan PET (to study synthesis of serotonin) can detect the epileptic focus within malformations of cortical development and helps in differentiating epileptogenic from non-epileptogenic tubers in patients with tuberous

  1. Fluroine-18 labeled 28-carbomethoxy-3{beta}-(4-chlorophenyl)-8-[-3-fluoropropyl] nortropane(FPT): Synthesis and tissue distribution of a potential, radioligand for mapping cocaine receptor sites by PET

    SciTech Connect

    Keil, R.; Goodman, M.M.; Shoup, T.

    1995-05-01

    Highly potent and selective radioligands for the dopamine transporter labeled with fluorine-18 (t {1/2}=110 min) are attractive probes for longitudinal in vivo mapping of cocaine receptor sites in the caudate by PET. Recently, we reported an iodine-123 labeled 3{beta}-aryl analog of cocaine, 2{beta}-carbomethoxy-3{beta}-(4-chlorophenyl)-8-((E)-3-iodopropen-1-yl)nortropane, which was 125 times more potent than cocaine in inhibiting [I-125] RTI-55 binding to rat striatal homogenates and which showed high striatal (S) uptake (0.61% dose/g) and high S to cerebellum (C) ratio S/C=16.5 at 120 min in rats. These results demonstrated bulk tolerance at the 8-position of this I-123 analog. These findings prompted us to synthesize a new radioligand fluorine-18 labeled 2{beta}-carbomethoxy-3{beta}-(4-chlorophenyl)-8-3-fluoropropylnortropane (FPT) as a potential cocaine receptor PET imaging agent. Treatment of 2{beta}-carbomethoxy-3{beta}-(chlorophenyl) nortropane (1) with 1-bromo-3-fluoropropane (2) in CH3CN at 80{degrees}C afforded FPT (3). In Vitro binding studies in rat striatal homogenates using [I-125] RTI-55 resulted in a Ki (nM) of 8.2 for FPT. [F-18]FPT (3) was prepared by treating 1,3-diiodopropane (4) with NCA K[F-18]/K222 for 5 min in CH3CN at 85{degrees}C to give [F-18] 1-fluoro-3-iodopropane (5) in 50% E.O.B. yield. Coupling of [F-18] 5 with 1 in CH3CN at 60{degrees}C afforded [F-18]FPT in 5% yield (not optimized) E.O.B. following HPLC purification in a total synthesis time of 100 min.. [F-18]5 was >99% radiochemically pure with a specific activity of 8 Ci/{mu}mole. Following intravenous administration to rats [F-18]FPT showed high uptake in the striatum (S) with rapid washout from the cerebellum to afford a high S/C ratios=6.2 at 120 min. Primate imaging will also be presented. These results suggest that FPT is an excellent candidate for mapping cocaine receptor sites by PET.

  2. Parasites, pets, and people.

    PubMed

    Marx, M B

    1991-03-01

    It is important for the family physician to understand that patients' relationships with their pets play an important role in helping maintain mental and physical health yet provide the potential for causing illness in the patient. Toxocara canis (dog roundworm) and Toxocara cati (cat roundworm) are the ascarids most commonly responsible for VLM and ocular larva migrans in humans. These roundworms live in their adult stage in the small intestine of the dog and cat where their eggs are passed in the feces. The eggs containing the infective larva are very sticky, thus an infant crawling around on the floor can easily pick these up on fingers that almost invariably end up in the mouth. Infections are usually mild and asymptomatic but with a persistent eosinophilia. Ocular larva migrans is the form usually occurring in older children and adults. Some public health veterinarians recommend that a puppy or kitten should not be obtained as a companion for a child who is not old enough to read, thus bypassing the crawling and toddler stages. Hookworm eggs, shed in the feces of infected dogs or cats, develop into the infective second stage within a week. Humans are usually infected when bare areas of skin such as bare feet or the torso come in contact with soil contaminated with the larvae. The second-stage larvae are able to penetrate the intact skin of humans and the foot pads of dogs and cats. In the United States, the common dog hookworm, A. caninum, is a widespread parasite. Human intestinal ancylostomiasis caused by this species is rare, with only six cases recorded in the literature. Infection in humans or animals by the common tapeworm of dogs and cats (Dipylidium caninum) requires ingestion of the intermediate host, the dog or cat flea containing the larva (cysticercoids) of the agent. Many cases in humans are asymptomatic. Dipylidiasis affects mainly infants and young children who may swallow a flea that hops up while the infant is crawling on the floor or fondling

  3. FDG-PET in colorectal cancer.

    PubMed

    de Geus-Oei, Lioe-Fee; Ruers, Theo J M; Punt, Cornelis J A; Leer, Jan Willem; Corstens, Frans H M; Oyen, Wim J G

    2006-10-31

    [18F]Fluorodeoxyglucose (FDG) positron emission tomography (PET) is a useful imaging tool in the evolving management of patients with colorectal carcinoma. This technique is able to measure and visualize metabolic changes in cancer cells. This feature results in the ability to distinguish viable tumor from scar tissue, in the detection of tumor foci at an earlier stage than possible by conventional anatomic imaging and in the measurement of alterations in tumor metabolism, indicative of tumor response to therapy. Nowadays, FDG-PET plays a pivotal role in staging patients before surgical resection of recurrence and metastases, in the localization of recurrence in patients with an unexplained rise in serum carcinoembryonic antigen and in assessment of residual masses after treatment. In the presurgical evaluation, FDG-PET may be best used in conjunction with anatomic imaging in order to combine the benefits of both anatomical (CT) and functional (PET) information, which leads to significant improvements in preoperative liver staging and preoperative judgment on the feasibility of resection. Integration of FDG-PET into the management algorithm of these categories of patients alters and improves therapeutic management, reduces morbidity due to futile surgery, leads to substantial cost savings and probably also to a better patient outcome. FDG-PET also appears to have great potential in monitoring the success of local ablative therapies soon after intervention and in the prediction and evaluation of response to radiotherapy, systemic therapy, and combinations thereof. This review aims to outline the current and future role of FDG-PET in the field of colorectal cancer.

  4. Glyconanomaterials: synthesis, characterization, and ligand presentation.

    PubMed

    Wang, Xin; Ramström, Olof; Yan, Mingdi

    2010-05-04

    Glyconanomaterials, nanomaterials carrying surface-tethered carbohydrate ligands, have emerged and demonstrated increasing potential in biomedical imaging, therapeutics, and diagnostics. These materials combine the unique properties of nanometer-scale objects with the ability to present multiple copies of carbohydrate ligands, greatly enhancing the weak affinity of individual ligands to their binding partners. Critical to the performance of glyconanomaterials is the proper display of carbohydrate ligands, taking into consideration of the coupling chemistry, the type and length of the spacer linkage, and the ligand density. This article provides an overview of the coupling chemistry for attaching carbohydrate ligands to nanomaterials, and discusses the need for thorough characterization of glyconanomaterials, especially quantitative analyses of the ligand density and binding affinities. Using glyconanoparticles synthesized by a versatile photocoupling chemistry, methods for determining the ligand density by colorimetry and the binding affinity with lectins by a fluorescence competition assay are determined. The results show that the multivalent presentation of carbohydrate ligands significantly enhances the binding affinity by several orders of magnitude in comparison to the free ligands in solution. The effect is sizeable even at low surface ligand density. The type and length of the spacer linkage also affect the binding affinity, with the longer linkage promoting the association of bound ligands with the corresponding lectins.

  5. Glyconanomaterials: Synthesis, Characterization, and Ligand Presentation

    PubMed Central

    Wang, Xin

    2010-01-01

    Glyconanomaterials, nanomaterials carrying surface-tethered carbohydrate ligands, have emerged and demonstrated increasing potential in biomedical imaging, therapeutics, and diagnostics. These materials combine the unique properties of nanometer-scale objects with the ability to present multiple copies of carbohydrate ligands, greatly enhancing the weak affinity of individual ligands to their binding partners. Critical to the performance of glyconanomaterials is the proper display of carbohydrate ligands, taking into consideration of the coupling chemistry, the type and length of the spacer linkage, and the ligand density. This article provides an overview of the coupling chemistry for attaching carbohydrate ligands to nanomaterials, and discusses the need for thorough characterization of glyconanomaterials, especially quantitative analyses of the ligand density and binding affinities. Using glyconanoparticles synthesized by a versatile photocoupling chemistry, methods for determining the ligand density by colorimetry and the binding affinity with lectins by a fluorescence competition assay are determined. The results show that the multivalent presentation of carbohydrate ligands significantly enhances the binding affinity by several orders of magnitude in comparison to the free ligands in solution. The effect is sizeable even at low surface ligand density. The type and length of the spacer linkage also affect the binding affinity, with the longer linkage promoting the association of bound ligands with the corresponding lectins. PMID:20301131

  6. Understanding the complexation of Eu3 + with potential ligands used for preferential separation of lanthanides and actinides in various stages of nuclear fuel cycle: A luminescence investigation

    NASA Astrophysics Data System (ADS)

    Sengupta, Arijit; Kadam, R. M.

    2017-02-01

    A systematic photoluminescence based investigation was carried out to understand the complexation of Eu3 + with different ligands (TBP: tri-n-butyl phosphate, DHOA: di-n-hexyl octanamide, Cyanex 923: tri-n-alkyl phosphine oxide and Cyanex 272: Bis (2,4,4 trimethyl) pentyl phosphinic acid) used for preferential separation of lanthanides and actinides in various stages of nuclear fuel cycle. In case of TBP and DHOA complexes, 3 ligand molecules coordinated in monodentate fashion and 3 nitrate ion in bidentate fashion to Eu3 + to satisfy the 9 coordination of Eu. In case of Cyanex 923 and Cyanex 272 complexes, 3 ligand molecules, 3 nitrate ion and 3 water molecules coordinated to Eu3 + in monodentate fashion. The Eu complexes of TBP and DHOA were found to have D3h local symmetry while that for Cyanex 923 and Cyanex 272 were C3h. Judd-Ofelt analysis of these systems revealed that the covalency of Eusbnd O bond followed the trend DHOA > TBP > Cyanex 272 > Cyanex 923. Different photophysical properties like radiative and non-radiative life time, branching ratio for different transitions, magnetic and electric dipole moment transition probabilities and quantum efficiency were also evaluated and compared for these systems. The magnetic dipole transition probability was found to be almost independent of ligand field perturbation while electric dipole transition probability for 5D0-7F2 transition was found to be hypersensitive with ligand field with a trend DHOA > TBP > Cyanex 272 > Cyanex 923. Supplementary Table 2: Determination of inner sphere water molecules from the different empirical formulae reported in the literature.

  7. Fundamental Limits of Spatial Resolution in PET

    PubMed Central

    Moses, William W.

    2010-01-01

    The fundamental limits of spatial resolution in positron emission tomography (PET) have been understood for many years. The physical size of the detector element usually plays the dominant role in determining resolution, but the combined contributions from acollinearity, positron range, penetration into the detector ring, and decoding errors in the detector modules often combine to be of similar size. In addition, the sampling geometry and statistical noise further degrade the effective resolution. This paper describes quantitatively describes these effects, discusses potential methods for reducing the magnitude of these effects, and computes the ultimately achievable spatial resolution for clinical and pre-clinical PET cameras. PMID:21804677

  8. Immuno-PET for Clinical Theranostic Approaches

    PubMed Central

    Bailly, Clément; Cléry, Pierre-François; Faivre-Chauvet, Alain; Bourgeois, Mickael; Guérard, François; Haddad, Ferid; Barbet, Jacques; Chérel, Michel; Kraeber-Bodéré, Françoise; Carlier, Thomas; Bodet-Milin, Caroline

    2016-01-01

    Recent advances in molecular characterization of tumors have allowed identification of new molecular targets on tumor cells or biomarkers. In medical practice, the identification of these biomarkers slowly but surely becomes a prerequisite before any treatment decision, leading to the concept of personalized medicine. Immuno-positron emission tomography (PET) fits perfectly with this approach. Indeed, monoclonal antibodies (mAbs) labelled with radionuclides represent promising probes for theranostic approaches, offering a non-invasive solution to assess in vivo target expression and distribution. Immuno-PET can potentially provide useful information for patient risk stratification, diagnosis, selection of targeted therapies, evaluation of response to therapy, prediction of adverse effects or for titrating doses for radioimmunotherapy. This paper reviews some aspects and recent developments in labelling methods, biological targets, and clinical data of some novel PET radiopharmaceuticals. PMID:28036044

  9. Forensic entomology of decomposing humans and their decomposing pets.

    PubMed

    Sanford, Michelle R

    2015-02-01

    Domestic pets are commonly found in the homes of decedents whose deaths are investigated by a medical examiner or coroner. When these pets become trapped with a decomposing decedent they may resort to feeding on the body or succumb to starvation and/or dehydration and begin to decompose as well. In this case report photographic documentation of cases involving pets and decedents were examined from 2009 through the beginning of 2014. This photo review indicated that in many cases the pets were cats and dogs that were trapped with the decedent, died and were discovered in a moderate (bloat to active decay) state of decomposition. In addition three cases involving decomposing humans and their decomposing pets are described as they were processed for time of insect colonization by forensic entomological approach. Differences in timing and species colonizing the human and animal bodies were noted as was the potential for the human or animal derived specimens to contaminate one another at the scene.

  10. Positron Emission Tomography (PET) Quantification of GABAA Receptors in the Brain of Fragile X Patients.

    PubMed

    D'Hulst, Charlotte; Heulens, Inge; Van der Aa, Nathalie; Goffin, Karolien; Koole, Michel; Porke, Kathleen; Van De Velde, Marc; Rooms, Liesbeth; Van Paesschen, Wim; Van Esch, Hilde; Van Laere, Koen; Kooy, R Frank

    2015-01-01

    Over the last several years, evidence has accumulated that the GABAA receptor is compromised in animal models for fragile X syndrome (FXS), a common hereditary form of intellectual disability. In mouse and fly models, agonists of the GABAA receptor were able to rescue specific consequences of the fragile X mutation. Here, we imaged and quantified GABAA receptors in vivo in brain of fragile X patients using Positron Emission Topography (PET) and [11C]flumazenil, a known high-affinity and specific ligand for the benzodiazepine site of GABAA receptors. We measured regional GABAA receptor availability in 10 fragile X patients and 10 control subjects. We found a significant reduction of on average 10% in GABAA receptor binding potential throughout the brain in fragile X patients. In the thalamus, the brain region showing the largest difference, the GABAA receptor availability was even reduced with 17%. This is one of the first reports of a PET study of human fragile X brain and directly demonstrates that the GABAA receptor availability is reduced in fragile X patients. The study reinforces previous hypotheses that the GABAA receptor is a potential target for rational pharmacological treatment of fragile X syndrome.

  11. Pets' Impact on Your Patients' Health: Leveraging Benefits and Mitigating Risk.

    PubMed

    Hodgson, Kate; Barton, Luisa; Darling, Marcia; Antao, Viola; Kim, Florence A; Monavvari, Alan

    2015-01-01

    Over two thirds of Americans live with pets and consider them important members of the family. Pets benefit human health (zooeyia) in 4 ways: as builders of social capital, as agents of harm reduction, as motivators for healthy behavior change, and as potential participants in treatment plans. Conversely, pets can present risks to their owners. They are potential sources of zoonotic disease and injury. Pets can also challenge a family's prioritization of financial and social resources. To activate the benefits of zooeyia and appropriately calibrate and mitigate zoonotic risk, physicians first need to know about the pets in their patients' families. Asking about pets is a simple and feasible approach to assess patients' environmental history and social capital. Asking about pets is a nonthreatening way to build rapport and demonstrates an interest in the whole family, which can improve the physician-patient therapeutic alliance. Physicians can use an interprofessional, collaborative approach with veterinarians to address zoonotic health risks and leverage zooeyia.

  12. Initial experience in primal-dual optimization reconstruction from sparse-PET patient data

    NASA Astrophysics Data System (ADS)

    Zhang, Zheng; Ye, Jinghan; Chen, Buxin; Perkins, Amy E.; Rose, Sean; Sidky, Emil Y.; Kao, Chien-Min; Xia, Dan; Tung, Chi-Hua; Pan, Xiaochuan

    2016-03-01

    There exists interest in designing a PET system with reduced detectors due to cost concerns, while not significantly compromising the PET utility. Recently developed optimization-based algorithms, which have demonstrated the potential clinical utility in image reconstruction from sparse CT data, may be used for enabling such design of innovative PET systems. In this work, we investigate a PET configuration with reduced number of detectors, and carry out preliminary studies from patient data collected by use of such sparse-PET configuration. We consider an optimization problem combining Kullback-Leibler (KL) data fidelity with an image TV constraint, and solve it by using a primal-dual optimization algorithm developed by Chambolle and Pock. Results show that advanced algorithms may enable the design of innovative PET configurations with reduced number of detectors, while yielding potential practical PET utilities.

  13. Valproic Acid Upregulates NKG2D Ligand Expression through an ERK-dependent Mechanism and Potentially Enhances NK Cell-mediated Lysis of Myeloma1

    PubMed Central

    Wu, Xiaosong; Tao, Yi; Hou, Jun; Meng, Xiuqin; Shi, Jumei

    2012-01-01

    Modulation of the antitumor immune response through the engagement of NKG2D receptors with their ligands (L) on targets represents a promising therapeutic approach against cancer. In this study, we tested the effect of valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, on the expression of NKG2D ligands in myeloma cells. We demonstrated that VPA was able to upregulate both protein and mRNA expression of major histocompatibility complex class I-related chain (MIC) A/B and UL16-binding protein (ULBP) 2 without any significant effect on the expression of ULBP1, ULBP3, and ULBP4 or induction of other natural killer (NK) cell ligands, such as NKp30-L, NKp44-L, and NKp46-L in myeloma cells. A 51Cr release assay and degranulation assay indicated that the induction of MICA/B and ULBP2 augmented NK cell-mediated lysis of myeloma cells, which was abolished by the addition of a blocking NKG2D antibody. Activation of constitutively phosphorylated extracellular signal-regulated kinase (ERK) by VPA is essential for the up-regulation of MICA/B and ULBP2 expressions. Inhibition of ERK using ERK inhibitor PD98059 decreased both MICA/B and ULBP2 expressions and NK cell cytotoxicity. Furthermore, overexpression of constitutively active ERK in ARK resulted in increased MICA/B and ULBP2 expressions and enhanced NK cell lysis. These data indicate that increased sensitivity of VPA-treated myeloma cells to NK cell lysis is caused by higher NKG2D ligand expression, resulting from more active ERK signaling pathway. Our results provide evidence that targeting ERK signaling pathway may be an additional mechanism supporting the antimyeloma activity of HDAC inhibitors and suggest its possible immunotherapeutic value for myeloma treatment. PMID:23308050

  14. The ADNI PET Core: 2015

    PubMed Central

    Jagust, William J.; Landau, Susan M.; Koeppe, Robert A.; Reiman, Eric M.; Chen, Kewei; Mathis, Chester A.; Price, Julie C.; Foster, Norman L.; Wang, Angela Y.

    2015-01-01

    INTRODUCTION This paper reviews the work done in the ADNI PET core over the past 5 years, largely concerning techniques, methods, and results related to amyloid imaging in ADNI. METHODS The PET Core has utilized [18F]florbetapir routinely on ADNI participants, with over 1600 scans available for download. Four different laboratories are involved in data analysis, and have examined factors such as longitudinal florbetapir analysis, use of FDG-PET in clinical trials, and relationships between different biomarkers and cognition. RESULTS Converging evidence from the PET Core has indicated that cross-sectional and longitudinal florbetapir analyses require different reference regions. Studies have also examined the relationship between florbetapir data obtained immediately after injection, which reflects perfusion, and FDG-PET results. Finally, standardization has included the translation of florbetapir PET data to a centiloid scale. CONCLUSION The PET Core has demonstrated a variety of methods for standardization of biomarkers such as florbetapir PET in a multicenter setting. PMID:26194311

  15. Disaster Preparedness for Your Pet

    MedlinePlus

    ... put pets, pet owners, and first responders in danger. Even if you try to create a safe ... Contact local veterinary clinics, boarding facilities, and local animal shelters. Visit the Humane Society website to find ...

  16. (68)Ga-PSMA PET/MR with multimodality image analysis for primary prostate cancer.

    PubMed

    Eiber, Matthias; Nekolla, Stephan G; Maurer, Tobias; Weirich, Gregor; Wester, Hans-Jürgen; Schwaiger, Markus

    2015-08-01

    Current imaging procedures for prostate cancer including positron emission tomography (PET) exhibit considerable limitations and are not always able to meet the diagnostic needs. Recently, a (68)Gallium-labeled ligand of the prostate-specific membrane antigen ((68)Ga-PSMA) has been introduced in PET-imaging of prostate cancer with first promising results. Due to relatively exclusive expression of PSMA in prostatic tissue as well as increased expression in prostate cancer, 68 Ga-PSMA was reported to exhibit a favorable lesion to background ratio. Together with the novel development of combined PET/MRI, the combination of excellent morphological detail, multiparametric functional information, and molecular PET data might lead to a significant improvement in detection of prostate cancer. We present an exemplarily case of primary staging using multiparametric (68)Ga-PSMA PET/MR by combining molecular and structural information.

  17. Cutaneous lymphomas in European pet rabbits (Oryctolagus cuniculus).

    PubMed

    Ritter, J M; von Bomhard, W; Wise, A G; Maes, R K; Kiupel, M

    2012-09-01

    Cutaneous lymphoma is a common skin neoplasm of pet rabbits in Europe but is rarely reported in pet rabbits in North America. These neoplasms have not been previously characterized, nor has the cause for the apparent predilection for cutaneous lymphoma in European pet rabbits compared with North American pet rabbits been investigated. In this retrospective study, the authors morphologically and immunohistochemically characterized 25 cutaneous lymphomas in European pet rabbits according to the World Health Organization classification. Tumors were classified as diffuse large B cell lymphomas, with 14 lymphomas exhibiting a centroblastic/centrocytic subtype and 11 tumors exhibiting a T cell-rich B cell subtype. To investigate a potential viral etiology of these lymphomas, 3 diffuse large B cell and 3 T cell-rich B cell lymphomas were evaluated by polymerase chain reaction for retroviral and herpesviral genes. Neither virus was detected. In contrast to other domestic animals, cutaneous lymphomas in European pet rabbits were highly pleomorphic and frequently contained multinucleated giant cells. Unexpectedly, the second most common subtype was T cell-rich B cell lymphoma, a subtype that is rare in species other than horses. Based on a limited number of samples, there was no support for a viral etiology that would explain the higher incidence of lymphoma in European pet rabbits compared with American pet rabbits. Further investigation into genetic and extrinsic factors associated with the development of these tumors is warranted.

  18. PET-based molecular imaging in neuroscience.

    PubMed

    Jacobs, A H; Li, H; Winkeler, A; Hilker, R; Knoess, C; Rüger, A; Galldiks, N; Schaller, B; Sobesky, J; Kracht, L; Monfared, P; Klein, M; Vollmar, S; Bauer, B; Wagner, R; Graf, R; Wienhard, K; Herholz, K; Heiss, W D

    2003-07-01

    Positron emission tomography (PET) allows non-invasive assessment of physiological, metabolic and molecular processes in humans and animals in vivo. Advances in detector technology have led to a considerable improvement in the spatial resolution of PET (1-2 mm), enabling for the first time investigations in small experimental animals such as mice. With the developments in radiochemistry and tracer technology, a variety of endogenously expressed and exogenously introduced genes can be analysed by PET. This opens up the exciting and rapidly evolving field of molecular imaging, aiming at the non-invasive localisation of a biological process of interest in normal and diseased cells in animal models and humans in vivo. The main and most intriguing advantage of molecular imaging is the kinetic analysis of a given molecular event in the same experimental subject over time. This will allow non-invasive characterisation and "phenotyping" of animal models of human disease at various disease stages, under certain pathophysiological stimuli and after therapeutic intervention. The potential broad applications of imaging molecular events in vivo lie in the study of cell biology, biochemistry, gene/protein function and regulation, signal transduction, transcriptional regulation and characterisation of transgenic animals. Most importantly, molecular imaging will have great implications for the identification of potential molecular therapeutic targets, in the development of new treatment strategies, and in their successful implementation into clinical application. Here, the potential impact of molecular imaging by PET in applications in neuroscience research with a special focus on neurodegeneration and neuro-oncology is reviewed.

  19. 18F-FDG PET/CT and PET/MRI Perform Equally Well in Cancer: Evidence from Studies on More Than 2,300 Patients

    PubMed Central

    Spick, Claudio; Herrmann, Ken; Czernin, Johannes

    2016-01-01

    18F-FDG PET/CT has become the reference standard in oncologic imaging against which the performance of other imaging modalities is measured. The promise of PET/MRI includes multiparametric imaging to further improve diagnosis and phenotyping of cancer. Rather than focusing on these capabilities, many investigators have examined whether 18F-FDG PET combined with mostly anatomic MRI improves cancer staging and restaging. After a description of PET/MRI scanner designs and a discussion of technical and operational issues, we review the available literature to determine whether cancer assessments are improved with PET/MRI. The available data show that PET/MRI is feasible and performs as well as PET/CT in most types of cancer. Diagnostic advantages may be achievable in prostate cancer and in bone metastases, whereas disadvantages exist in lung nodule assessments. We conclude that 18F-FDG PET/MRI and PET/CT provide comparable diagnostic information when MRI is used simply to provide the anatomic framework. Thus, PET/MRI could be used in lieu of PET/CT if this approach becomes economically viable and if reasonable workflows can be established. Future studies should explore the multiparametric potential of MRI. PMID:26742709

  20. Pet dander and difficult-to-control asthma: The burden of illness.

    PubMed

    Ownby, Dennis R

    2010-01-01

    There is evidence that allergy to common indoor pets, particularly cats and dogs, is closely associated with symptomatic asthma in the United States. Because the presence of pets in a home is a potentially modifiable factor, it is important to consider how much asthma morbidity and health care cost might be alleviated by the removal of pets from the homes of all persons with pet-allergic asthma. The percentage of pet-associated excess asthma morbidity was estimated as a proportion of all asthma-related health care costs for the United States.

  1. Towards optimal imaging with PET: an in silico feasibility study.

    PubMed

    McNamara, A L; Toghyani, M; Gillam, J E; Wu, K; Kuncic, Z

    2014-12-21

    The efficacy of Positron Emission Tomography (PET) imaging relies fundamentally on the ability of the system to accurately identify true coincidence events. With existing systems, this is currently accomplished with an energy acceptance criterion followed by correction techniques to remove suspected false coincidence events. These corrections generally result in signal and contrast loss and thus limit the PET system's ability to achieve optimum image quality. A key property of annihilation radiation is that the photons are polarised with respect to each other. This polarisation correlation offers a potentially powerful discriminator, independent of energy, to accurately identify true events. In this proof of concept study, we investigate how photon polarisation information can be exploited in PET imaging by developing a method to discriminate true coincidences using the polarisation correlation of annihilation pairs. We implement this method using a Geant4 PET simulation of a GE Advance/Discovery LS system and demonstrate the potential advantages of the polarisation coincidence selection method over a standard energy criterion method. Current PET ring detectors are not capable of exploiting the polarisation correlation of the photon pairs. Compton PET systems, however are promising candidates for this application. We demonstrate the feasibility of a two-component Compton camera system in identifying true coincidences with Monte Carlo simulations. Our study demonstrates the potential of improving signal gain using polarisation, particularly for high photon emission rates. We also demonstrate the ability of the Compton camera at exploiting this polarisation correlation in PET.

  2. Towards optimal imaging with PET: an in silico feasibility study

    NASA Astrophysics Data System (ADS)

    McNamara, A. L.; Toghyani, M.; Gillam, J. E.; Wu, K.; Kuncic, Z.

    2014-12-01

    The efficacy of Positron Emission Tomography (PET) imaging relies fundamentally on the ability of the system to accurately identify true coincidence events. With existing systems, this is currently accomplished with an energy acceptance criterion followed by correction techniques to remove suspected false coincidence events. These corrections generally result in signal and contrast loss and thus limit the PET system’s ability to achieve optimum image quality. A key property of annihilation radiation is that the photons are polarised with respect to each other. This polarisation correlation offers a potentially powerful discriminator, independent of energy, to accurately identify true events. In this proof of concept study, we investigate how photon polarisation information can be exploited in PET imaging by developing a method to discriminate true coincidences using the polarisation correlation of annihilation pairs. We implement this method using a Geant4 PET simulation of a GE Advance/Discovery LS system and demonstrate the potential advantages of the polarisation coincidence selection method over a standard energy criterion method. Current PET ring detectors are not capable of exploiting the polarisation correlation of the photon pairs. Compton PET systems, however are promising candidates for this application. We demonstrate the feasibility of a two-component Compton camera system in identifying true coincidences with Monte Carlo simulations. Our study demonstrates the potential of improving signal gain using polarisation, particularly for high photon emission rates. We also demonstrate the ability of the Compton camera at exploiting this polarisation correlation in PET.

  3. Some food toxic for pets

    PubMed Central

    Kovalkovičová, Natália; Šutiaková, Irena; Pistl, Juraj; Šutiak, Václav

    2009-01-01

    According to world statistics, dogs and cats are the species that owners most frequently seek assistance with potential poisonings, accounting 95–98% of all reported animal cases. Exposures occur more commonly in the summer and in December that is associated with the holiday season. The majority (>90%) of animal poisonings are accidental and acute in nature and occur near or at the animal owner's home. Feeding human foodstuff to pets may also prove dangerous for their health. The aim of this review was to present common food items that should not be fed (intentionally or unintentionally) to dogs, i.e. chocolate, caffeine, and other methylxanthines, grapes, raisins, onion, garlic, avocado, alcohol, nuts, xylitol contained in chewing gum and candies, etc. Onion and avocado are toxic for cats, too. The clinical effects of individual toxicants and possible therapy are also mentioned. Knowing what human food has the potential to be involved in serious toxicoses should allow veterinarians to better educate their clients on means of preventing pet poisonings. It can be concluded that the best advice must surely be to give animal fodder or treats specifically developed for their diets. PMID:21217849

  4. Carborane-conjugated 2-quinolinecarboxamide ligands of the translocator protein for boron neutron capture therapy.

    PubMed

    Cappelli, Andrea; Valenti, Salvatore; Mancini, Alessandra; Giuliani, Germano; Anzini, Maurizio; Altieri, Saverio; Bortolussi, Silva; Ferrari, Cinzia; Clerici, Anna Maria; Zonta, Cecilia; Carraro, Fabio; Filippi, Irene; Giorgi, Gianluca; Donati, Alessandro; Ristori, Sandra; Vomero, Salvatore; Concas, Alessandra; Biggio, Giovanni

    2010-12-15

    Potential boron neutron capture therapy (BNCT) agents have been designed on the basis of the evidence about translocator protein (TSPO) overexpression on the outer mitochondrial membrane of tumor cells. The structure of the first TSPO ligand bearing a carborane cage (compound 2d) has been modified in order to find a suitable candidate for in vivo studies. The designed compounds were synthesized and evaluated for their potential interaction with TSPO and tumor cells. In vitro biological evaluation showed in the case of fluoromethyl derivative 4b a nanomolar TSPO affinity very similar to that of 2d, a significantly lower cytotoxicity, and a slightly superior performance as boron carrier toward breast cancer cells. Moreover, compound 4b could be used as a ¹⁹F magnetic resonance imaging (MRI) agent as well as labeled with ¹¹C or ¹⁸F to obtain positron emission tomography (PET) radiotracers in order to apply the "see and treat" strategy in BNCT.

  5. Estimation from PET data of transient changes in dopamine concentration induced by alcohol: support for a non-parametric signal estimation method

    NASA Astrophysics Data System (ADS)

    Constantinescu, C. C.; Yoder, K. K.; Kareken, D. A.; Bouman, C. A.; O'Connor, S. J.; Normandin, M. D.; Morris, E. D.

    2008-03-01

    We previously developed a model-independent technique (non-parametric ntPET) for extracting the transient changes in neurotransmitter concentration from paired (rest & activation) PET studies with a receptor ligand. To provide support for our method, we introduced three hypotheses of validation based on work by Endres and Carson (1998 J. Cereb. Blood Flow Metab. 18 1196-210) and Yoder et al (2004 J. Nucl. Med. 45 903-11), and tested them on experimental data. All three hypotheses describe relationships between the estimated free (synaptic) dopamine curves (FDA(t)) and the change in binding potential (ΔBP). The veracity of the FDA(t) curves recovered by nonparametric ntPET is supported when the data adhere to the following hypothesized behaviors: (1) ΔBP should decline with increasing DA peak time, (2) ΔBP should increase as the strength of the temporal correlation between FDA(t) and the free raclopride (FRAC(t)) curve increases, (3) ΔBP should decline linearly with the effective weighted availability of the receptor sites. We analyzed regional brain data from 8 healthy subjects who received two [11C]raclopride scans: one at rest, and one during which unanticipated IV alcohol was administered to stimulate dopamine release. For several striatal regions, nonparametric ntPET was applied to recover FDA(t), and binding potential values were determined. Kendall rank-correlation analysis confirmed that the FDA(t) data followed the expected trends for all three validation hypotheses. Our findings lend credence to our model-independent estimates of FDA(t). Application of nonparametric ntPET may yield important insights into how alterations in timing of dopaminergic neurotransmission are involved in the pathologies of addiction and other psychiatric disorders.

  6. In vivo biodistribution of two ( sup 18 F)-labelled muscarinic cholinergic receptor ligands: 2-( sup 18 F)- and 4-( sup 18 F)-fluorodexetimide

    SciTech Connect

    Wilson, A.A.; Scheffel, U.A.; Dannals, R.F.; Stathis, M.; Ravert, H.T.; Wagner, H.N. Jr. )

    1991-01-01

    Two ({sup 18}F)-labelled analogues of the potent muscarinic cholinergic receptor (m-AChR) antagonist, dexetimide, were evaluated as potential ligands for imaging m-AChR by positron emission tomography (PET). Intravenous administration of both 2-({sup 18}F)- or 4-({sup 18}F)-fluorodexetimide resulted in high brain uptake of radioactivity in mice. High binding levels were observed in m-AChR rich areas, such as cortex and striatum, with low levels in the receptor-poor cerebellum. Uptake of radioactivity was saturable and could be blocked by pre-administration of dexetimide or atropine. Drugs with different sites of action were ineffective at blocking receptor binding. The results indicate that both radiotracers are promising candidates for use in PET studies.

  7. An Educational PET Camera Model

    ERIC Educational Resources Information Center

    Johansson, K. E.; Nilsson, Ch.; Tegner, P. E.

    2006-01-01

    Positron emission tomography (PET) cameras are now in widespread use in hospitals. A model of a PET camera has been installed in Stockholm House of Science and is used to explain the principles of PET to school pupils as described here.

  8. Quantitation of rare circulating tumor cells by folate receptor α ligand-targeted PCR in bladder transitional cell carcinoma and its potential diagnostic significance.

    PubMed

    Qi, Fuming; Liu, Yuchen; Zhao, Rongchang; Zou, Xiangjun; Zhang, Lei; Li, Jiaqiang; Wang, Yongqiang; Li, Feiyang; Zou, Xiaowen; Xia, Ye; Wang, Xuliang; Xing, Li; Li, Cailing; Lu, Jingxiao; Tang, Junlong; Zhou, Fangjian; Liu, Chunxiao; Gui, Yaoting; Cai, Zhiming; Sun, Xiaojuan

    2014-07-01

    Numerous attempts for detection of circulating tumor cells (CTC) have been made to develop reliable assays for early diagnosis of cancers. In this study, we validated the application of folate receptor α (FRα) as the tumor marker to detect CTC through tumor-specific ligand PCR (LT-PCR) and assessed its utility for diagnosis of bladder transitional cell carcinoma (TCC). Immunohistochemistry for FRα was performed on ten bladder TCC tissues. Enzyme-linked immunosorbent assay (ELISA) for FRα was performed on both urine and serum specimens from bladder TCC patients (n = 64 and n = 20, respectively) and healthy volunteers (n = 20 and n = 23, respectively). Western blot analysis and qRT-PCR were performed to confirm the expression of FRα in bladder TCC cells. CTC values in 3-mL peripheral blood were measured in 57 bladder TCC patients, 48 healthy volunteers, and 15 subjects with benign urologic pathologies by the folate receptor α ligand-targeted PCR. We found that FRα protein was overexpressed in both bladder TCC cells and tissues. The levels of FRα mRNA were also much higher in bladder cancer cell lines 5637 and SW780 than those of leukocyte. Values of FRα were higher in both serum and urine specimens of bladder TCC patients than those of control. CTC values were also higher in 3-mL peripheral blood of bladder TCC patients than those of control (median 26.5 Cu/3 mL vs 14.0 Cu/3 mL). Area under the receiver operating characteristic (ROC) curve for bladder TCC detection was 0.819, 95 % CI (0.738-0.883). At the cutoff value of 15.43 Cu/3 mL, the sensitivity and the specificity for detecting bladder cancer are 82.14 and 61.9 %, respectively. We concluded that quantitation of CTCs through FRα ligand-PCR could be a promising method for noninvasive diagnosis of bladder TCC.

  9. A Very High Spatial Resolution Detector for Small Animal PET

    SciTech Connect

    Kanai Shah, M.S.

    2007-03-06

    Positron Emission Tomography (PET) is an in vivo analog of autoradiography and has the potential to become a powerful new tool in imaging biological processes in small laboratory animals. PET imaging of small animals can provide unique information that can help in advancement of human disease models as well as drug development. Clinical PET scanners used for human imaging are bulky, expensive and do not have adequate spatial resolution for small animal studies. Hence, dedicated, low cost instruments are required for conducting small animal studies with higher spatial resolution than what is currently achieved with clinical as well as dedicated small animal PET scanners. The goal of the proposed project is to investigate a new all solid-state detector design for small animal PET imaging. Exceptionally high spatial resolution, good timing resolution, and excellent energy resolution are expected from the proposed detector design. The Phase I project was aimed at demonstrating the feasibility of producing high performance solid-state detectors that provide high sensitivity, spatial resolution, and timing characteristics. Energy resolution characteristics of the new detector were also investigated. The goal of the Phase II project is to advance the promising solid-state detector technology for small animal PET and determine its full potential. Detectors modules will be built and characterized and finally, a bench-top small animal PET system will be assembled and evaluated.

  10. Development of a Novel PET Tracer [18F]AlF-NOTA-C6 Targeting MMP2 for Tumor Imaging

    PubMed Central

    Cheng, Chao; Zhang, Dazhi; Zhang, Anyu; Wang, Lizhen; Jiang, Hongdie; Wang, Tao; Liu, Hongrui; Xu, Yuping; Yang, Runlin; Chen, Fei; Yang, Min; Zuo, Changjing

    2015-01-01

    Background and Objective The overexpression of gelatinases, that is, matrix metalloproteinase MMP2 and MMP9, has been associated with tumor progression, invasion, and metastasis. To image MMP2 in tumors, we developed a novel ligand termed [18F]AlF-NOTA-C6, with consideration that: c(KAHWGFTLD)NH2 (herein, C6) is a selective gelatinase inhibitor; Cy5.5-C6 has been visualized in many in vivo tumor models; positron emission tomography (PET) has a higher detection sensitivity and a wider field of view than optical imaging; fluorine-18 (18F) is the optimal PET radioisotope, and the creation of a [18F]AlF-peptide complex is a simple procedure. Methods C6 was conjugated to the bifunctional chelator NOTA (1, 4, 7-triazacyclononanetriacetic acid) for radiolabeling [18F]AlF conjugation. The MMP2-binding characteristics and tumor-targeting efficacy of [18F]AlF-NOTA-C6 were tested in vitro and in vivo. Results The non-decay corrected yield of [18F]AlF-NOTA-C6 was 46.2–64.2%, and the radiochemical purity exceeded 95%. [18F]AlF-NOTA-C6 was favorably retained in SKOV3 and PC3 cells, determined by cell uptake. Using NOTA-C6 as a competitive ligand, the uptake of [18F]AlF-NOTA-C6 in SKOV3 cells decreased in a dose-dependent manner. In biodistribution and PET imaging studies, higher radioactivity concentrations were observed in tumors. Pre-injection of C6 caused a marked reduction in tumor tissue uptake. Immunohistochemistry showed MMP2 in tumor tissues. Conclusions [18F]AlF-NOTA-C6 was easy to synthesize and has substantial potential as an imaging agent that targets MMP2 in tumors. PMID:26540114

  11. PET in oncology: will it replace the other modalities?

    PubMed

    Hoh, C K; Schiepers, C; Seltzer, M A; Gambhir, S S; Silverman, D H; Czernin, J; Maddahi, J; Phelps, M E

    1997-04-01

    Medical imaging technology is rapidly expanding and the role of each modality is being redefined constantly. PET has been around since the early sixties and gained clinical acceptance in oncology only after an extreme number of scientific publications. Although PET has the unique ability to image biochemical processes in vivo, this ability is not fully used as a clinical imaging tool. In this overview, the role of PET in relation to other tumor imaging modalities will be discussed and the reported results in the literature will be reviewed. In predicting the future of PET, technical improvements of other imaging modalities need to be dealt with. The fundamental physical principles for image formation with computed tomography (CT), ultrasound (US), magnetic resonance imaging (MRI), photon-emission tomography (PET), and single photon emission CT (SPECT) will not change. The potential variety of radiopharmaceuticals which may be developed is unlimited, however, and this provides nuclear imaging techniques with a significant advantage and adaptive features for future biologic imaging. The current applications of PET in oncology have been in characterizing tumor lesions, differentiating recurrent disease from treatment effects, staging tumors, evaluating the extent of disease, and monitoring therapy. The future developments in medicine may use the unique capabilities of PET not only in diagnostic imaging but also in molecular medicine and genetics. The articles discussed in this review were selected from a literature search covering the last 3 years, and in which comparisons of PET with conventional imaging were addressed specifically. PET studies with the glucose analogue fluorine-18-labeled deoxyglucose (FDG) have shown the ability of detecting tumor foci in a variety of histological neoplasms such as thyroid cancer, breast cancer, lymphoma, lung cancer, head and neck carcinoma, colorectal cancer, ovarian carcinoma, and musculoskeletal tumors. Also, the contribution

  12. Replication Capacity of Avian Influenza A(H9N2) Virus in Pet Birds and Mammals, Bangladesh

    PubMed Central

    Lenny, Brian J.; Shanmuganatham, Karthik; Sonnberg, Stephanie; Feeroz, Mohammed M.; Alam, S.M. Rabiul; Hasan, M. Kamrul; Jones-Engel, Lisa; McKenzie, Pamela; Krauss, Scott; Webster, Robert G.

    2015-01-01

    Avian influenza A(H9N2) is an agricultural and public health threat. We characterized an H9N2 virus from a pet market in Bangladesh and demonstrated replication in samples from pet birds, swine tissues, human airway and ocular cells, and ferrets. Results implicated pet birds in the potential dissemination and zoonotic transmission of this virus. PMID:26583371

  13. Replication Capacity of Avian Influenza A(H9N2) Virus in Pet Birds and Mammals, Bangladesh.

    PubMed

    Lenny, Brian J; Shanmuganatham, Karthik; Sonnberg, Stephanie; Feeroz, Mohammed M; Alam, S M Rabiul; Hasan, M Kamrul; Jones-Engel, Lisa; McKenzie, Pamela; Krauss, Scott; Webster, Robert G; Jones, Jeremy C

    2015-12-01

    Avian influenza A(H9N2) is an agricultural and public health threat. We characterized an H9N2 virus from a pet market in Bangladesh and demonstrated replication in samples from pet birds, swine tissues, human airway and ocular cells, and ferrets. Results implicated pet birds in the potential dissemination and zoonotic transmission of this virus.

  14. [Pets, veterinarians, and multicultural society].

    PubMed

    Klumpers, M; Endenburg, N

    2009-01-15

    Dutch society comprises a growing percentage of non-Western ethnic minority groups. Little is known about pet ownership among these groups. This study explores some aspects of pet ownership, and the position of veterinarians, among the four largest non-Western ethnic minority groups in the Netherlands. Information was gathered through street interviews with people from a Moroccan, Turkish, Surinamese, or Antillean (including Aruban) background. Five hundred people where interviewed, including 41 pet owners. Results showed that people from non-Western ethnic minorities kept pets less often than Dutch people, with fish and birds being the most frequently kept pets. The number of visits to the veterinary clinic was comparable to that of Dutch pet owners; however, reasons given for the last visit were different. People from non-Western ethnic minorities mostly visited a veterinarian if their pet was ill whereas Dutch people visited the veterinarian if their pet needed to be vaccinated. People from non-Western ethnic minorities were positive about veterinarians, considering that they had sufficient knowledge about and concern for their pets. Moreover, veterinarians were trusted and provided understandable information--the respondents felt that they could go to their veterinarian with any question or problem regarding their pets. Although most respondents considered a visit to the veterinarian expensive, they were more than willing to invest in their pet's health.

  15. Pet Allergy Quiz

    MedlinePlus

    ... term treatment for pet allergies. True False False: Allergy shots therapy (immunotherapy) has a proven track record as an effective form of long term treatment. Talk to your allergist / immunologist about whether this treatment approach is right for you. ... Utility navigation Donate ...

  16. Pets and Parenting.

    ERIC Educational Resources Information Center

    Mullis, Ann K.; And Others

    1987-01-01

    The authors describe a method for teaching parenting skills and helping students decide whether they want children by having them adopt a puppy or kitten for a 6-10 week period. They discuss how to use the pet adoption project in a family life education unit. (CH)

  17. PET/Computed Tomography Using New Radiopharmaceuticals in Targeted Therapy.

    PubMed

    Sharma, Punit; Kumar, Rakesh; Alavi, Abass

    2015-10-01

    Targeted therapy is gaining prominence in the management of different cancers. Given different mechanism of action compared with traditional chemoradiotherapy, selection of patients for targeted therapy and monitoring response to these agents is difficult with conventional imaging. Various new PET radiopharmaceuticals have been evaluated for molecular imaging of these targets to achieve specific patient selection and response monitoring. These PET/computed tomography (CT) agents target the cell surface receptors, hormone receptors, receptor tyrosine kinases, or angiogenesis components. This article reviews the established and potential role of PET/CT with new radiopharmaceuticals for guiding targeted therapy.

  18. Identification of the odor-active volatile compound (Z,Z)-4,7-tridecadienal as a potential ligand for the transmembrane receptor CD36.

    PubMed

    Tsuzuki, Satoshi; Amitsuka, Takahiko; Okahashi, Tatsuya; Kozai, Yuki; Yamasaki, Masayuki; Inoue, Kazuo; Fushiki, Tohru

    2016-01-01

    Cluster of differentiation 36 (CD36) is a broadly expressed transmembrane protein that has multiple ligands, including oxidized low-density lipoproteins. We found recently that CD36 is expressed in olfactory sensory neurons and postulated that it plays a role in the detection of distinct odorants in the nasal cavity. To date, however, there have been few examples of attempts to identify CD36-recognizable odorants. In this study, by an in vitro assay using a peptide mimic of the receptor, we provided evidence that CD36 recognizes (Z,Z)-4,7-tridecadienal, an odor-active volatile compound that is known to occur in Katsuobushi (dried, fermented, and smoked skipjack tuna commonly used in Japanese cuisine as a seasoning) and in the preorbital secretion of male oribi. In addition, by comparing the data with those of its related compounds, we provided information on the structural requirements of (Z,Z)-4,7-tridecadienal for recognition by CD36. For instance, we showed that flexible rotation around the C2-C3 bond of the volatile may be of importance in gaining access to CD36. Identification of (Z,Z)-4,7-tridecadienal as the ligand prompts us to hypothesize that CD36 could participate in the control of distinct mammalian behaviors (e.g., food selection) through its ability to recognize specific odorants in the environment.

  19. Estimating potential evapotranspiration with improved radiation estimation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Potential evapotranspiration (PET) is of great importance to estimation of surface energy budget and water balance calculation. The accurate estimation of PET will facilitate efficient irrigation scheduling, drainage design, and other agricultural and meteorological applications. However, accuracy o...

  20. Multimodal image coregistration and inducible selective cell ablation to evaluate imaging ligands.

    PubMed

    Virostko, John; Henske, Joseph; Vinet, Laurent; Lamprianou, Smaragda; Dai, Chunhua; Radhika, Aramandla; Baldwin, Ronald M; Ansari, Mohammad S; Hefti, Franz; Skovronsky, Daniel; Kung, Hank F; Herrera, Pedro L; Peterson, Todd E; Meda, Paolo; Powers, Alvin C

    2011-12-20

    We combined multimodal imaging (bioluminescence, X-ray computed tomography, and PET), tomographic reconstruction of bioluminescent sources, and two unique, complementary models to evaluate three previously synthesized PET radiotracers thought to target pancreatic beta cells. The three radiotracers {[(18)F]fluoropropyl-(+)-dihydrotetrabenazine ([(18)F]FP-DTBZ), [(18)F](+)-2-oxiranyl-3-isobutyl-9-(3-fluoropropoxy)-10-methoxy-2,3,4,6,7,11b-hexahydro-1H-pyrido[2,1-a]isoquinoline ((18)F-AV-266), and (2S,3R,11bR)-9-(3-fluoropropoxy)-2-(hydroxymethyl)-3-isobutyl-10-methoxy-2,3,4,6,7,11b-hexahydro-1H-pyrido[2,1-a]isoquinolin-2-ol ((18)F-AV-300)} bind vesicular monoamine transporter 2. Tomographic reconstruction of the bioluminescent signal in mice expressing luciferase only in pancreatic beta cells was used to delineate the pancreas and was coregistered with PET and X-ray computed tomography images. This strategy enabled unambiguous identification of the pancreas on PET images, permitting accurate quantification of the pancreatic PET signal. We show here that, after conditional, specific, and rapid mouse beta-cell ablation, beta-cell loss was detected by bioluminescence imaging but not by PET imaging, given that the pancreatic signal provided by three PET radiotracers was not altered. To determine whether these ligands bound human beta cells in vivo, we imaged mice transplanted with luciferase-expressing human islets. The human islets were imaged by bioluminescence but not with the PET ligands, indicating that these vesicular monoamine transporter 2-directed ligands did not specifically bind beta cells. These data demonstrate the utility of coregistered multimodal imaging as a platform for evaluation and validation of candidate ligands for imaging islets.

  1. MR/PET or PET/MRI: does it matter?

    PubMed

    Beyer, Thomas; Moser, Ewald

    2013-02-01

    After the very successful clinical introduction of combined PET/CT imaging a decade ago, a hardware combination of PET and MR is following suit. Today, three different approaches towards integrated PET/MR have been proposed: (1) a triple-modality system with a 3T MRI and a time-of-flight PET/CT installed in adjacent rooms, (2) a tandem system with a 3T MRI and a time-of-flight PET/CT in a co-planar installation with a joint patient handling system, and (3) a fully-integrated system with a whole-body PET system mounted inside a 3T MRI system. This special issue of MAGMA brings together contributions from key experts in the field of PET/MR, PET/CT and CT. The various papers share the author's perspectives on the state-of-the-art PET/MR imaging with any of the three approaches mentioned above. In addition to several reviews discussing advantages and challenges of combining PET and MRI for clinical diagnostics, first clinical data are also presented. We expect this special issue to nurture future improvements in hardware, clinical protocols, and efficient post-processing strategies to further assess the diagnostic value of combined PET/MR imaging. It remains to be seen whether a so-called "killer application" for PET/MRI will surface. In that case PET/MR is likely to excel in pre-clinical and selected research applications for now. This special issue helps the readers to stay on track of this exciting development.

  2. Precision Medicine in Multiple Sclerosis: Future of PET Imaging of Inflammation and Reactive Astrocytes

    PubMed Central

    Poutiainen, Pekka; Jaronen, Merja; Quintana, Francisco J.; Brownell, Anna-Liisa

    2016-01-01

    Non-invasive molecular imaging techniques can enhance diagnosis to achieve successful treatment, as well as reveal underlying pathogenic mechanisms in disorders such as multiple sclerosis (MS). The cooperation of advanced multimodal imaging techniques and increased knowledge of the MS disease mechanism allows both monitoring of neuronal network and therapeutic outcome as well as the tools to discover novel therapeutic targets. Diverse imaging modalities provide reliable diagnostic and prognostic platforms to better achieve precision medicine. Traditionally, magnetic resonance imaging (MRI) has been considered the golden standard in MS research and diagnosis. However, positron emission tomography (PET) imaging can provide functional information of molecular biology in detail even prior to anatomic changes, allowing close follow up of disease progression and treatment response. The recent findings support three major neuroinflammation components in MS: astrogliosis, cytokine elevation, and significant changes in specific proteins, which offer a great variety of specific targets for imaging purposes. Regardless of the fact that imaging of astrocyte function is still a young field and in need for development of suitable imaging ligands, recent studies have shown that inflammation and astrocyte activation are related to progression of MS. MS is a complex disease, which requires understanding of disease mechanisms for successful treatment. PET is a precise non-invasive imaging method for biochemical functions and has potential to enhance early and accurate diagnosis for precision therapy of MS. In this review we focus on modulation of different receptor systems and inflammatory aspect of MS, especially on activation of glial cells, and summarize the recent findings of PET imaging in MS and present the most potent targets for new biomarkers with the main focus on experimental MS research. PMID:27695400

  3. Bisphenol A (BPA) in the serum of pet dogs following short-term consumption of canned dog food and potential health consequences of exposure to BPA.

    PubMed

    Koestel, Zoe L; Backus, Robert C; Tsuruta, Kaoru; Spollen, William G; Johnson, Sarah A; Javurek, Angela B; Ellersieck, Mark R; Wiedmeyer, Charles E; Kannan, Kurunthachalam; Xue, Jingchuan; Bivens, Nathan J; Givan, Scott A; Rosenfeld, Cheryl S

    2017-02-01

    Bisphenol A (BPA) is a widely present endocrine disruptor chemical found in many household items. Moreover, this chemical can bioaccumulate in various terrestrial and aquatic sources; thereby ensuring continual exposure of animals and humans. For most species, including humans, diet is considered the primary route of exposure. However, there has been little investigation whether commercial-brands of dog foods contain BPA and potential health ramifications of BPA-dietary exposure in dogs. We sought to determine BPA content within dog food, whether short-term consumption of these diets increases serum concentrations of BPA, and potential health consequences, as assessed by potential hematological, serum chemistry, cortisol, DNA methylation, and gut microbiome changes, in dogs associated with short-term dietary exposure to BPA. Fourteen healthy privately-owned dogs were used in this study. Blood and fecal samples were collected prior to dogs being placed for two-weeks on one of two diets (with one considered to be BPA-free), and blood and fecal samples were collected again. Serum/plasma samples were analyzed for chemistry and hematology profiles, cortisol concentrations, 5-methylcytosine in lymphocytes, and total BPA concentrations. Fecal samples were used for microbiome assessments. Both diets contained BPA, and after two-weeks of being on either diet, dogs had a significant increase in circulating BPA concentrations (pre-samples=0.7±0.15ng/mL, post-samples=2.2±0.15ng/mL, p<0.0001). Elevated BPA concentrations positively correlated with increased plasma bicarbonate concentrations and associated with fecal microbiome alterations. Short-term feeding of canned dog food increased circulating BPA concentrations in dogs comparable to amounts detected in humans, and greater BPA concentrations were associated with serum chemistry and microbiome changes. Dogs, who share our internal and external environments with us, are likely excellent indicators of potential human health

  4. SYNTHESIS AND CHARACTERIZATION OF PYRIDINE END-FUNCTIONALIZED POLY (3-HEXYLTHIOPHENE)s: POTENTIAL LIGANDS FOR SQD/P3HT BHJs

    SciTech Connect

    Pickel, Deanna L; Kochemba, William Michael; Kilbey, II, S Michael

    2011-01-01

    Extensive research has been done to optimize donor-acceptor properties of bulk heterojunction organic photovoltaics (BHJ OPVs) leading to devices with relatively high power conversion efficiencies (>5%). Polymer-nanoparticle hybrid solar cells are one class of BHJ OPVs that incorporate nanoparticles (electron carrier) in a polymer matrix (hole carrier). Blending inorganic nanoparticles with an organic polymer matrix is challenging due to unfavorable interactions between the nanoparticle and polymer leading to aggregation and poor charge separation. One method to improve ordering of the BHJ is by use of ligands on the inorganic nanoparticles that facilitate homogenous dispersion within the polymer matrix. This paper will discuss the preparation of pyridine end-functionalized P3HTs by in situ quenching of the Grignard Metathesis Polymerization with functional Grignard reagents. The degree of functionality of the polymers is determined by MALDI-TOF MS. In addition, methods to optimize the functionality of the resulting polymer will also be discussed.

  5. Discovery of new potential hits of Plasmodium falciparum enoyl-ACP reductase through ligand- and structure-based drug design approaches.

    PubMed

    Neves, Bruno J; Bueno, Renata V; Braga, Rodolpho C; Andrade, Carolina H

    2013-04-15

    We here report the discovery of novel Plasmodium falciparum enoyl-ACP reductase (PfENR) inhibitors as new antimalarial hits through ligand- and structure-based drug design approaches. We performed 2D and 3D QSAR studies on a set of rhodanine analogues using hologram QSAR (HQSAR), comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) techniques. Statistical and satisfactory results were obtained for the best HQSAR (r(2) of 0.968 and qLOO(2) of 0.751), CoMFA (r(2) of 0.955 and qLOO(2) of 0.806) and CoMSIA (r(2) of 0.965 and qLOO(2) of 0.659) models. The information gathered from the QSAR models guided us to design new PfENR inhibitors. Three new hits were predicted with potency in the submicromolar range and presented drug-like properties.

  6. Talking with Children about Furry Classroom Pets.

    ERIC Educational Resources Information Center

    Texas Child Care, 1994

    1994-01-01

    Notes that rodents and rabbits share many characteristics that make them suitable classroom pets and gives background information on rabbits, guinea pigs, hamsters, and gerbils. Offers advice on buying a classroom pet, the pet's home, feeding, helping the children handle the pet, and pet health and family planning. (TJQ)

  7. PET/CT imaging in lung cancer: indications and findings*

    PubMed Central

    Hochhegger, Bruno; Alves, Giordano Rafael Tronco; Irion, Klaus Loureiro; Fritscher, Carlos Cezar; Fritscher, Leandro Genehr; Concatto, Natália Henz; Marchiori, Edson

    2015-01-01

    The use of PET/CT imaging in the work-up and management of patients with lung cancer has greatly increased in recent decades. The ability to combine functional and anatomical information has equipped PET/CT to look into various aspects of lung cancer, allowing more precise disease staging and providing useful data during the characterization of indeterminate pulmonary nodules. In addition, the accuracy of PET/CT has been shown to be greater than is that of conventional modalities in some scenarios, making PET/CT a valuable noninvasive method for the investigation of lung cancer. However, the interpretation of PET/CT findings presents numerous pitfalls and potential confounders. Therefore, it is imperative for pulmonologists and radiologists to familiarize themselves with the most relevant indications for and limitations of PET/CT, seeking to protect their patients from unnecessary radiation exposure and inappropriate treatment. This review article aimed to summarize the basic principles, indications, cancer staging considerations, and future applications related to the use of PET/CT in lung cancer. PMID:26176525

  8. An overview of PET/MR, focused on clinical applications.

    PubMed

    Catalano, Onofrio Antonio; Masch, William Roger; Catana, Ciprian; Mahmood, Umar; Sahani, Dushyant Vasudeo; Gee, Michael Stanley; Menezes, Leon; Soricelli, Andrea; Salvatore, Marco; Gervais, Debra; Rosen, Bruce Robert

    2017-02-01

    Hybrid PET/MR scanners are innovative imaging devices that simultaneously or sequentially acquire and fuse anatomical and functional data from magnetic resonance (MR) with metabolic information from positron emission tomography (PET) (Delso et al. in J Nucl Med 52:1914-1922, 2011; Zaidi et al. in Phys Med Biol 56:3091-3106, 2011). Hybrid PET/MR scanners have the potential to greatly impact not only on medical research but also, and more importantly, on patient management. Although their clinical applications are still under investigation, the increased worldwide availability of PET/MR scanners, and the growing published literature are important determinants in their rising utilization for primarily clinical applications. In this manuscript, we provide a summary of the physical features of PET/MR, including its limitations, which are most relevant to clinical PET/MR implementation and to interpretation. Thereafter, we discuss the most important current and emergent clinical applications of such hybrid technology in the abdomen and pelvis, both in the field of oncologic and non-oncologic imaging, and we provide, when possible, a comparison with clinically consolidated imaging techniques, like for example PET/CT.

  9. First-in-Human Assessment of the Novel PDE2A PET Radiotracer 18F-PF-05270430

    PubMed Central

    Waterhouse, Rikki N.; Nabulsi, Nabeel; Lin, Shu-Fei; Labaree, David; Ropchan, Jim; Tarabar, Sanela; DeMartinis, Nicholas; Ogden, Adam; Banerjee, Anindita; Huang, Yiyun; Carson, Richard E.

    2016-01-01

    This was a first-in-human study of the novel phosphodiesterase-2A (PDE2A) PET ligand 18F-PF-05270430. The primary goals were to determine the appropriate tracer kinetic model to quantify brain uptake and to examine the within-subject test–retest variability. Methods: In advance of human studies, radiation dosimetry was determined in nonhuman primates. Six healthy male subjects participated in a test–retest protocol with dynamic scans and metabolite-corrected input functions. Nine brain regions of interest were studied, including the striatum, white matter, neocortical regions, and cerebellum. Multiple modeling methods were applied to calculate volume of distribution (VT) and binding potentials relative to the nondisplaceable tracer in tissue (BPND), concentration of tracer in plasma (BPP), and free tracer in tissue (BPF). The cerebellum was selected as a reference region to calculate binding potentials. Results: The dosimetry study provided an effective dose of less than 0.30 mSv/MBq, with the gallbladder as the critical organ; the human target dose was 185 MBq. There were no adverse events or clinically detectable pharmacologic effects reported. Tracer uptake was highest in the striatum, followed by neocortical regions and white matter, and lowest in the cerebellum. Regional time–activity curves were well fit by multilinear analysis-1, and a 70-min scan duration was sufficient to quantify VT and the binding potentials. BPND, with mean values ranging from 0.3 to 0.8, showed the best intrasubject and intersubject variability and reliability. Test–retest variability in the whole brain (excluding the cerebellum) of VT, BPND, and BPP were 8%, 16%, and 17%, respectively. Conclusion: 18F-PF-05270430 shows promise as a PDE2A PET ligand, albeit with low binding potential values. PMID:27103022

  10. Quantitative assessment of human and pet exposure to Salmonella associated with dry pet foods.

    PubMed

    Lambertini, Elisabetta; Buchanan, Robert L; Narrod, Clare; Ford, Randall M; Baker, Robert C; Pradhan, Abani K

    2016-01-04

    Recent Salmonella outbreaks associated with dry pet foods and treats highlight the importance of these foods as previously overlooked exposure vehicles for both pets and humans. In the last decade efforts have been made to raise the safety of this class of products, for instance by upgrading production equipment, cleaning protocols, and finished product testing. However, no comprehensive or quantitative risk profile is available for pet foods, thus limiting the ability to establish safety standards and assess the effectiveness of current and proposed Salmonella control measures. This study sought to develop an ingredients-to-consumer quantitative microbial exposure assessment model to: 1) estimate pet and human exposure to Salmonella via dry pet food, and 2) assess the impact of industry and household-level mitigation strategies on exposure. Data on prevalence and concentration of Salmonella in pet food ingredients, production process parameters, bacterial ecology, and contact transfer in the household were obtained through literature review, industry data, and targeted research. A probabilistic Monte Carlo modeling framework was developed to simulate the production process and basic household exposure routes. Under the range of assumptions adopted in this model, human exposure due to handling pet food is null to minimal if contamination occurs exclusively before extrusion. Exposure increases considerably if recontamination occurs post-extrusion during coating with fat, although mean ingested doses remain modest even at high fat contamination levels, due to the low percent of fat in the finished product. Exposure is highly variable, with the distribution of doses ingested by adult pet owners spanning 3Log CFU per exposure event. Child exposure due to ingestion of 1g of pet food leads to significantly higher doses than adult doses associated with handling the food. Recontamination after extrusion and coating, e.g., via dust or equipment surfaces, may also lead to

  11. Imaging quality of (44)Sc in comparison with five other PET radionuclides using Derenzo phantoms and preclinical PET.

    PubMed

    Bunka, Maruta; Müller, Cristina; Vermeulen, Christiaan; Haller, Stephanie; Türler, Andreas; Schibli, Roger; van der Meulen, Nicholas P

    2016-04-01

    PET is the favored nuclear imaging technique because of the high sensitivity and resolution it provides, as well as the possibility for quantification of accumulated radioactivity. (44)Sc (T1/2=3.97h, Eβ(+)=632keV) was recently proposed as a potentially interesting radionuclide for PET. The aim of this study was to investigate the image quality, which can be obtained with (44)Sc, and compare it with five other, frequently employed PET nuclides using Derenzo phantoms and a small-animal PET scanner. The radionuclides were produced at the medical cyclotron at CRS, ETH Zurich ((11)C, (18)F), at the Injector II research cyclotron at CRS, PSI ((64)Cu, (89)Zr, (44)Sc), as well as via a generator system ((68)Ga). Derenzo phantoms, containing solutions of each of these radionuclides, were scanned using a GE Healthcare eXplore VISTA small-animal PET scanner. The image resolution was determined for each nuclide by analysis of the intensity signal using the reconstructed PET data of a hole diameter of 1.3mm. The image quality of (44)Sc was compared to five frequently-used PET radionuclides. In agreement with the positron range, an increasing relative resolution was determined in the sequence of (68)Ga<(44)Sc<(89)Zr<(11)C<(64)Cu<(18)F. The performance of (44)Sc was in agreement with the theoretical expectations based on the energy of the emitted positrons.

  12. Honey-based PET or PET/chitosan fibrous wound dressings: effect of honey on electrospinning process.

    PubMed

    Arslan, Aysu; Simşek, Murat; Aldemir, Sevcan Dalkıranoğlu; Kazaroğlu, Nur Merve; Gümüşderelioğlu, Menemşe

    2014-07-01

    In this study, fibrous mats were fabricated via electrospinning from solutions of polyethylene terephthalate (PET), PET/chitosan, and PET/honey at different concentrations. The effect of honey and chitosan on electrospinning process was investigated and compared. Fibers containing chitosan had a beaded or ribbon-like/branched morphology, but this morphology improved in the presence of honey. The diameter of electrospun fibers decreased with an increased ratio of honey in PET solution. In addition, fiber deposition area in the collector increased by increasing the honey content. PET/chitosan and PET/honey fibrous mats reached an equilibrium water content in 15 min and their water uptake capacities, which are important for exudating wounds, were found in the range of 280-430% on dry basis. Cytotoxicity evaluation demonstrated that fibers exhibited no cytotoxic activity. This study discloses that PET fibrous mats especially electrospun in the presence of honey could be proposed as potential wound dressing materials owing to their improved processing abilities besides their suitable structural properties.

  13. Predictive and prognostic value of FDG-PET

    PubMed Central

    Oyen, Wim J.G.

    2008-01-01

    Abstract The predictive and prognostic value of fluorodeoxyglucose (FDG)-positron emission tomography (PET) in non-small-cell lung carcinoma, colorectal carcinoma and lymphoma is discussed. The degree of FDG uptake is of prognostic value at initial presentation, after induction treatment prior to resection and in the case of relapse of non-small cell lung cancer (NSCLC). In locally advanced and advanced stages of NSCLC, FDG-PET has been shown to be predictive for clinical outcome at an early stage of treatment. In colorectal carcinoma, limited studies are available on the prognostic value of FDG-PET, however, the technique appears to have great potential in monitoring the success of local ablative therapies soon after intervention and in the prediction and evaluation of response to radiotherapy, systemic therapy, and combinations thereof. The prognostic value of end-of treatment FDG-PET for FDG-avid lymphomas has been established, and the next step is to define how to use this information to optimize patient outcome. In Hodgkin's lymphoma, FDG-PET has a high negative predictive value, however, histological confirmation of positive findings should be sought where possible. For non-Hodgkin's lymphoma, the opposite applies. The newly published standardized guidelines for interpretation formulates specific criteria for visual interpretation and for defining PET positivity in the liver, spleen, lung, bone marrow and small residual lesions. The introduction of these guidelines should reduce variability among studies. Interim PET offers a reliable method for early prediction of long-term remission, however it should only be performed in prospective randomized controlled trials. Many of the diagnostic and management questions considered in this review are relevant to other tumour types. Further research in this field is of great importance, since it may lead to a change in the therapeutic concept of cancer. The preliminary findings call for systematic inclusion of FDG-PET

  14. Contribution of FDOPA PET to radiotherapy planning for advanced glioma

    NASA Astrophysics Data System (ADS)

    Dowson, Nicholas; Fay, Michael; Thomas, Paul; Jeffree, Rosalind; McDowall, Robert; Winter, Craig; Coulthard, Alan; Smith, Jye; Gal, Yaniv; Bourgeat, Pierrick; Salvado, Olivier; Crozier, Stuart; Rose, Stephen

    2014-03-01

    Despite radical treatment with surgery, radiotherapy and chemotherapy, advanced gliomas recur within months. Geographic misses in radiotherapy planning may play a role in this seemingly ineluctable recurrence. Planning is typically performed on post-contrast MRIs, which are known to underreport tumour volume relative to FDOPA PET scans. FDOPA PET fused with contrast enhanced MRI has demonstrated greater sensitivity and specificity than MRI alone. One sign of potential misses would be differences between gross target volumes (GTVs) defined using MRI alone and when fused with PET. This work examined whether such a discrepancy may occur. Materials and Methods: For six patients, a 75 minute PET scan using 3,4-dihydroxy-6-18F-fluoro-L-phynel-alanine (18F-FDOPA) was taken within 2 days of gadolinium enhanced MRI scans. In addition to standard radiotherapy planning by an experienced radiotherapy oncologist, a second gross target volume (GTV) was defined by an experienced nuclear medicine specialist for fused PET and MRI, while blinded to the radiotherapy plans. The volumes from standard radiotherapy planning were compared to the PET defined GTV. Results: The comparison indicated radiotherapy planning would change in several cases if FDOPA PET data was available. PET-defined contours were external to 95% prescribed dose for several patients. However, due to the radiotherapy margins, the discrepancies were relatively small in size and all received a dose of 50 Gray or more. Conclusions: Given the limited size of the discrepancies it is uncertain that geographic misses played a major role in patient outcome. Even so, the existence of discrepancies indicates that FDOPA PET could assist in better defining margins when planning radiotherapy for advanced glioma, which could be important for highly conformal radiotherapy plans.

  15. Hydroxypyridinone Chelators: From Iron Scavenging to Radiopharmaceuticals for PET Imaging with Gallium-68

    PubMed Central

    Cusnir, Ruslan; Imberti, Cinzia; Hider, Robert C.; Blower, Philip J.; Ma, Michelle T.

    2017-01-01

    Derivatives of 3,4-hydroxypyridinones have been extensively studied for in vivo Fe3+ sequestration. Deferiprone, a 1,2-dimethyl-3,4-hydroxypyridinone, is now routinely used for clinical treatment of iron overload disease. Hexadentate tris(3,4-hydroxypyridinone) ligands (THP) complex Fe3+ at very low iron concentrations, and their high affinities for oxophilic trivalent metal ions have led to their development for new applications as bifunctional chelators for the positron emitting radiometal, 68Ga3+, which is clinically used for molecular imaging in positron emission tomography (PET). THP-peptide bioconjugates rapidly and quantitatively complex 68Ga3+ at ambient temperature, neutral pH and micromolar concentrations of ligand, making them amenable to kit-based radiosynthesis of 68Ga PET radiopharmaceuticals. 68Ga-labelled THP-peptides accumulate at target tissue in vivo, and are excreted largely via a renal pathway, providing high quality PET images. PMID:28075350

  16. Structural, spectral, DFT, pH-metric and biological studies on Cr(III), Mn(II) and Fe(III) complexes of dithione heterocyclic thiosemicarbazide ligand

    NASA Astrophysics Data System (ADS)

    Abu El-Reash, Gaber M.; El-Gammal, Ola A.; El-Gamil, Mohammed M.

    2013-03-01

    Cr(III), Mn(II) and Fe(III) complexes derived from the quadruple potential dithione heterocyclic thiosemicarbazide ligand (H2PET) have been prepared and characterized by conventional techniques. The isolated complexes were assigned the formulae, [Cr(HPET)(H2O)2Cl2]·3H2O, [Mn(HPET)(H2O)Cl]2 and [Fe(HPET)(H2O)2Cl2]·H2O, respectively. IR data revealed that the ligand behaves as monobasic bidentate through (Cdbnd N)py and (Csbnd S) groups in both Cr(III) and Fe(III) complexes. In the binuclear Mn(II) complex, H2PET acts as NSNS monobasic tetradente via (Cdbnd N)py, (Csbnd S), (Cdbnd S) and the new azomethine, (Ndbnd C)* groups. An octahedral geometry for all complexes was proposed. The bond lengths, bond angles, HOMO, LUMO and dipole moment have been calculated by DFT using materials studio program to confirm the geometry of H2PET and its metal complexes. The ligand association constant and the stability constants of its complexes in addition to the thermodynamic parameters were calculated from pH metrically at 298, 308 and 318°K in 50% dioxane-water mixture, respectively. Also, the kinetic and thermodynamic parameters for the different thermal degradation steps of the complexes were determined by Coats-Redfern and Horowitz-Metzger methods. Moreover, the anti-oxidant (using ABTS and DPPH methods), anti-hemolytic, and cytotoxic activities of the compounds have been tested.

  17. Using Technology to Better Characterize the Apollo Sample Suite: A Retroactive PET Analysis and Potential Model for Future Sample Return Missions

    NASA Technical Reports Server (NTRS)

    Zeigler, R. A.

    2015-01-01

    From 1969-1972 the Apollo missions collected 382 kg of lunar samples from six distinct locations on the Moon. Studies of the Apollo sample suite have shaped our understanding of the formation and early evolution of the Earth-Moon system, and have had important implications for studies of the other terrestrial planets (e.g., through the calibration of the crater counting record) and even the outer planets (e.g., the Nice model of the dynamical evolution of the Solar System). Despite nearly 50 years of detailed research on Apollo samples, scientists are still developing new theories about the origin and evolution of the Moon. Three areas of active research are: (1) the abundance of water (and other volatiles) in the lunar mantle, (2) the timing of the formation of the Moon and the duration of lunar magma ocean crystallization, (3) the formation of evolved lunar lithologies (e.g., granites) and implications for tertiary crustal processes on the Moon. In order to fully understand these (and many other) theories about the Moon, scientists need access to "new" lunar samples, particularly new plutonic samples. Over 100 lunar meteorites have been identified over the past 30 years, and the study of these samples has greatly aided in our understanding of the Moon. However, terrestrial alteration and the lack of geologic context limit what can be learned from the lunar meteorites. Although no "new" large plutonic samples (i.e., hand-samples) remain to be discovered in the Apollo sample collection, there are many large polymict breccias in the Apollo collection containing relatively large (approximately 1 cm or larger) previously identified plutonic clasts, as well as a large number of unclassified lithic clasts. In addition, new, previously unidentified plutonic clasts are potentially discoverable within these breccias. The question becomes how to non-destructively locate and identify new lithic clasts of interest while minimizing the contamination and physical degradation of

  18. GW-501516 GlaxoSmithKline/Ligand.

    PubMed

    Pelton, Patricia

    2006-04-01

    GlaxoSmithKline and Ligand are developing GW-501516, a peroxisome proliferator-activator receptor-delta agonist for the potential treatment of dyslipidemia. Phase II clinical trials of this compound are ongoing.

  19. Extended suicide with a pet.

    PubMed

    Cooke, Brian K

    2013-01-01

    The combination of the killing of a pet and a suicide is a perplexing scenario that is largely unexplored in the literature. Many forensic psychiatrists and psychologists may be unaccustomed to considering the significance of the killing of a pet. The subject is important, however, because many people regard their pets as members of their family. A case is presented of a woman who killed her pet dog and herself by carbon monoxide poisoning. The purpose of this article is to provide an initial exploration of the topic of extended suicide with a pet. Forensic mental health evaluations may have a role in understanding the etiology of this event and in opining as to the culpability of individuals who attempt to or successfully kill a pet and then commit suicide. Because the scientific literature is lacking, there is a need to understand this act from a variety of perspectives. First, a social and anthropological perspective will be presented that summarizes the history of the practice of killing of one's pet, with a focus on the ancient Egyptians. A clinical context will examine what relationship animals have to mental illness. A vast body of existing scientific data showing the relevance of human attachment to pets suggests that conclusions from the phenomena of homicide-suicide and filicide-suicide are applicable to extended suicide with a pet. Finally, recommendations will be proposed for both clinical and forensic psychiatrists faced with similar cases.

  20. Determination of formal redox potentials in aqueous solution of copper(II) complexes with ligands having nitrogen and oxygen donor atoms and comparison with their EPR and UV-Vis spectral features.

    PubMed

    Tabbì, Giovanni; Giuffrida, Alessandro; Bonomo, Raffaele P

    2013-11-01

    Formal redox potentials in aqueous solution were determined for copper(II) complexes with ligands having oxygen and nitrogen as donor atoms. All the chosen copper(II) complexes have well-known stereochemistries (pseudo-octahedral, square planar, square-based pyramidal, trigonal bipyramidal or tetrahedral) as witnessed by their reported spectroscopic, EPR and UV-visible (UV-Vis) features, so that a rough correlation between the measured redox potential and the typical geometrical arrangement of the copper(II) complex could be established. Negative values have been obtained for copper(II) complexes in tetragonally elongated pseudo-octahedral geometries, when measured against Ag/AgCl reference electrode. Copper(II) complexes in tetrahedral environments (or flattened tetrahedral geometries) show positive redox potential values. There is a region, always in the field of negative redox potentials which groups the copper(II) complexes exhibiting square-based pyramidal arrangements. Therefore, it is suggested that a measurement of the formal redox potential could be of great help, when some ambiguities might appear in the interpretation of spectroscopic (EPR and UV-Vis) data. Unfortunately, when the comparison is made between copper(II) complexes in square-based pyramidal geometries and those in square planar environments (or a pseudo-octahedral) a little perturbed by an equatorial tetrahedral distortion, their redox potentials could fall in the same intermediate region. In this case spectroscopic data have to be handled with great care in order to have an answer about a copper complex geometrical characteristics.

  1. Campylobacter coli infection in pet birds in southern Italy.

    PubMed

    Dipineto, Ludovico; Borrelli, Luca; Pace, Antonino; Romano, Violante; D'Orazio, Stefano; Varriale, Lorena; Russo, Tamara Pasqualina; Fioretti, Alessandro

    2017-01-06

    Avian species are considered as the main reservoir of Campylobacter spp. However, few data are available on the presence of this microorganism in pet birds. This study was therefore performed to determine the prevalence of Campylobacter spp. in pet birds bred in southern Italy. Faecal samples were collected from 88 cages housing different species of pet birds and examined by bacteriological culture and polymerase chain reaction. A total of 13.6% of the cage samples were positive for Campylobacter coli. Other Campylobacter spp. were not found. The study shows that C. coli can be isolated from the cages of apparently healthy pet birds, which should therefore be considered as potential carriers of C. coli and a possible source of infection for humans and companion animals.

  2. [The role of PET in lung cancer staging].

    PubMed

    Gärtner, Florian C; Buermann, Jens; Skowasch, Dirk; Biersack, Hans-Jürgen; Essler, Markus

    2015-04-01

    The precise staging of lymph-node and distant metastases is pivotal for the choice of surgical procedures and overall therapy planning for patients with lung cancer. FDG-PET/CT plays a central role in the diagnostic algorithm of patients with potentially curable disease. In patients with histologically proven lung cancer, FDG-PET/CT provides a higher diagnostic accuracy in the staging of lymph-node and distant metastases compared to staging with CT alone. Furthermore, as a whole body examination, FDG-PET/CT may replace further additional examinations. Prospective studies have also shown that the number of unnecessary thoracotomies and mediastinoscopies can be reduced by the inclusion of FDG-PET in the preoperative staging.

  3. Prevalence of Salmonella spp. in pet turtles and their environment.

    PubMed

    Back, Du-San; Shin, Gee-Wook; Wendt, Mitchell; Heo, Gang-Joon

    2016-09-01

    Pet turtles are known as a source of Salmonella infection to humans when handled in captivity. Thirty four turtles purchased from pet shops and online markets in Korea were examined to determine whether the turtles and their environment were contaminated with Salmonella spp. Salmonella spp. were isolated from fecal samples of 17 turtles. These isolates were identified as S. enterica through 16S rRNA gene sequencing. The isolation rate of Salmonella spp. from the soil and water samples increased over time. We concluded that a high percentage of turtles being sold in pet shops were infected with Salmonella spp., and their environments tend to become contaminated over time unless they are maintained properly. These results indicate that pet turtles could be a potential risk of salmonellosis in Korea.

  4. Immunocompromised patients and their pets: still best friends?

    PubMed

    Elad, Daniel

    2013-09-01

    The emergence of immunosuppressive human diseases and therapies in the last decades has raised the question of the risks and benefits for this group of patients deriving from their interaction with pets and the necessity to balance them in the best interest of the pet owner. Risks are related to the possibility of contracting zoonotic infections that are more severe and occasionally lethal in immunocompromised patients. To mitigate the risks and allow the owner to keep the pet, guidelines have been devised. The cooperation and communication between the owner, the physician and the veterinarian are fundamental for a rational approach in evaluating of the potential health risks associated with pets as sources of zoonotic diseases. The final decision should, however, be made by the owner, who alone will enjoy the benefits of the relationship but also be the one to bear the consequences.

  5. Prevalence of Salmonella spp. in pet turtles and their environment

    PubMed Central

    Back, Du-San; Shin, Gee-Wook; Wendt, Mitchell

    2016-01-01

    Pet turtles are known as a source of Salmonella infection to humans when handled in captivity. Thirty four turtles purchased from pet shops and online markets in Korea were examined to determine whether the turtles and their environment were contaminated with Salmonella spp. Salmonella spp. were isolated from fecal samples of 17 turtles. These isolates were identified as S. enterica through 16S rRNA gene sequencing. The isolation rate of Salmonella spp. from the soil and water samples increased over time. We concluded that a high percentage of turtles being sold in pet shops were infected with Salmonella spp., and their environments tend to become contaminated over time unless they are maintained properly. These results indicate that pet turtles could be a potential risk of salmonellosis in Korea. PMID:27729933

  6. MULTIMODALITY IMAGING: BEYOND PET/CT AND SPECT/CT

    PubMed Central

    Cherry, Simon R.

    2009-01-01

    Multimodality imaging with PET/CT and SPECT/CT has become commonplace in clinical practice and in preclinical and basic medical research. Do other combinations of imaging modalities have a similar potential to impact medical science and clinical medicine? The combination of PET or SPECT with MRI is an area of active research at the present time, while other, perhaps less obvious combinations, including CT/MR and PET/optical also are being studied. In addition to the integration of the instrumentation, there are parallel developments in synthesizing imaging agents that can be viewed by multiple imaging modalities. Is the fusion of PET and SPECT with CT the ultimate answer in multimodality imaging, or is it just the first example of a more general trend towards harnessing the complementary nature of the different modalities on integrated imaging platforms? PMID:19646559

  7. Chemocentric informatics approach to drug discovery: identification and experimental validation of selective estrogen receptor modulators as ligands of 5-hydroxytryptamine-6 receptors and as potential cognition enhancers.

    PubMed

    Hajjo, Rima; Setola, Vincent; Roth, Bryan L; Tropsha, Alexander

    2012-06-28

    We have devised a chemocentric informatics methodology for drug discovery integrating independent approaches to mining biomolecular databases. As a proof of concept, we have searched for novel putative cognition enhancers. First, we generated Quantitative Structure-Activity Relationship (QSAR) models of compounds binding to 5-hydroxytryptamine-6 receptor (5-HT(6)R), a known target for cognition enhancers, and employed these models for virtual screening to identify putative 5-HT(6)R actives. Second, we queried chemogenomics data from the Connectivity Map ( http://www.broad.mit.edu/cmap/ ) with the gene expression profile signatures of Alzheimer's disease patients to identify compounds putatively linked to the disease. Thirteen common hits were tested in 5-HT(6)R radioligand binding assays and ten were confirmed as actives. Four of them were known selective estrogen receptor modulators that were never reported as 5-HT(6)R ligands. Furthermore, nine of the confirmed actives were reported elsewhere to have memory-enhancing effects. The approaches discussed herein can be used broadly to identify novel drug-target-disease associations.

  8. Exposure to nontraditional pets at home and to animals in public settings: risks to children.

    PubMed

    Pickering, Larry K; Marano, Nina; Bocchini, Joseph A; Angulo, Frederick J

    2008-10-01

    Exposure to animals can provide many benefits during the growth and development of children. However, there are potential risks associated with animal exposures, including exposure to nontraditional pets in the home and animals in public settings. Educational materials, regulations, and guidelines have been developed to minimize these risks. Pediatricians, veterinarians, and other health care professionals can provide advice on selection of appropriate pets as well as prevention of disease transmission from nontraditional pets and when children contact animals in public settings.

  9. PSMA-PET/CT-Positive Paget Disease in a Patient with Newly Diagnosed Prostate Cancer: Imaging and Bone Biopsy Findings.

    PubMed

    Froehner, Michael; Toma, Marieta; Zöphel, Klaus; Novotny, Vladimir; Laniado, Michael; Wirth, Manfred P

    2017-01-01

    A 67-year-old man diagnosed with Gleason score 4 + 5 = 9 clinically localized prostate cancer with (68)Ga-labeled prostate-specific membrane antigen-targeted ligand positron emission tomography/computed tomography (PSMA-PET/CT) positive Paget bone disease is described. Immunohistochemical staining revealed weak PSMA positivity of the bone lesion supporting the hypothesis that neovasculature might explain positive PSMA-PET/CT findings in Paget disease.

  10. PSMA-PET/CT-Positive Paget Disease in a Patient with Newly Diagnosed Prostate Cancer: Imaging and Bone Biopsy Findings

    PubMed Central

    Toma, Marieta; Zöphel, Klaus; Novotny, Vladimir; Laniado, Michael

    2017-01-01

    A 67-year-old man diagnosed with Gleason score 4 + 5 = 9 clinically localized prostate cancer with 68Ga-labeled prostate-specific membrane antigen-targeted ligand positron emission tomography/computed tomography (PSMA-PET/CT) positive Paget bone disease is described. Immunohistochemical staining revealed weak PSMA positivity of the bone lesion supporting the hypothesis that neovasculature might explain positive PSMA-PET/CT findings in Paget disease.

  11. Model peptides provide new insights into the role of histidine residues as potential ligands in human cellular copper acquisition via Ctr1.

    PubMed

    Haas, Kathryn L; Putterman, Allison B; White, Daniel R; Thiele, Dennis J; Franz, Katherine J

    2011-03-30

    Cellular acquisition of copper in eukaryotes is primarily accomplished through the Ctr family of copper transport proteins. In both humans and yeast, methionine-rich "Mets" motifs in the amino-terminal extracellular domain of Ctr1 are thought to be responsible for recruitment of copper at the cell surface. Unlike yeast, mammalian Ctr1 also contains extracellular histidine-rich motifs, although a role for these regions in copper uptake has not been explored in detail. Herein, synthetic model peptides containing the first 14 residues of the extracellular domain of human Ctr1 (MDHSHHMGMSYMDS) have been prepared and evaluated for their apparent binding affinity to both Cu(I) and Cu(II). These studies reveal a high affinity Cu(II) binding site (log K = 11.0 ± 0.3 at pH 7.4) at the amino-terminus of the peptide as well as a high affinity Cu(I) site (log K = 10.2 ± 0.2 at pH 7.4) that utilizes adjacent HH residues along with an additional His or Met ligand. These model studies suggest that the histidine domains may play a direct role in copper acquisition from serum copper-binding proteins and in facilitating the reduction of Cu(II) to the active Ctr1 substrate, Cu(I). We tested this hypothesis by expressing a Ctr1 mutant lacking only extracellular histidine residues in Ctr1-knockout mouse embryonic fibroblasts. Results from live cell studies support the hypothesis that extracellular amino-terminal His residues directly participate in the copper transport function of Ctr1.

  12. Model Peptides Provide New Insights into the Role of Histidine Residues as Potential Ligands in Human Cellular Copper Acquisition via Ctr1

    PubMed Central

    Haas, Kathryn L.; Putterman, Allison B.; White, Daniel R.; Thiele, Dennis J.; Franz, Katherine J.

    2011-01-01

    Cellular acquisition of copper in eukaryotes is primarily accomplished through the Ctr family of copper transport proteins. In both humans and yeast, methionine-rich “Mets” motifs in the amino-terminal extracellular domain of Ctr1 are thought to be responsible for recruitment of copper at the cell surface. Unlike yeast, mammalian Ctr1 also contains extracellular histidine-rich motifs, although a role for these regions in copper uptake has not been explored in detail. Herein, synthetic model peptides containing the first 14 residues of the extracellular domain of human Ctr1 (MDHSHHMGMSYMDS) have been prepared and evaluated for their apparent binding affinity to both Cu(I) and Cu(II). These studies reveal a high affinity Cu(II) binding site (logK = 11.0 ± 0.3 at pH 7.4) at the amino-terminus of the peptide as well as a high affinity Cu(I) site (logK = 10.2 ± 0.2 at pH 7.4) that utilizes adjacent HH residues along with an additional His or Met ligand. These model studies suggest that the histidine domains may play a direct role in copper acquisition from serum copper-binding proteins and in facilitating the reduction of Cu(II) to the active Ctr1 substrate, Cu(I). We tested this hypothesis by expressing a Ctr1 mutant lacking only extracellular histidine residues in Ctr1-knockout mouse embryonic fibroblasts. Results from live cell studies support the hypothesis that extracellular amino-terminal His residues directly participate in the copper transport function of Ctr1. PMID:21375246

  13. Preparation and biodistribution of copper-67 complexes with tetradentate Schiff-base ligands.

    PubMed

    John, E K; Bott, A J; Green, M A

    1994-04-01

    Uncharged, lipophilic, low molecular weight copper complexes labeled with generator-produced copper-62 are of interest as potential radiopharmaceutials for imaging the brain with positron emission tomography (PET). We report here the synthesis and biodistribution of a series of [67Cu]copper(II) complexes with tetradentate N2O2(2-)Schiff-base ligands. The compounds studied varied in lipophilicity from log P = 1.7 to log P = 3.6, where P is the octanol/water partition coefficient. In rat biodistribution studies the tracers were generally found to penetrate the blood-brain barrier following intravenous injection, but some far better than others. For closely related compounds brain uptake at 1 min postinjection increased with increasing lipophilicity, although log P was clearly not the sole determinant of high brain uptake. Substantial variations were also observed in the rate at which these various compounds are cleared from brain, with a few exhibiting the prolonged cerebral retention of tracer that would be desired for imaging with 62Cu and PET.

  14. Flexible ligand docking using a genetic algorithm

    NASA Astrophysics Data System (ADS)

    Oshiro, C. M.; Kuntz, I. D.; Dixon, J. Scott

    1995-04-01

    Two computational techniques have been developed to explore the orientational and conformational space of a flexible ligand within an enzyme. Both methods use the Genetic Algorithm (GA) to generate conformationally flexible ligands in conjunction with algorithms from the DOCK suite of programs to characterize the receptor site. The methods are applied to three enzyme-ligand complexes: dihydrofolate reductase-methotrexate, thymidylate synthase-phenolpthalein and HIV protease-thioketal haloperidol. Conformations and orientations close to the crystallographically determined structures are obtained, as well as alternative structures with low energy. The potential for the GA method to screen a database of compounds is also examined. A collection of ligands is evaluated simultaneously, rather than docking the ligands individually into the enzyme.

  15. Temperature dependence of the ligand field strength in systems with modulated potential-energy surfaces. A suggestion for interpreting spectroscopic properties of metalloproteins

    NASA Astrophysics Data System (ADS)

    Bacci, M.

    1984-07-01

    The structural and spectroscopic properties of physical systems having different potential-energy wells are strongly affected by temperature where energy barriers are comparable to the thermal energy. A theoretical analysis has been performed using an asymmetric double-well potential and, on the basis of the results obtained, an interpretation of the temperature-dependent properties of some real systems, such as the active sites in copper proteins, is proposed.

  16. Supplements for exotic pets.

    PubMed

    Mejia-Fava, Johanna; Colitz, Carmen M H

    2014-09-01

    The use of supplements has become commonplace in an effort to complement traditional therapy and as part of long-term preventive health plans. This article discusses historical and present uses of antioxidants, vitamins, and herbs. By complementing traditional medicine with holistic and alternative nutrition and supplements, the overall health and wellness of exotic pets can be enhanced and balanced. Further research is needed for understanding the strengths and uses of supplements in exotic species. Going back to the animals' origin and roots bring clinicians closer to nature and its healing powers.

  17. Dinuclear manganese complexes containing chiral 1,4,7-triazacyclononane-derived ligands and their catalytic potential for the oxidation of olefins, alkanes, and alcohols.

    PubMed

    Romakh, Vladimir B; Therrien, Bruno; Süss-Fink, Georg; Shul'pin, Georgiy B

    2007-02-19

    Five new 1,4,7-triazacyclononane-derived compounds, sodium 3-(4,7-dimethyl-1,4,7-triazacyclononan-1-yl)propionate (Na[LMe2R']) as well as the enantiopure derivatives (S)-1-(2-methylbutyl)-4,7-dimethyl-1,4,7-triazacyclononane (S-LMe2R''), SS-trans-2,5,8-trimethyl-2,5,8-triazabicyclo[7.4.01,9]tridecane (SS-LBMe3), (S)-1-(2-hydroxypropyl)-4,7-dimethyl-1,4,7-triazacyclononane (S-LMe2R), and (R)-1-(2-hydroxypropyl)-4,7-dimethyl-1,4,7-triazacyclononane (R-LMe2R), have been synthesized. Reaction of manganese dichloride with the chiral macrocycles S-LMe2R and R-LMe2R in aqueous ethanol gives, upon oxidation with hydrogen peroxide, the brown dinuclear Mn(III)-Mn(IV) complexes which are enantiomers, [Mn2(S-LMe2R)2(mu-O)2]3+ (S,S-1) and [Mn2(R-LMe2R)2(mu-O)2]3+ (R,R-1). The single-crystal X-ray structure analyses of [S,S-1][PF6]3.0.5(CH3)2CO and [R,R-1][PF6]3.0.5(CH3)2CO show both enantiomers to contain Mn(III) and Mn(IV) centers, each of which being coordinated to three nitrogen atoms of a triazacyclononane ligand and each of which being bridged by two oxo and by two chiral hydroxypropyl pendent arms of the macrocycle. The enantiomeric complexes S,S-1 and R,R-1 were found to catalyze the oxidation of olefins, alkanes, and alcohols with hydrogen peroxide. In the epoxidation of indene the enantiomeric excess values attain 13%. The bond selectivities of the oxidation of linear and branched alkanes suggest the crucial step in this process to be the attack of a sterically hindered high-valent manganese-oxo species on the C-H bond.

  18. PET guidance for liver radiofrequency ablation: an evaluation

    NASA Astrophysics Data System (ADS)

    Lei, Peng; Dandekar, Omkar; Mahmoud, Faaiza; Widlus, David; Malloy, Patrick; Shekhar, Raj

    2007-03-01

    Radiofrequency ablation (RFA) is emerging as the primary mode of treatment of unresectable malignant liver tumors. With current intraoperative imaging modalities, quick, precise, and complete localization of lesions remains a challenge for liver RFA. Fusion of intraoperative CT and preoperative PET images, which relies on PET and CT registration, can produce a new image with complementary metabolic and anatomic data and thus greatly improve the targeting accuracy. Unlike neurological images, alignment of abdominal images by combined PET/CT scanner is prone to errors as a result of large nonrigid misalignment in abdominal images. Our use of a normalized mutual information-based 3D nonrigid registration technique has proven powerful for whole-body PET and CT registration. We demonstrate here that this technique is capable of acceptable abdominal PET and CT registration as well. In five clinical cases, both qualitative and quantitative validation showed that the registration is robust and accurate. Quantitative accuracy was evaluated by comparison between the result from the algorithm and clinical experts. The accuracy of registration is much less than the allowable margin in liver RFA. Study findings show the technique's potential to enable the augmentation of intraoperative CT with preoperative PET to reduce procedure time, avoid repeating procedures, provide clinicians with complementary functional/anatomic maps, avoid omitting dispersed small lesions, and improve the accuracy of tumor targeting in liver RFA.

  19. Sparsity-constrained PET image reconstruction with learned dictionaries

    NASA Astrophysics Data System (ADS)

    Tang, Jing; Yang, Bao; Wang, Yanhua; Ying, Leslie

    2016-09-01

    PET imaging plays an important role in scientific and clinical measurement of biochemical and physiological processes. Model-based PET image reconstruction such as the iterative expectation maximization algorithm seeking the maximum likelihood solution leads to increased noise. The maximum a posteriori (MAP) estimate removes divergence at higher iterations. However, a conventional smoothing prior or a total-variation (TV) prior in a MAP reconstruction algorithm causes over smoothing or blocky artifacts in the reconstructed images. We propose to use dictionary learning (DL) based sparse signal representation in the formation of the prior for MAP PET image reconstruction. The dictionary to sparsify the PET images in the reconstruction process is learned from various training images including the corresponding MR structural image and a self-created hollow sphere. Using simulated and patient brain PET data with corresponding MR images, we study the performance of the DL-MAP algorithm and compare it quantitatively with a conventional MAP algorithm, a TV-MAP algorithm, and a patch-based algorithm. The DL-MAP algorithm achieves improved bias and contrast (or regional mean values) at comparable noise to what the other MAP algorithms acquire. The dictionary learned from the hollow sphere leads to similar results as the dictionary learned from the corresponding MR image. Achieving robust performance in various noise-level simulation and patient studies, the DL-MAP algorithm with a general dictionary demonstrates its potential in quantitative PET imaging.

  20. Sparsity-constrained PET image reconstruction with learned dictionaries.

    PubMed

    Tang, Jing; Yang, Bao; Wang, Yanhua; Ying, Leslie

    2016-09-07

    PET imaging plays an important role in scientific and clinical measurement of biochemical and physiological processes. Model-based PET image reconstruction such as the iterative expectation maximization algorithm seeking the maximum likelihood solution leads to increased noise. The maximum a posteriori (MAP) estimate removes divergence at higher iterations. However, a conventional smoothing prior or a total-variation (TV) prior in a MAP reconstruction algorithm causes over smoothing or blocky artifacts in the reconstructed images. We propose to use dictionary learning (DL) based sparse signal representation in the formation of the prior for MAP PET image reconstruction. The dictionary to sparsify the PET images in the reconstruction process is learned from various training images including the corresponding MR structural image and a self-created hollow sphere. Using simulated and patient brain PET data with corresponding MR images, we study the performance of the DL-MAP algorithm and compare it quantitatively with a conventional MAP algorithm, a TV-MAP algorithm, and a patch-based algorithm. The DL-MAP algorithm achieves improved bias and contrast (or regional mean values) at comparable noise to what the other MAP algorithms acquire. The dictionary learned from the hollow sphere leads to similar results as the dictionary learned from the corresponding MR image. Achieving robust performance in various noise-level simulation and patient studies, the DL-MAP algorithm with a general dictionary demonstrates its potential in quantitative PET imaging.

  1. Investigation of optimization-based reconstruction with an image-total-variation constraint in PET

    NASA Astrophysics Data System (ADS)

    Zhang, Zheng; Ye, Jinghan; Chen, Buxin; Perkins, Amy E.; Rose, Sean; Sidky, Emil Y.; Kao, Chien-Min; Xia, Dan; Tung, Chi-Hua; Pan, Xiaochuan

    2016-08-01

    Interest remains in reconstruction-algorithm research and development for possible improvement of image quality in current PET imaging and for enabling innovative PET systems to enhance existing, and facilitate new, preclinical and clinical applications. Optimization-based image reconstruction has been demonstrated in recent years of potential utility for CT imaging applications. In this work, we investigate tailoring the optimization-based techniques to image reconstruction for PET systems with standard and non-standard scan configurations. Specifically, given an image-total-variation (TV) constraint, we investigated how the selection of different data divergences and associated parameters impacts the optimization-based reconstruction of PET images. The reconstruction robustness was explored also with respect to different data conditions and activity up-takes of practical relevance. A study was conducted particularly for image reconstruction from data collected by use of a PET configuration with sparsely populated detectors. Overall, the study demonstrates the robustness of the TV-constrained, optimization-based reconstruction for considerably different data conditions in PET imaging, as well as its potential to enable PET configurations with reduced numbers of detectors. Insights gained in the study may be exploited for developing algorithms for PET-image reconstruction and for enabling PET-configuration design of practical usefulness in preclinical and clinical applications.

  2. PET Imaging of Angiogenesis

    PubMed Central

    Niu, Gang; Chen, Xiaoyuan

    2009-01-01

    Synopsis Angiogenesis is a highly-controlled process that is dependent on the intricate balance of both promoting and inhibiting factors, involved in various physiological and pathological processes. A comprehensive understanding of the molecular mechanisms that regulate angiogenesis has resulted in the design of new and more effective therapeutic strategies. Due to insufficient sensitivity to detect therapeutic effects by using standard clinical endpoints or by looking for physiological improvement, a multitude of imaging techniques have been developed to assess tissue vasculature on the structural, functional and molecular level. Imaging is expected to provide a novel approach to noninvasively monitor angiogenesis, to optimize the dose of new antiangiogenic agents and to assess the efficacy of therapies directed at modulation of the angiogenic process. All these methods have been successfully used preclinically and will hopefully aid in antiangiogenic drug development in animal studies. In this review article, the application of PET in angiogenesis imaging at both functional and molecular level will be discussed. For PET imaging of angiogenesis related molecular markers, we emphasize integrin αvβ3, VEGF/VEGFR, and MMPs. PMID:20046926

  3. 36 CFR 1002.15 - Pets.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 36 Parks, Forests, and Public Property 3 2011-07-01 2011-07-01 false Pets. 1002.15 Section 1002.15....15 Pets. (a) The following are prohibited: (1) Possessing a pet in a public building, public... possession of pets by the Board. This paragraph shall not apply to guide dogs accompanying visually...

  4. 36 CFR 2.15 - Pets.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Pets. 2.15 Section 2.15 Parks... USE AND RECREATION § 2.15 Pets. (a) The following are prohibited: (1) Possessing a pet in a public... area closed to the possession of pets by the superintendent. This subparagraph shall not apply to...

  5. 36 CFR 2.15 - Pets.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 36 Parks, Forests, and Public Property 1 2011-07-01 2011-07-01 false Pets. 2.15 Section 2.15 Parks... USE AND RECREATION § 2.15 Pets. (a) The following are prohibited: (1) Possessing a pet in a public... area closed to the possession of pets by the superintendent. This subparagraph shall not apply to...

  6. 36 CFR 1002.15 - Pets.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Pets. 1002.15 Section 1002.15....15 Pets. (a) The following are prohibited: (1) Possessing a pet in a public building, public... possession of pets by the Board. This paragraph shall not apply to guide dogs accompanying visually...

  7. 7 CFR 502.11 - Pets.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 6 2011-01-01 2011-01-01 false Pets. 502.11 Section 502.11 Agriculture Regulations of... CONDUCT ON BELTSVILLE AGRICULTURE RESEARCH CENTER PROPERTY, BELTSVILLE, MARYLAND § 502.11 Pets. Pets... vaccinations. Pets that are the property of employees residing on BARC must be up to date on their...

  8. 7 CFR 502.11 - Pets.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 6 2010-01-01 2010-01-01 false Pets. 502.11 Section 502.11 Agriculture Regulations of... CONDUCT ON BELTSVILLE AGRICULTURE RESEARCH CENTER PROPERTY, BELTSVILLE, MARYLAND § 502.11 Pets. Pets... vaccinations. Pets that are the property of employees residing on BARC must be up to date on their...

  9. Interacting with a Computer-Simulated Pet: Factors Influencing Children's Humane Attitudes and Empathy

    ERIC Educational Resources Information Center

    Tsai, Yueh-Feng; Kaufman, David

    2014-01-01

    Previous research by Tsai and Kaufman (2010a, 2010b) has suggested that computer-simulated virtual pet dogs can be used as a potential medium to enhance children's development of empathy and humane attitudes toward animals. To gain a deeper understanding of how and why interacting with a virtual pet dog might influence children's social and…

  10. PET-Based Thoracic Radiation Oncology.

    PubMed

    Simone, Charles B; Houshmand, Sina; Kalbasi, Anusha; Salavati, Ali; Alavi, Abass

    2016-07-01

    Fluorodeoxyglucose-PET is increasingly being integrated into multiple aspects of oncology. PET/computed tomography (PET/CT) has become especially important in radiation oncology. With the increasing use of advanced techniques like intensity-modulated radiation therapy and proton therapy, PET/CT scans have played critical roles in the target delineation of tumors for radiation oncologists delivering conformal treatment techniques. Use of PET/CT is well established in lung cancer and several other thoracic malignancies. This article details the current uses of PET/CT in thoracic radiation oncology with a focus on lung cancer and describes expected future roles of PET/CT for thoracic tumors.

  11. Positron emission tomography (PET) for cholangiocarcinoma

    PubMed Central

    Breitenstein, S.; Apestegui, C.

    2008-01-01

    The combination of positron emission tomography (PET) with computed tomography (PET-CT) provides simultaneous metabolic and anatomic information on tumors in the same imaging session. Sensitivity of PET/PET-CT is higher for intrahepatic (>90%) than for extrahepatic cholangiocarcinoma (CCA) (about 60%). The detection rate of distant metastasis is 100%. PET, and particularly PET-CT, improves the results and impacts on the oncological management in CCA compared with other imaging modalities. Therefore, PET-CT is recommended in the preoperative staging of intrahepatic (strength of recommendation: moderate) and extrahepatic (strength of recommendation: low) CCA. PMID:18773069

  12. Towards Implementing an MR-based PET Attenuation Correction Method for Neurological Studies on the MR-PET Brain Prototype

    PubMed Central

    Catana, Ciprian; van der Kouwe, Andre; Benner, Thomas; Michel, Christian J.; Hamm, Michael; Fenchel, Matthias; Fischl, Bruce; Rosen, Bruce; Schmand, Matthias; Sorensen, A. Gregory

    2013-01-01

    method was implemented considering all these factors and our preliminary results suggest that this method could potentially be as accurate as the segmented CT method and it could be used for quantitative neurological MR-PET studies. PMID:20810759

  13. Understanding regulations affecting pet foods.

    PubMed

    Dzanis, David A

    2008-08-01

    In the United States, pet foods are subject to regulation at both the federal and the state levels. The US Food and Drug Administration has jurisdiction over all animal feeds (including pet foods, treats, chews, supplements, and ingredients) in interstate commerce, which includes imported products. Many states adopt and enforce at least in part the Association of American Feed Control Officials Model Bill and Model Regulations for Pet Food and Specialty Pet Food. Thus, all pet foods in multi-state distribution are subject to a host of labeling requirements covering aspects such as product names, ingredient lists, nutrient content guarantees, and nutritional adequacy statements. Ingredients must be GRAS (generally recognized as safe) substances, approved food additives, or defined by Association of American Feed Control Officials for their intended use. Pet food labels may not bear claims that are false or misleading or that state or imply use for the treatment or prevention of disease. Pet foods that are found to be adulterated or misbranded may be subject to seizure or other enforcement actions.

  14. Pet poultry training for veterinary practitioners.

    PubMed

    Crespo, Rocio; Faux, Cynthia; Dhillon, Singh A; Newberry, Ruth C; Moore, Dale A

    2010-01-01

    Keeping backyard poultry in urban areas is a burgeoning trend in the United States. As such, we believe urban pet poultry owners are increasingly likely to seek veterinary services from urban companion-animal practitioners. Traditionally, poultry species have been classified as production animals. Most small-animal practitioners have limited experience or knowledge of these species and hesitate to accept these animals at their practices. We developed a one-day course to train veterinarians in pet poultry (as opposed to commercial poultry) medicine. The course covers poultry examination, diseases, and treatments and provides an introduction to poultry breeds and behavior and the basics of nutrition and husbandry. We believe this type of continuing education program is important for veterinarians because they are often on the front line of human public health issues. In addition, courses of this type increase the number of veterinarians trained to spot serious avian diseases, including foreign diseases and diseases with zoonotic potential. Most important, veterinarians with this training develop the knowledge to contribute to the health and well-being of pet poultry along with their clients' other companion animals.

  15. Family pet ownership during childhood: findings from a UK birth cohort and implications for public health research.

    PubMed

    Westgarth, Carri; Heron, Jon; Ness, Andy R; Bundred, Peter; Gaskell, Rosalind M; Coyne, Karen P; German, Alexander J; McCune, Sandra; Dawson, Susan

    2010-10-01

    In developed nations, approximately half of household environments contain pets. Studies of Human-Animal Interaction (HAI) have proposed that there are health benefits and risks associated with pet ownership. However, accurately demonstrating and understanding these relationships first requires a better knowledge of factors associated with ownership of different pet types. A UK birth cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC), were used to collect pet ownership data from the mothers, from gestation to child age 10 years old. 14,663 children were included in the study, of which mothers of 13,557 reported pet information at gestation, and 7,800 by age 10. Pet types recorded include cat, dog, rabbit, rodent, bird, fish and tortoise/turtle. The dataset also contains a number of demographic, socioeconomic and behavioural variables relevant to human health behaviour. Logistic regression was used to build multivariable models for ownership of each pet type at age 7 years. Family pet ownership increased during childhood, in particular rabbits, rodents and fish. A number of socioeconomic and demographic factors were associated with ownership of different pet types and the effects differed depending on the pet type studied. Variables which require consideration by researchers include gender, presence of older siblings, ethnicity, maternal and paternal education, maternal and paternal social class, maternal age, number of people in the household, house type, and concurrent ownership of other pets. Whether the mother had pets during her childhood was a strong predictor of pet ownership in all models. In HAI studies, care should be taken to control for confounding factors, and to treat each pet type individually. ALSPAC and other similar birth cohorts can be considered a potential resource for research into the effects of pet ownership during childhood.

  16. Simultaneous acquisition of magnetic resonance spectroscopy (MRS) data and positron emission tomography (PET) images with a prototype MR-compatible, small animal PET imager

    NASA Astrophysics Data System (ADS)

    Raylman, Raymond R.; Majewski, Stan; Velan, S. Sendhil; Lemieux, Susan; Kross, Brian; Popov, Vladimir; Smith, Mark F.; Weisenberger, Andrew G.

    2007-06-01

    Multi-modality imaging (such as PET-CT) is rapidly becoming a valuable tool in the diagnosis of disease and in the development of new drugs. Functional images produced with PET, fused with anatomical images created by MRI, allow the correlation of form with function. Perhaps more exciting than the combination of anatomical MRI with PET, is the melding of PET with MR spectroscopy (MRS). Thus, two aspects of physiology could be combined in novel ways to produce new insights into the physiology of normal and pathological processes. Our team is developing a system to acquire MRI images and MRS spectra, and PET images contemporaneously. The prototype MR-compatible PET system consists of two opposed detector heads (appropriate in size for small animal imaging), operating in coincidence mode with an active field-of-view of ˜14 cm in diameter. Each detector consists of an array of LSO detector elements coupled through a 2-m long fiber optic light guide to a single position-sensitive photomultiplier tube. The use of light guides allows these magnetic field-sensitive elements of the PET imager to be positioned outside the strong magnetic field of our 3T MRI scanner. The PET scanner imager was integrated with a 12-cm diameter, 12-leg custom, birdcage coil. Simultaneous MRS spectra and PET images were successfully acquired from a multi-modality phantom consisting of a sphere filled with 17 brain relevant substances and a positron-emitting radionuclide. There were no significant changes in MRI or PET scanner performance when both were present in the MRI magnet bore. This successful initial test demonstrates the potential for using such a multi-modality to obtain complementary MRS and PET data.

  17. PET Imaging and Biodistribution of Silicon Quantum Dots in Mice

    PubMed Central

    2011-01-01

    Investigation of nanomaterial disposition and fate in the body is critical before such material can be translated into clinical application. Herein a new macrocyclic ligand−64Cu2+ complex was synthesized and used to label dextran-coated silicon quantum dots (QD), with an average hydrodynamic diameter of 15.1 ± 7.6 nm. The chelate showed exceptional stability, demonstrated by no loss radiolabel under a ligand competition reaction with EDTA. The QDs’ biodistribution in mice was quantitatively evaluated by in vivo positron emission tomography (PET) imaging and ex vivo gamma counting. Results showed that they were excreted via renal filtration shortly postinjection and also accumulated in the liver. PMID:21546997

  18. High-Resolution PET Imaging with Therapeutic Antibody-based PD-1/PD-L1 Checkpoint Tracers

    PubMed Central

    Hettich, Michael; Braun, Friederike; Bartholomä, Mark D.; Schirmbeck, Reinhold; Niedermann, Gabriele

    2016-01-01

    Checkpoint-blocking antibodies like those targeting the PD-1/PD-L1 pathway have revolutionized oncology. We developed radiotracers based on therapeutic checkpoint-blocking antibodies permitting sensitive and high-resolution PET imaging of both PD-1 and PD-L1 in immunocompetent mice. ImmunoPET of naive mice revealed similar overall expression patterns for PD-1 and PD-L1 in secondary lymphoid organs (spleen and lymph nodes). Interestingly, PD-L1 was also detected in brown adipose tissue (BAT), confirming the notion that BAT is immunologically relevant. Under pathophysiological conditions, strong expression of the receptor/ligand pair was also found in non-lymphoid tissues. Both were specifically detected in malignant tumors. PD-1 was readily detected after combined immunoradiotherapy causing massive tumor infiltration by PD-1+ lymphocytes. PD-L1 tracer uptake was reduced in PD-L1 knockout tumors. Moreover, monitoring the expression changes of PD-L1 in response to its main inducer, the effector T cell cytokine IFN-γ, revealed robust upregulation in the lung. This suggests that T cell responses in the lung, a vital organ continuously exposed to a variety of antigens, are strongly restrained by the PD-1 checkpoint. In turn, this could explain the association of PD-1 checkpoint inhibition with potentially fatal immune-mediated pneumonitis and partially also its efficacy in lung cancer. PMID:27446497

  19. Synthesis and Preliminary Evaluation of a 2-Oxoquinoline Carboxylic Acid Derivative for PET Imaging the Cannabinoid Type 2 Receptor

    PubMed Central

    Mu, Linjing; Slavik, Roger; Müller, Adrienne; Popaj, Kasim; Čermak, Stjepko; Weber, Markus; Schibli, Roger; Krämer, Stefanie D.; Ametamey, Simon M.

    2014-01-01

    Cannabinoid receptor subtype 2 (CB2) has been shown to be up-regulated in activated microglia and therefore plays an important role in neuroinflammatory and neurodegenerative diseases such as multiple sclerosis, amyotrophic lateral sclerosis and Alzheimer’s disease. The CB2 receptor is therefore considered as a very promising target for therapeutic approaches as well as for imaging. A promising 2-oxoquinoline derivative designated KP23 was synthesized and radiolabeled and its potential as a ligand for PET imaging the CB2 receptor was evaluated. [11C]KP23 was obtained in 10%–25% radiochemical yield (decay corrected) and 99% radiochemical purity. It showed high stability in phosphate buffer, rat and mouse plasma. In vitro autoradiography of rat and mouse spleen slices, as spleen expresses a high physiological expression of CB2 receptors, demonstrated that [11C]KP23 exhibits specific binding towards CB2. High spleen uptake of [11C]KP23 was observed in dynamic in vivo PET studies with Wistar rats. In conclusion, [11C]KP23 showed promising in vitro and in vivo characteristics. Further evaluation with diseased animal model which has higher CB2 expression levels in the brain is warranted. PMID:24662272

  20. Discovery of novel conformationally constrained tropane-based biaryl and arylacetylene ligands as potent and selective norepinephrine transporter inhibitors and potential antidepressants.

    PubMed

    Zhou, Jia; Kläss, Thomas; Johnson, Kenneth M; Giberson, Kelly M; Kozikowski, Alan P

    2005-05-16

    To further explore the structure-activity relationships of conformationally constrained tropanes, a number of new biaryl and arylacetylene analogs were designed and synthesized. Some of these compounds such as 3a-b, 3d, 3f-h, 5b, and 7g were found to be highly potent and selective or mixed norepinephrine transporter (NET) inhibitors with Ki values of 0.8-9.4 nM. Moreover, all of these compounds display weak to extremely weak muscarinic receptor binding affinity, indicating that as potential antidepressants, they may overcome certain side effects that are of concern with other antidepressants, which are thought to be mediated by their anticholinergic properties.

  1. Cobalt(II), nickel(II) and copper(II) complexes of a hexadentate pyridine amide ligand. Effect of donor atom (ether vs. thioether) on coordination geometry, spin-state of cobalt and M(III)-M(II) redox potential.

    PubMed

    Pandey, Sharmila; Das, Partha Pratim; Singh, Akhilesh Kumar; Mukherjee, Rabindranath

    2011-10-28

    Using an acyclic hexadentate pyridine amide ligand, containing a -OCH(2)CH(2)O- spacer between two pyridine-2-carboxamide units (1,4-bis[o-(pyrydine-2-carboxamidophenyl)]-1,4-dioxabutane (H(2)L(9)), in its deprotonated form), four new complexes, [Co(II)(L(9))] (1) and its one-electron oxidized counterpart [Co(III)(L(9))][NO(3)]·2H(2)O (2), [Ni(II)(L(9))] (3) and [Cu(II)(L(9))] (4), have been synthesized. Structural analyses revealed that the Co(II) centre in 1 and the Ni(II) centre in 3 are six-coordinate, utilizing all the available donor sites and the Cu(II) centre in 4 is effectively five-coordinated (one of the ether O atoms does not participate in coordination). The structural parameters associated with the change in the metal coordination environment have been compared with corresponding complexes of thioether-containing hexadentate ligands. The μ(eff) values at 298 K of 1-4 correspond to S = 3/2, S = 0, S = 1 and S = 1/2, respectively. Absorption spectra for all the complexes have been investigated. EPR spectral properties of the copper(II) complex 4 have been investigated, simulated and analyzed. Cyclic voltammetric experiments in CH(2)Cl(2) reveal quasireversible Co(III)-Co(II), Ni(III)-Ni(II) and Cu(II)-Cu(I) redox processes. In going from ether O to thioether S coordination, the effect of the metal coordination environment on the redox potential values of Co(III)-Co(II) (here the effect of spin-state as well), Ni(III)-Ni(II) and Cu(II)-Cu(I) processes have been systematically analyzed.

  2. Glial inhibitors influence the mRNA and protein levels of mGlu2/3, 5 and 7 receptors and potentiate the analgesic effects of their ligands in a mouse model of neuropathic pain.

    PubMed

    Osikowicz, Maria; Skup, Malgorzata; Mika, Joanna; Makuch, Wioletta; Czarkowska-Bauch, Julita; Przewlocka, Barbara

    2009-12-15

    Metabotropic glutamate (mGlu) receptors, which are present on neurons and glial cells, have been shown to play a role in neuropathic pain. The present study sought to investigate how the glial inhibitors minocycline and pentoxifylline alter the effect that chronic constriction injury (CCI) has on the expression of mGlu receptors and on their associated ligands. RT-PCR analysis revealed that seven days after CCI, the mRNA levels of glial markers C1q and GFAP, as well as those of mGlu5 and mGlu3, but not mGlu7, were elevated in the lumbar spinal cord - ipsilateral to the injury. The protein levels of the microglial marker OX42, the astroglial marker GFAP, and mGlu5 receptor protein were increased, whereas the levels of mGlu2/3 and mGlu7 receptor proteins were reduced. Preemptive and repeated intraperitoneal (i.p.) administration (16 and 1h before nerve injury and then twice daily for seven days) of minocycline (30mg/kg) and pentoxifylline (20mg/kg) prevented the injury-induced changes in the levels of mGlu3 and mGlu5 receptor mRNAs and the injury-induced changes in the protein levels of all the receptors. Repeated administration of minocycline and pentoxifylline significantly attenuated CCI-induced allodynia (von Frey test) and hyperalgesia (cold plate test) measured on day seven after injury and potentiated the antiallodynic and antihyperalgesic effects of single i.p. and intrathecal (i.t.) injections of mGlu receptor ligands: MPEP, LY379268 or AMN082. We conclude that attenuation of injury-induced glial activation can reduce glutamatergic activity, thereby contributing to regulation of pain sensation.

  3. Synthesis, structure-affinity relationships, and radiolabeling of selective high-affinity 5-HT4 receptor ligands as prospective imaging probes for positron emission tomography.

    PubMed

    Xu, Rong; Hong, Jinsoo; Morse, Cheryl L; Pike, Victor W

    2010-10-14

    In a search for high-affinity receptor ligands that might serve for development as radioligands for the imaging of brain 5-HT(4) receptors in vivo with positron emission tomography (PET), structural modifications were made to the high-affinity 5-HT(4) antagonist (1-butylpiperidin-4-yl)methyl 8-amino-7-iodo-2,3-dihydrobenzo[b][1,4]dioxine-5-carboxylate (1, SB 207710). These modifications were made mainly on the aryl side of the ester bond to permit possible rapid labeling of the carboxylic acid component with a positron emitter, either carbon-11 (t(1/2) = 20.4 min) or fluorine-18 (t(1/2) = 109.7 min), and included (i) replacement of the iodine atom with a small substituent such as nitrile, methyl, or fluoro, (ii) methylation of the 8-amino group, (iii) opening of the dioxan ring, and (iv) alteration of the length of the N-alkyl goup. High-affinity ligands were discovered for recombinant human 5-HT(4) receptors with amenability to labeling with a positron emitter and potential for development as imaging probes. The ring-opened radioligand, (([methoxy-(11)C]1-butylpiperidin-4-yl)methyl 4-amino-3-methoxybenzoate; [(11)C]13), showed an especially favorable array of properties for future evaluation as a PET radioligand for brain 5-HT(4) receptors.

  4. Heteroleptic Copper(I) Complexes of “Scorpionate” Bis-pyrazolyl Carboxylate Ligand with Auxiliary Phosphine as Potential Anticancer Agents: An Insight into Cytotoxic Mode

    NASA Astrophysics Data System (ADS)

    Khan, Rais Ahmad; Usman, Mohammad; Dhivya, Rajakumar; Balaji, Perumalsamy; Alsalme, Ali; Allohedan, Hamad; Arjmand, Farukh; Alfarhan, Khalid; Akbarsha, Mohammad Abdulkader; Marchetti, Fabio; Pettinari, Claudio; Tabassum, Sartaj

    2017-03-01

    New copper(I) complexes [CuCl(PPh3)(L)] (1: L = LA = 4-carboxyphenyl)bis(3,5-dimethylpyrazolyl)methane (2: L = LB = 3-carboxyphenyl)bis(3,5-dimethylpyrazolyl)methane) were prepared and characterised by elemental analysis and various spectroscopic techniques such as FT-IR, NMR, UV–Vis, and ESI-MS. The molecular structures of complexes 1 and 2 were analyzed by theoretical B3LYP/DFT method. Furthermore, in vitro DNA binding studies were carried out to check the ability of complexes 1 and 2 to interact with native calf thymus DNA (CT-DNA) using absorption titration, fluorescence quenching and circular dichroism, which is indicative of more avid binding of the complex 1. Moreover, DNA mobility assay was also conducted to study the concentration-dependent cleavage pattern of pBR322 DNA by complex 1, and the role of ROS species to have a mechanistic insight on the cleavage pattern, which ascertained substantial roles by both hydrolytic and oxidative pathways. Additionally, we analyzed the potential of the interaction of complex 1 with DNA and enzyme (Topo I and II) with the aid of molecular modeling. Furthermore, cytotoxic activity of complex 1 was tested against HepG2 cancer cell lines. Thus, the potential of the complex 1 is promising though further in vivo investigations may be required before subjecting it to clinical trials.

  5. Heteroleptic Copper(I) Complexes of “Scorpionate” Bis-pyrazolyl Carboxylate Ligand with Auxiliary Phosphine as Potential Anticancer Agents: An Insight into Cytotoxic Mode

    PubMed Central

    Khan, Rais Ahmad; Usman, Mohammad; Dhivya, Rajakumar; Balaji, Perumalsamy; Alsalme, Ali; AlLohedan, Hamad; Arjmand, Farukh; AlFarhan, Khalid; Akbarsha, Mohammad Abdulkader; Marchetti, Fabio; Pettinari, Claudio; Tabassum, Sartaj

    2017-01-01

    New copper(I) complexes [CuCl(PPh3)(L)] (1: L = LA = 4-carboxyphenyl)bis(3,5-dimethylpyrazolyl)methane; (2: L = LB = 3-carboxyphenyl)bis(3,5-dimethylpyrazolyl)methane) were prepared and characterised by elemental analysis and various spectroscopic techniques such as FT-IR, NMR, UV–Vis, and ESI-MS. The molecular structures of complexes 1 and 2 were analyzed by theoretical B3LYP/DFT method. Furthermore, in vitro DNA binding studies were carried out to check the ability of complexes 1 and 2 to interact with native calf thymus DNA (CT-DNA) using absorption titration, fluorescence quenching and circular dichroism, which is indicative of more avid binding of the complex 1. Moreover, DNA mobility assay was also conducted to study the concentration-dependent cleavage pattern of pBR322 DNA by complex 1, and the role of ROS species to have a mechanistic insight on the cleavage pattern, which ascertained substantial roles by both hydrolytic and oxidative pathways. Additionally, we analyzed the potential of the interaction of complex 1 with DNA and enzyme (Topo I and II) with the aid of molecular modeling. Furthermore, cytotoxic activity of complex 1 was tested against HepG2 cancer cell lines. Thus, the potential of the complex 1 is promising though further in vivo investigations may be required before subjecting it to clinical trials. PMID:28338061

  6. An emerging evidence base for PET-CT in the management of childhood rhabdomyosarcoma: systematic review

    PubMed Central

    Norman, Gill; Fayter, Debra; Lewis-Light, Kate; Chisholm, Julia; McHugh, Kieran; Levine, Daniel; Jenney, Meriel; Mandeville, Henry; Gatz, Suzanne; Phillips, Bob

    2015-01-01

    Introduction Rhabdomyosarcoma (RMS) management depends on risk stratification at diagnosis and treatment response. Assessment methods include CT, MRI, bone scintigraphy, histological analysis and bone marrow biopsy. Advanced functional imaging (FI) has potential to improve staging accuracy and management strategies. Methods and analysis We conducted a systematic review (PROSPERO 2013:CRD42013006128) of diagnostic accuracy and clinical effectiveness of FI in histologically proven paediatric RMS. PRISMA guidance was followed. We searched 10 databases to November 2013. Studies with ≥10 patients with RMS which compared positron emission tomography (PET), PET-CT or diffusion-weighted imaging (DWI) MRI to conventional imaging at any treatment stage were included. Study quality was assessed. Limited, heterogeneous effectiveness data required narrative synthesis, illustrated by plotting sensitivity and specificity in receiver operating curve (ROC) space. Results Eight studies (six PET-CT, two PET) with 272 RMS patients in total were included. No DWI-MRI studies met inclusion criteria. Pooled estimates were not calculated due to sparseness of data. Limited evidence indicated initial PET-CT results were predictive of survival. PET-CT changed management of 7/40 patients. Nodal involvement PET-CT: sensitivity ranged from 80% to 100%; specificity from 89% to 100%. Distant metastatic involvement: PET-CT sensitivity ranged from 95% to 100%; specificity from 80% to100%. Data on metastases in different sites were sparse. Limited data were found on outcome prediction by PET-CT response. Dissemination and ethics PET/PET-CT may increase initial staging accuracy in paediatric RMS, specifically in the detection of nodal involvement and distant metastatic spread. There is a need to further assess PET-CT for this population, ideally in a representative, unbiased and transparently selected cohort of patients. PMID:25573522

  7. Carbon-11 radiolabeling of iron-oxide nanoparticles for dual-modality PET/MR imaging

    NASA Astrophysics Data System (ADS)

    Sharma, Ramesh; Xu, Youwen; Kim, Sung Won; Schueller, Michael J.; Alexoff, David; Smith, S. David; Wang, Wei; Schlyer, David

    2013-07-01

    Dual-modality imaging, using Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) simultaneously, is a powerful tool to gain valuable information correlating structure with function in biomedicine. The advantage of this dual approach is that the strengths of one modality can balance the weaknesses of the other. However, success of this technique requires developing imaging probes suitable for both. Here, we report on the development of a nanoparticle labeling procedure via covalent bonding with carbon-11 PET isotope. Carbon-11 in the form of [11C]methyl iodide was used as a methylation agent to react with carboxylic acid (-COOH) and amine (-NH2) functional groups of ligands bound to the nanoparticles (NPs). The surface coating ligands present on superparamagnetic iron-oxide nanoparticles (SPIO NPs) were radiolabeled to achieve dual-modality PET/MR imaging capabilities. The proof-of-concept dual-modality PET/MR imaging using the radiolabeled SPIO NPs was demonstrated in an in vivo experiment.Dual-modality imaging, using Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) simultaneously, is a powerful tool to gain valuable information correlating structure with function in biomedicine. The advantage of this dual approach is that the strengths of one modality can balance the weaknesses of the other. However, success of this technique requires developing imaging probes suitable for both. Here, we report on the development of a nanoparticle labeling procedure via covalent bonding with carbon-11 PET isotope. Carbon-11 in the form of [11C]methyl iodide was used as a methylation agent to react with carboxylic acid (-COOH) and amine (-NH2) functional groups of ligands bound to the nanoparticles (NPs). The surface coating ligands present on superparamagnetic iron-oxide nanoparticles (SPIO NPs) were radiolabeled to achieve dual-modality PET/MR imaging capabilities. The proof-of-concept dual-modality PET/MR imaging using the radiolabeled

  8. [(68) Ga]-HP-DO3A-nitroimidazole: a promising agent for PET detection of tumor hypoxia.

    PubMed

    Wu, Yunkou; Hao, Guiyang; Ramezani, Saleh; Saha, Debabrata; Zhao, Dawen; Sun, Xiankai; Sherry, A Dean

    2015-01-01

    The goal of this study is to evaluate a new (68) Ga-based imaging agent for detecting tumor hypoxia using positron emission tomography (PET). The new hypoxia targeting agent reported here, [(68) Ga]-HP-DO3A-nitroimidazole ([(68) Ga]-HP-DO3A-NI), was constructed by linking a nitroimidazole moiety with the macrocyclic ligand component of ProHance®, HP-DO3A. The hypoxia targeting capability of this agent was evaluated in A549 lung cancer cells in vitro and in SCID mice bearing subcutaneous A549 tumor xenografts. The cellular uptake assays showed that significantly more [(68) Ga]-HP-DO3A-NI accumulates in hypoxic tumor cells at 30, 60 and 120 min than in the same cells exposed to 21% O2 . The agent also accumulated in hypoxic tumors in vivo to give a tumor/muscle ratio (T/M) of 5.0 ± 1.2 (n = 3) as measured by PET at 2 h post-injection (p.i.). This was further confirmed by ex vivo biodistribution data. In addition, [(68) Ga]-HP-DO3A-NI displayed very favorable pharmacokinetic properties, as it was cleared largely through the kidneys with little to no accumulation in liver, heart or lung (%ID/g < 0.5%) at 2 h p.i. The specificity of the agent for hypoxic tissues was further validated in a comparative study with a control compound, [(68) Ga]-HP-DO3A, which lacks the nitroimidazole moiety, and by PET imaging of tumor-bearing mice breathing air versus 100% O2 . Given the commercial availability of cGMP (68) Ge/(68) Ga generators and the ease of (68) Ga labeling, the new agent could potentially be widely applied for imaging tumor hypoxia prior to radiation therapy.

  9. Veterinarians' role for pet owners facing pet loss

    PubMed Central

    Fernandez-Mehler, P.; Gloor, P.; Sager, E.; Lewis, F. I.; Glaus, T. M

    2013-01-01

    Owners' satisfaction with, and expectations from, their veterinarians around euthanasia, including questions on disposal of pet remains subject to animal species, clients' gender, age, family conditions, area of living and type of veterinary clinic visited were evaluated by questionnaire. Questionnaires were to be filled out by clients consecutively visiting the individual practices and hospitals for any kind of consultations. Of 2350 questionnaires distributed, 2008 were returned and available for analysis. Owner satisfaction concerning the procedure of euthanasia was high (92 per cent, 1173/1272). After the event of euthanasia, 14 per cent (170/1250) had changed their veterinarian, even though 75 per cent of these 170 had been satisfied with the procedure. Most owners (88 per cent) expected veterinarians to talk about their pet's final destination, and 38 per cent expected this to happen early in the pet's life. For 81 per cent clients, the veterinarian was the primary informant about the possibilities concerning the disposal of pet remains, and 33 per cent indicated their veterinarian as the contact person to talk about pet loss. Area of living, or veterinary specialisation, only marginally influenced the answers. Veterinarians play an important role to inform their clients concerning questions around euthanasia and the care of pet remains, and to support them during the process of mourning. PMID:23492929

  10. Veterinarians' role for pet owners facing pet loss.

    PubMed

    Fernandez-Mehler, P; Gloor, P; Sager, E; Lewis, F I; Glaus, T M

    2013-05-25

    Owners' satisfaction with, and expectations from, their veterinarians around euthanasia, including questions on disposal of pet remains subject to animal species, clients' gender, age, family conditions, area of living and type of veterinary clinic visited were evaluated by questionnaire. Questionnaires were to be filled out by clients consecutively visiting the individual practices and hospitals for any kind of consultations. Of 2350 questionnaires distributed, 2008 were returned and available for analysis. Owner satisfaction concerning the procedure of euthanasia was high (92 per cent, 1173/1272). After the event of euthanasia, 14 per cent (170/1250) had changed their veterinarian, even though 75 per cent of these 170 had been satisfied with the procedure. Most owners (88 per cent) expected veterinarians to talk about their pet's final destination, and 38 per cent expected this to happen early in the pet's life. For 81 per cent clients, the veterinarian was the primary informant about the possibilities concerning the disposal of pet remains, and 33 per cent indicated their veterinarian as the contact person to talk about pet loss. Area of living, or veterinary specialisation, only marginally influenced the answers. Veterinarians play an important role to inform their clients concerning questions around euthanasia and the care of pet remains, and to support them during the process of mourning.

  11. CB2 cannabinoid receptor agonist, JWH-015 triggers apoptosis in immune cells: Potential role for CB2 selective ligands as immunosuppressive agents

    PubMed Central

    Lombard, Catherine; Nagarkatti, Mitzi; Nagarkatti, Prakash

    2007-01-01

    Cannabinoids are known to interact with CB1 and CB2 receptors expressed in the nervous and immune system, respectively and mediate a wide range of effects, including anti-inflammatory properties. However, cannabinoids that bind CB1 are also psychoactive thereby limiting their clinical use. In this study, we investigated the immunosuppressive properties of JWH-015, a synthetic CB2-selective agonist. We found that JWH-015 triggered apoptosis in thymocytes in vitro and inhibited the proliferative response of T and B cells to mitogens through induction of apoptosis. JWH-015 induced cross-talk between extrinsic and intrinsic pathways of apoptosis involving caspase-8, caspase-9, and caspase-3 as well as loss of mitochondrial membrane potential. Finally, administration of JWH-015 in vivo caused thymic atrophy, apoptosis, and decreased peripheral T cell response to mitogens. Together, this study suggests that CB2 selective agonists, devoid of psychotropic effect, may serve as novel anti-inflammatory/immunosuppressive agents. PMID:17185040

  12. F-18-fluoro-2-deoxyglucose positron emission tomography (PET) and PET/computed tomography imaging in primary staging of patients with malignant melanoma: a systematic review

    PubMed Central

    2012-01-01

    Purpose The aim of this systematic review was to systematically assess the potential patient-relevant benefit (primary aim) and diagnostic and prognostic accuracy (secondary aim) of positron emission tomography (PET) and PET/computed tomography (CT) in primary staging of malignant melanoma. This systematic review updates the previous evidence for PET(/CT) in malignant melanoma. Materials and methods For the first aim, randomized controlled trials (RCTs) investigating patient-relevant outcomes and comparing PET and PET(/CT) with each other or with conventional imaging were considered. For the secondary aim, a review of reviews was conducted, which was amended by an update search for primary studies. MEDLINE, EMBASE and four databases of the Cochrane Library were searched. The risk of bias was assessed using a modified QUADAS tool. Results No RCTs investigating the patient-relevant benefit of PET(/CT) and no prognostic accuracy studies were found. Seventeen diagnostic accuracy studies of varying quality were identified. For patients with American Joint Committee on Cancer (AJCC) stages I and II, sensitivity mostly ranged from 0 to 67%. Specificity ranged from 77 to 100%. For AJCC stages III and IV, sensitivity ranged from 68 to 87% and specificity from 92 to 98%. Conclusion There is currently no evidence of a patient-relevant benefit of PET(/CT) in the primary staging of malignant melanoma. RCTs investigating patient-relevant outcomes are therefore required. The diagnostic accuracy of PET(/CT) appears to increase with higher AJCC stages. PMID:23237499

  13. Anti-amnesic and neuroprotective potentials of the mixed muscarinic receptor/sigma 1 (σ1) ligand ANAVEX2-73, a novel aminotetrahydrofuran derivative.

    PubMed

    Villard, Vanessa; Espallergues, Julie; Keller, Emeline; Vamvakides, Alexandre; Maurice, Tangui

    2011-08-01

    Tetrahydro-N, N-dimethyl-2, 2-diphenyl-3-furanmethanamine hydrochloride (ANAVEX2-73) binds to muscarinic acetylcholine and sigma(1) (σ(1)) receptors with affinities in the low micromolar range. We characterized its anti-amnesic and neuroprotective potentials in pharmacological and pathological amnesia models. Spatial working memory was evaluated using spontaneous alternation in the Y-maze and non-spatial memory using passive avoidance procedures. ANAVEX2-73 (0.01-3.0 mg/kg i.p.) alleviated the scopolamine- and dizocilpine-induced learning impairments. ANAVEX2-73 (300 µg/kg) also reversed the learning deficits in mice injected with Aβ(25-35) peptide, a non-transgenic Alzheimer's disease model. When the drug was injected simultaneously with Aβ(25-35), 7 days before the tests, it blocked the appearance of learning impairments. This protective activity was confirmed since ANAVEX2-73 blocked the Aβ(25-35)-induced oxidative stress in the hippocampus. This effect was differentially sensitive to the muscarinic receptor antagonist scopolamine or the σ(1) protein antagonist BD1047, confirming the mixed muscarinic/σ(1) pharmacological action. Finally, its unique demethyl metabolite, ANAVEX19-144, was also effective and ANAVEX2-73 presented a longer duration of action, effective 12 h before Aβ(25-35), than its related compound ANAVEX1-41. The neuroprotective activity of ANAVEX2-73, its mixed cholinergic/σ(1) activity, its low active dose range and its long duration of action together reinforce its therapeutic potential in Alzheimer's disease.

  14. Advantages of improved timing accuracy in PET cameras using LSOscintillator

    SciTech Connect

    Moses, William W.

    2002-12-02

    PET scanners based on LSO have the potential forsignificantly better coincidence timing resolution than the 6 ns fwhmtypically achieved with BGO. This study analyzes the performanceenhancements made possible by improved timing as a function of thecoincidence time resolution. If 500 ps fwhm coincidence timing resolutioncan be achieved in a complete PET camera, the following four benefits canbe realized for whole-body FDG imaging: 1) The random event rate can bereduced by using a narrower coincidence timing window, increasing thepeak NECR by~;50 percent. 2) Using time-of-flight in the reconstructionalgorithm will reduce the noise variance by a factor of 5. 3) Emissionand transmission data can be acquired simultaneously, reducing the totalscan time. 4) Axial blurring can be reduced by using time-of-flight todetermine the correct axial plane that each event originated from. Whiletime-of-flight was extensively studied in the 1980's, practical factorslimited its effectiveness at that time and little attention has been paidto timing in PET since then. As these potential improvements aresubstantial and the advent of LSO PET cameras gives us the means toobtain them without other sacrifices, efforts to improve PET timingshould resume after their long dormancy.

  15. Amino Acids in Nine Ligand-Prefer Ramachandran Regions.

    PubMed

    Cao, Chen; Wang, Lincong; Chen, Xiaoyang; Zou, Shuxue; Wang, Guishen; Xu, Shutan

    2015-01-01

    Several secondary structures, such as π-helix and left-handed helix, have been frequently identified at protein ligand-binding sites. A secondary structure is considered to be constrained to a specific region of dihedral angles. However, a comprehensive analysis of the correlation between main chain dihedral angles and ligand-binding sites has not been performed. We undertook an extensive analysis of the relationship between dihedral angles in proteins and their distance to ligand-binding sites, frequency of occurrence, molecular potential energy, amino acid composition, van der Waals contacts, and hydrogen bonds with ligands. The results showed that the values of dihedral angles have a strong preference for ligand-binding sites at certain regions in the Ramachandran plot. We discovered that amino acids preceding the ligand-prefer ϕ/ψ box residues are exposed more to solvents, whereas amino acids following ligand-prefer ϕ/ψ box residues form more hydrogen bonds and van der Waals contacts with ligands. Our method exhibited a similar performance compared with the program Ligsite-csc for both ligand-bound structures and ligand-free structures when just one ligand-binding site was predicted. These results should be useful for the prediction of protein ligand-binding sites and for analysing the relationship between structure and function.

  16. Chemistry of Marine Ligands and Siderophores

    NASA Astrophysics Data System (ADS)

    Vraspir, Julia M.; Butler, Alison

    2009-01-01

    Marine microorganisms are presented with unique challenges to obtain essential metal ions required to survive and thrive in the ocean. The production of organic ligands to complex transition metal ions is one strategy to both facilitate uptake of specific metals, such as iron, and to mitigate the potential toxic effects of other metal ions, such as copper. A number of important trace metal ions are complexed by organic ligands in seawater, including iron, cobalt, nickel, copper, zinc, and cadmium, thus defining the speciation of these metal ions in the ocean. In the case of iron, siderophores have been identified and structurally characterized. Siderophores are low molecular weight iron-binding ligands produced by marine bacteria. Although progress has been made toward the identity of in situ iron-binding ligands, few compounds have been identified that coordinate the other trace metals. Deciphering the chemical structures and production stimuli of naturally produced organic ligands and the organisms they come from is fundamental to understanding metal speciation and bioavailability. The current evidence for marine ligands, with an emphasis on siderophores, and discussion of the importance and implications of metal-binding ligands in controlling metal speciation and cycling within the world's oceans are presented.

  17. Development of fluorinated CB(2) receptor agonists for PET studies.

    PubMed

    Lueg, Corinna; Schepmann, Dirk; Günther, Robert; Brust, Peter; Wünsch, Bernhard

    2013-12-01

    A convergent strategy was followed to modify systematically carbazole based CB(2) receptor ligands. The length of the N-(fluoroalkyl) group (n in 7), the length of the alkanamide (m in 7) and the substitution pattern of the phenyl moiety (X and Y in 7) were varied systematically. The highest CB(2) affinity was found for the 2-fluoroethyl substituted carbazole derivative 20a (Ki=5.8nM) containing the propionamide and the 2-bromo-4-fluorophenyl moiety. According to docking studies 20a fits nicely into the binding pocket of the CB(2) receptor, but elongation of the fluoroethyl side chain leads to a different binding mode of the ligands. The high CB(2) affinity together with the high selectivity over the CB(2) subtype qualifies the fluoroethyl derivative 20a to be developed as a PET tracer.

  18. Analysis of Pet Coke Samples

    EPA Pesticide Factsheets

    EPA required KCBX to submit samples of the petroleum coke stored at their North and South Chicago terminals to EPA's Chicago Regional Laboratory for analysis of pollutant levels. Results will be compared to coal and pet coke sampled in Detroit.

  19. Take Care with Pet Reptiles

    MedlinePlus

    ... CDC Features Take Care with Pet Reptiles and Amphibians Language: English Español (Spanish) Recommend on Facebook Tweet ... helpful resources. Safe Handling Tips for Reptiles and Amphibians Always wash your hands thoroughly after handling reptiles ...

  20. Behavior problems in geriatric pets.

    PubMed

    Landsberg, Gary; Araujo, Joseph A

    2005-05-01

    Aging pets often suffer a decline in cognitive function (eg, memory,learning, perception, awareness) likely associated with age-dependent brain alterations. Clinically, cognitive dysfunction may result in various behavioral signs, including disorientation; forgetting of previously learned behaviors, such as house training; alterations in the manner in which the pet interacts with people or other pets;onset of new fears and anxiety; decreased recognition of people, places, or pets; and other signs of deteriorating memory and learning ability. Many medical problems, including other forms of brain pathologic conditions, can contribute to these signs. The practitioner must first determine the cause of the behavioral signs and then determine an appropriate course of treatment, bearing in mind the constraints of the aging process. A diagnosis of cognitive dysfunction syndrome is made once other medical and behavioral causes are ruled out.

  1. Should Immunocompromised Patients Have Pets?

    PubMed Central

    Steele, Russell W.

    2008-01-01

    Purpose: To evaluate the risks and benefits of pet ownership by immunodeficient patients, focusing primarily on organisms that colonize animals and are transmitted to humans. Those diseases that are known to be progressive or more severe in patients with altered immune function are emphasized. Methods: A review of the medical and veterinary literature pertaining to zoonoses transmitted by domestic animals was completed. Information pertaining to issues involving immunosuppressed patients including AIDS was carefully evaluated and summarized for inclusion. Results: There are significant clinical and psychosocial benefits to pet ownership. However, numerous diseases can be acquired from these animals which may be more severe in immunocompromised individuals. Conclusion: Simple guidelines for pet ownership by immunosuppressed patients can be implemented to reduce their risk of disease and allow them to safely interchange with their pets. PMID:21603465

  2. 10 "Poison Pills" for Pets

    MedlinePlus

    ... left on the bedside table. Zolpidem may make cats wobbly and sleepy, but most pets become very ... very common pain killer found in most households. Cats are extremely sensitive to acetaminophen, but dogs can ...

  3. Design of respiration averaged CT for attenuation correction of the PET data from PET/CT

    SciTech Connect

    Chi, Pai-Chun Melinda; Mawlawi, Osama; Nehmeh, Sadek A.; Erdi, Yusuf E.; Balter, Peter A.; Luo, Dershan; Mohan, Radhe; Pan Tinsu

    2007-06-15

    Our previous patient studies have shown that the use of respiration averaged computed tomography (ACT) for attenuation correction of the positron emission tomography (PET) data from PET/CT reduces the potential misalignment in the thorax region by matching the temporal resolution of the CT to that of the PET. In the present work, we investigated other approaches of acquiring ACT in order to reduce the CT dose and to improve the ease of clinical implementation. Four-dimensional CT (4DCT) data sets for ten patients (17 lung/esophageal tumors) were acquired in the thoracic region immediately after the routine PET/CT scan. For each patient, multiple sets of ACTs were generated based on both phase image averaging (phase approach) and fixed cine duration image averaging (cine approach). In the phase approach, the ACTs were calculated from CT images corresponding to the significant phases of the respiratory cycle: ACT{sub 050phs} from end-inspiration (0%) and end-expiration (50%), ACT{sub 2070phs} from mid-inspiration (20%) and mid-expiration (70%), ACT{sub 4phs} from 0%, 20%, 50% and 70%, and ACT{sub 10phs} from all ten phases, which was the original approach. In the cine approach, which does not require 4DCT, the ACTs were calculated based on the cine images from cine durations of 1 to 6 s at 1 s increments. PET emission data for each patient were attenuation corrected with each of the above mentioned ACTs and the tumor maximum standard uptake value (SUV{sub max}), average SUV (SUV{sub avg}), and tumor volume measurements were compared. Percent differences were calculated between PET data corrected with various ACTs and that corrected with ACT{sub 10phs}. In the phase approach, the ACT{sub 10phs} can be approximated by the ACT{sub 4phs} to within a mean percent difference of 2% in SUV and tumor volume measurements. In cine approach, ACT{sub 10phs} can be approximated to within a mean percent difference of 3% by ACTs computed from cine durations {>=}3 s. Acquiring CT

  4. Ligand modeling and design

    SciTech Connect

    Hay, B.P.

    1997-10-01

    The purpose of this work is to develop and implement a molecular design basis for selecting organic ligands that would be used in the cost-effective removal of specific radionuclides from nuclear waste streams. Organic ligands with metal ion specificity are critical components in the development of solvent extraction and ion exchange processes that are highly selective for targeted radionuclides. The traditional approach to the development of such ligands involves lengthy programs of organic synthesis and testing, which in the absence of reliable methods for screening compounds before synthesis, results in wasted research effort. The author`s approach breaks down and simplifies this costly process with the aid of computer-based molecular modeling techniques. Commercial software for organic molecular modeling is being configured to examine the interactions between organic ligands and metal ions, yielding an inexpensive, commercially or readily available computational tool that can be used to predict the structures and energies of ligand-metal complexes. Users will be able to correlate the large body of existing experimental data on structure, solution binding affinity, and metal ion selectivity to develop structural design criteria. These criteria will provide a basis for selecting ligands that can be implemented in separations technologies through collaboration with other DOE national laboratories and private industry. The initial focus will be to select ether-based ligands that can be applied to the recovery and concentration of the alkali and alkaline earth metal ions including cesium, strontium, and radium.

  5. Mycoflora in commercial pet foods.

    PubMed

    Bueno, D J; Silva, J O; Oliver, G

    2001-05-01

    This article reports on the identification of mycoflora of 21 dry pet foods (12 belonging to dogs and 9 to cats) that corresponded to 8 commercial brands made in Argentina and imported. The isolation frequency and relative density of the prevalent fungal genera are compared too. Ten genera and fungi classified as Mycelia sterilia were identified. The predominant genera were Aspergillus (62%), Rhizopus (48%), and Mucor (38%). The most prevalent among Aspergillus was Aspergillus flavus followed by Aspergillus niger and Aspergillus terreus. The predominant Mucor was Mucor racemosus followed by Mucor plumbeus and Mucor globosus. The moisture content of these foods ranged from 5.6 to 10.0% and from 7.2 to 9.9% for dog and cat foods, respectively. A greater moisture content in food for the senior category (9.5 +/- 0.2) was observed only in comparison to adult and kitten/puppy. If the moisture content can be maintained at these levels, mold growth would be prevented or at least it would remain at an insignificant level. Some genera and species isolated and identified from the foods analyzed are potentially producing toxins, which are known as mycotoxins. This involves a risk for animal health.

  6. MR-PET image coregistration for quantitation of striatal dopamine D{sub 2} receptors

    SciTech Connect

    Wang, G.J.; Volkow, N.D.; Levy, A.V.

    1996-05-01

    Our goal was to assess the utility of MR-PET image coregistration to quantify dopamine D{sub 2} receptors in striatum. Twenty-nine normal subjects were investigated with PET and [{sup 11}C]raclopride and with MRI. D{sub 2} receptors were quantified using the ratio of the distribution volume in striatum to that in cerebellum. Measures obtained using regions selected directly from the PET images were compared with those obtained from MR images and then projected to coregistered PET images. There were no differences between measures selected from the PET images (3.9 {+-} 0.5) and those from the MR images (3.9 {+-} 0.65). The values for these two measures were significantly correlated and corresponded to r = 0.9, P < 0.0001. Regions of interest selected directly from PET images, where there is a large contrast between the region of interest and background, as for the case of dopamine D{sub 2} ligands, are almost identical to those obtained from coregistered MR images. 24 refs., 4 figs., 1 tab.

  7. Bromine-80m-labeled estrogens: Auger-electron emitting, estrogen receptor-directed ligands with potential for therapy of estrogen receptor positive cancers

    SciTech Connect

    DeSombre, E.R.; Mease, R.C.; Hughes, A.; Harper, P.V.; DeJesus, O.T.; Friedman, A.M.

    1988-01-01

    A triphenylbromoethylene, 1,1-bis(p-hydroxyphenyl)-2-bromo-2-phenylethylene, Br-BHPE, and a bromosteroidal estrogen, 17..cap alpha..- bromovinylestradiol, BrVE/sub 2/, were labeled with the Auger electron emitting nuclide bromine-80m, prepared by the (p,n) reaction with /sup 80/Se. To assess their potential as estrogen receptor (ER) directed therapeutic substrates the bromine-80m labeled estrogens were injected into immature female rats and the tissue distribution studied at 0.5 and 2 hours. Both radiobromoestrogens showed substantial diethylstilbesterol (DES)-inhibitable localization in the ER rich tissues, uterus, pituitary, ovary and vagina at both time points. While the percent dose per gram tissue was higher for the Br-BHPE, the BrVE/sub 2/ showed higher tissue to blood ratios, especially at 2 hr, reflecting the lower blood concentrations of radiobromine following administration of the steroidal bromoestrogen. Comparing intraperitoneal, intravenous and subcutaneous routes of administration for the radiobromine labeled Br-BHPE, the intraperitoneal route was particularly advantageous to provide maximum, DES-inhibitable concentrations in the peritoneal, ER-rich target organs, the uterus, ovary and vagina. While uterine concentrations after BrBHPE were from 10--48% dose/g and after BrVE/sub 2/ were 15--25% dose/g, similar treatment with /sup 80m/Br as sodium bromide showed uniform low concentrations in all tissues at about the levels seen in blood. The effective specific activity of (/sup 80m/Br)BrBHPE, assayed by specific binding to ER in rat uterine cytosol, was 8700 Ci/mmole. 23 refs., 9 figs., 2 tabs.

  8. Nutritional sustainability of pet foods.

    PubMed

    Swanson, Kelly S; Carter, Rebecca A; Yount, Tracy P; Aretz, Jan; Buff, Preston R

    2013-03-01

    Sustainable practices meet the needs of the present without compromising the ability of future generations to meet their needs. Applying these concepts to food and feed production, nutritional sustainability is the ability of a food system to provide sufficient energy and essential nutrients required to maintain good health in a population without compromising the ability of future generations to meet their nutritional needs. Ecological, social, and economic aspects must be balanced to support the sustainability of the overall food system. The nutritional sustainability of a food system can be influenced by several factors, including the ingredient selection, nutrient composition, digestibility, and consumption rates of a diet. Carbon and water footprints vary greatly among plant- and animal-based ingredients, production strategy, and geographical location. Because the pet food industry is based largely on by-products and is tightly interlinked with livestock production and the human food system, however, it is quite unique with regard to sustainability. Often based on consumer demand rather than nutritional requirements, many commercial pet foods are formulated to provide nutrients in excess of current minimum recommendations, use ingredients that compete directly with the human food system, or are overconsumed by pets, resulting in food wastage and obesity. Pet food professionals have the opportunity to address these challenges and influence the sustainability of pet ownership through product design, manufacturing processes, public education, and policy change. A coordinated effort across the industry that includes ingredient buyers, formulators, and nutritionists may result in a more sustainable pet food system.

  9. PET Imaging in Huntington's Disease.

    PubMed

    Roussakis, Andreas-Antonios; Piccini, Paola

    2015-01-01

    To date, little is known about how neurodegeneration and neuroinflammation propagate in Huntington's disease (HD). Unfortunately, no treatment is available to cure or reverse the progressive decline of function caused by the disease, thus considering HD a fatal disease. Mutation gene carriers typically remain asymptomatic for many years although alterations in the basal ganglia and cortex occur early on in mutant HD gene-carriers. Positron Emission Tomography (PET) is a functional imaging technique of nuclear medicine which enables in vivo visualization of numerous biological molecules expressed in several human tissues. Brain PET is most powerful to study in vivo neuronal and glial cells function as well as cerebral blood flow in a plethora of neurodegenerative disorders including Parkinson's disease, Alzheimer's and HD. In absence of HD-specific biomarkers for monitoring disease progression, previous PET studies in HD were merely focused on the study of dopaminergic terminals, cerebral blood flow and glucose metabolism in manifest and premanifest HD-gene carriers. More recently, research interest has been exploring novel PET targets in HD including the state of phosphodiesterse expression and the role of activated microglia. Hence, a better understanding of the HD pathogenesis mechanisms may lead to the development of targeted therapies. PET imaging follow-up studies with novel selective PET radiotracers such as 11C-IMA-107 and 11C-PBR28 may provide insight on disease progression and identify prognostic biomarkers, elucidate the underlying HD pathology and assess novel pharmaceutical agents and over time.

  10. Advances in Clinical PET/MRI Instrumentation.

    PubMed

    Herzog, Hans; Lerche, Christoph

    2016-04-01

    In 2010, the first whole-body PET/MRI scanners installed for clinical use were the sequential Philips PET/MRI with PMT-based, TOF-capable technology and the integrated simultaneous Siemens PET/MRI. Avalanche photodiodes as non-magneto-sensitive readout electronics allowed PET integrated within the MRI. The experiences with these scanners showed that improvements of software aspects, such as attenuation correction, were necessary and that efficient protocols combining optimally PET and MRI must be still developed. In 2014, General Electric issued an integrated PET/MRI with SiPM-based PET detectors, allowing TOF-PET. Looking at the MRI components of current PET/MR imaging systems, primary improvements come from sequences and new coils.

  11. Are Pets in the Bedroom a Problem?

    PubMed

    Krahn, Lois E; Tovar, M Diane; Miller, Bernie

    2015-12-01

    The presence of pets in the bedroom can alter the sleep environment in ways that could affect sleep. Data were collected by questionnaire and interview from 150 consecutive patients seen at the Center for Sleep Medicine, Mayo Clinic in Arizona. Seventy-four people (49%) reported having pets, with 31 (41% of pet owners) having multiple pets. More than half of pet owners (56%) allowed their pets to sleep in the bedroom. Fifteen pet owners (20%) described their pets as disruptive, whereas 31 (41%) perceived their pets as unobtrusive or even beneficial to sleep. Health care professionals working with patients with sleep concerns should inquire about the presence of companion animals in the sleep environment to help them find solutions and optimize their sleep.

  12. 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

  13. PET/CT and radiotherapy in prostate cancer.

    PubMed

    De Jong, I J; De Haan, T D; Wiegman, E M; Van Den Bergh, A C M; Pruim, J; Breeuwsma, A J

    2010-10-01

    Radiotherapy is one of the corner stone treatments for patients with prostate cancer. Especially for locally advanced tumors radiotherapy +/- adjuvant androgen deprivation treatment is standard of care. This brings up the need for accurate assessment of extra prostatic tumor growth and/or the presence of nodal metastases for selection of the optimal radiation dose and treatment volume. Morphological imaging like transrectal ultra sound, computed tomography (CT) and magnetic resonance imaging (MRI) are routinely used but are limited in their accuracy in detecting extra prostatic extension and nodal metastases. In this article we present a structured review of the literature on positron emission tomography (PET)/CT and radiotherapy in prostate cancer patients with emphasis on: 1) the pretreatment assessment of extra prostatic tumor extension, nodal and distant metastases; 2) the intraprostatic tumor characterization and radiotherapy treatment planning; and 3) treatment evaluation and the use of PET/CT in guidance of salvage treatment. PET/CT is not an appropriate imaging technique for accurate T-staging of prostate cancer prior to radiotherapy. Although macroscopic disease beyond the prostatic capsule and into the periprostatic fat or in seminal vesicle is often accurately detected, the microscopic extension of prostate cancer remains undetected. Choline PET/CT holds a great potential as a single step diagnostic procedure of lymph nodes and skeleton, which could facilitate radiotherapy treatment planning. At present the use of PET/CT for treatment planning in radiotherapy is still experimental. Choline PET based tumor delineation is not yet standardized and different segmentation-algorithms are under study. However, dose escalation using dose-painting is feasible with only limited increases of the doses to the bladder and rectum wall. PET/CT using either acetate or choline is able to detect recurrent prostate cancer after radiotherapy but stratification of patients

  14. Sliding tethered ligands add topological interactions to the toolbox of ligand-receptor design.

    PubMed

    Bauer, Martin; Kékicheff, Patrick; Iss, Jean; Fajolles, Christophe; Charitat, Thierry; Daillant, Jean; Marques, Carlos M

    2015-09-09

    Adhesion in the biological realm is mediated by specific lock-and-key interactions between ligand-receptor pairs. These complementary moieties are ubiquitously anchored to substrates by tethers that control the interaction range and the mobility of the ligands and receptors, thus tuning the kinetics and strength of the binding events. Here we add sliding anchoring to the toolbox of ligand-receptor design by developing a family of tethered ligands for which the spacer can slide at the anchoring point. Our results show that this additional sliding degree of freedom changes the nature of the adhesive contact by extending the spatial range over which binding may sustain a significant force. By introducing sliding tethered ligands with self-regulating length, this work paves the way for the development of versatile and reusable bio-adhesive substrates with potential applications for drug delivery and tissue engineering.

  15. A General Ligand Design for Gold Catalysis allowing Ligand-Directed Anti Nucleophilic Attack of Alkynes

    PubMed Central

    Wang, Yanzhao; Wang, Zhixun; Li, Yuxue; Wu, Gongde; Cao, Zheng; Zhang, Liming

    2014-01-01

    Most homogenous gold catalyses demand ≥0.5 mol % catalyst loading. Due to the high cost of gold, these reactions are unlikely to be applicable in medium or large scale applications. Here we disclose a novel ligand design based on the privileged biphenyl-2-phosphine framework that offers a potentially general approach to dramatically lowering catalyst loading. In this design, an amide group at the 3’ position of the ligand framework directs and promotes nucleophilic attack at the ligand gold complex-activated alkyne, which is unprecedented in homogeneous gold catalysis considering the spatial challenge of using ligand to reach antiapproaching nucleophile in a linear P-Au-alkyne centroid structure. With such a ligand, the gold(I) complex becomes highly efficient in catalyzing acid addition to alkynes, with a turnover number up to 99,000. Density functional theory calculations support the role of the amide moiety in directing the attack of carboxylic acid via hydrogen bonding. PMID:24704803

  16. Canine Comfort: Pet Affinity Buffers the Negative Impact of Ambivalence over Emotional Expression on Perceived Social Support.

    PubMed

    Bryan, Jennifer L; Quist, Michelle C; Young, Chelsie M; Steers, Mai-Ly N; Foster, Dawn W; Lu, Qian

    2014-10-01

    This study evaluated pet affinity as a buffer between ambivalence over emotional expression (AEE) and social support. AEE occurs when one desires to express emotions but is reluctant to do so and is related to negative psychological outcomes. Individuals high in AEE may have difficulty receiving social support and thus may not gain accompanying benefits. Social support has been associated with positive health outcomes, and pet support is positively associated with human social support. The present study explores the potential protective effect of pet affinity. One hundred ninety-eight undergraduate dog owners completed measures assessing perceived social support, pet affinity, and AEE. AEE was expected to be negatively associated with social support, and pet affinity was expected to buffer the negative effects of AEE on social support. We found that AEE was negatively associated with perceived social support. An interaction between pet affinity and AEE emerged such that the negative association between AEE and social support was weaker among those higher in pet affinity. Thus, at high levels of AEE, those who felt a close connection with their pets reported more perceived social support than those less connected with their pets. Overall, these findings emphasize the potential benefits of pet affinity.

  17. Canine Comfort: Pet Affinity Buffers the Negative Impact of Ambivalence over Emotional Expression on Perceived Social Support

    PubMed Central

    Bryan, Jennifer L.; Quist, Michelle C.; Young, Chelsie M.; Steers, Mai-Ly N.; Foster, Dawn W.; Lu, Qian

    2015-01-01

    This study evaluated pet affinity as a buffer between ambivalence over emotional expression (AEE) and social support. AEE occurs when one desires to express emotions but is reluctant to do so and is related to negative psychological outcomes. Individuals high in AEE may have difficulty receiving social support and thus may not gain accompanying benefits. Social support has been associated with positive health outcomes, and pet support is positively associated with human social support. The present study explores the potential protective effect of pet affinity. One hundred ninety-eight undergraduate dog owners completed measures assessing perceived social support, pet affinity, and AEE. AEE was expected to be negatively associated with social support, and pet affinity was expected to buffer the negative effects of AEE on social support. We found that AEE was negatively associated with perceived social support. An interaction between pet affinity and AEE emerged such that the negative association between AEE and social support was weaker among those higher in pet affinity. Thus, at high levels of AEE, those who felt a close connection with their pets reported more perceived social support than those less connected with their pets. Overall, these findings emphasize the potential benefits of pet affinity. PMID:25960586

  18. Multi-atlas attenuation correction supports full quantification of static and dynamic brain PET data in PET-MR.

    PubMed

    Merida, Ines; Reilhac, Anthonin; Redoute, Jerome; Heckemann, Rolf; Costes, Nicolas; Hammers, Alexander

    2017-02-09

    Introduction In simultaneous PET-MR, attenuation maps are not directly available. Essential for absolute radioactivity quantification, they need to be derived from MR or PET data to correct for gamma photon attenuation by the imaged object. We evaluate a multi-atlas attenuation correction method for brain imaging (MaxProb) on static [18F]FDG PET and, for the first time, on dynamic PET, using the serotoninergic tracer [18F]MPPF. Methods A database of 40 MR/CT image pairs (atlases) was used. The MaxProb method synthesises subject-specific pseudo-CTs by registering each atlas to the target subject space. Atlas CT intensities are then fused via label propagation and majority voting. Here, we compared these pseudo-CTs with the real CTs in a leave-one-out design, contrasting the MaxProb approach with a simplified single-atlas method (SingleAtlas). We evaluated the impact of pseudo-CT accuracy on reconstructed PET images, compared to PET data reconstructed with real CT, at the regional and voxel levels for the following: radioactivity images; time-activity curves; and kinetic parameters (non-displaceable binding potential, BPND). Results On static [18F]FDG, the mean bias for MaxProb ranged between 0 and 1% for 73 out of 84 regions assessed, and exceptionally peaked at 2.5% for only one region. Statistical parametric map analysis of MaxProb-corrected PET data showed significant differences in less than 0.02% of the brain volume, whereas SingleAtlas-corrected data showed significant differences in 20% of the brain volume. On dynamic [18F]MPPF, most regional errors on BPND ranged from -1 to +3% (maximum bias 5%) for the MaxProb method. With SingleAtlas, errors were larger and had higher variability in most regions. PET quantification bias increased over the duration of the dynamic scan for SingleAtlas, but not for MaxProb. We show that this effect is due to the interaction of the spatial tracer-distribution heterogeneity variation over time with the degree of accuracy of the

  19. Multi-atlas attenuation correction supports full quantification of static and dynamic brain PET data in PET-MR

    NASA Astrophysics Data System (ADS)

    Mérida, Inés; Reilhac, Anthonin; Redouté, Jérôme; Heckemann, Rolf A.; Costes, Nicolas; Hammers, Alexander

    2017-04-01

    In simultaneous PET-MR, attenuation maps are not directly available. Essential for absolute radioactivity quantification, they need to be derived from MR or PET data to correct for gamma photon attenuation by the imaged object. We evaluate a multi-atlas attenuation correction method for brain imaging (MaxProb) on static [18F]FDG PET and, for the first time, on dynamic PET, using the serotoninergic tracer [18F]MPPF. A database of 40 MR/CT image pairs (atlases) was used. The MaxProb method synthesises subject-specific pseudo-CTs by registering each atlas to the target subject space. Atlas CT intensities are then fused via label propagation and majority voting. Here, we compared these pseudo-CTs with the real CTs in a leave-one-out design, contrasting the MaxProb approach with a simplified single-atlas method (SingleAtlas). We evaluated the impact of pseudo-CT accuracy on reconstructed PET images, compared to PET data reconstructed with real CT, at the regional and voxel levels for the following: radioactivity images; time-activity curves; and kinetic parameters (non-displaceable binding potential, BPND). On static [18F]FDG, the mean bias for MaxProb ranged between 0 and 1% for 73 out of 84 regions assessed, and exceptionally peaked at 2.5% for only one region. Statistical parametric map analysis of MaxProb-corrected PET data showed significant differences in less than 0.02% of the brain volume, whereas SingleAtlas-corrected data showed significant differences in 20% of the brain volume. On dynamic [18F]MPPF, most regional errors on BPND ranged from -1 to  +3% (maximum bias 5%) for the MaxProb method. With SingleAtlas, errors were larger and had higher variability in most regions. PET quantification bias increased over the duration of the dynamic scan for SingleAtlas, but not for MaxProb. We show that this effect is due to the interaction of the spatial tracer-distribution heterogeneity variation over time with the degree of accuracy of the attenuation maps. This

  20. Ligand clouds around protein clouds: a scenario of ligand binding with intrinsically disordered proteins.

    PubMed

    Jin, Fan; Yu, Chen; Lai, Luhua; Liu, Zhirong

    2013-01-01

    Intrinsically disordered proteins (IDPs) were found to be widely associated with human diseases and may serve as potential drug design targets. However, drug design targeting IDPs is still in the very early stages. Progress in drug design is usually achieved using experimental screening; however, the structural disorder of IDPs makes it difficult to characterize their interaction with ligands using experiments alone. To better understand the structure of IDPs and their interactions with small molecule ligands, we performed extensive simulations on the c-Myc₃₇₀₋₄₀₉ peptide and its binding to a reported small molecule inhibitor, ligand 10074-A4. We found that the conformational space of the apo c-Myc₃₇₀₋₄₀₉ peptide was rather dispersed and that the conformations of the peptide were stabilized mainly by charge interactions and hydrogen bonds. Under the binding of the ligand, c-Myc₃₇₀₋₄₀₉ remained disordered. The ligand was found to bind to c-Myc₃₇₀₋₄₀₉ at different sites along the chain and behaved like a 'ligand cloud'. In contrast to ligand binding to more rigid target proteins that usually results in a dominant bound structure, ligand binding to IDPs may better be described as ligand clouds around protein clouds. Nevertheless, the binding of the ligand and a non-ligand to the c-Myc₃₇₀₋₄₀₉ target could be clearly distinguished. The present study provides insights that will help improve rational drug design that targets IDPs.

  1. PET/MRI insert using digital SiPMs: Investigation of MR-compatibility.

    PubMed

    Wehner, Jakob; Weissler, Bjoern; Dueppenbecker, Peter; Gebhardt, Pierre; Schug, David; Ruetten, Walter; Kiessling, Fabian; Schulz, Volkmar

    2014-01-11

    In this work, we present an initial MR-compatibility study performed with the world's first preclinical PET/MR insert based on fully digital silicon photo multipliers (dSiPM). The PET insert allows simultaneous data acquisition of both imaging modalities and thus enables the true potential of hybrid PET/MRI. Since the PET insert has the potential to interfere with all of the MRI's subsystems (strong magnet, gradients system, radio frequency (RF) system) and vice versa, interference studies on both imaging systems are of great importance to ensure an undisturbed operation. As a starting point to understand the interference, we performed signal-to-noise ratio (SNR) measurements as well as dedicated noise scans on the MRI side to characterize the influence of the PET electronics on the MR receive chain. Furthermore, improvements of sub-components' shielding of the PET system are implemented and tested inside the MRI. To study the influence of the MRI on the PET performance, we conducted highly demanding stress tests with gradient and RF dominated MR sequences. These stress tests unveil a sensitivity of the PET's electronics to gradient switching.

  2. Ligand modeling and design

    SciTech Connect

    Hay, B.

    1996-10-01

    The purpose of this work is to develop and implement a molecular design basis for selecting organic ligands that would be used tin applications for the cost-effective removal of specific radionuclides from nuclear waste streams.

  3. Multiple ligand simultaneous docking: orchestrated dancing of ligands in binding sites of protein.

    PubMed

    Li, Huameng; Li, Chenglong

    2010-07-30

    Present docking methodologies simulate only one single ligand at a time during docking process. In reality, the molecular recognition process always involves multiple molecular species. Typical protein-ligand interactions are, for example, substrate and cofactor in catalytic cycle; metal ion coordination together with ligand(s); and ligand binding with water molecules. To simulate the real molecular binding processes, we propose a novel multiple ligand simultaneous docking (MLSD) strategy, which can deal with all the above processes, vastly improving docking sampling and binding free energy scoring. The work also compares two search strategies: Lamarckian genetic algorithm and particle swarm optimization, which have respective advantages depending on the specific systems. The methodology proves robust through systematic testing against several diverse model systems: E. coli purine nucleoside phosphorylase (PNP) complex with two substrates, SHP2NSH2 complex with two peptides and Bcl-xL complex with ABT-737 fragments. In all cases, the final correct docking poses and relative binding free energies were obtained. In PNP case, the simulations also capture the binding intermediates and reveal the binding dynamics during the recognition processes, which are consistent with the proposed enzymatic mechanism. In the other two cases, conventional single-ligand docking fails due to energetic and dynamic coupling among ligands, whereas MLSD results in the correct binding modes. These three cases also represent potential applications in the areas of exploring enzymatic mechanism, interpreting noisy X-ray crystallographic maps, and aiding fragment-based drug design, respectively.

  4. Silicon Detectors for PET and SPECT

    NASA Astrophysics Data System (ADS)

    Cochran, Eric R.

    Silicon detectors use state-of-the-art electronics to take advantage of the semiconductor properties of silicon to produce very high resolution radiation detectors. These detectors have been a fundamental part of high energy, nuclear, and astroparticle physics experiments for decades, and they hold great potential for significant gains in both PET and SPECT applications. Two separate prototype nuclear medicine imaging systems have been developed to explore this potential. Both devices take advantage of the unique properties of high resolution pixelated silicon detectors, designed and developed as part of the CIMA collaboration and built at The Ohio State University. The first prototype is a Compton SPECT imaging system. Compton SPECT, also referred to as electronic collimation, is a fundamentally different approach to single photon imaging from standard gamma cameras. It removes the inherent coupling of spatial resolution and sensitivity in mechanically collimated systems and provides improved performance at higher energies. As a result, Compton SPECT creates opportunities for the development of new radiopharmaceuticals based on higher energy isotopes as well as opportunities to expand the use of current isotopes such as 131I due to the increased resolution and sensitivity. The Compton SPECT prototype consists of a single high resolution silicon detector, configured in a 2D geometry, in coincidence with a standard NaI scintillator detector. Images of point sources have been taken for 99mTc (140 keV), 131I (364keV), and 22Na (511 keV), demonstrating the performance of high resolution silicon detectors in a Compton SPECT system. Filtered back projection image resolutions of 10 mm, 7.5 mm, and 6.7 mm were achieved for the three different sources respectively. The results compare well with typical SPECT resolutions of 5-15 mm and validate the claims of improved performance in Compton SPECT imaging devices at higher source energies. They also support the potential of

  5. Recent Developments in Positron Emission Tomography (PET) Instrumentation

    DOE R&D Accomplishments Database

    Derenzo, S. E.; Budinger, T. F.

    1986-04-01

    This paper presents recent detector developments and perspectives for positron emission tomography (PET) instrumentation used for medical research, as well as the physical processes in positron annihilation, photon scattering and detection, tomograph design considerations, and the potentials for new advances in detectors.

  6. Early Recognition of Chronic Traumatic Encephalopathy through FDDNP PET Imaging

    DTIC Science & Technology

    2014-10-01

    cumulative head trauma. All operational aspects of this study have been accomplished including local IRB approval, identification of potential... head injuries sustained in battle have been associated with the development of chronic traumatic encephalopathy (CTE). Pathological series have...will examine whether FDDNP PET imaging correlates with, and/or can predict, decline in cognitive function in those exposed to cumulative head trauma

  7. PRN Notice 96-6: Pet Pesticide Product Label Statements

    EPA Pesticide Factsheets

    This notice specifies statements that should be added to the labels of pesticide products registered for use on dogs and/or cats. These label statements will help to ensure that products bear labeling to reduce the potential for misuse of pet products.

  8. Recent developments in positron emission tomography (PET) instrumentation

    SciTech Connect

    Derenzo, S.E.; Budinger, T.F.

    1986-04-01

    This paper presents recent detector developments and perspectives for positron emission tomography (PET) instrumentation used for medical research, as well as the physical processes in positron annihilation, photon scattering and detection, tomograph design considerations, and the potentials for new advances in detectors. 117 refs., 4 figs., 4 tabs.

  9. Exposure to pets and allergies in children.

    PubMed

    Hölscher, Bernd; Frye, Christian; Wichmann, H-Erich; Heinrich, Joachim

    2002-10-01

    Currently, there is ongoing discussion regarding potential protective effects of exposure to pets during early childhood on the development of atopic disorders in children later in life. We used data from three consecutive cross-sectional surveys to study the relationship between contact with dogs, cats and other pets, and allergic diseases in schoolchildren 5-14 years of age. In three study areas of the former East Germany, 7,611 questionnaires were received from 5,360 different children who were examined between 1992 and 1999 as school entrants, or third- or sixth-graders. Allergic sensitization to common aeroallergens (birch, grass, mite, cat) was assessed by specific serum immunoglobulin E (IgE) concentrations [using radioallergosorbent testing (RAST)] for 85% of the children. After adjustment for possible confounders, inverse associations were found between contact with dogs in the first year of life and lifetime prevalences of asthma [odds ratio (OR) = 0.68; 95% confidence interval (CI): 0.43-1.08], hay fever (OR = 0.61; 95% CI: 0.39-0.95), eczema (OR = 0.76; 95% CI: 0.61-0.94), itchy rash (OR = 0.76; 95% CI: 0.61-0.94), and pollen sensitization (RAST >/= 4: OR = 0.56; 95% CI: 0.38-0.82). These effects were more pronounced for children with atopic parents. Similar associations were observed for current contact with dogs. We identified no clear relationships for the other pets (cats, rodents, birds), with the exception that children currently exposed to cats were more likely to be sensitized against cats. In conclusion, this study supports the hypothesis of a potential protective mechanism related to dog exposure in early life, especially for children of atopic parents. However, this association was found only for dogs and not for cats.

  10. An investigation on the use of shredded waste PET bottles as aggregate in lightweight concrete.

    PubMed

    Akçaözoğlu, Semiha; Atiş, Cengiz Duran; Akçaözoğlu, Kubilay

    2010-02-01

    In this work, the utilization of shredded waste Poly-ethylene Terephthalate (PET) bottle granules as a lightweight aggregate in mortar was investigated. Investigation was carried out on two groups of mortar samples, one made with only PET aggregates and, second made with PET and sand aggregates together. Additionally, blast-furnace slag was also used as the replacement of cement on mass basis at the replacement ratio of 50% to reduce the amount of cement used and provide savings. The water-binder (w/b) ratio and PET-binder (PET/b) ratio used in the mixtures were 0.45 and 0.50, respectively. The size of shredded PET granules used in the preparation of mortar mixtures were between 0 and 4 mm. The results of the laboratory study and testing carried out showed that mortar containing only PET aggregate, mortar containing PET and sand aggregate, and mortars modified with slag as cement replacement can be drop into structural lightweight concrete category in terms of unit weight and strength properties. Therefore, it was concluded that there is a potential for the use of shredded waste PET granules as aggregate in the production of structural lightweight concrete. The use of shredded waste PET granules due to its low unit weight reduces the unit weight of concrete which results in a reduction in the death weight of a structural concrete member of a building. Reduction in the death weight of a building will help to reduce the seismic risk of the building since the earthquake forces linearly dependent on the dead-weight. Furthermore, it was also concluded that the use of industrial wastes such as PET granules and blast-furnace slag in concrete provides some advantages, i.e., reduction in the use of natural resources, disposal of wastes, prevention of environmental pollution, and energy saving.

  11. An investigation on the use of shredded waste PET bottles as aggregate in lightweight concrete

    SciTech Connect

    Akcaoezoglu, Semiha; Atis, Cengiz Duran; Akcaoezoglu, Kubilay

    2010-02-15

    In this work, the utilization of shredded waste Poly-ethylene Terephthalate (PET) bottle granules as a lightweight aggregate in mortar was investigated. Investigation was carried out on two groups of mortar samples, one made with only PET aggregates and, second made with PET and sand aggregates together. Additionally, blast-furnace slag was also used as the replacement of cement on mass basis at the replacement ratio of 50% to reduce the amount of cement used and provide savings. The water-binder (w/b) ratio and PET-binder (PET/b) ratio used in the mixtures were 0.45 and 0.50, respectively. The size of shredded PET granules used in the preparation of mortar mixtures were between 0 and 4 mm. The results of the laboratory study and testing carried out showed that mortar containing only PET aggregate, mortar containing PET and sand aggregate, and mortars modified with slag as cement replacement can be drop into structural lightweight concrete category in terms of unit weight and strength properties. Therefore, it was concluded that there is a potential for the use of shredded waste PET granules as aggregate in the production of structural lightweight concrete. The use of shredded waste PET granules due to its low unit weight reduces the unit weight of concrete which results in a reduction in the death weight of a structural concrete member of a building. Reduction in the death weight of a building will help to reduce the seismic risk of the building since the earthquake forces linearly dependant on the dead-weight. Furthermore, it was also concluded that the use of industrial wastes such as PET granules and blast-furnace slag in concrete provides some advantages, i.e., reduction in the use of natural resources, disposal of wastes, prevention of environmental pollution, and energy saving.

  12. Parasites in pet reptiles.

    PubMed

    Rataj, Aleksandra Vergles; Lindtner-Knific, Renata; Vlahović, Ksenija; Mavri, Urška; Dovč, Alenka

    2011-05-30

    Exotic reptiles originating from the wild can be carriers of many different pathogens and some of them can infect humans. Reptiles imported into Slovenia from 2000 to 2005, specimens of native species taken from the wild and captive bred species were investigated. A total of 949 reptiles (55 snakes, 331 lizards and 563 turtles), belonging to 68 different species, were examined for the presence of endoparasites and ectoparasites. Twelve different groups (Nematoda (5), Trematoda (1), Acanthocephala (1), Pentastomida (1) and Protozoa (4)) of endoparasites were determined in 26 (47.3%) of 55 examined snakes. In snakes two different species of ectoparasites were also found. Among the tested lizards eighteen different groups (Nematoda (8), Cestoda (1), Trematoda (1), Acanthocephala (1), Pentastomida (1) and Protozoa (6)) of endoparasites in 252 (76.1%) of 331 examined animals were found. One Trombiculid ectoparasite was determined. In 563 of examined turtles eight different groups (Nematoda (4), Cestoda (1), Trematoda (1) and Protozoa (2)) of endoparasites were determined in 498 (88.5%) animals. In examined turtles three different species of ectoparasites were seen. The established prevalence of various parasites in reptiles used as pet animals indicates the need for examination on specific pathogens prior to introduction to owners.

  13. Parasites in pet reptiles

    PubMed Central

    2011-01-01

    Exotic reptiles originating from the wild can be carriers of many different pathogens and some of them can infect humans. Reptiles imported into Slovenia from 2000 to 2005, specimens of native species taken from the wild and captive bred species were investigated. A total of 949 reptiles (55 snakes, 331 lizards and 563 turtles), belonging to 68 different species, were examined for the presence of endoparasites and ectoparasites. Twelve different groups (Nematoda (5), Trematoda (1), Acanthocephala (1), Pentastomida (1) and Protozoa (4)) of endoparasites were determined in 26 (47.3%) of 55 examined snakes. In snakes two different species of ectoparasites were also found. Among the tested lizards eighteen different groups (Nematoda (8), Cestoda (1), Trematoda (1), Acanthocephala (1), Pentastomida (1) and Protozoa (6)) of endoparasites in 252 (76.1%) of 331 examined animals were found. One Trombiculid ectoparasite was determined. In 563 of examined turtles eight different groups (Nematoda (4), Cestoda (1), Trematoda (1) and Protozoa (2)) of endoparasites were determined in 498 (88.5%) animals. In examined turtles three different species of ectoparasites were seen. The established prevalence of various parasites in reptiles used as pet animals indicates the need for examination on specific pathogens prior to introduction to owners. PMID:21624124

  14. 68Ga-PSMA PET/CT Imaging in Multiple Myeloma.

    PubMed

    Sasikumar, Arun; Joy, Ajith; Pillai, M R A; Nanabala, Raviteja; Thomas, Boben

    2017-02-01

    The potential applications of Ga-labeled prostate-specific membrane antigen (PSMA) PET/CT in the imaging of prostate cancer are now well established. A few case reports regarding the potential use of Ga-PSMA PET/CT in nonprostate cancer malignancies are also published. Apparently, the tumor neoangiogenesis is the mechanism attributed to increased Ga-PSMA uptake in the tumor sites in nonprostatic malignancies. We describe the use of Ga-PSMA PET/CT in imaging multiple myeloma. The intense Ga-PSMA avidity of the lesions also opens up the possibility of theranostics with Lu-PSMA.

  15. 68Ga-PSMA PET/CT in Osteosarcoma in Fibrous Dysplasia.

    PubMed

    Sasikumar, Arun; Joy, Ajith; Pillai, M R A; Alex, Tony M; Narayanan, Geetha

    2017-03-24

    Fibrous dysplasia (FD) is a benign bone lesion with a rare but potential for malignant transformation. Neither Tc-MDP nor F-FDG PET/CT can differentiate between FD and areas of malignant transformation in FD. We described a case of osteosarcoma developing in FD with selective uptake of tracer in malignant transformation areas demonstrated on a Ga-PSMA PET/CT scan. Our case highlights the ability of Ga-PSMA PET/CT to map tumor neoangiogenesis in osteosarcoma arising in FD, which can have potential implications in prognostication, possibility of antiangiogenesis-based therapeutic options, and in response assessment following chemotherapy.

  16. Novel Strategy for Preparing Dual-Modality Optical/PET Imaging Probes via Photo-Click Chemistry.

    PubMed

    Sun, Lingyi; Ding, Jiule; Xing, Wei; Gai, Yongkang; Sheng, Jing; Zeng, Dexing

    2016-05-18

    Preparation of small molecule based dual-modality probes remains a challenging task due to the complicated synthetic procedure. In this study, a novel concise and generic strategy for preparing dual-modality optical/PET imaging probes via photo-click chemistry was developed, in which the diazole photo-click linker functioned not only as a bridge between the targeting-ligand and the PET imaging moiety, but also as the fluorophore for optical imaging. A dual-modality AE105 peptidic probe was successfully generated via this strategy and subsequently applied in the fluorescent staining of U87MG cells and the (68)Ga based PET imaging of mice bearing U87MG xenograft. In addition, dual-modality monoclonal antibody cetuximab has also been generated via this strategy and labeled with (64)Cu for PET imaging studies, broadening the application of this strategy to include the preparation of macromolecule based imaging probes.

  17. Brain tissue segmentation in PET-CT images using probabilistic atlas and variational Bayes inference.

    PubMed

    Xia, Yong; Wang, Jiabin; Eberl, Stefan; Fulham, Michael; Feng, David Dagan

    2011-01-01

    PET-CT provides aligned anatomical (CT) and functional (PET) images in a single scan, and has the potential to improve brain PET image segmentation, which can in turn improve quantitative clinical analyses. We propose a statistical segmentation algorithm that incorporates the prior anatomical knowledge represented by probabilistic brain atlas into the variational Bayes inference to delineate gray matter (GM), white matter (WM) and cerebrospinal fluid (CSF) in brain PET-CT images. Our approach adds an additional novel aspect by allowing voxels to have variable and adaptive prior probabilities of belonging to each class. We compared our algorithm to the segmentation approaches implemented in the expectation maximization segmentation (EMS) and statistical parametric mapping (SPM8) packages in 26 clinical cases. The results show that our algorithm improves the accuracy of brain PET-CT image segmentation.

  18. Somatostatin receptor based PET/CT in patients with the suspicion of cardiac sarcoidosis: an initial comparison to cardiac MRI.

    PubMed

    Lapa, Constantin; Reiter, Theresa; Kircher, Malte; Schirbel, Andreas; Werner, Rudolf A; Pelzer, Theo; Pizarro, Carmen; Skowasch, Dirk; Thomas, Lena; Schlesinger-Irsch, Ulrike; Thomas, Daniel; Bundschuh, Ralph A; Bauer, Wolfgang R; Gärtner, Florian C

    2016-11-22

    Diagnosis of cardiac sarcoidosis is often challenging. Whereas cardiac magnetic resonance imaging (CMR) and positron emission tomography/computed tomography (PET/CT) with 18F-fluorodeoxyglucose (FDG) are most commonly used to evaluate patients, PET/CT using radiolabeled somatostatin receptor (SSTR) ligands for visualization of inflammation might represent a more specific alternative. This study aimed to investigate the feasibility of SSTR-PET/CT for detecting cardiac sarcoidosis in comparison to CMR.15 patients (6 males, 9 females) with sarcoidosis and suspicion on cardiac involvement underwent SSTR-PET/CT imaging and CMR. Images were visually scored. The AHA 17-segment model of the left myocardium was used for localization and comparison of inflamed myocardium for both imaging modalities. In semi-quantitative analysis, mean (SUVmean) and maximum standardized uptake values (SUVmax) of affected myocardium were calculated and compared with both remote myocardium and left ventricular (LV) cavity.SSTR-PET was positive in 7/15, CMR in 10/15 patients. Of the 3 CMR+/PET- subjects, one patient with minor involvement (<25% of wall thickness in CMR) was missed by PET. The remaining two CMR+/PET- patients displayed no adverse cardiac events during follow-up.In the 17-segment model, PET/CT yielded 27 and CMR 29 positive segments. Overall concordance of the 2 modalities was 96.1% (245/255 segments analyzed). SUVmean and SUVmax in inflamed areas were 2.0±1.2 and 2.6±1.2, respectively. The lesion-to-remote myocardium and lesion-to-LV cavity ratios were 1.8±0.2 and 1.9±0.2 for SUVmean and 2.0±0.3 and 1.7±0.3 for SUVmax, respectively.Detection of cardiac sarcoidosis by SSTR-PET/CT is feasible. Our data warrant further analysis in larger prospective series.

  19. Urokinase-type plasminogen activator receptor (uPAR) as a promising new imaging target: potential clinical applications

    PubMed Central

    Persson, Morten; Kjaer, Andreas

    2013-01-01

    Urokinase-type plasminogen activator receptor (uPAR) has been shown to be of special importance during cancer invasion and metastasis. However, currently, tissue samples are needed for measurement of uPAR expression limiting the potential as a clinical routine. Therefore, non-invasive methods are needed. In line with this, uPAR has recently been identified as a very promising imaging target candidate. uPAR consists of three domains attached to the cell membrane via a glycosylphosphatidylinositol (GPI) anchor and binds it natural ligand uPA with high affinity to localize plasminogen activation at the cell surface. Due to the importance of uPAR in cancer invasion and metastasis, a number of high-affinity ligands have been identified during the last decades. These ligands have recently been used as starting point for the development of a number of ligands for imaging of uPAR using various imaging modalities such as optical imaging, magnetic resonance imaging, single photon emission computer tomography (SPECT) and positron emission topography (PET). In this review, we will discuss recent advances in the development of uPAR-targeted imaging ligands according to imaging modality. In addition, we will discuss the potential future clinical application for uPAR imaging as a new imaging biomarker. PMID:23701192

  20. Quantitative PET imaging with the 3T MR-BrainPET

    NASA Astrophysics Data System (ADS)

    Weirich, C.; Scheins, J.; Lohmann, P.; Tellmann, L.; Byars, L.; Michel, C.; Rota Kops, E.; Brenner, D.; Herzog, H.; Shah, N. J.

    2013-02-01

    The new hybrid imaging technology of MR-PET allows for simultaneous acquisition of versatile MRI contrasts and the quantitative metabolic imaging with PET. In order to achieve the quantification of PET images with minimal residual error the application of several corrections is crucial. In this work we present our results on quantification with the 3T MR BrainPET scanner.

  1. Constitutive androstane receptor (CAR) as a potential sensing biomarker of persistent organic pollutants (POPs) in aquatic mammal: molecular characterization, expression level, and ligand profiling in Baikal seal (Pusa sibirica).

    PubMed

    Sakai, Hiroki; Iwata, Hisato; Kim, Eun-Young; Tsydenova, Oyuna; Miyazaki, Nobuyuki; Petrov, Evgeny A; Batoev, Valeriy B; Tanabe, Shinsuke

    2006-11-01

    Applied Chemistry No. PCB153; 2,2',4,4',5,5'-hexachlorobiphenyl and PCB180; 2,2',3,4,4',5,5'-heptachlorobiphenyl), and 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (p,p'-DDT) and its metabolite, 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE). The seal CAR responded more sensitively to PCBs than the mouse CAR. Based on the results of CAR transactivation assay, the lowest observable effect levels of Kanechlor-500, PCB153, PCB180, p,p'-DDT, and p,p'-DDE in Baikal seal were estimated to be 10, 20, 20, 10, and 10 ppm on wet weight basis, respectively. These results suggest that CAR is conserved in diverse mammalian species including seals. Whereas the seal CAR-mediated gene transcription may potentially be a sensitive response to the exposure of certain POPs, the ligand profile of seal CAR may be different from those of other mammalian CARs. This study indicates that CAR-mediated responses may be useful information to assess the ecotoxicological risk of xenobiotics such as POPs in wildlife but the previous results derived from rodent and human CAR may not be applicable to the risk assessment in wild species.

  2. Exercises in PET Image Reconstruction

    NASA Astrophysics Data System (ADS)

    Nix, Oliver

    These exercises are complementary to the theoretical lectures about positron emission tomography (PET) image reconstruction. They aim at providing some hands on experience in PET image reconstruction and focus on demonstrating the different data preprocessing steps and reconstruction algorithms needed to obtain high quality PET images. Normalisation, geometric-, attenuation- and scatter correction are introduced. To explain the necessity of those some basics about PET scanner hardware, data acquisition and organisation are reviewed. During the course the students use a software application based on the STIR (software for tomographic image reconstruction) library 1,2 which allows them to dynamically select or deselect corrections and reconstruction methods as well as to modify their most important parameters. Following the guided tutorial, the students get an impression on the effect the individual data precorrections have on image quality and what happens if they are forgotten. Several data sets in sinogram format are provided, such as line source data, Jaszczak phantom data sets with high and low statistics and NEMA whole body phantom data. The two most frequently used reconstruction algorithms in PET image reconstruction, filtered back projection (FBP) and the iterative OSEM (ordered subset expectation maximation) approach are used to reconstruct images. The exercise should help the students gaining an understanding what the reasons for inferior image quality and artefacts are and how to improve quality by a clever choice of reconstruction parameters.

  3. Recent Understandings of Pet Allergies

    PubMed Central

    Ownby, Dennis; Johnson, Christine Cole

    2016-01-01

    Allergic reactions to pets have been recognized for at least a hundred years. Yet our understanding of the effects of all of the interactions between pet exposures and human immune responses continues to grow. Allergists, epidemiologists, and immunologists have spent years trying to better understand how exposures to pet allergens lead to allergic sensitization (the production of allergen-specific immunoglobulin class E [IgE] antibodies) and subsequent allergic disease. A major new development in this understanding is the recognition that pet exposures consist of not only allergen exposures but also changes in microbial exposures. Exposures to certain pet-associated microbes, especially in the neonatal period, appear to be able to dramatically alter how a child’s immune system develops and this in turn reduces the risk of allergic sensitization and disease. An exciting challenge in the next few years will be to see whether these changes can be developed into a realistic preventative strategy with the expectation of significantly reducing allergic disease, especially asthma. PMID:26918180

  4. 13- and 14-membered macrocyclic ligands containing methylcarboxylate or methylphosphonate pendant arms: chemical and biological evaluation of their (153)Sm and (166)Ho complexes as potential agents for therapy or bone pain palliation.

    PubMed

    Marques, Fernanda; Gano, Lurdes; Paula Campello, M; Lacerda, Sara; Santos, Isabel; Lima, Luís M P; Costa, Judite; Antunes, Patrícia; Delgado, Rita

    2006-02-01

    The stability constants of La(3+), Sm(3+) and Ho(3+) complexes with 13- and 14-membered macrocycles having methylcarboxylate (trita and teta) or methylphosphonate (tritp and tetp) arms were determined. All the ligands were labelled with (153)Sm and (166)Ho in order to evaluate the effect of the macrocyclic cavity size and type of appended arms on their in vitro and in vivo behaviour. The radiolabelling efficiency was found to be higher than 98% for all the complexes, except for those of tetp. All radiocomplexes studied are hydrophilic with an overall negative charge and low plasmatic protein binding. Good in vitro stability in physiological media and human serum was found for all complexes, except the (153)Sm/(166)Ho-teta, which are unstable in phosphate buffer (pH 7.4). In vitro hydroxyapatite (HA) adsorption studies indicated that (153)Sm/(166)Ho-tritp complexes bind to HA having the (166)Ho complex the highest degree of adsorption (>80%, 10 mg). Biodistribution studies in mice demonstrated that (153)Sm/(166)Ho-trita complexes have a fast tissue clearance with more than 95% of the injected activity excreted after 2 h, value that is comparable to the corresponding dota complexes. In contrast, the (153)Sm-teta complex has a significantly lower total excretion. (153)Sm/(166)Ho-tritp complexes are retained by the bone, particularly (166)Ho-tritp that has 5-6% (% I.D./g) bone uptake and also a high rate of total excretion. Thus, these studies support the potential interest of (153)Sm/(166)Ho-trita complexes for therapy when conjugated to a biomolecule and the potential usefulness of the (166)Ho-tritp complex in bone pain palliation.

  5. Retrospective data-driven respiratory gating for PET using TOF information.

    PubMed

    Mengdie Wang; Ning Guo; Hui Zhang; Elfhakri, Georges; Guangshu Hu; Quanzheng Li

    2015-08-01

    Traditional data-driven respiratory gating method is capable of detecting breathing cycles directly from positron emission tomography (PET) data, but usually fails at low SNR, particularly at low dose PET/CT study. Time-of-flight (TOF) PET has the potential to improve the SNR. In order for TOF information to reduce the statistical noise and boost the performance of respiratory gating, we present a robust data-driven respiratory gating method using TOF information, which retrospectively derived the respiratory signal from the acquired TOF-PET data. The PET data was acquired in list mode format and analyzed in sinogram space. The method was demonstrated with patient datasets acquired on a TOF PET/CT system. Data-driven gating methods by center of mass (COM) and principle component analysis (PCA) algorithm were successfully performed on nonTOF PET and TOF PET dataset. To assess the accuracy of the data-driven respiratory signal, a hardware-based signal was acquired for comparison. The study showed that retrospectively respiratory gating using TOF sinograms has improved the SNR, and outperforms the non-TOF gating under both COM and PCA algorithms.

  6. Simultaneous fMRI-PET of the opioidergic pain system in human brain.

    PubMed

    Wey, Hsiao-Ying; Catana, Ciprian; Hooker, Jacob M; Dougherty, Darin D; Knudsen, Gitte M; Wang, Danny J J; Chonde, Daniel B; Rosen, Bruce R; Gollub, Randy L; Kong, Jian

    2014-11-15

    MRI and PET provide complementary information for studying brain function. While the potential use of simultaneous MRI/PET for clinical diagnostic and disease staging has been demonstrated recently; the biological relevance of concurrent functional MRI-PET brain imaging to dissect neurochemically distinct components of the blood oxygenation level dependent (BOLD) fMRI signal has not yet been shown. We obtained sixteen fMRI-PET data sets from eight healthy volunteers. Each subject participated in randomized order in a pain scan and a control (nonpainful pressure) scan on the same day. Dynamic PET data were acquired with an opioid radioligand, [(11)C]diprenorphine, to detect endogenous opioid releases in response to pain. BOLD fMRI data were collected at the same time to capture hemodynamic responses. In this simultaneous human fMRI-PET imaging study, we show co-localized responses in thalamus and striatum related to pain processing, while modality specific brain networks were also found. Co-localized fMRI and PET signal changes in the thalamus were positively correlated suggesting that pain-induced changes in opioid neurotransmission contribute a significant component of the fMRI signal change in this region. Simultaneous fMRI-PET provides unique opportunities allowing us to relate specific neurochemical events to functional hemodynamic activation and to investigate the impacts of neurotransmission on neurovascular coupling of the human brain in vivo.

  7. Optimization of the protocols for the use of contrast agents in PET/CT studies.

    PubMed

    Pelegrí Martínez, L; Kohan, A A; Vercher Conejero, J L

    The introduction of PET/CT scanners in clinical practice in 1998 has improved care for oncologic patients throughout the clinical pathway, from the initial diagnosis of disease through the evaluation of the response to treatment to screening for possible recurrence. The CT component of a PET/CT study is used to correct the attenuation of PET studies; CT also provides anatomic information about the distribution of the radiotracer. CT is especially useful in situations where PET alone can lead to false positives and false negatives, and CT thereby improves the diagnostic performance of PET. The use of intravenous or oral contrast agents and optimal CT protocols have improved the detection and characterization of lesions. However, there are circumstances in which the systematic use of contrast agents is not justified. The standard acquisition in PET/CT scanners is the whole body protocol, but this can lead to artifacts due to the position of patients and respiratory movements between the CT and PET acquisitions. This article discusses these aspects from a constructive perspective with the aim of maximizing the diagnostic potential of PET/CT and providing better care for patients.

  8. Clinical applications of PET/MRI: current status and future perspectives.

    PubMed

    Nensa, Felix; Beiderwellen, Karsten; Heusch, Philipp; Wetter, Axel

    2014-01-01

    Fully integrated positron emission tomography (PET)/magnetic resonance imaging (MRI) scanners have been available for a few years. Since then, the number of scanner installations and published studies have been growing. While feasibility of integrated PET/MRI has been demonstrated for many clinical and preclinical imaging applications, now those applications where PET/MRI provides a clear benefit in comparison to the established reference standards need to be identified. The current data show that those particular applications demanding multiparametric imaging capabilities, high soft tissue contrast and/or lower radiation dose seem to benefit from this novel hybrid modality. Promising results have been obtained in whole-body cancer staging in non-small cell lung cancer and multiparametric tumor imaging. Furthermore, integrated PET/MRI appears to have added value in oncologic applications requiring high soft tissue contrast such as assessment of liver metastases of neuroendocrine tumors or prostate cancer imaging. Potential benefit of integrated PET/MRI has also been demonstrated for cardiac (i.e., myocardial viability, cardiac sarcoidosis) and brain (i.e., glioma grading, Alzheimer's disease) imaging, where MRI is the predominant modality. The lower radiation dose compared to PET/computed tomography will be particularly valuable in the imaging of young patients with potentially curable diseases.However, further clinical studies and technical innovation on scanner hard- and software are needed. Also, agreements on adequate refunding of PET/MRI examinations need to be reached. Finally, the translation of new PET tracers from preclinical evaluation into clinical applications is expected to foster the entire field of hybrid PET imaging, including PET/MRI.

  9. Optimizing electrostatic affinity in ligand-receptor binding: Theory, computation, and ligand properties

    NASA Astrophysics Data System (ADS)

    Kangas, Erik; Tidor, Bruce

    1998-11-01

    The design of a tight-binding molecular ligand involves a tradeoff between an unfavorable electrostatic desolvation penalty incurred when the ligand binds a receptor in aqueous solution and the generally favorable intermolecular interactions made in the bound state. Using continuum electrostatic models we have developed a theoretical framework for analyzing this problem and have shown that the ligand-charge distribution can be optimized to produce the most favorable balance of these opposing free energy contributions [L.-P. Lee and B. Tidor, J. Chem. Phys. 106, 8681 (1997)]. Herein the theoretical framework is extended and calculations are performed for a wide range of model receptors. We examine methods for computing optimal ligands (including cases where there is conformational change) and the resulting properties of optimized ligands. In particular, indicators are developed to aid in the determination of the deficiencies in a specific ligand or basis. A connection is established between the optimization problem here and a generalized image problem, from which an inverse-image basis set can be defined; this basis is shown to perform very well in optimization calculations. Furthermore, the optimized ligands are shown to have favorable electrostatic binding free energies (in contrast to many natural ligands), there is a strong correlation between the receptor desolvation penalty and the optimized binding free energy for fixed geometry, and the ligand and receptor cannot generally be mutually optimal. Additionally, we introduce the display of complementary desolvation and interaction potentials and the deviation of their relationship from ideal as a useful tool for judging effective complementarity. Scripts for computing and displaying these potentials with GRASP are available at http://mit.edu/tidor.

  10. PET Metabolic Biomarkers for Cancer

    PubMed Central

    Croteau, Etienne; Renaud, Jennifer M.; Richard, Marie Anne; Ruddy, Terrence D.; Bénard, François; deKemp, Robert A.

    2016-01-01

    The body’s main fuel sources are fats, carbohydrates (glucose), proteins, and ketone bodies. It is well known that an important hallmark of cancer cells is the overconsumption of glucose. Positron emission tomography (PET) imaging using the glucose analog 18F-fluorodeoxyglucose (18F-FDG) has been a powerful cancer diagnostic tool for many decades. Apart from surgery, chemotherapy and radiotherapy represent the two main domains for cancer therapy, targeting tumor proliferation, cell division, and DNA replication—all processes that require a large amount of energy. Currently, in vivo clinical imaging of metabolism is performed almost exclusively using PET radiotracers that assess oxygen consumption and mechanisms of energy substrate consumption. This paper reviews the utility of PET imaging biomarkers for the detection of cancer proliferation, vascularization, metabolism, treatment response, and follow-up after radiation therapy, chemotherapy, and chemotherapy-related side effects. PMID:27679534

  11. Understanding advertising in pet nutrition.

    PubMed Central

    Brown, R G

    1994-01-01

    Advertising is part of the effort to attract attention of consumers to products, in this case, pet foods. It is generally benign in its effect, but it can be misleading, although rarely deliberately so. It uses a specialized vocabulary, which must be mastered if one is to understand what is intended. For all of the expense and effort, advertising figures directly in relatively few decisions to purchase. Its main intention is to call our attention to a particular pet food and to give that product an image. If the pet food does not perform in the consumer's hands, then all of the advertising on earth will not be persuasive. On the other hand, if a product performs well, the word-of-mouth will be positive and that mode of advertising is one of the most effective. PMID:8076285

  12. Promoting the exotic pet practice.

    PubMed

    Harris, Don J

    2005-09-01

    The marketing and promotion of an exotic pet veterinary practice allows the use of strategies that are not necessarily available in other veterinary disciplines. The advantage that an exotics practice enjoys is that it is able to capitalize not only on the unique nature of the species being attended but also on the specialized features of the hospital itself that make it specifically appropriate in caring for exotic pets. Before marketing, however, comes the responsibility that the practice live up to the claims made in promotional materials. A practice cannot ethically be presented as an "exotics" practice if it is nothing more than a dog and cat facility that is willing to attend to exotic pets. It is the competence of the veterinary staff and the appropriateness of the facility that determines the suitability of the practice for exotics management.

  13. Latest achievements in PET techniques

    NASA Astrophysics Data System (ADS)

    Del Guerra, Alberto; Belcari, Nicola; Motta, Alfonso; Di Domenico, Giovanni; Sabba, Nicola; Zavattini, Guido

    2003-11-01

    Positron emission tomography (PET) has moved from a distinguished research tool in physiology, cardiology and neurology to become a major tool for clinical investigation in oncology, in cardiac applications and in neurological disorders. Much of the PET accomplishments is due to the remarkable improvements in the last 10 years both in hardware and software aspects. Nowadays a similar effort is made by many research groups towards the construction of dedicated PET apparatus in new emerging fields such as molecular medicine, gene therapy, breast cancer imaging and combined modalities. This paper reports on some recent results we have obtained in small animal imaging and positron emission mammography, based on the use of advanced technology in the field of scintillators and photodetectors, such as Position-Sensitive Detectors coupled to crystal matrices, combined use of scintillating fibers and Hybrid-Photo-Diodes readout, and Hamamatsu flat panels. New ideas and future developments are discussed.

  14. 36 CFR 13.1234 - Pets.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 36 Parks, Forests, and Public Property 1 2013-07-01 2013-07-01 false Pets. 13.1234 Section 13.1234 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL PARK... § 13.1234 Pets. Possessing a pet in the BCDA is prohibited....

  15. 36 CFR 13.1234 - Pets.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 36 Parks, Forests, and Public Property 1 2014-07-01 2014-07-01 false Pets. 13.1234 Section 13.1234 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL PARK... § 13.1234 Pets. Possessing a pet in the BCDA is prohibited....

  16. 36 CFR 13.1234 - Pets.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 36 Parks, Forests, and Public Property 1 2012-07-01 2012-07-01 false Pets. 13.1234 Section 13.1234 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL PARK... § 13.1234 Pets. Possessing a pet in the BCDA is prohibited....

  17. 7 CFR 503.11 - Pets.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 6 2014-01-01 2014-01-01 false Pets. 503.11 Section 503.11 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL RESEARCH SERVICE, DEPARTMENT OF AGRICULTURE CONDUCT ON PLUM ISLAND ANIMAL DISEASE CENTER § 503.11 Pets. No pets or animals of any kind may be...

  18. 7 CFR 503.11 - Pets.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 6 2010-01-01 2010-01-01 false Pets. 503.11 Section 503.11 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL RESEARCH SERVICE, DEPARTMENT OF AGRICULTURE CONDUCT ON PLUM ISLAND ANIMAL DISEASE CENTER § 503.11 Pets. No pets or animals of any kind may be...

  19. 7 CFR 503.11 - Pets.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 6 2011-01-01 2011-01-01 false Pets. 503.11 Section 503.11 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL RESEARCH SERVICE, DEPARTMENT OF AGRICULTURE CONDUCT ON PLUM ISLAND ANIMAL DISEASE CENTER § 503.11 Pets. No pets or animals of any kind may be...

  20. 36 CFR 13.1234 - Pets.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Pets. 13.1234 Section 13.1234 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL PARK... § 13.1234 Pets. Possessing a pet in the BCDA is prohibited....

  1. 7 CFR 500.10 - Pets.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 6 2010-01-01 2010-01-01 false Pets. 500.10 Section 500.10 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL RESEARCH SERVICE, DEPARTMENT OF AGRICULTURE NATIONAL ARBORETUM Conduct on U.S. National Arboreturm Property § 500.10 Pets. Pets brought upon...

  2. Saying Goodbye: Pet Loss and Its Implications

    ERIC Educational Resources Information Center

    Duffey, Thelma

    2005-01-01

    Pets can be loyal, loving, and entertaining members of a family. Their deaths are generally experienced as painful losses by the people who love them, even though the grief experience is often culturally disenfranchised. In this manuscript, we discuss the role that pets can play in a person's life; the effects that pet loss can have on the people…

  3. 7 CFR 500.10 - Pets.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 6 2011-01-01 2011-01-01 false Pets. 500.10 Section 500.10 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL RESEARCH SERVICE, DEPARTMENT OF AGRICULTURE NATIONAL ARBORETUM Conduct on U.S. National Arboreturm Property § 500.10 Pets. Pets brought upon...

  4. 36 CFR 13.1234 - Pets.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 36 Parks, Forests, and Public Property 1 2011-07-01 2011-07-01 false Pets. 13.1234 Section 13.1234 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL PARK... § 13.1234 Pets. Possessing a pet in the BCDA is prohibited....

  5. 7 CFR 503.11 - Pets.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 6 2012-01-01 2012-01-01 false Pets. 503.11 Section 503.11 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL RESEARCH SERVICE, DEPARTMENT OF AGRICULTURE CONDUCT ON PLUM ISLAND ANIMAL DISEASE CENTER § 503.11 Pets. No pets or animals of any kind may be...

  6. 7 CFR 503.11 - Pets.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 6 2013-01-01 2013-01-01 false Pets. 503.11 Section 503.11 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL RESEARCH SERVICE, DEPARTMENT OF AGRICULTURE CONDUCT ON PLUM ISLAND ANIMAL DISEASE CENTER § 503.11 Pets. No pets or animals of any kind may be...

  7. Pets in the family: practical approaches.

    PubMed

    Hodgson, Kate; Darling, Marcia

    2011-01-01

    Adapting family life cycle theory to include pets provides veterinarians with a framework for understanding and reinforcing the human-animal bond. The family genogram with pets is a practice tool that identifies all people and pets in the family, enhancing the practice of One Health at the community level.

  8. 7 CFR 502.11 - Pets.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... vaccinations. Pets that are the property of employees residing on BARC must be up to date on their vaccinations... 7 Agriculture 6 2014-01-01 2014-01-01 false Pets. 502.11 Section 502.11 Agriculture Regulations of... CONDUCT ON BELTSVILLE AGRICULTURE RESEARCH CENTER PROPERTY, BELTSVILLE, MARYLAND § 502.11 Pets....

  9. 7 CFR 500.10 - Pets.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 6 2014-01-01 2014-01-01 false Pets. 500.10 Section 500.10 Agriculture Regulations of... NATIONAL ARBORETUM Conduct on U.S. National Arboreturm Property § 500.10 Pets. Pets brought upon USNA property must have proper vaccinations and, except assistance trained animals, must be kept on leash at...

  10. 7 CFR 500.10 - Pets.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 6 2013-01-01 2013-01-01 false Pets. 500.10 Section 500.10 Agriculture Regulations of... NATIONAL ARBORETUM Conduct on U.S. National Arboreturm Property § 500.10 Pets. Pets brought upon USNA property must have proper vaccinations and, except assistance trained animals, must be kept on leash at...

  11. 7 CFR 502.11 - Pets.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... vaccinations. Pets that are the property of employees residing on BARC must be up to date on their vaccinations... 7 Agriculture 6 2012-01-01 2012-01-01 false Pets. 502.11 Section 502.11 Agriculture Regulations of... CONDUCT ON BELTSVILLE AGRICULTURE RESEARCH CENTER PROPERTY, BELTSVILLE, MARYLAND § 502.11 Pets....

  12. 7 CFR 502.11 - Pets.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... vaccinations. Pets that are the property of employees residing on BARC must be up to date on their vaccinations... 7 Agriculture 6 2013-01-01 2013-01-01 false Pets. 502.11 Section 502.11 Agriculture Regulations of... CONDUCT ON BELTSVILLE AGRICULTURE RESEARCH CENTER PROPERTY, BELTSVILLE, MARYLAND § 502.11 Pets....

  13. 7 CFR 500.10 - Pets.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 6 2012-01-01 2012-01-01 false Pets. 500.10 Section 500.10 Agriculture Regulations of... NATIONAL ARBORETUM Conduct on U.S. National Arboreturm Property § 500.10 Pets. Pets brought upon USNA property must have proper vaccinations and, except assistance trained animals, must be kept on leash at...

  14. A Guide to Managing Your Classroom Pets.

    ERIC Educational Resources Information Center

    Caras, Robert

    1980-01-01

    The author suggests eight ideal classroom pets: hamsters; turtles; snakes; spiders; frogs and toads; fish; and birds. For each he gives suggestions on selecting the pet and housing and feeding it in the classroom. Desert terrariums and home pet care training are also discussed. (SJL)

  15. Driving with pets and motor vehicle collision involvement among older drivers: a prospective population-based study

    PubMed Central

    Huisingh, Carrie; Levitan, Emily B.; Irvin, Marguerite R.; Owsley, Cynthia; McGwin, Gerald

    2016-01-01

    Objective Distracted driving is a major cause of motor vehicle collision (MVC) involvement. Pets have been identified as potential distraction to drivers, particularly in the front. This type of distraction could be worse for those with impairment in the cognitive aspects of visual processing. The purpose of this study is to evaluate the association between driving with pets and rates of motor vehicle collision involvementin a cohort of older drivers. Methods A three-year prospective was conducted in a population-based sample of 2000 licensed drivers aged 70 years and older. At the baseline visit, a trained interviewer asked participants about pet ownership, whether they drive with pets, how frequently, and where the pet sits in the vehicle. Motor vehicle collision (MVC) involvement during the three-year study period was obtained from the Alabama Department of Public Safety. At-fault status was determined by the police officer who arrived on the scene. Participants were followed until the earliest of death, driving cessation, or end of the study period. Poisson regression was used to calculate crude and adjusted rate ratios (RR) examining the association between pet ownership, presence of a pet in a vehicle, frequency of driving with a pet, and location of the pet inside with vehicle with any and at-fault MVC involvement. We examined whether the associations differed by higher order visual processing impairment status, as measured by Useful Field Of View, Trails B, and Motor-free Visual Perception Test. Results Rates of crash involvement were similar for older adults who have ever driven with a pet compared to those who never drove with their pet (RR=1.15, 95% CI 0.76-1.75). Drivers who reported always or sometimes driving with their pet had higherMVC rates compared topet owners who never drive with a pet, but this association was not statistically significant (RR=1.39, 95% CI 0.86-2.24). In terms of location, those reporting having a pet frequently ride in the

  16. Nondestructive Analysis of Apollo Samples by Micro-CT and Micro-XRF Analysis: A PET Style Examination

    NASA Technical Reports Server (NTRS)

    Zeigler, Ryan A.

    2014-01-01

    An integral part of any sample return mission is the initial description and classification of returned samples by the preliminary examination team (PET). The goal of a PET is to characterize and classify the returned samples, making this information available to the general research community who can then conduct more in-depth studies on the samples. A PET strives to minimize the impact their work has on the sample suite, which often limits the PET work to largely visual measurements and observations like optical microscopy. More modern techniques can also be utilized by future PET to nondestructively characterize astromaterials in a more rigorous way. Here we present our recent analyses of Apollo samples 14321 and 14305 by micro-CT and micro-XRF (respectively), assess the potential for discovery of "new" Apollo samples for scientific study, and evaluate the usefulness of these techniques in future PET efforts.

  17. In Vitro and In Vivo Characterization of Two C-11-Labeled PET Tracers for Vesicular Acetylcholine Transporter

    PubMed Central

    Padakanti, Prashanth K.; Zhang, Xiang; Jin, Hongjun; Cui, Jinquan; Wang, Ruike; Li, Junfeng; Flores, Hubert P.; Parsons, Stanley M.; Perlmutter, Joel S.; Tu, Zhude

    2015-01-01

    Purpose The vesicular acetylcholine transporter (VAChT) is a specific biomarker for imaging presynaptic cholinergic neurons. Herein, two potent and selective 11C-labeled VAChT inhibitors were evaluated in rodents and nonhuman primates for imaging VAChT in vivo. Procedures For both (−)-[11C]2 and (−)-[11C]6, biodistribution, autoradiography, and metabolism studies were performed in male Sprague Dawley rats. Positron emission tomography (PET) brain studies with (−)-[11C]2 were performed in adult male cynomolgus macaques; 2 h dynamic data was acquired, and the regions of interest were drawn by co-registration of the PET images with the MRI. Results The resolved enantiomers (−)-2 and (−)-6 were very potent and selective for VAChT in vitro (Ki<5 nM for VAChT with >35-fold selectivity for VAChT vs. σ receptors); both radioligands, (−)-[11C]2 and (−)-[11C]6, demonstrated high accumulation in the VAChT-enriched striatum of rats. (−)-[11C]2 had a higher striatum to cerebellum ratio of 2.4-fold at 60 min; at 30 min, striatal uptake reached 0.550±0.086 %ID/g. Uptake was also specific and selective; following pretreatment with (±)-2, striatal uptake of (−)-[11C]2 in rats at 30 min decreased by 50 %, while pretreatment with a potent sigma ligand had no significant effect on striatal uptake in rats. In addition, (−)-[11C]2 displayed favorable in vivo stability in rat blood and brain. PET studies of (−)-[11C]2 in nonhuman primates indicate that it readily crosses the blood-brain barrier (BBB) and provides clear visualization of the striatum; striatal uptake reaches the maximum at 60 min, at which time the target to nontarget ratio reached ~2-fold. Conclusions The radioligand (−)-[11C]2 has high potential to be a suitable PET radioligand for imaging VAChT in the brain of living subjects. PMID:24865402

  18. Posttranslational regulation of Fas ligand function

    PubMed Central

    Voss, Matthias; Lettau, Marcus; Paulsen, Maren; Janssen, Ottmar

    2008-01-01

    The TNF superfamily member Fas ligand acts as a prototypic death factor. Due to its ability to induce apoptosis in Fas (APO-1, CD95) expressing cells, Fas ligand participates in essential effector functions of the immune system. It is involved in natural killer cell- and T cell-mediated cytotoxicity, the establishment of immune privilege, and in termination of immune responses by induction of activation-induced cell death. In addition, Fas ligand-positive tumours may evade immune surveillance by killing Fas-positive tumour-infiltrating cells. Given these strong cytotoxic capabilities of Fas ligand, it is obvious that its function has to be strictly regulated to avoid uncontrolled damage. In hematopoietic cells, the death factor is stored in secretory lysosomes and is mobilised to the immunological synapse only upon activation. The selective sorting to and the release from this specific lysosomal compartment requires interactions of the Fas ligand cytosolic moiety, which mediates binding to various adapter proteins involved in trafficking and cytoskeletal reorganisation. In addition, Fas ligand surface expression is further regulated by posttranslational ectodomain shedding and subsequent regulated intramembrane proteolysis, releasing a soluble ectodomain cytokine into the extracellular space and an N-terminal fragment with a potential role in intracellular signalling processes. Moreover, other posttranslational modifications of the cytosolic domain, including phosphorylation and ubiquitylation, have been described to affect various aspects of Fas ligand biology. Since FasL is regarded as a potential target for immunotherapy, the further characterisation of its biological regulation and function will be of great importance for the development and evaluation of future therapeutic strategies. PMID:19114018

  19. Quantitative analysis of PET studies.

    PubMed

    Weber, Wolfgang A

    2010-09-01

    Quantitative analysis can be included relatively easily in clinical PET-imaging protocols, but in order to obtain meaningful quantitative results one needs to follow a standardized protocol for image acquisition and data analysis. Important factors to consider are the calibration of the PET scanner, the radiotracer uptake time and the approach for definition of regions of interests. Using such standardized acquisition protocols quantitative parameters of tumor metabolism or receptor status can be derived from tracer kinetic analysis and simplified approaches such as calculation of standardized uptake values (SUVs).

  20. [Pets for the mentally ill].

    PubMed

    Jonas, C; Feline, A

    1981-07-01

    After studying the historical importance of the domestic animal through the ages and the role of the "pet" animal in the contemporary world, the authors present an analysis of the literature dealing with the function of the animal in child development and the use of animals as therapeutic "tools". The author's then consider, based on a series of observations, the relationship certain mentally ill patients may establish with one or several pet animals and the significance this object relation may have for the patient : animals become invested as counter depressive or delusional objects, auxiliary means for identification and projection, symbiotic relationship, as well as encouraging feeling of security and responsibility.

  1. Synthesis and evaluation of methylated arylazepine compounds for PET imaging of 5-HT(2c) receptors.

    PubMed

    Granda, Michael L; Carlin, Stephen M; Moseley, Christian K; Neelamegam, Ramesh; Mandeville, Joseph B; Hooker, Jacob M

    2013-02-20

    The serotonin 5-HT(2c) receptor is implicated in a number of diseases including obesity, depression, anxiety, and schizophrenia. In order to ascribe the role of 5-HT(2c) in these diseases, a method for measuring 5-HT(2c )density and function in vivo, such as with positron emission tomography (PET), must be developed. Many high-affinity and relatively selective ligands exist for 5-HT(2c) but cannot be accessed with current radiosynthetic methods for use as PET radiotracers. We propose that N-methylation of an arylazepine moiety, a frequent structural feature in 5-HT(2c) ligands, may be a suitable method for producing new radiotracers for 5-HT(2c). The impact of N-methylation has not been previously reported. For the agonists that we selected herein, N-methylation was found to increase affinity up to 8-fold without impairing selectivity. Compound 5, an N-methylated azetidine-derived arylazepine, was found to be brain penetrant and reached a brain/blood ratio of 2.05:1. However, our initial test compound was rapidly metabolized within 20 min of administration and exhibited high nonspecific binding. N-Methylation, with 16 ± 3% isolated radiochemical yield (decay corrected), is robust and may facilitate screening other 5-HT(2c) ligands as radiotracers for PET.

  2. Synthesis and Evaluation of Methylated Arylazepine Compounds for PET Imaging of 5-HT2c Receptors

    PubMed Central

    2012-01-01

    The serotonin 5-HT2c receptor is implicated in a number of diseases including obesity, depression, anxiety, and schizophrenia. In order to ascribe the role of 5-HT2c in these diseases, a method for measuring 5-HT2c density and function in vivo, such as with positron emission tomography (PET), must be developed. Many high-affinity and relatively selective ligands exist for 5-HT2c but cannot be accessed with current radiosynthetic methods for use as PET radiotracers. We propose that N-methylation of an arylazepine moiety, a frequent structural feature in 5-HT2c ligands, may be a suitable method for producing new radiotracers for 5-HT2c. The impact of N-methylation has not been previously reported. For the agonists that we selected herein, N-methylation was found to increase affinity up to 8-fold without impairing selectivity. Compound 5, an N-methylated azetidine-derived arylazepine, was found to be brain penetrant and reached a brain/blood ratio of 2.05:1. However, our initial test compound was rapidly metabolized within 20 min of administration and exhibited high nonspecific binding. N-Methylation, with 16 ± 3% isolated radiochemical yield (decay corrected), is robust and may facilitate screening other 5-HT2c ligands as radiotracers for PET. PMID:23421677

  3. PET/MR in oncology: an introduction with focus on MR and future perspectives for hybrid imaging.

    PubMed

    Balyasnikova, Svetlana; Löfgren, Johan; de Nijs, Robin; Zamogilnaya, Yanna; Højgaard, Liselotte; Fischer, Barbara M

    2012-01-01

    After more than 20 years of research, a fully integrated PET/MR scanner was launched in 2010 enabling simultaneous acquisition of PET and MR imaging. Currently, no clinical indication for combined PET/MR has been established, however the expectations are high. In this paper we will discuss some of the challenges inherent in this new technology, but focus on potential applications for simultaneous PET/MR in the field of oncology. Methods and tracers for use with the PET technology will be familiar to most readers of this journal; thus this paper aims to provide a short and basic introduction to a number of different MRI techniques, such as DWI-MR (diffusion weighted imaging MR), DCE-MR (dynamic contrast enhanced MR), MRS (MR spectroscopy) and MR for attenuation correction of PET. All MR techniques presented in this paper have shown promising results in the treatment of patients with solid tumors and could be applied together with PET increasing the amount of information about the tissues of interest. The potential clinical benefit of applying PET/MR in staging, radiotherapy planning and treatment evaluation in oncology, as well as the research perspectives for the use of PET/MR in the development of new tracers and drugs will be discussed.

  4. A Systematic Review and Meta-Analysis of the Campylobacter spp. Prevalence and Concentration in Household Pets and Petting Zoo Animals for Use in Exposure Assessments

    PubMed Central

    Pintar, Katarina D. M.; Christidis, Tanya; Thomas, M. Kate; Anderson, Maureen; Nesbitt, Andrea; Keithlin, Jessica; Marshall, Barbara; Pollari, Frank

    2015-01-01

    Animal contact is a potential transmission route for campylobacteriosis, and both domestic household pet and petting zoo exposures have been identified as potential sources of exposure. Research has typically focussed on the prevalence, concentration, and transmission of zoonoses from farm animals to humans, yet there are gaps in our understanding of these factors among animals in contact with the public who don’t live on or visit farms. This study aims to quantify, through a systematic review and meta-analysis, the prevalence and concentration of Campylobacter carriage in household pets and petting zoo animals. Four databases were accessed for the systematic review (PubMed, CAB direct, ProQuest, and Web of Science) for papers published in English from 1992–2012, and studies were included if they examined the animal population of interest, assessed prevalence or concentration with fecal, hair coat, oral, or urine exposure routes (although only articles that examined fecal routes were found), and if the research was based in Canada, USA, Europe, Australia, and New Zealand. Studies were reviewed for qualitative synthesis and meta-analysis by two reviewers, compiled into a database, and relevant studies were used to create a weighted mean prevalence value. There were insufficient data to run a meta-analysis of concentration values, a noted study limitation. The mean prevalence of Campylobacter in petting zoo animals is 6.5% based on 7 studies, and in household pets the mean is 24.7% based on 34 studies. Our estimated concentration values were: 7.65x103cfu/g for petting zoo animals, and 2.9x105cfu/g for household pets. These results indicate that Campylobacter prevalence and concentration are lower in petting zoo animals compared with household pets and that both of these animal sources have a lower prevalence compared with farm animals that do not come into contact with the public. There is a lack of studies on Campylobacter in petting zoos and/or fair animals in

  5. A Systematic Review and Meta-Analysis of the Campylobacter spp. Prevalence and Concentration in Household Pets and Petting Zoo Animals for Use in Exposure Assessments.

    PubMed

    Pintar, Katarina D M; Christidis, Tanya; Thomas, M Kate; Anderson, Maureen; Nesbitt, Andrea; Keithlin, Jessica; Marshall, Barbara; Pollari, Frank

    2015-01-01

    Animal contact is a potential transmission route for campylobacteriosis, and both domestic household pet and petting zoo exposures have been identified as potential sources of exposure. Research has typically focussed on the prevalence, concentration, and transmission of zoonoses from farm animals to humans, yet there are gaps in our understanding of these factors among animals in contact with the public who don't live on or visit farms. This study aims to quantify, through a systematic review and meta-analysis, the prevalence and concentration of Campylobacter carriage in household pets and petting zoo animals. Four databases were accessed for the systematic review (PubMed, CAB direct, ProQuest, and Web of Science) for papers published in English from 1992-2012, and studies were included if they examined the animal population of interest, assessed prevalence or concentration with fecal, hair coat, oral, or urine exposure routes (although only articles that examined fecal routes were found), and if the research was based in Canada, USA, Europe, Australia, and New Zealand. Studies were reviewed for qualitative synthesis and meta-analysis by two reviewers, compiled into a database, and relevant studies were used to create a weighted mean prevalence value. There were insufficient data to run a meta-analysis of concentration values, a noted study limitation. The mean prevalence of Campylobacter in petting zoo animals is 6.5% based on 7 studies, and in household pets the mean is 24.7% based on 34 studies. Our estimated concentration values were: 7.65x103cfu/g for petting zoo animals, and 2.9x105cfu/g for household pets. These results indicate that Campylobacter prevalence and concentration are lower in petting zoo animals compared with household pets and that both of these animal sources have a lower prevalence compared with farm animals that do not come into contact with the public. There is a lack of studies on Campylobacter in petting zoos and/or fair animals in

  6. CB receptor ligands from plants.

    PubMed

    Woelkart, Karin; Salo-Ahen, Outi M H; Bauer, Rudolf

    2008-01-01

    Advances in understanding the physiology and pharmacology of the endogenous cannabinoid system have potentiated the interest of cannabinoid receptors as potential therapeutic targets. Cannabinoids have been shown to modulate a variety of immune cell functions and have therapeutic implications on central nervous system (CNS) inflammation, chronic inflammatory conditions such as arthritis, and may be therapeutically useful in treating autoimmune conditions such as multiple sclerosis. Many of these drug effects occur through cannabinoid receptor signalling mechanisms and the modulation of cytokines and other gene products. Further, endocannabinoids have been found to have many physiological and patho-physiological functions, including mood alteration and analgesia, control of energy balance, gut motility, motor and co-ordination activities, as well as alleviation of neurological, psychiatric and eating disorders. Plants offer a wide range of chemical diversity and have been a growing domain in the search for effective cannabinoid ligands. Cannabis sativa L. with the known plant cannabinoid, Delta(9-)tetrahydrocannabinol (THC) and Echinacea species with the cannabinoid (CB) receptor-binding lipophilic alkamides are the best known herbal cannabimimetics. This review focuses on the state of the art in CB ligands from plants, as well their possible therapeutic and immunomodulatory effects.

  7. Biased ligands: pathway validation for novel GPCR therapeutics.

    PubMed

    Rominger, David H; Cowan, Conrad L; Gowen-MacDonald, William; Violin, Jonathan D

    2014-06-01

    G protein-coupled receptors (GPCRs), in recent years, have been shown to signal via multiple distinct pathways. Furthermore, biased ligands for some receptors can differentially stimulate or inhibit these pathways versus unbiased endogenous ligands or drugs. Biased ligands can be used to gain a deeper understanding of the molecular targets and cellular responses associated with a GPCR, and may be developed into therapeutics with improved efficacy, safety and/or tolerability. Here we review examples and approaches to pathway validation that establish the relevance and therapeutic potential of distinct pathways that can be selectively activated or blocked by biased ligands.

  8. Substituted benzamides as ligands for visualization of dopamine receptor binding in the human brain by positron emission tomography

    SciTech Connect

    Farde, L.; Ehrin, E.; Eriksson, L.; Greitz, T.; Hall, H.; Hedstroem, C.G.; Litton, J.E.; Sedvall, G.

    1985-06-01

    Two substituted benzamides, FLB 524 and raclopride, were labeled with C and examined for their possible use as ligands for positron emission tomography (PET) scan studies on dopamine-2 (D-2) receptors in the brains of monkeys and healthy human subjects. Both ligands allowed the in vivo visualization of D-2 receptor binding in the corpus striatum caudate nucleus/putamen complex in PET-scan images. ( C)Raclopride showed a high ratio of specific striatal to nonspecific cerebellar binding, and the kinetics of binding of this ligand made it optimal for PET studies. The in vivo binding of ( C)raclopride in the striatum of cynomolgus monkeys was markedly reduced by displacement with haloperidol. In healthy human subjects, ( C)raclopride binding in the caudate nucleus/putamen was 4- to 5-fold greater than nonspecific binding in the cerebellum. In comparison with previously available ligands for PET-scan studies on central dopamine receptors in man, ( C)raclopride appears to be advantageous with regard to (i) specificity of binding to D-2 receptors, (ii) the high ratio between binding in dopamine-rich (caudate, putamen) and dopamine-poor (cerebellum) human brain regions, and (iii) rapid association and reversibility of specific binding.

  9. A novel thermally stable hydroperoxo-copper(II) complex in a Cu(N2O2) chromophore of a potential N4O2 donor Schiff base ligand: synthesis, structure and catalytic studies.

    PubMed

    Biswas, Surajit; Dutta, Arpan; Debnath, Mainak; Dolai, Malay; Das, Kalyan K; Ali, Mahammad

    2013-09-28

    The generation and study of metal-hydroperoxo/metal-peroxo (LCu(II)-OOH or LCu(II)-OO˙) complexes is a fascinating area of research of many chemical and biochemical researchers, because of their involvement as active intermediates in many biological and industrial catalytic oxidation processes. For this purpose we have designed a bulky hexa-coordinating ligand with potential N4O2 donor atoms which could provide an opportunity to synthesize a mononuclear Cu(II) complex with an aim to utilize it in the catalytic oxidation of aromatic hydrocarbons by an environmentally benign oxidant, H2O2. The Cu(II) complex (1) was structurally characterized and found to have square-planar geometry with the two pyrazolyl groups remaining in dangling mode. A novel mononuclear complex [Et3NH][LCu(II)-OOH] (2) was found to form in the reaction between 1 and H2O2 in the presence of Et3N. The presence of this dangling groups favours the stability of hydroperoxo species, [LCu-OOH](-) (2) through H-bonding with the coordinated phenoxo oxygen atom, which was confirmed by ESI-MS(+) and MS(-) (m/z) mass analysis and DFT calculations. This complex was found to be thermally stable at room temperature [k(d) = (5.67 ± 0.03) × 10(-5) s(-1) at 25 °C] and may be due to the formation of O-O-H···O(phenoxo) H-bonding as delineated by the DFT calculations. Complex 1 was found to be an efficient catalyst for the oxidation of aromatic hydrocarbons to the corresponding aldehyde and alcohol in 2:1 mole ratio with TON ~300.

  10. A unified Fourier theory for time-of-flight PET data.

    PubMed

    Li, Yusheng; Matej, Samuel; Metzler, Scott D

    2016-01-21

    Fully 3D time-of-flight (TOF) PET scanners offer the potential of previously unachievable image quality in clinical PET imaging. TOF measurements add another degree of redundancy for cylindrical PET scanners and make photon-limited TOF-PET imaging more robust than non-TOF PET imaging. The data space for 3D TOF-PET data is five-dimensional with two degrees of redundancy. Previously, consistency equations were used to characterize the redundancy of TOF-PET data. In this paper, we first derive two Fourier consistency equations and Fourier-John equation for 3D TOF PET based on the generalized projection-slice theorem; the three partial differential equations (PDEs) are the dual of the sinogram consistency equations and John's equation. We then solve the three PDEs using the method of characteristics. The two degrees of entangled redundancy of the TOF-PET data can be explicitly elicited and exploited by the solutions of the PDEs along the characteristic curves, which gives a complete understanding of the rich structure of the 3D x-ray transform with TOF measurement. Fourier rebinning equations and other mapping equations among different types of PET data are special cases of the general solutions. We also obtain new Fourier rebinning and consistency equations (FORCEs) from other special cases of the general solutions, and thus we obtain a complete scheme to convert among different types of PET data: 3D TOF, 3D non-TOF, 2D TOF and 2D non-TOF data. The new FORCEs can be used as new Fourier-based rebinning algorithms for TOF-PET data reduction, inverse rebinnings for designing fast projectors, or consistency conditions for estimating missing data. Further, we give a geometric interpretation of the general solutions--the two families of characteristic curves can be obtained by respectively changing the azimuthal and co-polar angles of the biorthogonal coordinates in Fourier space. We conclude the unified Fourier theory by showing that the Fourier consistency equations are

  11. A unified Fourier theory for time-of-flight PET data

    PubMed Central

    Li, Yusheng; Matej, Samuel; Metzler, Scott D

    2016-01-01

    Fully 3D time-of-flight (TOF) PET scanners offer the potential of previously unachievable image quality in clinical PET imaging. TOF measurements add another degree of redundancy for cylindrical PET scanners and make photon-limited TOF-PET imaging more robust than non-TOF PET imaging. The data space for 3D TOF-PET data is five-dimensional with two degrees of redundancy. Previously, consistency equations were used to characterize the redundancy of TOF-PET data. In this paper, we first derive two Fourier consistency equations and Fourier-John equation for 3D TOF PET based on the generalized projection-slice theorem; the three partial differential equations (PDEs) are the dual of the sinogram consistency equations and John's equation. We then solve the three PDEs using the method of characteristics. The two degrees of entangled redundancy of the TOF-PET data can be explicitly elicited and exploited by the solutions of the PDEs along the characteristic curves, which gives a complete understanding of the rich structure of the 3D X-ray transform with TOF measurement. Fourier rebinning equations and other mapping equations among different types of PET data are special cases of the general solutions. We also obtain new Fourier rebinning and consistency equations (FORCEs) from other special cases of the general solutions, and thus we obtain a complete scheme to convert among different types of PET data: 3D TOF, 3D non-TOF, 2D TOF and 2D non-TOF data. The new FORCEs can be used as new Fourier-based rebinning algorithms for TOF-PET data reduction, inverse rebinnings for designing fast projectors, or consistency conditions for estimating missing data. Further, we give a geometric interpretation of the general solutions—the two families of characteristic curves can be obtained by respectively changing the azimuthal and co-polar angles of the biorthogonal coordinates in Fourier space. We conclude the unified Fourier theory by showing that the Fourier consistency equations are

  12. A unified Fourier theory for time-of-flight PET data

    NASA Astrophysics Data System (ADS)

    Li, Yusheng; Matej, Samuel; Metzler, Scott D.

    2016-01-01

    Fully 3D time-of-flight (TOF) PET scanners offer the potential of previously unachievable image quality in clinical PET imaging. TOF measurements add another degree of redundancy for cylindrical PET scanners and make photon-limited TOF-PET imaging more robust than non-TOF PET imaging. The data space for 3D TOF-PET data is five-dimensional with two degrees of redundancy. Previously, consistency equations were used to characterize the redundancy of TOF-PET data. In this paper, we first derive two Fourier consistency equations and Fourier-John equation for 3D TOF PET based on the generalized projection-slice theorem; the three partial differential equations (PDEs) are the dual of the sinogram consistency equations and John’s equation. We then solve the three PDEs using the method of characteristics. The two degrees of entangled redundancy of the TOF-PET data can be explicitly elicited and exploited by the solutions of the PDEs along the characteristic curves, which gives a complete understanding of the rich structure of the 3D x-ray transform with TOF measurement. Fourier rebinning equations and other mapping equations among different types of PET data are special cases of the general solutions. We also obtain new Fourier rebinning and consistency equations (FORCEs) from other special cases of the general solutions, and thus we obtain a complete scheme to convert among different types of PET data: 3D TOF, 3D non-TOF, 2D TOF and 2D non-TOF data. The new FORCEs can be used as new Fourier-based rebinning algorithms for TOF-PET data reduction, inverse rebinnings for designing fast projectors, or consistency conditions for estimating missing data. Further, we give a geometric interpretation of the general solutions—the two families of characteristic curves can be obtained by respectively changing the azimuthal and co-polar angles of the biorthogonal coordinates in Fourier space. We conclude the unified Fourier theory by showing that the Fourier consistency equations

  13. Recent Advances and Future Advances in Time-of-Flight PET

    PubMed Central

    Moses, William W.

    2007-01-01

    Simple theory predicts that the statistical noise variance in PET can be reduced by an order of magnitude by using time-of-flight (TOF) information. This reduction can be obtained by improving the coincidence timing resolution, and so would be achievable in clinical, whole body studies using with PET systems that differ little from existing cameras. The potential impact of this development is large, especially for oncology studies in large patients, where it is sorely needed. TOF PET was extensively studied in the 1980’s but died away in the 1990’s, as it was impossible to reliably achieve sufficient timing resolution without sacrificing other important PET performance aspects, such as spatial resolution and efficiency. Recent advances in technology (scintillators, photodetectors, and high speed electronics) have renewed interest in TOF PET, which is experiencing a rebirth. However, there is still much to be done, both in instrumentation development and evaluating the true benefits of TOF in modern clinical PET. This paper looks at what has been accomplished and what needs to be done before time-of-flight PET can reach its full potential. PMID:18836513

  14. Palliative care and compound in household pets.

    PubMed

    Gaskins, Jessica L

    2012-01-01

    Palliative care is not a term solely used for humans when discussing health care; the term is also used when discussing veterinary patients. Pets are considered part of the family by pet owners, and they have a special relationship that only another pet owner can fully understand. This article discusses some of the healthcare problems that affect pets (and their owners), statistics on the most commonly used medications for veterinary patients, quality of life, and discussions on the veterinary pharmacist-owner-palliative pet relationship and how compounding pharmacists can prepare patient-specific medications.

  15. Development of PET/MRI with insertable PET for simultaneous PET and MR imaging of human brain

    SciTech Connect

    Jung, Jin Ho; Choi, Yong Jung, Jiwoong; Kim, Sangsu; Lim, Hyun Keong; Im, Ki Chun; Oh, Chang Hyun; Park, Hyun-wook; Kim, Kyung Min; Kim, Jong Guk

    2015-05-15

    Purpose: The purpose of this study was to develop a dual-modality positron emission tomography (PET)/magnetic resonance imaging (MRI) with insertable PET for simultaneous PET and MR imaging of the human brain. Methods: The PET detector block was composed of a 4 × 4 matrix of detector modules, each consisting of a 4 × 4 array LYSO coupled to a 4 × 4 Geiger-mode avalanche photodiode (GAPD) array. The PET insert consisted of 18 detector blocks, circularly mounted on a custom-made plastic base to form a ring with an inner diameter of 390 mm and axial length of 60 mm. The PET gantry was shielded with gold-plated conductive fabric tapes with a thickness of 0.1 mm. The charge signals of PET detector transferred via 4 m long flat cables were fed into the position decoder circuit. The flat cables were shielded with a mesh-type aluminum sheet with a thickness of 0.24 mm. The position decoder circuit and field programmable gate array-embedded DAQ modules were enclosed in an aluminum box with a thickness of 10 mm and located at the rear of the MR bore inside the MRI room. A 3-T human MRI system with a Larmor frequency of 123.7 MHz and inner bore diameter of 60 cm was used as the PET/MRI hybrid system. A custom-made radio frequency (RF) coil with an inner diameter of 25 cm was fabricated. The PET was positioned between gradient and the RF coils. PET performance was measured outside and inside the MRI scanner using echo planar imaging, spin echo, turbo spin echo, and gradient echo sequences. MRI performance was also evaluated with and without the PET insert. The stability of the newly developed PET insert was evaluated and simultaneous PET and MR images of a brain phantom were acquired. Results: No significant degradation of the PET performance caused by MR was observed when the PET was operated using various MR imaging sequences. The signal-to-noise ratio of MR images was slightly degraded due to the PET insert installed inside the MR bore while the homogeneity was

  16. Adsorption of surfactin produced from Bacillus subtilis using nonwoven PET (polyethylene terephthalate) fibrous membranes functionalized with chitosan.

    PubMed

    Behary, N; Perwuelz, A; Campagne, C; Lecouturier, D; Dhulster, P; Mamede, A S

    2012-02-01

    This article deals with an alternative method for bio-separation of surfactin produced by Bacillus subtilis using sorption method on nonwoven PET (polyethylene terephthalate) fibrous membranes functionalized with chitosan. In the first part of the study, surface functionalization of the PET nonwoven fibrous membranes is carried out with aqueous 65% deacetylated chitosan solution with or without a prior surface activation using air-atmospheric plasma treatment. Very small modification of the PET fibrous nonwoven air-permeability confirms the functionalization of PET fibre surface with little reduction of membrane porosity. The functionalized membranes are then characterized by physico-chemical methods: X-ray Photoelectron Spectroscopy (XPS), Wettability and zeta potential. Chitosan increases drastically the zeta potential of PET at all pH values though a prior plasma treatment of the PET membrane reduces slightly the increase in zeta potential values. Sorption of surfactin quantified by HPLC shows that the extent of surfactin sorption on PET nonwovens depends on the surface functionalization method. Surface functionalization with chitosan results in immediate sorption of the entire quantity of surfactin. A prior surface activation by air atmospheric plasma treatment of the PET membranes before chitosan application retards the sorption of entire surfactin which takes place after 1.5h, only. Increased zeta potential and increased hydrophobic behavior in the presence of chitosan without plasma activation would explain the interesting surfactin sorption results.

  17. Economical aspect of PET/CT-guided diagnosis of suspected infective endocarditis in a patient with implantable cardioverter-defibrillator.

    PubMed

    Farkowski, Michal M; Milkowski, Maciej; Dziuk, Mirosław; Pytkowski, Mariusz; Marciniak, Marta; Kraska, Alicja; Szwed, Hanna; Sterlinski, Maciej

    2014-01-01

    We present a case report of potential reduction of hospitalization costs due to utilization of PET/CT in a diagnostic work-up of a patient with an implantable cardioverter-defibrillator and suspicion of infective endocarditis. The PET/CT scan would have shorten hospital stay, prevented clinical complications and reduced the cost of hospitalization by 45%.

  18. Segmentation of brain PET-CT images based on adaptive use of complementary information

    NASA Astrophysics Data System (ADS)

    Xia, Yong; Wen, Lingfeng; Eberl, Stefan; Fulham, Michael; Feng, Dagan

    2009-02-01

    Dual modality PET-CT imaging provides aligned anatomical (CT) and functional (PET) images in a single scanning session, which can potentially be used to improve image segmentation of PET-CT data. The ability to distinguish structures for segmentation is a function of structure and modality and varies across voxels. Thus optimal contribution of a particular modality to segmentation is spatially variant. Existing segmentation algorithms, however, seldom account for this characteristic of PET-CT data and the results using these algorithms are not optimal. In this study, we propose a relative discrimination index (RDI) to characterize the relative abilities of PET and CT to correctly classify each voxel into the correct structure for segmentation. The definition of RDI is based on the information entropy of the probability distribution of the voxel's class label. If the class label derived from CT data for a particular voxel has more certainty than that derived from PET data, the corresponding RDI will have a higher value. We applied the RDI matrix to balance adaptively the contributions of PET and CT data to segmentation of brain PET-CT images on a voxel-by-voxel basis, with the aim to give the modality with higher discriminatory power a larger weight. The resultant segmentation approach is distinguished from traditional approaches by its innovative and adaptive use of the dual-modality information. We compared our approach to the non-RDI version and two commonly used PET-only based segmentation algorithms for simulation and clinical data. Our results show that the RDI matrix markedly improved PET-CT image segmentation.

  19. A filtering approach based on Gaussian-powerlaw convolutions for local PET verification of proton radiotherapy.

    PubMed

    Parodi, Katia; Bortfeld, Thomas

    2006-04-21

    Because proton beams activate positron emitters in patients, positron emission tomography (PET) has the potential to play a unique role in the in vivo verification of proton radiotherapy. Unfortunately, the PET image is not directly proportional to the delivered radiation dose distribution. Current treatment verification strategies using PET therefore compare the actual PET image with full-blown Monte Carlo simulations of the PET signal. In this paper, we describe a simpler and more direct way to reconstruct the expected PET signal from the local radiation dose distribution near the distal fall-off region, which is calculated by the treatment planning programme. Under reasonable assumptions, the PET image can be described as a convolution of the dose distribution with a filter function. We develop a formalism to derive the filter function analytically. The main concept is the introduction of 'Q' functions defined as the convolution of a Gaussian with a powerlaw function. Special Q functions are the Gaussian itself and the error function. The convolution of two Q functions is another Q function. By fitting elementary dose distributions and their corresponding PET signals with Q functions, we derive the Q function approximation of the filter. The new filtering method has been validated through comparisons with Monte Carlo calculations and, in one case, with measured data. While the basic concept is developed under idealized conditions assuming that the absorbing medium is homogeneous near the distal fall-off region, a generalization to inhomogeneous situations is also described. As a result, the method can determine the distal fall-off region of the PET signal, and consequently the range of the proton beam, with millimetre accuracy. Quantification of the produced activity is possible. In conclusion, the PET activity resulting from a proton beam treatment can be determined by locally filtering the dose distribution as obtained from the treatment planning system. The

  20. Synthesis and preliminary evaluation of [18F]-labeled 2-oxoquinoline derivatives for PET imaging of cannabinoid CB2 receptor

    PubMed Central

    Turkman, Nashaat; Paolillo, Vincenzo; Shavrin, Aleksander; Yeh, Hsin Hsien; Flores, Leo; Soghomonian, Suren; Ravinovich, Brian; Volgin, Andrei; Gelovani, Juri; Alauddin, Mian

    2011-01-01

    Introduction The cannabinoid receptor type 2 (CB2) is an important target for development of drugs and imaging agents for diseases, such as neuroinflammation, neurodegeneration, and cancer. Recently we reported synthesis and results of in vitro receptor binding of a focused library of fluorinated 2-oxoquinoline derivatives as CB2 receptor ligands. Some of the compounds demonstrated as good CB2-specific ligands with Ki values in the nanomolar to sub-nanomolar concentrations; therefore, we pursued the development of their 18F-labeled analogues that should be useful for PET imaging of CB2 receptor expression. Here, we report the radiosynthesis of two 18F-labeled 2-oxoquinoline derivatives, and preliminary in vitro and ex-vivo evaluation of one compound as a CB2-specific radioligand. Methods 4-[18F]Fluorobenzyl amine [18F]-3 was prepared by radiofluorination of 4-cyano-N,N,N-trimethylanilinium triflate salt followed by reduction with LiAlH4 and then coupled with acid chlorides 11 and 12 to afford [18F]-13 and [18F]-14. In vitro CB2 receptor binding assay was performed using U87 cells transduced with CB2- and CB1-receptor. Ex-vivo autoradiography was performed with [18F]-14 on spleen, CB2- and CB1-expressing and wild type U87 subcutaneous tumors grown in mice. Results The radiochemical yields of [18F]-13 and [18F]-14 were 10%-15.0% with an average of 12% (n=10); radiochemical purity was > 99% with specific activity 1200 mCi/μmole. The dissociation constant Kd for [18F]-14 was 3.4 nM. Ex-vivo autoradiography showed accumulation of [18F]-14 in the CB2-expressing tumor. Conclusion Two new [18F]-labeled CB2 ligands have been synthesized. Compound [18F]-14 appears to be a potential PET imaging agent for the assessment of CB2 receptor expression in vivo. PMID:22226022

  1. A New Positron Emission Tomography (PET) Radioligand for Imaging Sigma-1 Receptors in Living Subjects

    PubMed Central

    Zavaleta, Cristina L.; Nielsen, Carsten H.; Mesangeau, Christophe; Vuppala, Pradeep K.; Chan, Carmel; Avery, Bonnie A.; Fishback, James A.; Matsumoto, Rae R.; Gambhir, Sanjiv S.; McCurdy, Christopher R.; Chin, Frederick T.

    2014-01-01

    Sigma-1 receptor (S1R) radioligands have the potential to detect and monitor various neurological diseases. Herein we report the synthesis, radiofluorination and evaluation of a new S1R ligand 6-(3-fluoropropyl)-3-(2-(azepan-1-yl)ethyl)benzo[d]thiazol-2(3H)-one ([18F]FTC-146, [18F]13). [18F]13 was synthesized by nucleophilic fluorination, affording a product with >99% radiochemical purity (RCP) and specific activity (SA) of 2.6 ± 1.2 Ci/Amol (n = 13) at end of synthesis (EOS). Positron emission tomography (PET) and ex vivo autoradiography studies of [18F]13 in mice showed high uptake of the radioligand in S1R rich regions of the brain. Pre treatment with 1 mg/kg haloperidol (2), non radioactive 13, or BD1047 (18) reduced the binding of [18F]13 in the brain at 60 min by 80%, 82% and 81% respectively, suggesting that [18F]13 accumulation in mouse brain represents specific binding to S1Rs. These results indicate that [18F]13 is a promising candidate radiotracer for further evaluation as a tool for studying S1Rs in living subjects. PMID:22853801

  2. Quantitative simultaneous PET-MR imaging

    NASA Astrophysics Data System (ADS)

    Ouyang, Jinsong; Petibon, Yoann; Huang, Chuan; Reese, Timothy G.; Kolnick, Aleksandra L.; El Fakhri, Georges

    2014-06-01

    Whole-body PET is currently limited by the degradation due to patient motion. Respiratory motion degrades imaging studies of the abdomen. Similarly, both respiratory and cardiac motions significantly hamper the assessment of myocardial ischemia and/or metabolism in perfusion and viability cardiac PET studies. Based on simultaneous PET-MR, we have developed robust and accurate MRI methods allowing the tracking and measurement of both respiratory and cardiac motions during abdominal or cardiac studies. Our list-mode iterative PET reconstruction framework incorporates the measured motion fields into PET emission system matrix as well as the time-dependent PET attenuation map and the position dependent point spread function. Our method significantly enhances the PET image quality as compared to conventional methods.

  3. High-Resolution PET Detector. Final report

    SciTech Connect

    Karp, Joel

    2014-03-26

    The objective of this project was to develop an understanding of the limits of performance for a high resolution PET detector using an approach based on continuous scintillation crystals rather than pixelated crystals. The overall goal was to design a high-resolution detector, which requires both high spatial resolution and high sensitivity for 511 keV gammas. Continuous scintillation detectors (Anger cameras) have been used extensively for both single-photon and PET scanners, however, these instruments were based on NaI(Tl) scintillators using relatively large, individual photo-multipliers. In this project we investigated the potential of this type of detector technology to achieve higher spatial resolution through the use of improved scintillator materials and photo-sensors, and modification of the detector surface to optimize the light response function.We achieved an average spatial resolution of 3-mm for a 25-mm thick, LYSO continuous detector using a maximum likelihood position algorithm and shallow slots cut into the entrance surface.

  4. Zoonoses in pet birds: review and perspectives

    PubMed Central

    2013-01-01

    Pet birds are a not-so-well known veterinarian’s clientship fraction. Bought individually or in couples, as families often do (which is a lucrative business for pet shops or local breeders) or traded (sometimes illegally) for their very high genetic or exotic value, these birds, commonly canaries, parakeets or parrots, are regularly sold at high prices. These animals, however, are potential carriers and/or transmitters of zoonotic diseases. Some of them could have an important impact on human health, like chlamydophilosis, salmonellosis or even highly pathogenic avian influenza A H5N1. This review paper, although non exhaustive, aims at enlightening, by the description of several cases of bird-human transmission, the risks encountered by bird owners, including children. Public health consequences will be discussed and emphasis will be made on some vector-borne diseases, known to be emergent or which are underestimated, like those transmitted by the red mite Dermanyssus gallinae. Finally, biosecurity and hygiene, as well as prevention guidelines will be developed and perspectives proposed. PMID:23687940

  5. Ligand fitting with CCP4

    PubMed Central

    2017-01-01

    Crystal structures of protein–ligand complexes are often used to infer biology and inform structure-based drug discovery. Hence, it is important to build accurate, reliable models of ligands that give confidence in the interpretation of the respective protein–ligand complex. This paper discusses key stages in the ligand-fitting process, including ligand binding-site identification, ligand description and conformer generation, ligand fitting, refinement and subsequent validation. The CCP4 suite contains a number of software tools that facilitate this task: AceDRG for the creation of ligand descriptions and conformers, Lidia and JLigand for two-dimensional and three-dimensional ligand editing and visual analysis, Coot for density interpretation, ligand fitting, analysis and validation, and REFMAC5 for macromolecular refinement. In addition to recent advancements in automatic carbohydrate building in Coot (LO/Carb) and ligand-validation tools (FLEV), the release of the CCP4i2 GUI provides an integrated solution that streamlines the ligand-fitting workflow, seamlessly passing results from one program to the next. The ligand-fitting process is illustrated using instructive practical examples, including problematic cases such as post-translational modifications, highlighting the need for careful analysis and rigorous validation. PMID:28177312

  6. Occipital Hypometabolism on FDG PET/CT Scan in a Child with Hodgkin's Lymphoma

    PubMed Central

    Tatci, Ebru; Ozmen, Ozlem; Gokcek, Atila; Demir, Haci Ahmet; Gulleroglu, Nadide Basak

    2016-01-01

    It is known that Fluorodeoxyglucose (FDG) Positron Emission/Computed Tomography (PET/CT) images may be helpful for evaluation of brain function in newborns. Here we described the fluorine-18 [18-F] FDG PET/CT imaging findings of encephalomalacia due to perinatal asphyxia in a child with refractory Hodgkin's Lymphoma (HL) who underwent PET/CT scan to stage the primary disease. Prominent hypometabolism was incidentally detected in the occipital regions bilaterally apart from the FDG uptakes in the malign lymphatic infiltrations. This case highlights the potential coexistence of a malignancy and a functional brain disorder. PMID:27965911

  7. Cat-Scratch Disease: A Pitfall for Lymphoma Evaluation by FDG-PET/CT.

    PubMed

    Dubreuil, Julien; Dony, Arthur; Salles, Gilles; Traverse-Glehen, Alexandra; Giammarile, Francesco; Skanjeti, Andrea

    2017-02-01

    FDG-PET/CT is a standard of care in staging and response assessment of Hodgkin lymphoma. Hence, it is important to recognize pitfalls owing to the potential therapeutic impact. We report a case of a 29-year-old woman affected by stage III bulky Hodgkin lymphoma. The interim FDG-PET/CT showed a complete metabolic response. After three new cycles of chemotherapy, the patient showed fever and lymphadenopathy at clinic examination, PET/CT revealed several FDG uptakes at lymph nodes in inguinal and iliac region. Pathologic analyses, after biopsy and serologic examinations, led to the diagnosis of cat-scratch disease.

  8. Subacute Cortical Infarct Showing Uptake on 68Ga-PSMA PET/CT.

    PubMed

    Chan, Mico; Hsiao, Edward

    2017-02-01

    Ga prostate-specific membrane antigen (PSMA) PET/CT is increasingly used to evaluate extent of disease in prostate carcinoma. We present a case of subacute cortical cerebral infarct showing focal uptake on PSMA PET/CT. It is an important potential cause of false-positive uptake in this imaging cohort. The patient is an 85-year-old man with a background of nonbacterial thrombotic endocarditis and previous cerebrovascular events. He was referred for PSMA PET/CT for staging of high-risk prostate cancer.

  9. Postnatal development of hypoplastic thymus in semi-lethal dwarf pet/pet males.

    PubMed

    Chiba, Junko; Suzuki, Hiroetsu; Aoyama, Hiroaki; Katayama, Kentaro; Suzuki, Katsushi

    2011-04-01

    The petit rat (pet/pet) is a new semi-lethal dwarf mutant with anomalies in the thymus and testes, defects inherited as a single autosomal recessive trait. At birth, these pet/pet rats show low birth weight and extremely small thymuses; at 140 days of age, their thymuses show abnormal involution. In the present study, we examined early postnatal development of hypoplastic pet/pet thymuses. In addition to being hypoplastic at birth, pet/pet thymus growth was almost completely impaired during the early postnatal period. As shown by cellular incorporation of BrdU, the mitotic activity was lower in pet/pet than in normal thymuses, and terminal deoxynucleotidyl transferase dUTP nick end labeling assays showed that apoptosis occurred more often in pet/pet than in normal thymus cells during the first few days after birth. These results indicate that postnatal development of the hypoplastic pet/pet thymus is defective due to the reduced proliferation and increased apoptosis of thymic cells.

  10. Striatal phosphodiesterase 10A and medial prefrontal cortical thickness in patients with schizophrenia: a PET and MRI study.

    PubMed

    Bodén, R; Persson, J; Wall, A; Lubberink, M; Ekselius, L; Larsson, E-M; Antoni, G

    2017-03-07

    The enzyme phosphodiesterase 10A (PDE10A) is abundant in striatal medium spiny neurons and has been implicated in the pathophysiology of schizophrenia in animal models and is investigated as a possible new pharmacological treatment target. A reduction of prefrontal cortical thickness is common in schizophrenia, but how this relates to PDE10A expression is unknown. Our study aim was to compare, we believe for the first time, the striatal non-displaceable binding potential (BPND) of the new validated PDE10A ligand [(11)C]Lu AE92686 between patients with schizophrenia and healthy controls. Furthermore, we aimed to assess the correlation of PDE10A BPND to cortical thickness. Sixteen healthy male controls and 10 male patients with schizophrenia treated with clozapine, olanzapine or quetiapine were investigated with positron emission tomography (PET) and magnetic resonance imaging (MRI). Striatal binding potential (BPND) of [(11)C]Lu AE92686 was acquired through dynamic PET scans and cortical thickness by structural MRI. Clinical assessments of symptoms and cognitive function were performed and the antipsychotic dosage was recorded. Patients with schizophrenia had a significantly lower BPND of [(11)C]Lu AE92686 in striatum (P=0.003) than healthy controls. The striatal BPND significantly correlated to cortical thickness in the medial prefrontal cortex and superior frontal gyrus across patients with schizophrenia and healthy controls. No significant correlation was observed between the BPND for [(11)C]Lu AE92686 in striatum and age, schizophrenia symptoms, antipsychotic dosage, coffee consumption, smoking, duration of illness or cognitive function in the patients. In conclusion, PDE10A may be important for functioning in the striato-cortical interaction and in the pathophysiology of schizophrenia.

  11. Facile synthesis of SSR180575 and discovery of 7-chloro-N,N,5-trimethyl-4-oxo-3(6-[18F]fluoropyridin-2-yl)-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-acetamide, a potent pyridazinoindole ligand for PET imaging of TSPO in cancer

    PubMed Central

    Cheung, Yiu-Yin; Nickels, Michael L.; Tang, Dewei; Buck, Jason R.

    2014-01-01

    A novel synthesis of the translocator protein (TSPO) ligand 7-chloro-N,N,5-trimethyl-4-oxo-3-phenyl-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-acetamide (SSR180575, 3) was achieved in four steps from commercially available starting materials. Focused structure−activity relationship development about the pyridazinoindole ring at the N3 position led to the discovery of 7-chloro-N,N,5-trimethyl-4-oxo-3(6-fluoropyridin-2-yl)-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-acetamide (14), a novel ligand of comparable affinity. Radiolabeling with fluorine-18 (18F) yielded 7-chloro-N,N,5-trimethyl-4-oxo-3(6-[18F]fluoropyridin-2-yl)-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-acetamide (18F-14) in high radiochemical yield and specific activity. In vivo studies of [18F]-14 revealed this agent as a promising probe for molecular imaging of glioma. PMID:25172419

  12. [11C]SMe-ADAM, an imaging agent for the brain serotonin transporter: synthesis, pharmacological characterization and microPET studies in rats.

    PubMed

    Zessin, Jörg; Deuther-Conrad, Winnie; Kretzschmar, Marion; Wüst, Frank; Pawelke, Beate; Brust, Peter; Steinbach, Jörg; Bergmann, Ralf

    2006-01-01

    N,N-Dimethyl-2-(2-amino-4-methylthiophenylthio)benzylamine (SMe-ADAM, 1) is a highly potent and selective inhibitor of the serotonin transporter (SERT). This compound was labeled with carbon-11 by methylation of the S-desmethyl precursor 10 with [(11)C]methyl iodide to obtain the potential positron emission tomography (PET) radioligand [(11)C]SMe-ADAM. The radiochemical yield was 27 +/- 5%, and the specific radioactivity was 26-40 GBq/micromol at the end of synthesis. Ex vivo and in vivo biodistribution experiments in rats demonstrated a rapid accumulation of the radiotracer in brain regions known to be rich in SERT, such as the thalamus/hypothalamus region (3.59 +/- 0.41%ID/g at 5 min after injection). The specific uptake reached a thalamus to cerebellum ratio of 6.74 +/- 0.95 at 60 min postinjection. The [(11)C]SMe-ADAM uptake in the thalamus was significantly decreased by pretreatment with fluoxetine to 38 +/- 11% of the control value. Furthermore, no metabolites of [(11)C]SMe-ADAM could be detected in the SERT-rich regions of the rat brain. It is concluded that [(11)C]SMe-ADAM may be a suitable PET ligand for SERT imaging in the living brain.

  13. Optimized PET imaging for 4D treatment planning in radiotherapy: the virtual 4D PET strategy.

    PubMed

    Gianoli, Chiara; Riboldi, Marco; Fontana, Giulia; Giri, Maria G; Grigolato, Daniela; Ferdeghini, Marco; Cavedon, Carlo; Baroni, Guido

    2015-02-01

    The purpose of the study is to evaluate the performance of a novel strategy, referred to as "virtual 4D PET", aiming at the optimization of hybrid 4D CT-PET scan for radiotherapy treatment planning. The virtual 4D PET strategy applies 4D CT motion modeling to avoid time-resolved PET image acquisition. This leads to a reduction of radioactive tracer administered to the patient and to a total acquisition time comparable to free-breathing PET studies. The proposed method exploits a motion model derived from 4D CT, which is applied to the free-breathing PET to recover respiratory motion and motion blur. The free-breathing PET is warped according to the motion model, in order to generate the virtual 4D PET. The virtual 4D PET strategy was tested on images obtained from a 4D computational anthropomorphic phantom. The performance was compared to conventional motion compensated 4D PET. Tests were also carried out on clinical 4D CT-PET scans coming from seven lung and liver cancer patients. The virtual 4D PET strategy was able to recover lesion motion, with comparable performance with respect to the motion compensated 4D PET. The compensation of the activity blurring due to motion was successfully achieved in terms of spill out removal. Specific limitations were highlighted in terms of partial volume compensation. Results on clinical 4D CT-PET scans confirmed the efficacy in 4D PET count statistics optimization, as equal to the free-breathing PET, and recovery of lesion motion. Compared to conventional motion compensation strategies that explicitly require 4D PET imaging, the virtual 4D PET strategy reduces clinical workload and computational costs, resulting in significant advantages for radiotherapy treatment planning.

  14. A systematic review of PET and PET/CT in oncology: A way to personalize cancer treatment in a cost-effective manner?

    PubMed Central

    2010-01-01

    strongest evidence for the cost-effectiveness of PET is still in the staging of non-small cell lung cancer. Management decisions relating to the assessment of treatment response or radiotherapy treatment planning require further research to show the impact of PET on patient management and its cost-effectiveness. Because of the potential for increased patient throughput and the possible greater accuracy, the cost-effectiveness of PET/CT may be superior to that of PET. Only four studies of the cost-effectiveness of PET/CT were found in this review, and this is clearly an area for future research. PMID:20932288

  15. Recent developments in time-of-flight PET.

    PubMed

    Vandenberghe, S; Mikhaylova, E; D'Hoe, E; Mollet, P; Karp, J S

    2016-12-01

    While the first time-of-flight (TOF)-positron emission tomography (PET) systems were already built in the early 1980s, limited clinical studies were