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Sample records for 11c pittsburgh compound

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

    PubMed

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

    2015-05-01

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

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

    PubMed

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

    2015-05-01

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

  3. 1-.sup.11 C-D-Glucose and related compounds

    DOEpatents

    Shiue, Chyng-Yann; Wolf, Alfred P.

    1984-03-27

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

  4. 1-/sup 11/C-D-glucose and related compounds

    SciTech Connect

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

    1982-01-26

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

  5. Using Pittsburgh Compound B for In Vivo PET Imaging of Fibrillar Amyloid-Beta

    PubMed Central

    Cohen, Ann D.; Rabinovici, Gil D.; Mathis, Chester A.; Jagust, William J.; Klunk, William E.; Ikonomovic, Milos D.

    2012-01-01

    The development of Aβ-PET imaging agents has allowed for detection of fibrillar Aβ deposition in vivo and marks a major advancement in understanding the role of Aβ in Alzheimer’s disease (AD). Imaging Aβ thus has many potential clinical benefits: early or perhaps preclinical detection of disease and accurately distinguishing AD from dementias of other non-Aβ causes in patients presenting with mild or atypical symptoms or confounding comorbidities (in which the distinction is difficult to make clinically). From a research perspective, imaging Aβ allows us to study relationships between amyloid pathology and changes in cognition, brain structure, and function across the continuum from normal aging to mild cognitive impairment (MCI) to AD; and to monitor the effectiveness of anti-Aβ drugs and relate them to neurodegeneration and clinical symptoms. Here, we will discuss the application of one of the most broadly studied and widely used Aβ imaging agents, Pittsburgh Compound-B (PiB). PMID:22840744

  6. Pittsburgh compound B imaging and cerebrospinal fluid amyloid-β in a multicentre European memory clinic study

    PubMed Central

    Leuzy, Antoine; Chiotis, Konstantinos; Hasselbalch, Steen G.; Rinne, Juha O.; de Mendonça, Alexandre; Otto, Markus; Lleó, Alberto; Castelo-Branco, Miguel; Santana, Isabel; Johansson, Jarkko; Anderl-Straub, Sarah; von Arnim, Christine A. F.; Beer, Ambros; Blesa, Rafael; Fortea, Juan; Herukka, Sanna-Kaisa; Portelius, Erik; Pannee, Josef; Zetterberg, Henrik; Blennow, Kaj

    2016-01-01

    The aim of this study was to assess the agreement between data on cerebral amyloidosis, derived using Pittsburgh compound B positron emission tomography and (i) multi-laboratory INNOTEST enzyme linked immunosorbent assay derived cerebrospinal fluid concentrations of amyloid-β42; (ii) centrally measured cerebrospinal fluid amyloid-β42 using a Meso Scale Discovery enzyme linked immunosorbent assay; and (iii) cerebrospinal fluid amyloid-β42 centrally measured using an antibody-independent mass spectrometry-based reference method. Moreover, we examined the hypothesis that discordance between amyloid biomarker measurements may be due to interindividual differences in total amyloid-β production, by using the ratio of amyloid-β42 to amyloid-β40. Our study population consisted of 243 subjects from seven centres belonging to the Biomarkers for Alzheimer’s and Parkinson’s Disease Initiative, and included subjects with normal cognition and patients with mild cognitive impairment, Alzheimer’s disease dementia, frontotemporal dementia, and vascular dementia. All had Pittsburgh compound B positron emission tomography data, cerebrospinal fluid INNOTEST amyloid-β42 values, and cerebrospinal fluid samples available for reanalysis. Cerebrospinal fluid samples were reanalysed (amyloid-β42 and amyloid-β40) using Meso Scale Discovery electrochemiluminescence enzyme linked immunosorbent assay technology, and a novel, antibody-independent, mass spectrometry reference method. Pittsburgh compound B standardized uptake value ratio results were scaled using the Centiloid method. Concordance between Meso Scale Discovery/mass spectrometry reference measurement procedure findings and Pittsburgh compound B was high in subjects with mild cognitive impairment and Alzheimer’s disease, while more variable results were observed for cognitively normal and non-Alzheimer’s disease groups. Agreement between Pittsburgh compound B classification and Meso Scale Discovery/mass spectrometry

  7. Pittsburgh compound B imaging and cerebrospinal fluid amyloid-β in a multicentre European memory clinic study.

    PubMed

    Leuzy, Antoine; Chiotis, Konstantinos; Hasselbalch, Steen G; Rinne, Juha O; de Mendonça, Alexandre; Otto, Markus; Lleó, Alberto; Castelo-Branco, Miguel; Santana, Isabel; Johansson, Jarkko; Anderl-Straub, Sarah; von Arnim, Christine A F; Beer, Ambros; Blesa, Rafael; Fortea, Juan; Herukka, Sanna-Kaisa; Portelius, Erik; Pannee, Josef; Zetterberg, Henrik; Blennow, Kaj; Nordberg, Agneta

    2016-09-01

    The aim of this study was to assess the agreement between data on cerebral amyloidosis, derived using Pittsburgh compound B positron emission tomography and (i) multi-laboratory INNOTEST enzyme linked immunosorbent assay derived cerebrospinal fluid concentrations of amyloid-β42; (ii) centrally measured cerebrospinal fluid amyloid-β42 using a Meso Scale Discovery enzyme linked immunosorbent assay; and (iii) cerebrospinal fluid amyloid-β42 centrally measured using an antibody-independent mass spectrometry-based reference method. Moreover, we examined the hypothesis that discordance between amyloid biomarker measurements may be due to interindividual differences in total amyloid-β production, by using the ratio of amyloid-β42 to amyloid-β40 Our study population consisted of 243 subjects from seven centres belonging to the Biomarkers for Alzheimer's and Parkinson's Disease Initiative, and included subjects with normal cognition and patients with mild cognitive impairment, Alzheimer's disease dementia, frontotemporal dementia, and vascular dementia. All had Pittsburgh compound B positron emission tomography data, cerebrospinal fluid INNOTEST amyloid-β42 values, and cerebrospinal fluid samples available for reanalysis. Cerebrospinal fluid samples were reanalysed (amyloid-β42 and amyloid-β40) using Meso Scale Discovery electrochemiluminescence enzyme linked immunosorbent assay technology, and a novel, antibody-independent, mass spectrometry reference method. Pittsburgh compound B standardized uptake value ratio results were scaled using the Centiloid method. Concordance between Meso Scale Discovery/mass spectrometry reference measurement procedure findings and Pittsburgh compound B was high in subjects with mild cognitive impairment and Alzheimer's disease, while more variable results were observed for cognitively normal and non-Alzheimer's disease groups. Agreement between Pittsburgh compound B classification and Meso Scale Discovery/mass spectrometry reference

  8. Pittsburgh Compound B and the Postmortem Diagnosis of Alzheimer’s Disease

    PubMed Central

    Niedowicz, Dana M.; Beckett, Tina L.; Matveev, Sergey; Weidner, Adam M.; Baig, Irfan; Kryscio, Richard J.; Mendiondo, Marta S.; LeVine, Harry; Keller, Jeffrey N.; Murphy, M. Paul

    2012-01-01

    Objective Deposition of the amyloid-β (Aβ) peptide in neuritic plaques is a requirement for the diagnosis of Alzheimer’s disease (AD). Although the continued development of in vivo imaging agents such as Pittsburgh Compound B (PiB) is promising, the diagnosis of AD is still challenging. This can be partially attributed to our lack of a detailed understanding of the interrelationship between the various pools and species of Aβ and other common indices of AD pathology. We hypothesized that recent advances in our ability to accurately measure Aβ postmortem (for example, using PiB), could form the basis of a simple means to deliver an accurate AD diagnosis. Methods We conducted a comprehensive analysis of the amount of Aβ40 and Aβ42 in increasingly insoluble fractions, oligomeric Aβ, and fibrillar Aβ (as defined by PiB binding), as well as plaques (diffuse and neuritic), and neurofibrillary tangles (NFTs) in autopsy specimens from age-matched, cognitively normal controls (N=23) and AD (N=22) cases, across multiple brain regions. Results Both PiB binding and the amount of SDS soluble Aβ were able to predict disease status; however, SDS soluble Aβ was a better measure. Oligomeric Aβ was not a predictor of disease status. PiB binding was strongly related to plaque count, although diffuse plaques were a stronger correlate than neuritic plaques. Interpretation Although postmortem PiB binding was somewhat useful in distinguishing AD from control cases, SDS soluble Aβ measured by standard immunoassay was substantially better. These findings have important implications for the development of imaging based biomarkers of AD. PMID:23109151

  9. Postmortem Pittsburgh Compound B (PiB) Binding Increases with Alzheimer's Disease Progression

    PubMed Central

    Beckett, Tina L.; Webb, Robin L.; Niedowicz, Dana M.; Holler, Christopher J.; Matveev, Sergey; Baig, Irfan; LeVine, Harry; Keller, Jeffrey N.; Murphy, M. Paul

    2013-01-01

    The development of imaging reagents is of considerable interest in the Alzheimer's disease (AD) field. Some of these, such as Pittsburgh Compound B (PiB), were designed to bind to the amyloid-β peptide (Aβ), the major component of amyloid deposits in the AD brain. Although these agents were designed for imaging amyloid deposits in vivo, a major avenue of evaluation relies on postmortem cross validation with established indices of AD pathology. In this study, we evaluated changes in the postmortem binding of PiB and its relationship to other aspects of Aβ-related pathology in a series of AD cases and age-matched controls. We also examined cases of preclinical AD (PCAD) and amnestic mild cognitive impairment (MCI), both considered early points in the AD continuum. PiB binding was found to increase with the progression of the disease, and paralleled increases in the less soluble forms of Aβ, including SDS-stable Aβ oligomers. Increased PiB binding and its relationship to Aβ was only significant in a brain region vulnerable to the development of AD pathology (the superior and middle temporal gyri) but not in an unaffected region (cerebellum). This implies that the amyloid deposited in disease affected regions may possess fundamental, brain region specific characteristics that may not as yet be fully appreciated. These data support the idea that PiB is a useful diagnostic tool for AD, particularly in the early stage of the disease, and also show that PiB could be a useful agent for the discovery of novel disease-related properties of amyloid. PMID:22766739

  10. A Distinct Subfraction of Aβ is Responsible for the High-Affinity Pittsburgh Compound B (PIB) Binding Site in Alzheimer’s Disease Brain

    PubMed Central

    Matveev, Sergey V.; Spielmann, H. Peter; Metts, Brittney M.; Chen, Jing; Onono, Fredrick; Zhu, Haining; Scheff, Stephen W.; Walker, Lary C.; LeVine, Harry

    2014-01-01

    The positron emitting (PET) 11C-labeled Pittsburgh Compound B (PIB) ligand is used to image β-amyloid (Aβ) deposits in the brains of living subjects with the intent of detecting early stages of Alzheimer’s disease (AD). However, deposits of human-sequence Aβ in APP transgenic mice and nonhuman primates bind very little PIB. The high stoichiometry of PIB:Aβ binding in human AD suggests that the PIB binding site may represent a particularly pathogenic entity and/or report local pathologic conditions. In this study, 3H-PIB was employed to track purification of the PIB binding site in > 90% yield from frontal cortical tissue of autopsy-diagnosed AD subjects. The purified PIB binding site comprises a distinct, highly insoluble subfraction of the Aβ in AD brain with low buoyant density due to an SDS-resistant association with a limited subset of brain proteins and lipids with physical properties similar to lipid rafts and to a ganglioside:Aβ complex in AD and Down Syndrome brain. Both the protein and lipid components are required for PIB binding. Elucidation of human-specific biological components and pathways will be important in guiding improvement of the animal models for AD and in identifying new potential therapeutic avenues. PMID:24995708

  11. Massive accumulation of 11C-Pittsburg compound B in the occipital lobes of a patient with early-onset dementia accompanied by muscle weakness and hypertonicity.

    PubMed

    Ito, Kimiteru; Sano, Terunori; Kamiya, Kouhei; Nakata, Yasuhiro; Shigemoto, Yoko; Sato, Noriko; Oya, Yasushi; Matsuda, Hiroshi

    2013-12-01

    A 44-year-old woman underwent 11C-Pittsburg compound B (11C-PiB), 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT), 99mTc-ethyl-cysteinate-dimer single photon emission computed tomography, and magnetic resonance imaging after presenting with progressive dementia, muscle weakness, and hypertonicity. Some of her family members had died of muscle weakness with early-onset dementia of unknown etiology. Neurological and psychological examinations revealed moderate dementia in general fields and muscle weakness in her upper limbs. 11C-PiB PET/CT revealed abnormal accumulations of amyloid in the bilateral occipital lobes, while physiological uptakes of 11C-PiB in areas that normally show high uptake, such as white matter, appeared relatively decreased. Meanwhile, cerebrospinal fluid (CSF) amyloid-β was decreased, and CSF total and phosphorylated tau proteins were increased. This case may be representative of a new category of amyloid deposition disease characterized by early-onset dementia, muscle weakness, and hypertonicity, or at least, a new uptake pattern of PiB in variant AD.

  12. Comparative double-tracer whole-body autoradiography: uptake of 11C-, 18F- and 3H-labeled compounds in rat tumors.

    PubMed

    d'Argy, R; Paul, R; Frankenberg, L; Stålnacke, C G; Lundqvist, H; Kangas, L; Halldin, C; Någren, K; Roeda, D; Haaparanta, M

    1988-01-01

    The uptake of various labeled compounds by tumors was studied by double-tracer whole-body autoradiography (DTWBA) in rats. Each animal carried two types of tumors: mammary carcinomas and the Walker 256 carcinosarcomas. The markers used were [18F]- and [3H]fluorodeoxyglucose (glucose utilization), [3H]thymidine (cell proliferation), [11C]methionine (amino acid metabolism) and [11C]- and [3H]toremifene (estrogen-receptor-avid agents). In each experiment, the distribution of a substance labeled with short-lived radionuclide (11C or 18F) was compared with that of another substance labeled with a long-lived nuclide (3H). Quantification was done by combining computerized image analysis of the autoradiograms with liquid scintillation counting of punched tissue pieces obtained from the cryosections. The relationships between the uptakes of the various radiopharmaceuticals were recorded in tumors and normal tissues. The dynamics of [18F]fluorodeoxyglucose and [11C]methionine were determined in tumors and some selected tissues by positron emission tomography (PET). The uptake rate between fluorodeoxyglucose and thymidine in the mammary tumor was five times higher than the ratio in the Walker tumor. The corresponding figure for FDG/methionine was four times. Thymidine, compared with methionine, was twice as efficient. Thus, the mammary tumors were best imaged with FDG or thymidine. The non-steroid antiestrogen toremifene was taken up in very low amounts by these tumors. By DTWBA, experimental tumors may serve as their own control. PMID:2978293

  13. Atmospheric volatile organic compound measurements during the Pittsburgh Air Quality Study: Results, interpretation, and quantification of primary and secondary contributions

    NASA Astrophysics Data System (ADS)

    Millet, Dylan B.; Donahue, Neil M.; Pandis, Spyros N.; Polidori, Andrea; Stanier, Charles O.; Turpin, Barbara J.; Goldstein, Allen H.

    2005-04-01

    Primary and secondary contributions to ambient levels of volatile organic compounds (VOCs) and aerosol organic carbon (OC) are determined using measurements at the Pittsburgh Air Quality Study (PAQS) during January-February and July-August 2002. Primary emission ratios for gas and aerosol species are defined by correlation with species of known origin, and contributions from primary and secondary/biogenic sources and from the regional background are then determined. Primary anthropogenic contributions to ambient levels of acetone, methylethylketone, and acetaldehyde were found to be 12-23% in winter and 2-10% in summer. Secondary production plus biogenic emissions accounted for 12-27% of the total mixing ratios for these compounds in winter and 26-34% in summer, with background concentrations accounting for the remainder. Using the same method, we determined that on average 16% of aerosol OC was secondary in origin during winter versus 37% during summer. Factor analysis of the VOC and aerosol data is used to define the dominant source types in the region for both seasons. Local automotive emissions were the strongest contributor to changes in atmospheric VOC concentrations; however, they did not significantly impact the aerosol species included in the factor analysis. We conclude that longer-range transport and industrial emissions were more important sources of aerosol during the study period. The VOC data are also used to characterize the photochemical state of the atmosphere in the region. The total measured OH loss rate was dominated by nonmethane hydrocarbons and CO (76% of the total) in winter and by isoprene, its oxidation products, and oxygenated VOCs (79% of the total) in summer, when production of secondary organic aerosol was highest.

  14. Associating a negatively charged GdDOTA-derivative to the Pittsburgh compound B for targeting Aβ amyloid aggregates.

    PubMed

    Martins, André F; Oliveira, Alexandre C; Morfin, Jean-François; Laurents, Douglas V; Tóth, Éva; Geraldes, Carlos F G C

    2016-03-01

    We have conjugated the tetraazacyclododecane-tetraacetate (DOTA) chelator to Pittsburgh compound B (PiB) forming negatively charged lanthanide complexes, Ln(L4), with targeting capabilities towards aggregated amyloid peptides. The amphiphilic Gd(L4) chelate undergoes micellar aggregation in aqueous solution, with a critical micellar concentration of 0.68 mM, lower than those for the neutral complexes of similar structure. A variable temperature (17)O NMR and NMRD study allowed the assessment of the water exchange rate, k ex (298) = 9.7 × 10(6) s(-1), about the double of GdDOTA, and for the description of the rotational dynamics for both the monomeric and the micellar forms of Gd(L4). With respect to the analogous neutral complexes, the negative charge induces a significant rigidity of the micelles formed, which is reflected by slower and more restricted local motion of the Gd(3+) centers as evidenced by higher relaxivities at 20-60 MHz. Surface Plasmon Resonance results indicate that the charge does not affect significantly the binding strength to Aβ1-40 [K d = 194 ± 11 μM for La(L4)], but it does enhance the affinity constant to human serum albumin [K a = 6530 ± 68 M(-1) for Gd(L4)], as compared to neutral counterparts. Protein-based NMR points to interaction of Gd(L4) with Aβ1-40 in the monomer state as well, in contrast to neutral complexes interacting only with the aggregated form. Circular dichroism spectroscopy monitored time- and temperature-dependent changes of the Aβ1-40 secondary structure, indicating that Gd(L4) stabilizes the random coil relative to the α-helix and β-sheet. TEM images confirm that the Gd(L4) complex reduces the formation of aggregated fibrils. PMID:26613605

  15. Associating a negatively charged GdDOTA-derivative to the Pittsburgh compound B for targeting Aβ amyloid aggregates.

    PubMed

    Martins, André F; Oliveira, Alexandre C; Morfin, Jean-François; Laurents, Douglas V; Tóth, Éva; Geraldes, Carlos F G C

    2016-03-01

    We have conjugated the tetraazacyclododecane-tetraacetate (DOTA) chelator to Pittsburgh compound B (PiB) forming negatively charged lanthanide complexes, Ln(L4), with targeting capabilities towards aggregated amyloid peptides. The amphiphilic Gd(L4) chelate undergoes micellar aggregation in aqueous solution, with a critical micellar concentration of 0.68 mM, lower than those for the neutral complexes of similar structure. A variable temperature (17)O NMR and NMRD study allowed the assessment of the water exchange rate, k ex (298) = 9.7 × 10(6) s(-1), about the double of GdDOTA, and for the description of the rotational dynamics for both the monomeric and the micellar forms of Gd(L4). With respect to the analogous neutral complexes, the negative charge induces a significant rigidity of the micelles formed, which is reflected by slower and more restricted local motion of the Gd(3+) centers as evidenced by higher relaxivities at 20-60 MHz. Surface Plasmon Resonance results indicate that the charge does not affect significantly the binding strength to Aβ1-40 [K d = 194 ± 11 μM for La(L4)], but it does enhance the affinity constant to human serum albumin [K a = 6530 ± 68 M(-1) for Gd(L4)], as compared to neutral counterparts. Protein-based NMR points to interaction of Gd(L4) with Aβ1-40 in the monomer state as well, in contrast to neutral complexes interacting only with the aggregated form. Circular dichroism spectroscopy monitored time- and temperature-dependent changes of the Aβ1-40 secondary structure, indicating that Gd(L4) stabilizes the random coil relative to the α-helix and β-sheet. TEM images confirm that the Gd(L4) complex reduces the formation of aggregated fibrils.

  16. Combination of dynamic (11)C-PIB PET and structural MRI improves diagnosis of Alzheimer's disease.

    PubMed

    Liu, Linwen; Fu, Liping; Zhang, Xi; Zhang, Jinming; Zhang, Xiaojun; Xu, Baixuan; Tian, Jiahe; Fan, Yong

    2015-08-30

    Structural magnetic resonance imaging (sMRI) is an established technique for measuring brain atrophy, and dynamic positron emission tomography with (11)C-Pittsburgh compound B ((11)C-PIB PET) has the potential to provide both perfusion and amyloid deposition information. It remains unclear, however, how to better combine perfusion, amyloid deposition and morphological information extracted from dynamic (11)C-PIB PET and sMRI with the goal of improving the diagnosis of Alzheimer's disease (AD) and mild cognitive impairment (MCI). We adopted a linear sparse support vector machine to build classifiers for distinguishing AD and MCI subjects from cognitively normal (CN) subjects based on different combinations of regional measures extracted from imaging data, including perfusion and amyloid deposition information extracted from early and late frames of (11)C-PIB separately, and gray matter volumetric information extracted from sMRI data. The experimental results demonstrated that the classifier built upon the combination of imaging measures extracted from early and late frames of (11)C-PIB as well as sMRI achieved the highest classification accuracy in both classification studies of AD (100%) and MCI (85%), indicating that multimodality information could aid in the diagnosis of AD and MCI. PMID:26095348

  17. Pittsburgh compound B-negative dementia: a possibility of misdiagnosis of patients with non-alzheimer disease-type dementia as having AD.

    PubMed

    Shimada, Hiroyuki; Ataka, Suzuka; Takeuchi, Jun; Mori, Hiroshi; Wada, Yasuhiro; Watanabe, Yasuyoshi; Miki, Takami

    2011-09-01

    Amyloid imaging has been used to detect amyloid deposition in the brain. We performed Pittsburgh compound B (PiB)-positron emission tomography on 63 patients with dementia having cognitive decline or memory disturbance. In addition, we measured the patients' apolipoprotein E4 (apo E4) status and cerebrospinal fluid (CSF) levels of amyloid-β (Aβ)1-42, tau, and P-tau. Finally, the patients were diagnosed as having probable Alzheimer disease (AD) on the basis of their neuropsychological findings and because they met the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria. Among the patients diagnosed with probable AD, 10 patients were PiB negative. The CSF levels of P-tau and tau in PiB-negative patients were significantly lower than those in the PiB-positive patients. In addition, the CSF levels of Aβ1-42 in the PiB-negative patients were significantly higher than those in the PiB-positive patients. None of the PiB-negative patients were apo E4 carriers. These results suggest that the PiB-negative patient group included not only AD patients but also non-AD-type dementia patients. However, our finding is based on a relatively small number of patients and therefore should be replicated in a larger cohort. In addition, it will be necessary to categorize these participants by longitudinal follow-up and postmortem pathological examinations.

  18. Pittsburgh School Gets Energized.

    ERIC Educational Resources Information Center

    Hill, Willliam W.

    2002-01-01

    Describes a project designed to create an energy efficient high school in the diocese of Pittsburgh. The project will save over $850,000 in energy, operations, and maintenance costs over fifteen years. The design improves the physical premises as well by adding windows and eliminating fluorescent lighting. Offers tips for developing similar…

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

    PubMed Central

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

    2015-01-01

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

  20. Our Pittsburgh Constellation

    NASA Astrophysics Data System (ADS)

    Turnshek, Diane

    2015-08-01

    Riding on the Pittsburgh mayor’s keen interest in astronomy and the ongoing change of 40,000 city lights from mercury and sodium vapor to shielded LEDs, we organized a series of city-wide celestial art projects to bring attention to the skies over Pittsburgh. Light pollution public talks were held at the University of Pittsburgh’s Allegheny Observatory and other colleges. Earth Hour celebrations kicked off an intensive year of astronomy outreach in the city. Lights went out on March 28, 2015 from 8:30 to 9:30 pm in over fifty buildings downtown and in Oakland (the “Eds and Meds” center, where many Pittsburgh universities and hospitals are located). Our art contest was announced at the De-Light Pittsburgh celebration at the Carnegie Science Center during Astronomy Weekend. “Our Pittsburgh Constellation” is an interactive Google map of all things astronomical in the city. Different colored stars mark locations of planetariums, star parties, classes, observatories, lecture series, museums, telescope manufacturers and participating art galleries. Contest entrants submitted artwork depicting their vision of the constellation figure that incorporates and connects all the “stars” in our custom city map. Throughout the year, over a dozen artists ran workshops on painting star clusters, galaxies, nebulae, comets, planets and aurorae with discussions of light pollution solutions and scientific explanations of what the patrons were painting, including demonstrations with emission tubes and diffraction grating glasses. We will display the celestial art created in this International Year of Light at an art gallery as part of the City’s Department of Innovation & Performance March 2016 Earth Hour gala. We are thankful for the Astronomical Footprint grant from the Heinz Endowments, which allowed us to bring the worlds of science and art together to enact social change.

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

    PubMed

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

    2013-11-01

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

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

    SciTech Connect

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

    1993-12-31

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

  3. The Pittsburgh Sleep Diary

    NASA Technical Reports Server (NTRS)

    Monk, T. H.; Reynolds CF, 3. d.; Kupfer, D. J.; Buysse, D. J.; Coble, P. A.; Hayes, A. J.; Machen, M. A.; Petrie, S. R.; Ritenour, A. M.

    1994-01-01

    Increasingly, there is a need in both research and clinical practice to document and quantify sleep and waking behaviors in a comprehensive manner. The Pittsburgh Sleep Diary (PghSD) is an instrument with separate components to be completed at bedtime and waketime. Bedtime components relate to the events of the day preceding the sleep, waketime components to the sleep period just completed. Two-week PghSD data is presented from 234 different subjects, comprising 96 healthy young middle-aged controls, 37 older men, 44 older women, 29 young adult controls and 28 sleep disorders patients in order to demonstrate the usefulness, validity and reliability of various measures from the instrument. Comparisons are made with polysomnographic and actigraphic sleep measures, as well as personality and circadian type questionnaires. The instrument was shown to have sensitivity in detecting differences due to weekends, age, gender, personality and circadian type, and validity in agreeing with actigraphic estimates of sleep timing and quality. Over a 12-31 month delay, PghSD measures of both sleep timing and sleep quality showed correlations between 0.56 and 0.81 (n = 39, P < 0.001).

  4. View of the Warrington Avenue Bridge portal, inbound from Pittsburgh ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    View of the Warrington Avenue Bridge portal, inbound from Pittsburgh - Pittsburgh & Castle Shannon Railroad, Warrington Avenue Bridge, Overbrook Trolley Line, Crossing Warrington Avenue, Pittsburgh, Allegheny County, PA

  5. View of the Warrington Avenue Bridge portal, outbound from Pittsburgh ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    View of the Warrington Avenue Bridge portal, outbound from Pittsburgh - Pittsburgh & Castle Shannon Railroad, Warrington Avenue Bridge, Overbrook Trolley Line, Crossing Warrington Avenue, Pittsburgh, Allegheny County, PA

  6. 1-/sup 11/C-2-deoxy-D-glucose and process for the preparation thereof

    DOEpatents

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

    1980-02-08

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

  7. Pittsburgh Adapts to Changing Times.

    ERIC Educational Resources Information Center

    States, Deidre

    1985-01-01

    The Samuel F. B. Morse School, built in 1874 and closed in 1980, is a historic landmark in Pittsburgh, Pennsylvania. Now the building serves as low-income housing for 70 elderly tenants and is praised as being an imaginative and creative use of an old school structure. (MLF)

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

    PubMed

    Gerasimov, Madina R; Ferrieri, Richard A; Pareto, Deborah; Logan, Jean; Alexoff, David; Ding, Yu-Shin

    2005-02-01

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

  9. 49 CFR 372.211 - Pittsburgh, PA.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 5 2010-10-01 2010-10-01 false Pittsburgh, PA. 372.211 Section 372.211... ZONES, AND TERMINAL AREAS Commercial Zones § 372.211 Pittsburgh, PA. The zone adjacent to, and... and is comprised of all points as follows: (a) The municipality of Pittsburgh, Pa., itself; (b)...

  10. Synthesis optimization of 2-(4-N-[11C]methylaminophenyl)-6-hydroxybenzothiazole ([11C]PIB), β-amyloid PET imaging tracer for Alzheimer's disease diagnosis.

    PubMed

    Coliva, A; Monterisi, C; Apollaro, A; Gatti, D; Penso, M; Gianolli, L; Perani, D; Gilardi, M C; Carpinelli, A

    2015-11-01

    [11C]PIB is the most used amyloid plaques-specific positron-emitting radiotracers. The radiosynthesis of this compound, carried out by methylation of its precursor with [11C]methyl triflate in 2-butanone, has been improved optimizing the initial concentration and the purification method. Two HPLC methods were compared: good radiochemical yields, specific activities, and chemical purity above 98% were achieved by using as eluant acetonitrile/citrate and formulation in 10% ethanol.

  11. Comparison of qualitative and quantitative imaging characteristics of [11C]PiB and [18F]flutemetamol in normal control and Alzheimer's subjects

    PubMed Central

    Mountz, James M.; Laymon, Charles M.; Cohen, Ann D.; Zhang, Zheng; Price, Julie C.; Boudhar, Sanaa; McDade, Eric; Aizenstein, Howard J.; Klunk, William E.; Mathis, Chester A.

    2015-01-01

    Introduction Neuritic amyloid plaques and neurofibrillary tangles, the hallmark pathologic lesions of Alzheimer's disease, are thought to develop before the symptoms of brain failure are clinically detectable. Imaging methods capable of detecting the presence of neuritic amyloid plaques should improve a clinician's ability to identify Alzheimer's disease during the earliest symptomatic phase and to identify at-risk individuals presymptomatically. Currently the best studied amyloid imaging ligand is [11C]Pittsburgh Compound B ([11C]PiB). However, the 20-minute half-life of this radiotracer limits its use. This study is designed to evaluate the performance characteristics of [18F]flutemetamol and to independently compare results to [11C]PiB in the same subjects. Methods Twenty-three subjects, 15 cognitively normal (NL) and 8 with a clinical diagnosis of Alzheimer's Dementia (AD), underwent [11C]PiB and [18F]flutemetamol PET scans within 28 days of study enrollment. We studied both normal and AD subjects to assess the uptake characteristics across a range of amyloid positivity. Blinded visual reads were conducted by five raters. Correlation analyses were performed between cortical SUVR for the two tracers and also between rater scores and SUVR for each tracer. Overall reader accuracy for classifying scans as amyloid positive or negative was determined for each tracer using SUVR classification as the standard. Results The linear correlation coefficient between global cortical SUVR for the two tracers was R2 = 0.85, indicating that both tracers have similar retention characteristics. The two tracers were well correlated for rater-determined AD-like positivity (Cohen κ = 0.82). Averaged visual ratings and global cortical SUVR disagreed on their classification in 2/23 [11C]PiB scans and 4/23 [18F]flutemetamol scans. Conclusions [11C]PiB and [18F]flutemetamol have similar retention characteristics across a range of amyloid negative to positive subjects. Both tracers

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

    PubMed Central

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

    2015-01-01

    Long-acting opioid agonists methadone and l-α-acetylmethadol (LAAM) prevent withdrawal in opioid-dependent persons. Attempts to synthesize [11C]-methadone for PET evaluation of brain disposition were unsuccessful. Owing, however, to structural and pharmacologic similarities, we aimed to develop [11C]LAAM as a PET ligand to probe the brain exposure of long-lasting opioids in humans. This manuscript describes [11C]LAAM synthesis and its biodistribution in mice. The radiochemical synthetic strategy afforded high radiochemical yield, purity and specific activity, thereby making the synthesis adaptable to automated modules. PMID:24935116

  13. 75 FR 81469 - Safety Zone; Allegheny River, Pittsburgh, PA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-28

    ... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zone; Allegheny River, Pittsburgh, PA AGENCY... First Night Pittsburgh fireworks display that will occur in the city of Pittsburgh, PA. Under 5 U.S.C... First Night Pittsburgh fireworks display that will occur in the city of Pittsburgh, PA. Background...

  14. NARSTO EPA SS PITTSBURGH RAPID SPMS DATA

    Atmospheric Science Data Center

    2014-04-25

    NARSTO EPA SS PITTSBURGH RAPID SPMS DATA Project Title:  NARSTO Discipline:  ... Parameters:  Particulates Order Data:  ASDC Order Tool:   Order Data Guide Documents:  ... Earth Related Data:  Environmental Protection Agency Supersites Pittsburgh, Pennsylvania SCAR-B ...

  15. PERSPECTIVE VIEW FROM NORTHWEST OF PITTSBURGH HIGH SCHOOL FOR THE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    PERSPECTIVE VIEW FROM NORTHWEST OF PITTSBURGH HIGH SCHOOL FOR THE CREATIVE AND PERFORMING ARTS, BUILT 2003 BY THE FIRM OF MACLACHLAN CORNELIUS AND FILONI. - Pittsburgh High School for the Creative & Performing Arts, 111 Ninth Street, Pittsburgh, Allegheny County, PA

  16. Environmental Survey preliminary report, Pittsburgh Energy Technology Center, Pittsburgh, Pennsylvania

    SciTech Connect

    Not Available

    1988-09-01

    This report presents the preliminary findings from the first phase of the Environmental Survey of the US Department of Energy (DOE) Pittsburgh Energy Technology Center (PETC) conducted December 7--11, 1987. The Survey is being conducted by an interdisciplinary team of environmental specialists, led and managed by the Office of Environment, Safety and Health's Office of Environmental Audit. Individual team specialists are outside experts being supplied by a private contractor. The objective of the Survey is to identify environmental problems and areas of environmental risk associated with PETC. The Survey covers all environmental media and all areas of environmental regulation. It is being performed in accordance with the DOE Environmental Survey Manual. This phase of the Survey involves the review of existing site environmental data, observations of the operations carried on at PETC, and interviews with site personnel. The Survey team developed a Sampling and Analysis (S A) Plan to assist in further assessing certain environmental problems identified during its on-site Survey activities at PETC. The S A Plan will be executed by the Oak Ridge National Laboratory (ORNL). When completed, the Plan's results will be incorporated into the PETC Survey findings for inclusion into the Environmental Survey Summary Report. 64 refs., 23 figs., 29 tabs.

  17. NARSTO EPA SS PITTSBURGH PM COMPOSITION DATA

    Atmospheric Science Data Center

    2014-04-25

    ... Transmission ICP - MS - Inductively Coupled Plasma Mass Spectrometer Ion Chromatograph Location:  Pittsburgh, ... Readme Files:  EPA Sites Get Google Earth Related Data:  Environmental Protection Agency ...

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

    PubMed

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

    2016-05-18

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

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

    PubMed

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

    2016-05-18

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

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

    PubMed Central

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

    2014-01-01

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

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

    DOEpatents

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

    1989-01-01

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

  2. [(11) C]Carbon monoxide in labeling chemistry and positron emission tomography tracer development: scope and limitations.

    PubMed

    Rahman, Obaidur

    2015-03-01

    [(11) C]Carbon monoxide is an attractive precursor for labeling carbonyl position in a wide range of organic compounds. The use of [(11) C]carbon monoxide in transition metal-mediated coupling reactions has been explored by several groups during the last 15 years, and an impressive number of the synthesis of [carbonyl-(11) C]compounds have been published to date. The application of radical-mediated [(11) C]carbonylation has also been explored in some extent. However, the main limitations to apply this potential precursor in (11) C-labeling chemistry are low concentration, poor solubility in commonly used organic solvents, and low reactivity. A couple of technical solutions such as high-pressure reactor system, microfluidic system, and different approaches to confine [(11) C]CO to the reaction media at ambient pressure have been developed over the years. Although considerable advances in [(11) C]carbon monoxide chemistry have been reported in recent years, its application in positron emission tomography tracer development is still an area of work in progress. This review summarizes all contributions to the area of radiolabeling using [(11) C]carbon monoxide published between 1995 and 2014 and discusses the scope and limitations of this method in clinical positron emission tomography tracer development.

  3. Fulfilling The Pittsburgh Promise[R]: Early Progress of Pittsburgh's Postsecondary Scholarship Program. Monograph

    ERIC Educational Resources Information Center

    Gonzalez, Gabriella C.; Bozick, Robert; Tharp-Taylor, Shannah; Phillips, Andrea

    2011-01-01

    This report presents a detailed assessment of the extent to which "The Pittsburgh Promise"--a postsecondary education scholarship intended to remedy the area's population decline, foster high school completion and college readiness among Pittsburgh district students, and prepare a capable and energetic workforce for the city--has met its goals to…

  4. Rat brain acetylcholinesterase visualized with [11C]physostigmine.

    PubMed

    Planas, A M; Crouzel, C; Hinnen, F; Jobert, A; Né, F; DiGiamberardino, L; Tavitian, B

    1994-06-01

    Physostigmine, a powerful cholinesterase inhibitor, has recently been labelled with 11C in view of its potential application for in vivo imaging of cerebral acetylcholinesterase (AChE) using positron emission tomography. Here we carried out autoradiography of the rat brain using [11C]physostigmine in order to characterize the cerebral targets of this ligand. Autoradiograms were obtained using phosphor storage plates which, compared to autoradiographic films, greatly improved the quality of 11C images. Following autoradiography, brain sections were stained for AChE activity, allowing a direct comparison of autoradiographic and histoenzymatic localizations. The distributions of 11C label and of AChE activity were found to be essentially super-imposable, both after in vivo injection of and after in vitro incubation with [11C]physostigmine. Densitometric analysis showed that radioactivity and enzymatic activity distributions were regionally correlated. The fixation of [11C]physostigmine to cerebral tissue was abolished after incubation of the rat brain sections with BW 284C51, a specific AChE inhibitor, but not after incubation with iso-OMPA, a specific inhibitor of butyrylcholinesterase. Unilateral excitotoxic lesions of the striatum that eliminated local AChE expression concomitantly reduced the binding of the ligand in the lesioned area. These results indicate that autoradiographic images of the rat brain obtained with [11C]physostigmine reflect AChE distribution, thus supporting the use of this radioligand to trace cerebral AChE activity in humans with positron emission tomography.

  5. VIEW LOOKING NORTHEAST WITH OPEN HEARTH TO THE LEFT, PITTSBURGH ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    VIEW LOOKING NORTHEAST WITH OPEN HEARTH TO THE LEFT, PITTSBURGH & LAKE ERIE RAILROAD TRACKS CENTER. - Pittsburgh Steel Company, Monessen Works, Open Hearth Plant, Donner Avenue, Monessen, Westmoreland County, PA

  6. Synthesis, isolation and purification of [11C]-choline

    PubMed Central

    Jadwiński, Michał; Chmura, Agnieszka; Gorczewski, Kamil; Sokół, Maria

    2016-01-01

    [11C]-choline is an effective PET tracer used for imaging of neoplastic lesions and metastases of the prostate cancer. However, its production can be a challenge for manufacturers, as it has not yet been described in Polish or European pharmacopoeia. In this study the technical aspects of [11C]-choline production are described and detailed process parameters are provided. The quality control procedures for releasing [11C]-choline as solutio iniectabilis are also presented. The purity and quality of the radiopharmaceutical obtained according to the proposed method were find to be high enough to safely administrate the radiopharmaceutical to patients. Application of an automated synthesizer makes it possible to carry out the entire process of [11C]-choline production, isolation and purification within 20 minutes. It is crucial to maintain all aspects of the process as short as possible, since the decay half-time of carbon-11 is 20.4 minutes. The resulting radiopharmaceutical is sterile and pyrogen-free and of a high chemical, radiochemical, and radionuclide purity proved by chromatographic techniques. The yield of the process is up to 20%. [11C]-choline PET scanning can be used as accurate and effective diagnostic tool in all centers equipped with [11C]-target containing cyclotron.

  7. Synthesis, isolation and purification of [(11)C]-choline.

    PubMed

    Szydło, Marcin; Jadwiński, Michał; Chmura, Agnieszka; Gorczewski, Kamil; Sokół, Maria

    2016-01-01

    [(11)C]-choline is an effective PET tracer used for imaging of neoplastic lesions and metastases of the prostate cancer. However, its production can be a challenge for manufacturers, as it has not yet been described in Polish or European pharmacopoeia. In this study the technical aspects of [(11)C]-choline production are described and detailed process parameters are provided. The quality control procedures for releasing [(11)C]-choline as solutio iniectabilis are also presented. The purity and quality of the radiopharmaceutical obtained according to the proposed method were find to be high enough to safely administrate the radiopharmaceutical to patients. Application of an automated synthesizer makes it possible to carry out the entire process of [(11)C]-choline production, isolation and purification within 20 minutes. It is crucial to maintain all aspects of the process as short as possible, since the decay half-time of carbon-11 is 20.4 minutes. The resulting radiopharmaceutical is sterile and pyrogen-free and of a high chemical, radiochemical, and radionuclide purity proved by chromatographic techniques. The yield of the process is up to 20%. [(11)C]-choline PET scanning can be used as accurate and effective diagnostic tool in all centers equipped with [(11)C]-target containing cyclotron. PMID:27660552

  8. Synthesis, isolation and purification of [(11)C]-choline.

    PubMed

    Szydło, Marcin; Jadwiński, Michał; Chmura, Agnieszka; Gorczewski, Kamil; Sokół, Maria

    2016-01-01

    [(11)C]-choline is an effective PET tracer used for imaging of neoplastic lesions and metastases of the prostate cancer. However, its production can be a challenge for manufacturers, as it has not yet been described in Polish or European pharmacopoeia. In this study the technical aspects of [(11)C]-choline production are described and detailed process parameters are provided. The quality control procedures for releasing [(11)C]-choline as solutio iniectabilis are also presented. The purity and quality of the radiopharmaceutical obtained according to the proposed method were find to be high enough to safely administrate the radiopharmaceutical to patients. Application of an automated synthesizer makes it possible to carry out the entire process of [(11)C]-choline production, isolation and purification within 20 minutes. It is crucial to maintain all aspects of the process as short as possible, since the decay half-time of carbon-11 is 20.4 minutes. The resulting radiopharmaceutical is sterile and pyrogen-free and of a high chemical, radiochemical, and radionuclide purity proved by chromatographic techniques. The yield of the process is up to 20%. [(11)C]-choline PET scanning can be used as accurate and effective diagnostic tool in all centers equipped with [(11)C]-target containing cyclotron.

  9. Synthesis, isolation and purification of [11C]-choline

    PubMed Central

    Jadwiński, Michał; Chmura, Agnieszka; Gorczewski, Kamil; Sokół, Maria

    2016-01-01

    [11C]-choline is an effective PET tracer used for imaging of neoplastic lesions and metastases of the prostate cancer. However, its production can be a challenge for manufacturers, as it has not yet been described in Polish or European pharmacopoeia. In this study the technical aspects of [11C]-choline production are described and detailed process parameters are provided. The quality control procedures for releasing [11C]-choline as solutio iniectabilis are also presented. The purity and quality of the radiopharmaceutical obtained according to the proposed method were find to be high enough to safely administrate the radiopharmaceutical to patients. Application of an automated synthesizer makes it possible to carry out the entire process of [11C]-choline production, isolation and purification within 20 minutes. It is crucial to maintain all aspects of the process as short as possible, since the decay half-time of carbon-11 is 20.4 minutes. The resulting radiopharmaceutical is sterile and pyrogen-free and of a high chemical, radiochemical, and radionuclide purity proved by chromatographic techniques. The yield of the process is up to 20%. [11C]-choline PET scanning can be used as accurate and effective diagnostic tool in all centers equipped with [11C]-target containing cyclotron. PMID:27660552

  10. VOCATIONAL EDUCATION IN THE PITTSBURGH PUBLIC SCHOOLS.

    ERIC Educational Resources Information Center

    DAUWALDER, DONALD D.

    THE ECONOMY, THE EMPLOYMENT-UNEMPLOYMENT RATIO, AND THE AMOUNT, TYPE, AND LEVEL OF AVAILABLE EDUCATION HAVE CONTRIBUTED TO THE GENERAL ECONOMIC DECLINE OF THE PITTSBURGH STANDARD METROPOLITAN STATISTICAL AREA (SMSA). A SURVEY WAS MADE TO ASSIST IN OVERCOMING THE SITUATION. THE PRESENT AND FUTURE STUDENT POPULATION NEED WAS EXAMINED AGAINST THE…

  11. Pittsburgh, Pennsylvania: Solar in Action (Brochure)

    SciTech Connect

    Not Available

    2011-10-01

    This brochure provides an overview of the challenges and successes of Pittsburgh, PA, a 2007 Solar America City awardee, on the path toward becoming a solar-powered community. Accomplishments, case studies, key lessons learned, and local resource information are given.

  12. 75 FR 56866 - Special Local Regulation; Monongahela River, Pittsburgh, PA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-17

    ... special local regulation is needed to safeguard participants of the Pittsburgh Dragon Boat Festival from... because immediate action is needed to safeguard participants during the Pittsburgh Dragon Boat Festival... immediate action is needed to safeguard participants during the Pittsburgh Dragon Boat Festival from...

  13. 76 FR 47993 - Safety Zone; Allegheny River; Pittsburgh, PA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-08

    ... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zone; Allegheny River; Pittsburgh, PA AGENCY... that will occur in the city of Pittsburgh, PA on August 6, 2011 (rain date August 7, 2011). Under 5 U.S... occur in the city of Pittsburgh, PA on August 6, 2011 (rain date August 7, 2011). Basis and Purpose...

  14. 3. Photocopy of original drawing belonging to the Pittsburgh Department ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    3. Photocopy of original drawing belonging to the Pittsburgh Department of Public Works, (n.d.). DRAWING NO. 1963: STRESS AND SECTION SHEET FOR 531' STEEL SPANS. - North Side Point Bridge, Spanning Allegheny River at Point of Pittsburgh, Pittsburgh, Allegheny County, PA

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

    PubMed

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

    2016-01-01

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

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

    SciTech Connect

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

    1994-03-01

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

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

    PubMed

    Lopci, E; Bello, L; Chiti, A

    2014-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    SciTech Connect

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

    2008-01-07

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

  20. Cu(I)-catalyzed (11)C carboxylation of boronic acid esters: a rapid and convenient entry to (11)C-labeled carboxylic acids, esters, and amides.

    PubMed

    Riss, Patrick J; Lu, Shuiyu; Telu, Sanjay; Aigbirhio, Franklin I; Pike, Victor W

    2012-03-12

    Rapid and direct: the carboxylation of boronic acid esters with (11)CO(2) provides [(11)C]carboxylic acids as a convenient entry into [(11)C]esters and [(11)C]amides. This conversion of boronates is tolerant to diverse functional groups (e.g., halo, nitro, or carbonyl). PMID:22308017

  1. 75 FR 71721 - Pittsburgh Area Maritime Security Committee; Vacancies

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-24

    ... SECURITY Coast Guard Pittsburgh Area Maritime Security Committee; Vacancies AGENCY: Coast Guard, DHS... the Pittsburgh Area Maritime Security Committee to submit their application for membership, to the... Secretary of the Department in which the Coast Guard is operating to establish Area Maritime...

  2. 76 FR 27892 - Special Local Regulation; Allegheny River, Pittsburgh, PA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-13

    ..., PA AGENCY: Coast Guard, DHS. ACTION: Temporary final rule. SUMMARY: The Coast Guard is establishing a... Pittsburgh, PA. The date of the Venture Outdoors Festival is tied to numerous other events and cannot be... in the city of Pittsburgh, PA. Persons or vessels shall not enter into, depart from, or move...

  3. University-Urban Interface Program. Pittsburgh Goals: Some Issues.

    ERIC Educational Resources Information Center

    Nehnevajsa, Jiri

    The Pittsburgh Goals Study about which this speech centers is SO 004 019. Issues identified by the leaders questioned which seem particularly crucial for the next five years in the development of Pittsburgh are: pollution control; public welfare system; drug problem; health services; low cost housing; rapid transit. Two more issues, Metropolitan…

  4. Pittsburgh and the Arts or How My Eye Was Formed.

    ERIC Educational Resources Information Center

    Roschwalb, Susanne A.

    The way the author's experiences of the city of Pittsburgh (Pennsylvania) shaped her visual literacy are explored. Along with the imagery of the steel mills, she experienced some artistic opportunities that helped shape the foundation of her life in art. Although no American city was as extensively industrialized as Pittsburgh, it was the artistic…

  5. 75 FR 24961 - Pittsburgh Area Maritime Security Committee; Vacancies

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-06

    ... SECURITY Coast Guard Pittsburgh Area Maritime Security Committee; Vacancies AGENCY: Coast Guard, DHS... the Pittsburgh Area Maritime Security Committee (AMSC) to submit their application for membership, to... Security Act (MTSA) of 2002 (Pub. L. 107-295) added section 70112 to Title 46 of the U.S. Code,...

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

    NASA Astrophysics Data System (ADS)

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

    2015-12-01

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

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

    SciTech Connect

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

    1982-08-01

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

  8. [11C]phenytoin revisited: synthesis by [11C]CO carbonylation and first evaluation as a P-gp tracer in rats

    PubMed Central

    2012-01-01

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

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

    PubMed

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

    2016-05-01

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

  10. A comparative small-animal PET evaluation of [11C]tariquidar, [11C]elacridar and (R)-[11C]verapamil for detection of P-glycoprotein expressing murine breast cancer

    PubMed Central

    Wanek, Thomas; Kuntner, Claudia; Bankstahl, Jens P.; Bankstahl, Marion; Stanek, Johann; Sauberer, Michael; Mairinger, Severin; Strommer, Sabine; Wacheck, Volker; Löscher, Wolfgang; Erker, Thomas; Müller, Markus; Langer, Oliver

    2013-01-01

    Purpose One important mechanism for chemoresistance of tumours is overexpression of the adenosine triphosphate-binding cassette transporter P-glycoprotein (Pgp). Pgp reduces intracellular concentrations of chemotherapeutic drugs. Aim of this study was to compare the suitability of the radiolabelled Pgp inhibitors [11C]tariquidar and [11C]elacridar with the Pgp substrate radiotracer (R)-[11C]verapamil to discriminate tumours expressing low and high levels of Pgp using small-animal PET imaging in a murine breast cancer model. Methods Murine mammary carcinoma cells (EMT6) were continuously exposed to doxorubicin to generate a Pgp overexpressing, doxorubicin-resistant cell line (EMT6AR1.0 cells). Both cell lines were subcutaneously injected in female athymic nude mice. One week after implantation, animals underwent PET scans with [11C]tariquidar (n=7), [11C]elacridar (n=6) and (R)-[11C]verapamil (n=7), before and after administration of unlabelled tariquidar (15 mg/kg). Pgp expression in tumour grafts was studied by Western blotting. Results [11C]Tariquidar showed significantly higher retention in Pgp overexpressing EMT6AR1.0 compared with EMT6 tumours (mean area under the time-activity curve in scan 1 from time 0 to 60 min, AUC0-60±SD: 38.8±2.2 min vs. 25.0±5.3 min, p=0.016, Wilcoxon matched pairs test). [11C]Elacridar and (R)-[11C]verapamil were not able to discriminate Pgp expression in tumour models. Following administration of unlabelled tariquidar, both EMT6Ar1.0 and EMT6 tumours showed increases in tumoural uptake of [11C]tariquidar, [11C]elacridar and (R)-[11C]verapamil. Conclusions Among the tested radiotracers, [11C]tariquidar performed best in discriminating high from low Pgp expressing tumours. Therefore [11C]tariquidar merits further investigation as a PET tracer to assess Pgp expression levels of solid tumours. PMID:21983837

  11. Inhibition of radical reactions for an improved potassium tert-butoxide-promoted (11) C-methylation strategy for the synthesis of α-(11) C-methyl amino acids.

    PubMed

    Suzuki, Chie; Kato, Koichi; Tsuji, Atsushi B; Zhang, Ming-Rong; Arano, Yasushi; Saga, Tsuneo

    2015-03-01

    α-(11) C-Methyl amino acids are useful tools for biological imaging studies. However, a robust procedure for the labeling of amino acids has not yet been established. In this study, the (11) C-methylation of Schiff-base-activated α-amino acid derivatives has been optimized for the radiosynthesis of various α-(11) C-methyl amino acids. The benzophenone imine analog of methyl 2-amino butyrate was (11) C-methylated with [(11) C]methyl iodide following its initial deprotonation with potassium tert-butoxide (KOtBu). The use of an alternative base such as tetrabutylammonium fluoride, triethylamine, and 1,8-diazabicyclo[5.4.0]undec-7-ene did not result in the (11) C-methylated product. Furthermore, the KOtBu-promoted (11) C-methylation of the Schiff-base-activated amino acid analog was enhanced by the addition of 1,2,4,5-tetramethoxybenzene or 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) and inhibited by the addition of 1,10-phenanthroline. These results suggest that inhibition of radical generation induced by KOtBu improves the α-(11) C-methylation of the Schiff-base-activated amino acids. The addition of a mixture of KOtBu and TEMPO to a solution of Schiff-base-activated amino acid ester and [(11) C]methyl iodide provided optimal results, and the tert-butyl ester and benzophenone imine groups could be readily hydrolyzed to give the desired α-(11) C-methyl amino acids with a high radiochemical conversion. This strategy could be readily applied to the synthesis of other α-(11) C-methyl amino acids.

  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. (11)C- and (18)F-Labeled Radioligands for P-Glycoprotein Imaging by Positron Emission Tomography.

    PubMed

    Cantore, Mariangela; Benadiba, Marcel; Elsinga, Philip H; Kwizera, Chantal; Dierckx, Rudi A J O; Colabufo, Nicola Antonio; Luurtsema, Gert

    2016-01-01

    P-Glycoprotein (P-gp) is an efflux transporter widely expressed at the human blood-brain barrier. It is involved in xenobiotics efflux and in onset and progression of neurodegenerative disorders. For these reasons, there is great interest in the assessment of P-gp expression and function by noninvasive techniques such as positron emission tomography (PET). Three radiolabeled aryloxazole derivatives: 2-[2-(2-methyl-((11)C)-5-methoxyphenyl)oxazol-4-ylmethyl]-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline ([(11)C]-5); 2-[2-(2-fluoromethyl-((18)F)-5-methoxyphenyl)oxazol-4-ylmethyl]-6,7-dimethoxy-1,2,3,4-tetra-hydroisoquinoline ([(18)F]-6); and 2-[2-(2-fluoroethyl-((18)F)-5-methoxyphenyl)oxazol-4-ylmethyl]-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline ([(18)F]-7), were tested in several in vitro biological assays to assess the effect of the aryl substituent in terms of potency and mechanism of action toward P-gp. Methyl derivative [(11)C]-5 is a potent P-gp substrate, whereas the corresponding fluoroethyl derivative [(18)F]-7 is a P-gp inhibitor. Fluoromethyl compound [(18)F]-6 is classified as a non-transported P-gp substrate, because its efflux increases after cyclosporine A modulation. These studies revealed a promising substrate and inhibitor, [(11)C]-5 and [(18)F]-7, respectively, for in vivo imaging of P-gp by using PET.

  14. POLLUTION PREVENTION OPPORTUNITY ASSESSMENT UNITED STATES ARMY CORPS OF ENGINEERS PITTSBURGH ENGINEER WAREHOUSE AND REPAIR STATION AND EMSWORTH LOCKS AND DAMS PITTSBURGH, PENNSYLVANIA

    EPA Science Inventory

    This report summarizes work conducted at the United States Army Corps of Engineers (USACE) Pittsburgh Engineering Warehouse and Repair Station (PEWARS) and Emsworth Locks and Dams in Pittsburgh, Pennsylvania under the U.S. Environmental Protection Agency's (EPA's) Waste Reduction...

  15. Studies with differentially labeled [11C]cocaine, [11C]norcocaine, [11C]benzoylecgonine, and [11C]- and 4'-[18F]fluorococaine to probe the extent to which [11C]cocaine metabolites contribute to PET images of the baboon brain.

    PubMed

    Gatley, S J; Yu, D W; Fowler, J S; MacGregor, R R; Schlyer, D J; Dewey, S L; Wolf, A P; Martin, T; Shea, C E; Volkow, N D

    1994-03-01

    The psychostimulant drug of abuse, cocaine (benzoylecgonine methyl ester), is rapidly metabolized by cleavage of its two ester groups, to give benzoylecgonine (BE) and ecgonine methyl ester, and by N-demethylation, to give N-norcocaine (NC). The recent use of [N-methyl-11CH3]cocaine to image brain cocaine binding sites with positron emission tomography (PET) raises the question of whether PET images partially reflect the distribution and kinetics of labeled cocaine metabolites. We prepared [O-methyl-11CH3]cocaine by methylation of the sodium salt of BE with [11C]CH3I, and showed that PET baboon brain scans, as well as regional brain kinetics and plasma time-activity curves corrected for the presence of labeled metabolites, are nearly identical to those seen with [N-methyl-11CH3]cocaine. This strongly suggests that 11C metabolites do not significantly affect PET images, because the metabolite pattern is different for the two labeled forms of cocaine. In particular, nearly half the 11C in blood plasma at 30 min was [11C]CO2 when [N-methyl-11CH3]cocaine was administered, whereas [11C]CO2 was not formed from [O-methyl-11CH3]cocaine. Only a trace of [11C]NC was detected in plasma after [O-methyl-11CH3]cocaine administration. Nearly identical brain PET data were also obtained when 4'-[N-methyl-11CH3]fluorococaine and 4'-[18F]fluorococaine (prepared by nucleophilic aromatic substitution from [18F]fluoride- and 4'-nitrococaine) were compared with [N-methyl-11CH3]cocaine. In vitro assays with rat brain membranes showed that cocaine and 4'-fluorococaine were equipotent at the dopamine reuptake site, but that 4'-fluorococaine was about 100 times more potent at the 5-hydroxytryptamine reuptake site.(ABSTRACT TRUNCATED AT 250 WORDS)

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

    DOE PAGES

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

    2015-09-21

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

  17. A Heat Vulnerability Index and Adaptation Solutions for Pittsburgh, Pennsylvania.

    PubMed

    Bradford, Kathryn; Abrahams, Leslie; Hegglin, Miriam; Klima, Kelly

    2015-10-01

    With increasing evidence of global warming, many cities have focused attention on response plans to address their populations' vulnerabilities. Despite expected increased frequency and intensity of heat waves, the health impacts of such events in urban areas can be minimized with careful policy and economic investments. We focus on Pittsburgh, Pennsylvania and ask two questions. First, what are the top factors contributing to heat vulnerability and how do these characteristics manifest geospatially throughout Pittsburgh? Second, assuming the City wishes to deploy additional cooling centers, what placement will optimally address the vulnerability of the at risk populations? We use national census data, ArcGIS geospatial modeling, and statistical analysis to determine a range of heat vulnerability indices and optimal cooling center placement. We find that while different studies use different data and statistical calculations, all methods tested locate additional cooling centers at the confluence of the three rivers (Downtown), the northeast side of Pittsburgh (Shadyside/Highland Park), and the southeast side of Pittsburgh (Squirrel Hill). This suggests that for Pittsburgh, a researcher could apply the same factor analysis procedure to compare data sets for different locations and times; factor analyses for heat vulnerability are more robust than previously thought.

  18. A Heat Vulnerability Index and Adaptation Solutions for Pittsburgh, Pennsylvania.

    PubMed

    Bradford, Kathryn; Abrahams, Leslie; Hegglin, Miriam; Klima, Kelly

    2015-10-01

    With increasing evidence of global warming, many cities have focused attention on response plans to address their populations' vulnerabilities. Despite expected increased frequency and intensity of heat waves, the health impacts of such events in urban areas can be minimized with careful policy and economic investments. We focus on Pittsburgh, Pennsylvania and ask two questions. First, what are the top factors contributing to heat vulnerability and how do these characteristics manifest geospatially throughout Pittsburgh? Second, assuming the City wishes to deploy additional cooling centers, what placement will optimally address the vulnerability of the at risk populations? We use national census data, ArcGIS geospatial modeling, and statistical analysis to determine a range of heat vulnerability indices and optimal cooling center placement. We find that while different studies use different data and statistical calculations, all methods tested locate additional cooling centers at the confluence of the three rivers (Downtown), the northeast side of Pittsburgh (Shadyside/Highland Park), and the southeast side of Pittsburgh (Squirrel Hill). This suggests that for Pittsburgh, a researcher could apply the same factor analysis procedure to compare data sets for different locations and times; factor analyses for heat vulnerability are more robust than previously thought. PMID:26333158

  19. A Heat Vulnerability Index and Adaptation Solutions for Pittsburgh, Pennsylvania

    NASA Astrophysics Data System (ADS)

    Klima, K.; Abrahams, L.; Bradford, K.; Hegglin, M.

    2015-12-01

    With increasing evidence of global warming, many cities have focused attention on response plans to address their populations' vulnerabilities. Despite expected increased frequency and intensity of heat waves, the health impacts of such events in urban areas can be minimized with careful policy and economic investments. We focus on Pittsburgh, Pennsylvania and ask two questions. First, what are the top factors contributing to heat vulnerability and how do these characteristics manifest geospatially throughout Pittsburgh? Second, assuming the City wishes to deploy additional cooling centers, what placement will optimally address the vulnerability of the at risk populations? We use national census data, ArcGIS geospatial modeling, and statistical analysis to determine a range of heat vulnerability indices and optimal cooling center placement. We find that while different studies use different data and statistical calculations, all methods tested locate additional cooling centers at the confluence of the three rivers (Downtown), the northeast side of Pittsburgh (Shadyside/ Highland Park), and the southeast side of Pittsburgh (Squirrel Hill). This suggests that for Pittsburgh, a researcher could apply the same factor analysis procedure to compare datasets for different locations and times; factor analyses for heat vulnerability are more robust than previously thought.

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

    NASA Astrophysics Data System (ADS)

    Nye, Jonathon Andrew

    2005-07-01

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

  1. [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.

  2. Lifestyle characteristics assessment of Japanese in Pittsburgh, USA.

    PubMed

    Hirooka, Nobutaka; Takedai, Teiichi; D'Amico, Frank

    2012-04-01

    Lifestyle-related chronic diseases such as cancer and cardiovascular disease are the greatest public health concerns. Evidence shows Japanese immigrants to a westernized environment have higher incidence of lifestyle-related diseases. However, little is known about lifestyle characteristics related to chronic diseases for Japanese in a westernized environment. This study is examining the gap in lifestyle by comparing the lifestyle prevalence for Japanese in the US with the Japanese National Data (the National Health and Nutrition Survey in Japan, J-NHANS) as well as the Japan National Health Promotion in the twenty-first Century (HJ21) goals. Japanese adults were surveyed in Pittsburgh, USA, regarding their lifestyle (e.g., diet, exercise, smoking, stress, alcohol, and oral hygiene). The prevalence was compared with J-NHANS and HJ21 goals. Ninety-three responded (response rate; 97.9%). Japanese men (n = 38) and women (n = 55) in Pittsburgh smoke less than Japanese in Japan (P < 0.001 for both genders). Japanese in Pittsburgh perform less physical activity in daily life and have lower prevalence of walking more than 1 h per day (P < 0.001 for both genders). Japanese women in Pittsburgh have significantly higher prevalence of stress than in Japan (P = 0.004). Japanese men in Pittsburgh do not reach HJ21 goal in weight management, BMI, use of medicine or alcohol to sleep, and sleep quality. Japanese women in Pittsburgh do not reach HJ21 goal in weight management and sleep quality. In conclusion, healthy lifestyle promotion including exercise and physical activity intervention for Japanese living in a westernized environment is warranted. PMID:21874580

  3. Preparing for Local Adaptation: Understanding Flood Risk Perceptions in Pittsburgh

    NASA Astrophysics Data System (ADS)

    Klima, K.; Wong-Parodi, G.

    2015-12-01

    The City of Pittsburgh experiences numerous floods every year. Aging and insufficient infrastructure contribute to flash floods and to over 20 billion gallons of combined sewer overflows annually, contaminating Pittsburgh's streets, basements, and waterways. Climate change is expected to further exacerbate this problem by causing more intense and more frequent extreme precipitation events in Western Pennsylvania. For a stormwater adaptation plan to be implemented effectively, the City will need informed public support. One way to achieve public understanding and support is through effective communication of the risks, benefits, and uncertainties of local flooding hazards and adaptation methods. In order to develop these communications effectively, the city and its partners will need to know what knowledge and attitudes the residents of Pittsburgh already hold about flood risks. Here we seek to (1) identify Pittsburgh residents' knowledge level, risk perception and attitudes towards flooding and storm water management, and (2) pre-test communications meant to inform and empower Pittsburghers about flood risks and adaptation strategies. We conduct a city-wide survey of 10,000 Pittsburgh renters and homeowners from four life situations: high risk, above poverty; high-risk, below poverty; low risk, above poverty; and low-risk, below poverty. Mixed media recruitment strategies (online and paper-based solicitations guided/organized by community organizations) assist in reaching all subpopulations. Preliminary results suggest participants know what stormwater runoff is, but have a weak understanding of how stormwater interacts with natural and built systems. Furthermore, although participants have a good understanding of the difference between green and gray infrastructure, this does not translate into a change in their willingness to pay for green infrastructure adaptation. This suggests additional communications about flood risks and adaptation strategies.

  4. Lifestyle characteristics assessment of Japanese in Pittsburgh, USA.

    PubMed

    Hirooka, Nobutaka; Takedai, Teiichi; D'Amico, Frank

    2012-04-01

    Lifestyle-related chronic diseases such as cancer and cardiovascular disease are the greatest public health concerns. Evidence shows Japanese immigrants to a westernized environment have higher incidence of lifestyle-related diseases. However, little is known about lifestyle characteristics related to chronic diseases for Japanese in a westernized environment. This study is examining the gap in lifestyle by comparing the lifestyle prevalence for Japanese in the US with the Japanese National Data (the National Health and Nutrition Survey in Japan, J-NHANS) as well as the Japan National Health Promotion in the twenty-first Century (HJ21) goals. Japanese adults were surveyed in Pittsburgh, USA, regarding their lifestyle (e.g., diet, exercise, smoking, stress, alcohol, and oral hygiene). The prevalence was compared with J-NHANS and HJ21 goals. Ninety-three responded (response rate; 97.9%). Japanese men (n = 38) and women (n = 55) in Pittsburgh smoke less than Japanese in Japan (P < 0.001 for both genders). Japanese in Pittsburgh perform less physical activity in daily life and have lower prevalence of walking more than 1 h per day (P < 0.001 for both genders). Japanese women in Pittsburgh have significantly higher prevalence of stress than in Japan (P = 0.004). Japanese men in Pittsburgh do not reach HJ21 goal in weight management, BMI, use of medicine or alcohol to sleep, and sleep quality. Japanese women in Pittsburgh do not reach HJ21 goal in weight management and sleep quality. In conclusion, healthy lifestyle promotion including exercise and physical activity intervention for Japanese living in a westernized environment is warranted.

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

    PubMed

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

    1988-01-01

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

  6. Pathways to Sustainability for Carnegie Library of Pittsburgh. Research Brief

    ERIC Educational Resources Information Center

    Li, Jennifer

    2008-01-01

    Like many U.S. public libraries, Carnegie Library of Pittsburgh faces financial uncertainty. CLP asked RAND to identify critical factors that affect the library's financial stability and to develop a framework to assess how these factors can be managed to provide a more stable financial base. RAND researchers reviewed the literature and…

  7. The Pittsburgh Girls Study: Overview and Initial Findings

    ERIC Educational Resources Information Center

    Keenan, Kate; Hipwell, Alison; Chung, Tammy; Stepp, Stephanie; Stouthamer-Loeber, Magda; Loeber, Rolf; McTigue, Kathleen

    2010-01-01

    The Pittsburgh Girls Study is a longitudinal, community-based study of 2,451 girls who were initially recruited when they were between the ages of 5 and 8 years. The primary aim of the study was testing developmental models of conduct disorder, major depressive disorder, and their co-occurrence in girls. In the current article, we summarize the…

  8. 75 FR 9867 - University of Pittsburgh, et al

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-04

    .... Instrument: Electron Microscope. Manufacturer: JEOL, Ltd., Japan. Intended Use: See notice at 75 FR 3895...: JEM-1400 Electron Microscope. Manufacturer: JEOL Ltd., Japan. Intended Use: See notice at 75 FR 3895... International Trade Administration University of Pittsburgh, et al.; Notice of Consolidated Decision...

  9. The "Pittsburgh Courier's" Double V Campaign in 1942.

    ERIC Educational Resources Information Center

    Washburn, Pat

    In February 1942, a letter to the editor of the Pittsburgh "Courier," the nation's largest black owned newspaper, started the "Double V" (for victory at home and victory abroad) campaign, which stressed the right of blacks to have equality in the United States since they were fighting inequality abroad. As the "Courier" devoted a great deal of…

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

    SciTech Connect

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

    1996-05-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-08-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2006-01-01

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

  13. The Pittsburgh Promise: A Community's Commitment to Its Young People

    ERIC Educational Resources Information Center

    Ghubril, Saleem

    2013-01-01

    The nonprofit community-based organization Pittsburgh Promise aims to help revitalize Pittsburgh and its public school system by offering college scholarships to any Pittsburgh Public School graduate who meets the academic requirements. Executive director Saleem Ghubril spoke with "Voices in Urban Education" guest editor Jacob Mishook…

  14. Bettis Atomic Power Laboratory. Bettis-Pittsburgh Site environmental summary report

    SciTech Connect

    2000-08-01

    This summary report provides a description of the nature and environmental aspects of work and facilities at the Bettis-Pittsburgh site, an historical perspective of Bettis-Pittsburgh operations that is not provided by the annual reports, and background information pertinent to understanding the environmental aspects of Bettis-Pittsburgh operations.

  15. Role for 11C-choline PET in active surveillance of prostate cancer

    PubMed Central

    Boychak, Oleksandr; Vos, Larissa; Makis, William; Buteau, Francois-Alexandre; Pervez, Nadeem; Parliament, Matthew; McEwan, Alexander J.B.; Usmani, Nawaid

    2015-01-01

    Introduction: Active surveillance (AS) is an increasingly popular management strategy for men diagnosed with low-risk indolent prostate cancer. Current tests (prostate-specific antigen [PSA], clinical staging, and prostate biopsies) to monitor indolent disease lack accuracy. 11C-choline positron emission tomography (PET) has excellent detection rates in local and distant recurrence of prostate cancer. We examine 11C-choline PET for identifying aggressive prostate cancer warranting treatment in the AS setting. Methods: In total, 24 patients on AS had clinical assessment and PSA testing every 6 months and 11C-choline PET and prostate biopsies annually. The sensitivity and specificity to identify prostate cancer and progressive disease (PD) were calculated for each 11C-choline PET scan. Results: In total, 62 biopsy-paired, serial 11C-choline PET scans were analyzed using a series of standard uptake value-maximum (SUVmax) cut-off thresholds. During follow-up (mean 25.3 months), 11 of the 24 low-risk prostate cancer patients developed PD and received definitive treatment. The prostate cancer detection rate with 11C-choline PET had moderate sensitivity (72.1%), but low specificity (45.0%). PD prediction from baseline 11C-choline PET had satisfactory sensitivity (81.8%), but low specificity (38.5%). The addition of clinical parameters to the baseline 11C-choline PET improved specificity (69.2%), with a slight reduction in sensitivity (72.7%) for PD prediction. Conclusions: Addition of 11C-choline PET imaging during AS may help to identify aggressive disease earlier than traditional methods. However, 11C-choline PET alone has low specificity due to overlap of SUV values with benign pathologies. Triaging low-risk prostate cancer patients into AS versus therapy will require further optimization of PET protocols or consideration of alternative strategies (i.e., magnetic resonance imaging, biomarkers). PMID:25844108

  16. The upper pennsylvanian pittsburgh coal bed: Resources and mine models

    USGS Publications Warehouse

    Watson, W.D.; Ruppert, L.F.; Tewalt, S.J.; Bragg, L.J.

    2001-01-01

    The U.S. Geological Survey recently completed a digital coal resource assessment model of the Upper Pennsylvanian Pittsburgh coal bed, which indicates that after subtracting minedout coal, 16 billion short tons (14 billion tonnes) remain of the original 34 billion short tons (31 billion tonnes) of coal. When technical, environmental, and social restrictions are applied to the remaining Pittsburgh coal model, only 12 billion short tons (11 billion tonnes) are available for mining. Our assessment models estimate that up to 0.61 billion short tons (0.55 billion tonnes), 2.7 billion short tons (2.4 billion tonnes), and 8.5 billion short tons (7.7 billion tonnes) could be available for surface mining, continuous mining, and longwall mining, respectively. This analysis is an example of a second-generation regional coal availability study designed to model recoverability characteristics for all the major coal beds in the United States. ?? 2001 International Association for Mathematical Geology.

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

    SciTech Connect

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

    2011-04-27

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

  18. Production and suppression of 11C in the solar neutrino experiment Borexino

    NASA Astrophysics Data System (ADS)

    Meindl, Quirin; Bellini, G.; Benziger, J.; Bonetti, S.; Avanzini, M. Buizza; Caccianiga, B.; Cadonati, L.; Calaprice, F.; Carraro, C.; Chavarria, A.; Chepurnov, A.; Dalnoki-Veress, F.; D'Angelo, D.; Davini, S.; de Kerret, H.; Derbin, A.; Etenko, A.; von Feilitzsch, F.; Fomenko, K.; Franco, D.; Galbiati, C.; Gazzana, S.; Ghiano, C.; Giammarchi, M.; Goeger-Neff, M.; Goretti, A.; Guardincerri, E.; Hardy, S.; Ianni, Aldo; Ianni, Andrea; Joyce, M.; Kobychev, V.; Korga, G.; Kryn, D.; Laubenstein, M.; Leung, M.; Lewke, T.; Litvinovich, E.; Loer, B.; Lombardi, P.; Ludhova, L.; Machulin, I.; Manecki, S.; Maneschg, W.; Manuzio, G.; Meindl, Q.; Meroni, E.; Miramonti, L.; Misiaszek, M.; Montanari, D.; Muratova, V.; Oberauer, L.; Obolensky, M.; Ortica, F.; Pallavicini, M.; Papp, L.; Perasso, L.; Perasso, S.; Pocar, A.; Raghavan, R. S.; Ranucci, G.; Razeto, A.; Re, A.; Risso, P.; Romani, A.; Rountree, D.; Sabelnikov, A.; Saldanha, R.; Salvo, C.; Schönert, S.; Simgen, H.; Skorokhvatov, M.; Smirnov, O.; Sotnikov, A.; Sukhotin, S.; Suvorov, Y.; Tartaglia, R.; Testera, G.; Vignaud, D.; Vogelaar, R. B.; Winter, J.; Wojcik, M.; Wright, A.; Wurm, M.; Xu, J.; Zaimidoroga, O.; Zavatarelli, S.; Zuzel, G.

    2011-04-01

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

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

    PubMed Central

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

    2014-01-01

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

  20. 11C-radiolabeling study of methanol decomposition on copper oxide modified mesoporous SBA-15 silica

    NASA Astrophysics Data System (ADS)

    Tsoncheva, Tanya; Sarkadi-Priboczki, Eva

    2011-05-01

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

  1. Quantification of [11C]yohimbine binding to α2 adrenoceptors in rat brain in vivo

    PubMed Central

    Phan, Jenny-Ann; Landau, Anne M; Wong, Dean F; Jakobsen, Steen; Nahimi, Adjmal; Doudet, Doris J; Gjedde, Albert

    2015-01-01

    We quantified the binding potentials (BPND) of [11C]yohimbine binding in rat brain to alpha-2 adrenoceptors to evaluate [11C]yohimbine as an in vivo marker of noradrenergic neurotransmission and to examine its sensitivity to the level of noradrenaline. Dual [11C]yohimbine dynamic positron emission tomography (PET) recordings were applied to five Sprague Dawley rats at baseline, followed by acute amphetamine administration (2 mg/kg) to induce elevation of the endogenous level of noradrenaline. The volume of distribution (VT) of [11C]yohimbine was obtained using Logan plot with arterial plasma input. Because alpha-2 adrenoceptors are distributed throughout the brain, the estimation of the BPND is complicated by the absence of an anatomic region of no displaceable binding. We used the Inhibition plot to acquire the reference volume, VND, from which we calculated the BPND. Acute pharmacological challenge with amphetamine induced a significant decline of [11C]yohimbine BPND of ~38% in all volumes of interest. The BPND was greatest in the thalamus and striatum, followed in descending order by, frontal cortex, pons, and cerebellum. The experimental data demonstrate that [11C]yohimbine binding is sensitive to a challenge known to increase the extracellular level of noradrenaline, which can benefit future PET investigations of pathologic conditions related to disrupted noradrenergic neurotransmission. PMID:25564241

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

    PubMed

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

    2015-04-01

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

  3. Comparison of L-[1-11C]methionine and L-methyl-[11C]methionine for measuring in vivo protein synthesis rates with PET.

    PubMed

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

    1988-08-01

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

  4. 11C-Acetate PET Imaging in Patients with Multiple Sclerosis

    PubMed Central

    Shimosegawa, Eku; Okuno, Tatsusada; Koda, Toru; Sugimoto, Tomoyuki; Mochizuki, Hideki; Hatazawa, Jun; Nakatsuji, Yuji

    2014-01-01

    Background Activation of glial cells is a cardinal feature in multiple sclerosis (MS) pathology, and acetate has been reported to be selectively uptaken by astrocytes in the CNS. The aim of this study was to investigate the efficacy of PET with 11C-acetate for MS diagnosis. Materials and Methods Six patients with relapsing-remitting MS and 6 healthy volunteers (HV) were enrolled. The 11C-acetate brain uptake on PET was measured in patients with MS and HV. Volume-of-interest analysis of cerebral gray and white matter based on the segmentation technique for co-registered MRI and voxel-based statistical parametric analysis were performed. Correlation between 11C-acetate uptake and the lesion number in T1- and T2- weighted MR images were also assessed. Results The standardized uptake value (SUV) of 11C-acetate was increased in both white and gray matter in MS patients compared to HV. Voxel-based statistical analysis revealed a significantly increased SUV relative to that in the bilateral thalami (SUVt) in a broad area of white matter, particularly in the subcortical white matter of MS patients. The numbers of T2 lesions and T1 black holes were significantly correlated with SUV of 11C-acetate in white and gray matter. Conclusions The 11C-acetate uptake significantly increased in MS patients and correlated to the number of MRI lesions. These preliminary data suggest that 11C-acetate PET can be a useful clinical examination for MS patients. PMID:25369426

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

    PubMed

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

    2016-08-22

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

  6. Abstracts of Papers Presented at the 2005 Pittsburgh Conference

    PubMed Central

    Stockwell, Peter B.

    2005-01-01

    To attend or not to attend, that is the question. The Pittsburgh Conference continues to pose this conundrum to conferees and exhibitors alike. This year's conference was the first to be presented without a set of paper abstracts—a good thing some would say but this old codger always used the paper abstracts to select papers of interest to our readership and to seek a full publication. The exhibit took its usual format but it seemed that there were less manufacturers present. The information presented to the attendees was also lacking and many companies' details were missing from the final program book, an omission no doubt on their behalf—my company was one of these—however I feel sure that past Pittcon organizers would have been more persistent in getting the required details for the audience. As is now the norm, many of the presentations take the form of posters displayed within the exhibition area. Without a driver to get the audience there, the traffic was slow, to say the least. Lecture presentations were also attended in a mixed fashion. So the Pittsburgh Conference show moves on, and again next year it will be held in Orlando from 12 March to 17 March 2006. No doubt I will be there making it a straight 31 in a row; in Pittsburgh Conference terms I am just a beginner with many of the attendees making more shows in a run than that. Selected abstracts dealing with topics of interest to the readers of this journal follow—hopefully many of these groups will be willing to publish their work either within this journal or elsewhere. PMID:18924631

  7. 11C-Colchicine distribution in tissues of colchicine -sensitive and -resistant neuroblastoma xenografts

    SciTech Connect

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

    1995-05-01

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

  8. Pre-clinical characterization of [11C]R05013853 as a novel radiotracer for imaging of the glycine transporter type 1 by positron emission tomography.

    PubMed

    Borroni, Edilio; Zhou, Yun; Ostrowitzki, Susanne; Alberati, Daniela; Kumar, Anil; Hainzl, Dominik; Hartung, Thomas; Hilton, John; Dannals, Robert F; Wong, Dean F

    2013-07-15

    A specific positron emission tomography (PET) radiotracer for the glycine transporter type 1 (GlyT1) would constitute an imaging biomarker to investigate the distribution of GlyT1 in normal individuals and those with neuropsychiatric disorders. In addition it could demonstrate the ability of a novel drug to reach its target in the brain and enable receptor occupancy studies, thus facilitating drug development. In this article we describe the evaluation in non-human primates of two candidate PET radiotracers ([(11)C]RO5013852 and [(11)C]RO5013853) previously characterized in the rat. Both radiotracers showed acceptable uptake in the baboon brain and heterogeneous distribution consistent with that reported for GlyT1. In vivo blockade studies with two specific glycine reuptake inhibitors (GRIs), RO5013853 and bitopertin (RG1678, reduced uptake of both tracers to homogenous levels across brain regions and demonstrated specificity of the signal. [(11)C]RO5013853 showed a larger specific signal and slightly higher brain uptake and was therefore selected for further characterization. Quantitative compartmental analysis of PET data showed that the 2-tissue compartment model with 5 parameters was the most appropriate to describe the kinetics of [(11)C]RO5013853. Two additional methods were used: a) the Logan graphical analysis using plasma input and, b) a linear parametric imaging approach with the 2-tissue compartmental model. These produced VT estimates of comparable magnitude, namely, pons, thalamus and cerebellum>caudate, putamen and cortical regions. High resolution autoradiography with tritiated RO5013853 was used to confirm the binding pattern observed by PET. In vivo metabolism studies in the baboon demonstrated the formation of a single, radiolabeled metabolite more polar than the parent compound. Finally, [(11)C]RO5013853 was used to quantify the degree of cerebral GlyT1 occupancy observed in the baboon following oral administration of bitopertin, a selective GRI

  9. Pd0-mediated rapid cross-coupling reactions, the rapid C-[11C]methylations, revolutionarily advancing the syntheses of short-lived PET molecular probes.

    PubMed

    Suzuki, Masaaki; Doi, Hisashi; Koyama, Hiroko; Zhang, Zhouen; Hosoya, Takamitsu; Onoe, Hirotaka; Watanabe, Yasuyoshi

    2014-06-01

    Positron emission tomography is a noninvasive method for monitoring drug (or diagnostic) behavior and its localization on the target molecules in the living systems, including the human body, using a short-lived positron-emitting radionuclide. New methodologies for introducing representative short-lived radionuclides, (11)C and (18)F, into the carbon frameworks of biologically active organic compounds have been established by developing rapid C-[(11)C]methylations and C-[(18)F]fluoromethylations using rapid Pd(0)-mediated cross-coupling reactions between [(11)C]methyl iodide (sp(3)-hybridized carbon) and an excess amount of organotributylstannane or organoboronic acid ester having sp(2) (phenyl, heteroaromatic, or alkenyl), sp(alkynyl), or sp(3) (benzyl and cinnamyl)-hybridized carbons; and [(18)F]fluoromethyl halide (iodide or bromide) and an organoboronic acid ester, respectively. These rapid reactions provide a firm foundation for an efficient and general synthesis of short-lived (11)C- or (18)F-labeled PET molecular probes to promote in vivo molecular imaging studies.

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

    SciTech Connect

    Washburn, L.C.; Byrd, B.L.; Sun, T.T.; Crook, J.E.; Hubner, K.F.; Coffey, J.L.; Watson, E.E.

    1985-01-01

    We have previously reported the radiation dosimetry of /sup 11/C-labeled DL-tryptophan and DL-valine, as well as clinical pancreatic imaging studies with these agents. Because of significant uptake in both normal pancreas and in pancreatic tumors (thought to be due to the presence of the D-enantiomer), differential diagnosis of pancreatic carcinoma was not feasible. High-performance liquid chromatographic (HPLC) methods were developed for rapid resolution of /sup 11/C-labeled DL-tryptophan and DL-valine. Radiation dose estimates to the various organs in man were calculated for the D- and L-enantiomers of /sup 11/C-labeled tryptophan and valine, based on tissue distribution data in rats. The dose estimates were sufficiently low that 20-mCi doses of each of the enantiomeric amino acids were approved by the FDA for intravenous administration to humans. 21 refs., 3 tabs.

  11. Comparison of dosimetry between PET/CT and PET alone using (11)C-ITMM.

    PubMed

    Ito, Kimiteru; Sakata, Muneyuki; Oda, Keiichi; Wagatsuma, Kei; Toyohara, Jun; Ishibashi, Kenji; Ishii, Kenji; Ishiwata, Kiichi

    2016-03-01

    We used a new tracer, N-[4-[6-(isopropylamino) pyrimidin-4-yl]-1,3-thiazol-2-yl]-4-(11)C-methoxy-N-methylbenzamide ((11)C-ITMM), to compare radiation doses from positron emission tomography (PET)/computed tomography (CT) with previously published doses from PET alone. Twelve healthy volunteers [six males (mean age ± SD, 27.7 ± 6.7 years) and six females (31.8 ± 14.5 years)] in 12 examinations were recruited. Dose estimations from PET/CT were compared with those from PET alone. Regions of interest (ROIs) in PET/CT were delineated on the basis of low-dose CT (LD-CT) images acquired during PET/CT. Internal and external radiation doses were estimated using OLINDA/EXM 1.0 and CT-Expo software. The effective dose (ED) for (11)C-ITMM calculated from PET/CT was estimated to be 4.7 ± 0.5 μSv/MBq for the male subjects and 4.1 ± 0.7 μSv/MBq for the female subjects. The mean ED for (11)C-ITMM calculated from PET alone in a previous report was estimated to be 4.6 ± 0.3 μSv/MBq (males, n = 3). The ED values for (11)C-ITMM calculated from PET/CT in the male subjects were almost identical to those from PET alone. The absorbed doses (ADs) of the gallbladder, stomach, red bone marrow, and spleen calculated from PET/CT were significantly different from those calculated from PET alone. The EDs of (11)C-ITMM calculated from PET/CT were almost identical to those calculated from PET alone. The ADs in several organs calculated from PET/CT differed from those from PET alone. LD-CT images acquired during PET/CT may facilitate organ identification.

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

    PubMed Central

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

    2016-01-01

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

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

    DOEpatents

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

    1986-04-17

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

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

    SciTech Connect

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

    1995-05-01

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

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

    SciTech Connect

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

    2010-04-20

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

  16. Synthesis and preclinical evaluation of the radiolabeled P-glycoprotein inhibitor [11C]MC113

    PubMed Central

    Mairinger, Severin; Wanek, Thomas; Kuntner, Claudia; Doenmez, Yaprak; Strommer, Sabine; Stanek, Johann; Capparelli, Elena; Chiba, Peter; Müller, Markus; Colabufo, Nicola A.; Langer, Oliver

    2013-01-01

    Objectives With the aim to develop a PET tracer to visualize P-glycoprotein (Pgp) expression levels in different organs, the Pgp inhibitor MC113 was labeled with 11C and evaluated using small-animal PET. Methods [11C]MC113 was synthesized by reaction of O-desmethyl MC113 with [11C]methyl triflate. Small-animal PET was performed with [11C]MC113 in FVB wild-type and Mdr1a/b(−/−) mice (n=3 per group) and in a mouse model of high (EMT6Ar1.0) and low (EMT6) Pgp expressing tumor grafts (n=5). In the tumor model, PET scans were performed before and after administration of the reference Pgp inhibitor tariquidar (15 mg/kg). Results Brain uptake of [11C]MC113, expressed as area under the time-activity curve from time 0 to 60 min (AUC0-60), was moderately but not significantly increased in Mdr1a/b(−/−) compared with wild-type mice (mean±SD AUC0-60, Mdr1a/b(−/−): 88±7 min, wild-type: 62±6 min, P=0.100, Mann Whitney test). In the tumor model, AUC0-60 values were not significantly different between EMT6Ar1.0 and EMT6 tumors. Neither in brain nor in tumors was activity concentration significantly changed in response to tariquidar administration. Half-maximum effect concentrations (IC50) for inhibition of Pgp-mediated rhodamine 123 efflux from CCRFvcr1000 cells were 375±60 nM for MC113 versus 8.5±2.5 nM for tariquidar. Conclusion [11C]MC113 showed higher brain uptake in mice than previously described Pgp PET tracers, suggesting that [11C]MC113 was only to a low extent effluxed by Pgp. However, [11C]MC113 was found unsuitable to visualize Pgp expression levels presumably due to insufficiently high Pgp binding affinity of MC113 in relation to Pgp densities in brain and tumors. PMID:22981987

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

    NASA Astrophysics Data System (ADS)

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

    2016-06-01

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

  18. Cofiring Wood and Coal to Stoker Boilers in Pittsburgh

    SciTech Connect

    Cobb, J.T., Jr.; Elder, W.W.

    1997-07-01

    The prime objective of the University of Pittsburgh's overall wood/coal cofiring program is the successful introduction of commercial cofiring of urban wood wastes into the stoker boilers of western Pennsylvania. Central to this objective is the demonstration test at the Pittsburgh Brewing Company. In this test the project team is working to show that two commercially-available clean wood wastes - tub-ground pallet waste and chipped clearance wood - can be included in the fuel fed daily to an industrial stoker boiler. Irrespective of its economic outcome, the technical success of the demonstration at the brewery will allow the local air quality regulation agency to permit a parametric test at the Bellefield Boiler Plant. The objective of this test is to obtain comprehensive data on all key parameters of this operational boiler while firing wood with coal. The data would then be used for thorough generic technical and economic analyses. The technical analysis would be added to the open literature for the general planning and operational guidance for boiler owners and operators. The economic analysis would gage the potential for providing this stoker fuel commercially in an urban setting and for purchasing it regularly for combustion in an urban stoker boiler.

  19. 18F-Choline, 11C-choline and 11C-acetate PET/CT: comparative analysis for imaging prostate cancer patients.

    PubMed

    Brogsitter, Claudia; Zöphel, Klaus; Kotzerke, Jörg

    2013-07-01

    Prostate cancer (PCA) is the second most common tumour in men worldwide. Whereas prostate specific antigen (PSA) is an established biochemical marker, the optimal imaging method for all clinical scenarios has not yet been found. With the rising number of PET centres there is an increasing availability and use of (18)F-/(11)C-choline or (11)C-acetate for staging of PCA. However, to date no final conclusion has been reached as to whether acetate or choline tracers should be preferred. In this review we provide an overview of the performance of choline and acetate PET for staging the primary and recurrent disease and lymph nodes in PCA, based on the literature of the last 10 years. Although predominantly choline has been used rather than acetate, both tracers performed in a similar manner in published studies. Choline as well as acetate have insufficient diagnostic accuracy for the staging of the primary tumour, due to a minimum detectable tumour size of 5 mm and inability to differentiate PCA from benign prostate hyperplasia, chronic prostatitis and high-grade intraepithelial neoplasia. Regarding lymph node staging, choline tracers have demonstrated a high specificity. Unfortunately, the sensitivity is only moderate. For staging recurrent disease, sensitivity depends on the level of serum PSA (PSA should be >2 ng/ml). This applies to both choline and acetate. However, despite these limitations, a significant number of patients with recurrent disease can benefit from PET imaging by a change in treatment planning.

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

    PubMed

    Qualai, Jamal; Li, Lin-Xi; Cantero, Jon; Tarrats, Antoni; Fernández, Marco Antonio; Sumoy, Lauro; Rodolosse, Annie; McSorley, Stephen J; Genescà, Meritxell

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  2. Occupancy of dopamine D2/3 receptors in rat brain by endogenous dopamine measured with the agonist positron emission tomography radioligand [11C]MNPA.

    PubMed

    Seneca, Nicholas; Zoghbi, Sami S; Skinbjerg, Mette; Liow, Jeih-San; Hong, Jinsoo; Sibley, David R; Pike, Victor W; Halldin, Christer; Innis, Robert B

    2008-10-01

    Estimates of dopamine D(2/3) receptor occupancy by endogenous dopamine using positron emission tomography (PET) in animals have varied almost threefold. This variability may have been caused by incomplete depletion of dopamine or by the use of antagonist radioligands, which appear less sensitive than agonist radioligands to changes in endogenous dopamine. PET scans were performed in rats with the agonist PET radioligand [(11)C]MNPA ([O-methyl-(11)C]2-methoxy-N-propylnorapomorphine). [(11)C]MNPA was injected as a bolus plus constant infusion to achieve steady-state concentration in the body and equilibrium receptor binding in the brain. Radioligand binding was compared at baseline and after treatment with reserpine plus alpha-methyl-para-tyrosine, which cause approximately 95% depletion of endogenous dopamine. Depletion of dopamine increased radioligand binding in striatum but had little effect in cerebellum. Striatal [(11)C]MNPA binding potential was 0.93 +/- 0.12 at baseline and increased to 1.99 +/- 0.25 after dopamine depletion. Occupancy of D(2/3) receptors by endogenous dopamine at baseline was calculated to be approximately 53%. Striatal binding was displaceable with raclopride, but not with BP 897 (a selective D(3) compound), thus confirming the D(2) receptor specificity of [(11)C]MNPA binding. Radioactivity extracted from rat brain contained only 8-10% radiometabolites and was insignificantly altered by administration of reserpine plus alpha-methyl-para-tyrosine. Hence, dopamine depletion did not increase the PET measurements via an effect on radiotracer metabolism. Our in vivo estimate of dopamine's occupancy of D(2/3) receptors at baseline is higher than that previously reported using antagonist radioligands and PET, but is similar to that reported using agonist radioligands and ex vivo measurements.

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

    SciTech Connect

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

    2015-09-15

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

  4. 29 CFR 1977.5 - Persons protected by section 11(c).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... employees are afforded the full protection of section 11(c). For purposes of the Act, an employee is defined.... See, U.S. v. Silk, 331 U.S. 704 (1947); Rutherford Food Corporation v. McComb, 331 U.S. 722 (1947)....

  5. 29 CFR 1977.5 - Persons protected by section 11(c).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 9 2014-07-01 2014-07-01 false Persons protected by section 11(c). 1977.5 Section 1977.5 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) DISCRIMINATION AGAINST EMPLOYEES EXERCISING RIGHTS UNDER THE...

  6. 29 CFR 1977.3 - General requirements of section 11(c) of the Act.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 9 2014-07-01 2014-07-01 false General requirements of section 11(c) of the Act. 1977.3 Section 1977.3 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) DISCRIMINATION AGAINST EMPLOYEES EXERCISING RIGHTS UNDER...

  7. 29 CFR 1977.3 - General requirements of section 11(c) of the Act.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

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

  8. 29 CFR 1977.5 - Persons protected by section 11(c).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 9 2012-07-01 2012-07-01 false Persons protected by section 11(c). 1977.5 Section 1977.5 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) DISCRIMINATION AGAINST EMPLOYEES EXERCISING RIGHTS UNDER THE...

  9. 29 CFR 1977.3 - General requirements of section 11(c) of the Act.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

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

  10. 29 CFR 1977.3 - General requirements of section 11(c) of the Act.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 9 2013-07-01 2013-07-01 false General requirements of section 11(c) of the Act. 1977.3 Section 1977.3 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) DISCRIMINATION AGAINST EMPLOYEES EXERCISING RIGHTS UNDER...

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

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 9 2012-07-01 2012-07-01 false General requirements of section 11(c) of the Act. 1977.3 Section 1977.3 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) DISCRIMINATION AGAINST EMPLOYEES EXERCISING RIGHTS UNDER...

  12. 29 CFR 1977.5 - Persons protected by section 11(c).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

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

  13. 29 CFR 1977.5 - Persons protected by section 11(c).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

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

  14. Development of a (11)C-labeled tetrazine for rapid tetrazine-trans-cyclooctene ligation.

    PubMed

    Herth, Matthias M; Andersen, Valdemar L; Lehel, Szabolcs; Madsen, Jacob; Knudsen, Gitte M; Kristensen, Jesper L

    2013-05-01

    Tetrazine-trans-cyclooctene ligations are remarkably fast and selective reactions even at low micro-molar concentrations. In bioorthogonal radiochemistry, tools that enable conjugation of radioactive probes to pre-targeted vectors are of great interest. Herein, we describe the successful development of the first (11)C-labelled tetrazine and its reaction with trans-cyclooctenol.

  15. Forging a New Partnership: The Story of Teacher Union and School District Collaboration in Pittsburgh

    ERIC Educational Resources Information Center

    Hamill, Sean D.

    2011-01-01

    This paper documents Pittsburgh's transformation from a typical, adversarial district-union dynamic to one of deep, substantive collaboration over the course of several years. This work has catapulted Pittsburgh to the vanguard of efforts to improve teacher effectiveness, and helped secure more than $80 million in philanthropic and federal grants.…

  16. 75 FR 38146 - Pittsburgh Coatings, Inc., Ambridge, PA; Notice of Revised Determination on Reconsideration

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-01

    ... Register on May 20, 2010 (75 FR 28301). The workers were engaged in employment related to the production of... Employment and Training Administration Pittsburgh Coatings, Inc., Ambridge, PA; Notice of Revised... facts obtained on reconsideration, I determine that workers of Pittsburgh Coatings, Inc.,...

  17. Improving School Leadership through Support, Evaluation, and Incentives: The Pittsburgh Principal Incentive Program. Monograph

    ERIC Educational Resources Information Center

    Hamilton, Laura S.; Engberg, John; Steiner, Elizabeth D.; Nelson, Catherine Awsumb; Yuan, Kun

    2012-01-01

    In 2007, the Pittsburgh Public Schools (PPS) received funding from the U.S. Department of Education's Teacher Incentive Fund (TIF) program to implement the Pittsburgh Urban Leadership System for Excellence (PULSE), a set of reforms designed to improve the quality of school leadership throughout the district. A major component of PULSE is the…

  18. Estimating Teacher and School Effectiveness in Pittsburgh: Value-Added Modeling and Results. Final Report

    ERIC Educational Resources Information Center

    Lipscomb, Stephen; Gill, Brian; Booker, Kevin; Johnson, Matthew

    2010-01-01

    At the request of Pittsburgh Public Schools (PPS) and the Pittsburgh Federation of Teachers (PFT), Mathematica is developing value-added models (VAMs) that aim to estimate the contributions of individual teachers, teams of teachers, and schools to the achievement growth of their students. The analyses described in this report are intended as an…

  19. Guide to Historic Hungarian Places in Greater Pittsburgh. Educational Curriculum Kit 3.

    ERIC Educational Resources Information Center

    Boros-Kazai, Andrew

    This booklet is a guide to buildings and other sites which have played a significant role in the history of the Hungarian community in Pittsburgh (Pennsylvania). A brief summary of the significance or present use is provided for: (1) the Hungarian Nationality room at the University of Pittsburgh's Cathedral of Learning; (2) special collections of…

  20. Imaging acetylcholinesterase density in peripheral organs in Parkinson's disease with 11C-donepezil PET.

    PubMed

    Gjerløff, Trine; Fedorova, Tatyana; Knudsen, Karoline; Munk, Ole L; Nahimi, Adjmal; Jacobsen, Steen; Danielsen, Erik H; Terkelsen, Astrid J; Hansen, John; Pavese, Nicola; Brooks, David J; Borghammer, Per

    2015-03-01

    Parkinson's disease is associated with early parasympathetic dysfunction leading to constipation and gastroparesis. It has been suggested that pathological α-synuclein aggregations originate in the gut and ascend to the brainstem via the vagus. Our understanding of the pathogenesis and time course of parasympathetic denervation in Parkinson's disease is limited and would benefit from a validated imaging technique to visualize the integrity of parasympathetic function. The positron emission tomography tracer 5-[(11)C]-methoxy-donepezil was recently validated for imaging acetylcholinesterase density in the brain and peripheral organs. Donepezil is a high-affinity ligand for acetylcholinesterase-the enzyme that catabolizes acetylcholine in cholinergic synapses. Acetylcholinesterase histology has been used for many years for visualizing cholinergic neurons. Using 5-[(11)C]-methoxy-donepezil positron emission tomography, we studied 12 patients with early-to-moderate Parkinson's disease (three female; age 64 ± 9 years) and 12 age-matched control subjects (three female; age 62 ± 8 years). We collected clinical information about motor severity, constipation, gastroparesis, and other parameters. Heart rate variability measurements and gastric emptying scintigraphies were performed in all subjects to obtain objective measures of parasympathetic function. We detected significantly decreased (11)C-donepezil binding in the small intestine (-35%; P = 0.003) and pancreas (-22%; P = 0.001) of the patients. No correlations were found between the (11)C-donepezil signal and disease duration, severity of constipation, gastric emptying time, and heart rate variability. In Parkinson's disease, the dorsal motor nucleus of the vagus undergoes severe degeneration and pathological α-synuclein aggregations are also seen in nerve fibres innervating the gastro-intestinal tract. In contrast, the enteric nervous system displays little or no loss of cholinergic neurons. Decreases in (11)C

  1. [PET using 11C-methionine in recognition of pseudoprogression in cerebral glioma after combined treatment].

    PubMed

    Skvortsova, T Yu; Brodskaya, Z L; Gurchin, A F

    2014-01-01

    The purpose of the study was to evaluate the value of PET using 11C-methionine (PET-Met) for distinction between true glioma progression and pseudoprogression (PsPr). 72 patients with treated cerebral glioma investigated by PET-Met were identified from prospective database. Entry criteria included new or progressive MR imaging enhancing lesions within first 6 months after irradiation and definite final diagnosis on the basis of the pathological study (n=17) or clinical-radiological follow-up on an average 16 months. PET examinations were assessed by visual inspection and calculating 11C-methionine uptake index (UI). Results. Pseudoprogression was defined as early radiological progression with subsequent regress or stabilization, without salvage therapy. 42 patients were considered to exhibit PsPr and 30 patients had true glioma progression. In PsPr group PET scans were either negative (n=6) or slightly increased tracer uptake (UI range 1.2-2.14) was seen in the site of contrast-enhanced lesion. The UI was 1.48±0.39 (mean±SD). In comparison with pretreatment PET 15 patients showed decrease 11C-methionine uptake on an average by 26%. In recurrence group PET-Met showed abnormal high focal 11C-methionine uptake in the lesion. The UI was 2.54±0.84 (range 1.54-5.4). An UI threshold value of greater than 1.9 optimized differentiation between glioma progression and PsPr with sensitivity of 83.5% and specificity of 97.0%. Conclusion. Metabolic characteristics of PsPr included negative tracer accumulation or slightly increased 11C-methionine uptake in the contrast-enhancing lesion with UI less than 1.9.

  2. An organizational survey of the Pittsburgh Energy Technology Center

    SciTech Connect

    Stock, D.A.; Shurberg, D.A.; Haber, S.B.

    1991-09-01

    An Organizational Survey (OS) was administrated at the Pittsburgh Energy Technology Center (PETC) that queried employees on the subjects of organizational culture, various aspects of communications, employee commitment, work group cohesion, coordination of work, environmental, safety, and health concerns, hazardous nature of work, safety and overall job satisfaction. The purpose of the OS is to measure in a quantitative and objective way the notion of culture''; that is, the values attitudes, and beliefs of the individuals working within the organization. In addition, through the OS, a broad sample of individuals can be reached that would probably not be interviewed or observed during the course of a typical assessment. The OS also provides a descriptive profile of the organization at one point in time that can then be compared to a profile taken at a different point in time to assess changes in the culture of the organization.

  3. An organizational survey of the Pittsburgh Energy Technology Center

    SciTech Connect

    Stock, D.A.; Shurberg, D.A.; Haber, S.B.

    1991-09-01

    An Organizational Survey (OS) was administrated at the Pittsburgh Energy Technology Center (PETC) that queried employees on the subjects of organizational culture, various aspects of communications, employee commitment, work group cohesion, coordination of work, environmental, safety, and health concerns, hazardous nature of work, safety and overall job satisfaction. The purpose of the OS is to measure in a quantitative and objective way the notion of ``culture``; that is, the values attitudes, and beliefs of the individuals working within the organization. In addition, through the OS, a broad sample of individuals can be reached that would probably not be interviewed or observed during the course of a typical assessment. The OS also provides a descriptive profile of the organization at one point in time that can then be compared to a profile taken at a different point in time to assess changes in the culture of the organization.

  4. Aging and space flight: findings from the University of Pittsburgh

    NASA Technical Reports Server (NTRS)

    Monk, T. H.

    1999-01-01

    For more than a decade, the Sleep and Chronobiology Center (SCC) at the University of Pittsburgh has received funding from the National Institute on Aging (NIA), the National Institute of Mental Health (NIMH) and the National Aeronautics and Space Administration (NASA) in order to study the sleep and circadian rhythms of healthy older people, as well as the sleep and circadian rhythms of astronauts and cosmonauts. We have always been struck by the strong synergism between the two endeavors. What happens to the sleep and circadian rhythms of people removed from the terrestrial time cues of Earth is in many ways similar to what happens to people who are advancing in years. Most obviously, sleep is shorter and sleep depth is reduced, but there are also more subtle similarities between the two situations, both in circadian rhythms and in sleep, and in the adaptive strategies needed to enhance 24h zeitgebers.

  5. Lighting retrofits at the Pittsburgh Zoo and Aviary

    SciTech Connect

    Sadowski, E.C.

    1995-09-01

    The Pittsburgh Zoo occupies approximately 52 acres in the City`s Highland Park. Thirty structures serve as animal holding facilities, public display buildings, classrooms, food service facilities, offices, warehouses, a veterinary hospital, and gift shops. The cost of energy for heating, cooling, lighting, pumping, food service, etc. is approximately $280,000 a year. Of this, about 79 percent, or $220,000, is spent for electricity. About 20 percent ($44,000) of that electricity cost is spent directly on lighting. In mid-1992 a series of retrofits to the lighting systems in the Zoo`s buildings was begun. These were completed in mid-1994. These improvements cost $127,690, and they are expected to reduce electricity costs by $24,500 a year. The most interesting projects were carried out in the Tropical Forest Building, the Aqua Zoo, and the Niches of the World Building.

  6. Pneumonia caused by Pittsburgh pneumonia agent: radiologic manifestations

    SciTech Connect

    Muder, R.R.; Reddy, S.C.; Yu, V.L.; Kroboth, F.J.

    1984-03-01

    Using an objective scoring system, chest radiographs were reviewed in 23 cases of pneumonia due to the Pittsburgh pneumonia agent (PPA, Tatlockia micdadei, Legionella micdadei), including six cases of pneumonia with simultaneous isolation of PPA and L pneumophila (Legionnaires' disease). Infiltrates were typically segmental to lobar; nodular infiltrates were noted in three cases. Spread to additional lobes after presentation occurred in four of 17 PPA infections. Pneumonia caused by both PPA and L pneumophila was unusually severe, with involvement of all lobes occurring in four of six cases, compared with one of 17 cases of PPA infection (p>0.02). Radiographic severity did not correlate with underlying disease, immune status, or outcome. The majority of patients receiving erythromycin demonstrated objective radiologic improvement. In a patients, population that included nonimmunosuppressed patient, nodule formation and rapid radiologic progression were not found to be characteristic of PPA pneumonia.

  7. Lighting retrofits at the Pittsburgh Zoo and Aviary

    SciTech Connect

    Sadowski, E.C.

    1995-06-01

    Energy bills for the Pittsburgh Zoo typically total $280,000 a year, of which about $220,000 are spent on electricity. Until recently, lighting accounted for 20 percent of this electricity use. This translated into an annual cost of $44,000. Recent advances in lighting technology have made it possible to perform lighting retrofits in Zoo facilities that reduce energy costs while also providing improved light quality and better lit and more natural looking exhibits and animal holding areas. Through an investment of $127,690 in these projects from mid-1992 through mid-1994, the Zoo expects to realize an annual savings in electricity costs of $24,500 and further savings from a reduction in maintenance and plant replacement costs. Retrofits to the lighting systems in the Tropical Forest Building, the Aquarium, and the Niches of the World Building were the most interesting and are described in detail. Providing a sufficient amount of ultraviolet light to maintain the health of reptiles was a particular challenge in the Niches of the World Building. Lack of separate meters and additions to the Zoo have made the determination of the actual performance of these retrofit projects impossible. A similar retrofit project at the Pittsburgh Aviary (now the National Aviary) in 1989 through 1990 provides savings figures that should be comparable to those expected at the Zoo, however. This project cost $100,000 and saved $21,008 in electricity costs during the first year of operation. Maintenance costs were reduced by approximately $5000 a year.

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

    SciTech Connect

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

    2008-11-10

    Aromatase, a member of the cytochrome P450 family, converts androgens such as androstenedione and testosterone to estrone and estradiol respectively. Letrozole (1-[bis-(4-cyanophenyl)methyl]-1H-1,2,4-triazole, Femara{reg_sign}) is a high affinity aromatase inhibitor (K{sub i}=11.5 nM) which has FDA approval for breast cancer treatment. Here we report the synthesis of carbon-11 labeled letrozole and its assessment as a radiotracer for brain aromatase in the baboon. Letrozole and its precursor (4-[(4-bromophenyl)-1H-1,2,4-triazol-1-ylmethyl]benzonitrile, 3) were prepared in two-step syntheses from 4-cyanobenzyl bromide and 4-bromobenzyl bromide, respectively. The [{sup 11}C]cyano group was introduced via the tetrakis(triphenylphosphine)palladium(0) catalyzed coupling of [{sup 11}C]cyanide with the bromo-precursor (3). PET studies in the baboon brain were carried out to assess regional distribution and kinetics, reproducibility of repeated measures and saturability. The free fraction of letrozole in the plasma, log D, and the [{sup 11}C-cyano]letrozole fraction in the arterial plasma were also measured. [{sup 11}C-cyano]Letrozole was synthesized in 60 min with a radiochemical yield of 79-80%, with a radiochemical purity greater than 98% and a specific activity of 4.16 {+-} 2.21 Ci/{micro}mol at the end of bombardment (n=4). PET studies in the baboon revealed initial rapid and high uptake and initial rapid clearance followed by slow clearance of carbon-11 from the brain with no difference between brain regions. The brain kinetics was not affected by co-injection of unlabeled letrozole (0.1 mg/kg). The free fraction of letrozole in plasma was 48.9% and log D was 1.84. [{sup 11}C-cyano]Letrozole is readily synthesized via a palladium catalyzed coupling reaction with [{sup 11}C]cyanide. Although it is unsuitable as a PET radiotracer for brain aromatase as revealed by the absence of regional specificity and saturability in brain regions, such as amygdala, which are known

  9. Radiosynthesis of 11C-Levetiracetam: A Potential Marker for PET Imaging of SV2A Expression

    PubMed Central

    2014-01-01

    The multistep preparation of 11C-levetiracetam (11C-LEV) was carried out by a one-pot radiosynthesis with 8.3 ± 1.6% (n = 8) radiochemical yield in 50 ± 5.0 min. Briefly, the propionaldehyde was converted to propan-1-imine in situ as labeling precursor by incubation with ammonia. Without further separation, the imine was reacted with 11C-HCN to form 11C-aminonitrile. This crude was then reacted with 4-chlorobutyryl chloride and followed by hydrolysis to yield 11C-LEV after purification by chiral high-performance liquid chromatography (HPLC). Both the radiochemical and enantiomeric purities of 11C-LEV were >98%. PMID:25313330

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

    PubMed Central

    Matsuda, Hiroshi; Kubota, Kazoo

    2016-01-01

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

  11. Spectroscopic Classification of Nova M31N 2015-11c

    NASA Astrophysics Data System (ADS)

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

    2015-12-01

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

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

    SciTech Connect

    Xie, Z.Q.; Cerny, J.; Guo, F.Q.; Joosten, R.; Larimer, R.M.; Lyneis, C.M.; McMahan, P.; Norman, E.B.; O'Neil, J.P.; Powell, J.; Rowe, M.W.; VanBrocklin, H.F.; Wutte, D.; Xu, X.J.; Haustein, P.

    1998-10-05

    High charge states, up to fully stripped {sup 11}C and {sup 14}O ion, beams have been produced with the electron cyclotron resonance ion sources (LBNL, ECR and AECR-U) at Lawrence Berkeley National Laboratory. The radioactive atoms of {sup 11}C and {sup 14}O were collected in batch mode with an LN{sub 2} trap and then bled into the ECR ion sources. Ionization efficiency as high as 11% for {sup 11}C{sup 4+} was achieved.

  13. Synthesis and biologic evaluation of 1-(/sup 11/C)-3,3-dimethylheptadecanoic acid

    SciTech Connect

    Jones, G.S. Jr.; Livni, E.; Strauss, H.W.; Hanson, R.N.; Elmaleh, D.R.

    1988-01-01

    1-(/sup 11/C)-3,3-dimethylheptadecanoic acid ((/sup 11/C)DMHDA) has been prepared for evaluation as a potential myocardial metabolism indicator based on an expected intrinsic stability toward beta-oxidative metabolic processes. Synthesis of this novel branched-chain fatty acid was accomplished by copper-catalyzed addition of tetradecylmagnesium bromide to diethylisopropylidenemalonate. Subsequent saponification and decarboxylation afforded 3,3-dimethylheptadecanoic acid (DMHDA) that was converted to the corresponding alkyl bromide by means of a modified Hunsdiecker reaction. Carboxylation of 2,2-dimethylhexadecylmagnesium bromide with /sup 11/CO/sub 2/ gave (/sup 11/C)DMHDA. Carbon-11 DMHDA showed moderate myocardial uptake in fasted rats, albeit lower than that reported for the 3-monomethyl analog. Considerable washout of radioactivity from the heart was also observed over the first 30 min postinjection. Imaging in dogs likewise showed disappointing heart uptake with much higher localization in the lung. These data suggest that gem-dimethyl substitution of the beta-position in long chain fatty acids is not only insufficient for enhanced myocardial uptake and retention, but also, may be deleterious when compared with beta-monomethylation.

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

    PubMed

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

    2016-05-01

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

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

    SciTech Connect

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

    2001-06-10

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

  16. Kinetic analysis of [11C]vorozole binding in the human brain with positron emission tomography.

    PubMed

    Logan, Jean; Kim, Sung Won; Pareto, Deborah; Telang, Frank; Wang, Gene-Jack; Fowler, Joanna S; Biegon, Anat

    2014-01-01

    Using positron emission tomography, we investigated the kinetics of [11C]vorozole ([11C]VOR), a radiotracer for the enzyme aromatase that catalyzes the last step in estrogen biosynthesis. Six subjects were scanned under baseline conditions followed by retest 2 weeks later. The retest was followed by a blocking study with 2.5 mg of the aromatase inhibitor letrozole. The binding potential (BP(A)ND) was estimated from a Lassen plot using the total tissue distribution volume (VT) for baseline and blocked. for the thalamus was found to be 15 times higher than that for the cerebellum. From the letrozole studies, we found that [11C]VOR exhibits a slow binding compartment (small k4) that has a nonspecific and a blockable component. Because of the sensitivity of VT to variations in k4, a common value was used for the four highest binding regions. We also considered the tissue uptake to plasma ratio for 60 to 90 minutes as an outcome measure. Using the ratio method, the difference between the highest and lowest was 2.4 compared to 3.5 for the VT. The ratio method underestimates the high regions but is less variable and may be more suitable for patient studies. Because of its kinetics and distribution, this tracer is not a candidate for a bolus infusion or reference tissue methods.

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

    SciTech Connect

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

    1982-01-01

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

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

    SciTech Connect

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

    1982-01-01

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

  19. Health hazard evaluation report No. HETA 90-010-2170, LTV Steel Company, Pittsburgh, Pennsylvania

    SciTech Connect

    Kinnes, G.M.; Letts, D.

    1991-12-01

    In response to a request from the United Steelworkers of America, an investigation was made of possible causative agents for allergic contact dermatitis in workers who clean the coke oven gas inlets at the LTV Steel Company (SIC-3312), Pittsburgh, Pennsylvania. The LTV Steel coke oven facility consists of five batteries, with a total of 315 by-product ovens. Almost 3 years ago a skin problem of potential occupational origin was identified among the heaters, helpers and patchers. A list of 26 workers with skin problems was developed by the union and management and provided to NIOSH investigators. The suspected causative agent was a condensate from coke oven underfiring gas which collected on gas nozzle seats in the gas heating pipes of specific batteries. The nine employees diagnosed as having occupational allergic contact dermatitis tested positive to at least one of the coke oven gas condensate fractions. Many compounds were identified in the condensate sample. The authors conclude that the dermatitis in some workers was probably caused by contact with the coke oven gas condensates. The authors recommend measures intended to prevent contact with the condensates.

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

    PubMed

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

    1984-01-01

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

  1. Elevated serotonin transporter binding in depressed patients with Parkinson's disease: a preliminary PET study with [11C]DASB.

    PubMed

    Boileau, Isabelle; Warsh, Jerry J; Guttman, Mark; Saint-Cyr, Jean A; McCluskey, Tina; Rusjan, Pablo; Houle, Sylvain; Wilson, Alan A; Meyer, Jeffrey H; Kish, Stephen J

    2008-09-15

    This study investigated whether abnormalities in serotonin transporter binding occur in Parkinson's disease (PD) patients with concurrent depression. We estimated serotonin transporter levels in seven clinically depressed early-stage PD patients and in seven healthy matched-control subjects during a single positron emission tomography (PET) scan with the serotonin transporter radioligand, [(11)C]DASB. Depressed PD patients displayed a wide-spread increase (8-68%) in [(11)C]DASB specific binding outside of the striatum, which was significant in dorsolateral (37%) and prefrontal (68%) cortices. Elevated [(11)C]DASB binding was positively correlated with depressive symptoms but not with disease severity or duration. Compatible with recent PET/[(11)C]DASB findings in major depression, the present preliminary data suggest that increased [(11)C]DASB binding, possibly reflecting greater serotonin transporter density (up-regulation), might be a pathological feature of depression in Parkinson's disease-and possibly a characteristic of depressive illness in general.

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

    SciTech Connect

    Guo, Fanqing

    2004-12-09

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

  3. Smoky ol' town: the significance of Pittsburgh in U.S. air pollution history

    SciTech Connect

    James Longhurst

    2007-06-15

    Pittsburgh came to be - and came to be dirtybecause of location, location, and location. Two navigable rivers met in the middle of a forest, and combined to form a third river. This was an irresistible meeting point for settlement, trade, and industry. It was an added bonus that this meeting point was at the center of the 'Pittsburgh seam' of coal. While the natural advantages of geography and geology initiated development, Pittsburgh's growth soon attracted man-made transportation networks to import resources from its hinterland and spread finished materials through the Midwest. As the city boomed into an industrial metropolis - the Iron City, the Steel City - through the late 19th and early 20th centuries, the smoke only became worse, and Pittsburgh became known, nationally and even internationally, for its dirt, grime, and filth. For many of the city's workers and businessmen, smoke was a sign of progress and economic success. From small-scale iron production, to the process of refining coal into 'coke,' to the Bessemer steel process, to J.P. Morgan and Andrew Carnegie's creation of the vertically-integrated U.S. Steel corporation, to the pioneering use of 'byproduct' coke ovens, Pittsburgh was home to successive technologies for transforming raw materials into finished or refined goods. Pittsburgh is both singular and representative; its story is at the forefront of pollution history, but the forces, trends, and events the city witnessed were the same in many cities across the nation. So while it is true that A&WMA's headquarters are in Pittsburgh for a reason, it is also true that its membership is spread across the nation and the world. That membership will most likely find something in these four themes from Pittsburgh's history that is representative of their own study. 7 refs., 3 photos.

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

    PubMed

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

    2015-06-19

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

  5. Effect of amphetamine on dopamine D2 receptor binding in nonhuman primate brain: a comparison of the agonist radioligand [11C]MNPA and antagonist [11C]raclopride.

    PubMed

    Seneca, Nicholas; Finnema, Sjoerd J; Farde, Lars; Gulyás, Balázs; Wikström, Håkan V; Halldin, Christer; Innis, Robert B

    2006-04-01

    PET measurements of stimulant-induced dopamine (DA) release are typically performed with antagonist radioligands that bind to both the high- and low-affinity state of the receptor. In contrast, an agonist radioligand binds preferentially to the high-affinity state and is expected to have greater sensitivity to DA, which is the endogenous agonist. [(11)C]MNPA, (R)-2-CH(3)O-N-n-propylnorapomorphine (MNPA), is a D(2) agonist radioligand with subnanomolar affinity to the D(2) receptor. The aim of the present study is to assess and compare the sensitivity of the agonist radioligand [(11)C]MNPA and antagonist radioligand [(11)C]raclopride to synaptic DA levels. Four cynomolgus monkeys were examined with [(11)C]MNPA and [(11)C]raclopride (16 PET measurements with each tracer) at baseline and after pretreatment with various doses of amphetamine. The effect of amphetamine was calculated by the change in binding potential (BP) analyzed with the multilinear reference tissue model (MRTM2). Amphetamine caused a reduction in [(11)C]MNPA BP of 4% at 0.1, 23% at 0.2, 25% at 0.5, and 46% at 1.0 mg/kg. [(11)C]Raclopride BP was reduced to a lesser extent by 2% at 0.1, 16% at 0.2, 15% at 0.5, and 23% at 1.0 mg/kg. The data were used to estimate the in vivo percentage of high-affinity state receptors to be approximately 60%. These results demonstrate that [(11)C]MNPA is more sensitive than [(11)C]raclopride to displacement by endogenous DA, and that it may provide additional information about the functional state of the D(2) receptor in illnesses such as schizophrenia and Parkinson's disease.

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

    PubMed Central

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

    2016-01-01

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

  7. L-(1-/sup 11/C)leucine: routine synthesis by enzymatic resolution

    SciTech Connect

    Barrio, J.R.; Keen, R.E.; Ropchan, J.R.; MacDonald, N.S.; Baumgartner, F.J.; Padgett, H.C.; Phelps, M.E.

    1983-06-01

    L-(1-/sup 11/C)leucine, suitable for the determination of cerebal protein synthesis rates in man using positron emission tomography, has been synthesized using a modified Bucherer-Strecker reaction sequence. The isolation of the pure L-amino acid isomer from the enantiomeric mixture, initially obtained using either an open or closed reaction vessel, was achieved using a D-amino acid oxidase/catalase enzyme complex immobilized on a Sepharose support. The O/sub 2/ required by the D-amino acid oxidase as the hydrogen acceptor was supplied by catalase. The L-(1-/sup 11/C)leucine was obtained with a radiochemical purity of >99% and with a radiochemical yield of 25%. Using a remote, semiautomated synthesis system, typical production time was 30 to 40 min after preparation of H/sup 11/CN. The use of immobilized enzymes for rapid and effective resolution of amino acid enantiomers eliminates the possibility of protein contamination and assures the production of a sterile, pyrogen-free product.

  8. Measurement of the cosmogenic 11C background with the Borexino Counting Test Facility

    SciTech Connect

    Franco, D.

    2007-03-28

    Within next year, two organic liquid scintillator detectors, Borexino and KamLAND, will start the measurement of the mono-energetic 7Be solar neutrino flux in real time. Besides this objective, both of them have the potential to detect neutrinos from the pep fusion reaction and the CNO cycle in the Sun.For this purpose, two conditions are required: an extremely low radioactive contamination level and the efficient identification of the 11C background, produced in reactions induced by the residual cosmic muon flux on 12C. In the process, a free neutron is almost always produced. 11C can be tagged on an event by event basis by looking at the three-fold coincidence with the parent muon track and the subsequent neutron capture on protons. We tested successfully this coincidence method with the Borexino Counting Test Facility. The results are reported here.Moreover, we discuss on the effective potential of Borexino and KamLAND in detecting pep+CNO neutrinos compared to SNO+, a detector specifically designed for measuring the pep+CNO {nu} flux and that will take data from 2009.

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

    SciTech Connect

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

    2015-12-15

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

  10. [11C]Flumazenil brain uptake is influenced by the blood-brain barrier efflux transporter P-glycoprotein

    PubMed Central

    2012-01-01

    Background [11C]Flumazenil and positron emission tomography (PET) are used clinically to assess gamma-aminobutyric acid (GABA)-ergic function and to localize epileptic foci prior to resective surgery. Enhanced P-glycoprotein (P-gp) activity has been reported in epilepsy and this may confound interpretation of clinical scans if [11C]flumazenil is a P-gp substrate. The purpose of this study was to investigate whether [11C]flumazenil is a P-gp substrate. Methods [11C]Flumazenil PET scans were performed in wild type (WT) (n = 9) and Mdr1a/1b, (the genes that encode for P-gp) double knockout (dKO) (n = 10) mice, and in naive rats (n = 10). In parallel to PET scanning, [11C]flumazenil plasma concentrations were measured in rats. For 6 of the WT and 6 of the dKO mice a second, [11C]flumazenil scan was acquired after administration of the P-gp inhibitor tariquidar. Cerebral [11C]flumazenil concentrations in WT and Mdr1a/1b dKO mice were compared (genetic disruption model). Furthermore, pre and post P-gp-blocking cerebral [11C]flumazenil concentrations were compared in all animals (pharmacological inhibition model). Results Mdr1a/1b dKO mice had approximately 70% higher [11C]flumazenil uptake in the brain than WT mice. After administration of tariquidar, cerebral [11C]flumazenil uptake in WT mice increased by about 80% in WT mice, while it remained the same in Mdr1a/1b dKO mice. In rats, cerebral [11C]flumazenil uptake increased by about 60% after tariquidar administration. Tariquidar had only a small effect on plasma clearance of flumazenil. Conclusions The present study showed that [11C]flumazenil is a P-gp substrate in rodents. Consequently, altered cerebral [11C]flumazenil uptake, as observed in epilepsy, may not reflect solely GABAA receptor density changes but also changes in P-gp activity. PMID:22455873

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

    PubMed Central

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

    2007-01-01

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

  12. The Pittsburgh Lung Screening Study (PLuSS)

    PubMed Central

    Wilson, David O.; Weissfeld, Joel L.; Fuhrman, Carl R.; Fisher, Stephen N.; Balogh, Paula; Landreneau, Rodney J.; Luketich, James D.; Siegfried, Jill M.

    2008-01-01

    Rationale: The role of computed tomography (CT) screening for lung cancer is controversial, currently under study, and not yet fully elucidated. Objectives: To report findings from initial and 1-year repeat screening low-radiation-dose CT of the chest and 3-year outcomes for 50- to 79-year-old current and ex-smokers in the Pittsburgh Lung Screening Study (PLuSS). Methods: Notified of findings on screening CT, subjects received diagnostic advice from both study and personal physicians. Tracking subjects for up to three years since initial screening, we obtained medical records to document diagnostic procedures, lung cancer diagnoses, and deaths. Measurements and Main Results: 3,642 and 3,423 subjects had initial and repeat screening. A total of 1,477 (40.6% of 3,624) were told about noncalcified lung nodules on the initial screening and, before repeat screening, 821 (55.6% of 1,477, 22.5% of 3,642) obtained one or more subsequent diagnostic imaging studies (CT, positron emission tomography [PET], or PET-CT). Tracking identified 80 subjects with lung cancer, including 53 subjects with tumor seen at initial screening. In all, 36 subjects (1.0% of the 3,642 screened), referred for abnormalities on either the initial or repeat screening, had a major thoracic surgical procedure (thoracotomy, video-assisted thoracoscopic surgery [VATS], median sternotomy, or mediastinoscopy) leading to a noncancer final diagnosis. Out of 82 subjects with thoracotomy or VATS to exclude malignancy in a lung nodule, 28 (34.1%) received a noncancer final diagnosis. Forty of 69 (58%) subjects with non–small cell lung cancer had stage I disease at diagnosis. Conclusions: Though leading to the discovery of early stage lung cancer, CT screening also led to many diagnostic follow-up procedures, including major thoracic surgical procedures with noncancer outcomes. PMID:18635890

  13. Northern and Central Appalachian region assessment: The Pittsburgh coal bed

    SciTech Connect

    Ruppert, L.; Tewalt, S.; Bragg, L.

    1996-12-31

    Approximately 40% of the Nation`s coal is produced in the six states (Ohio, Pennsylvania, West Virginia, Maryland, Virginia, and Kentucky) that occupy parts of the Northern and Central Appalachian region. Coal is, and will continue to be, the primary energy commodity in this region where more than 50 coal beds and coal zones are currently being mined. About one-half of the productions is from just eight coal beds or zones. Three of these, the Pittsburgh and Upper Freeport coal beds and the Kittanning coal zone, are located in the northern part of the region. The remaining beds or zones, the Pond Creek, Fire Clay, Alma, Upper Elkhorn No. 3, and the Pocahontas No. 3, are located primarily in the central part of the region. This study is designed to utilize the data and expertise existing within the USGS and the State Geological Surveys to produce bed-specific, digital, coal resource assessments for most of the top-producing coal beds and coal zones. Unlike past USGS assessments, this study will emphasize not only the quantity of coal but also the quality of the coal. Particular attention will be paid to the geochemical parameters that are thought to adversely effect combustion characteristics and possibly have adverse effects on the environment, including ash yield, sulfur, calorific value, and, the elements listed in the 1990 Clean Air Act Amendments. Geochemical databases produced for the assessed beds will be augmented by new, representative, coal analyses of major, minor, and trace elements. Products will include stratigraphic and geochemical data bases, original and remaining source calculations, and comprehensive digital maps at a scale of 1:250,000 or 1:500,000 of crop-line, coal thickness, coal structure, overburden thickness, mined-out areas, and geochemistry for each assessed coal beds.

  14. New aspects on the preparation of [11C]acetate--a simple and fast approach via distillation.

    PubMed

    Mitterhauser, Markus; Wadsak, Wolfgang; Krcal, Andreas; Schmaljohann, Joern; Bartosch, Ewald; Eidherr, Harald; Viernstein, Helmut; Kletter, Kurt

    2004-12-01

    [11C]Acetate, initially developed for nuclear cardiology has gained increased interest also for oncological problems. A conjoint problem of all preparation methods is the high sensitivity of the Grignard-precursor to moisture, demanding long cleaning and drying procedures of apparatus and reaction vials. Our rationale was to simplify and accelerate the preparation of [11C]acetate by the development of an inert, sterile and disposable system. The present publication deals with the remote-controlled preparation of [11C]acetate via distillation into a buffer ready to use.

  15. Dopamine receptors in pituitary adenomas: PET visualization with 11C-N-methylspiperone

    SciTech Connect

    Muhr, C.; Bergstroem, M.L.; Lundberg, P.O.; Bergstroem, K.H.; Hartvig, P.; Lundqvist, H.; Antoni, G.; Langstroem B2

    1986-03-01

    Two patients with pituitary tumors were examined with positron emission tomography (PET) after intravenous administration of 11C-N-methylspiperone. In repeat studies the patients were given 1 mg of intravenous haloperidol prior to the administration of the radioligand to block the dopamine receptors. High uptakes of the radiolabeled ligand were seen in one of the tumors. With haloperidol pretreatment the uptake was lower, probably mainly showing the remaining unspecific binding. The most marked uptake and the largest effect of haloperidol pretreatment was seen in a patient with a hormonally active prolactinoma. Dopamine receptor binding in pituitary tumors can be demonstrated in vivo with PET, and quantification of this binding is possible using a compartmental model. This technique may be useful in improving our understanding of the variable response to medical treatment of prolactinomas with dopamine agonists as well as in the prediction of the effect of such treatment.

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

    NASA Astrophysics Data System (ADS)

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

    2016-02-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2009-02-01

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

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

    PubMed

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

    2015-02-01

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

  19. 11C level structure via the 10B(p, γ) reaction

    NASA Astrophysics Data System (ADS)

    Wiescher, M.; Boyd, R. N.; Blatt, S. L.; Rybarcyk, L. J.; Spizuoco, J. A.; Azuma, R. E.; Clifford, E. T. H.; King, J. D.; Görres, J.; Rolfs, C.; Vlieks, A.

    1983-10-01

    The reaction 10B(p, γ)11C has been investigated in the energy range Ep=0.07-2.20 MeV. The broad resonant structure previously observed in the ground state transition near Ep=1.2 MeV has been seen also in γ-ray transitions to excited states. The observed excitation functions as well as the γ-ray angular distributions can be explained by assuming several broad overlapping resonances. The low-energy data (Ep<0.6 MeV) reveal the existence of two s-wave resonances at Ep=0.010 and 0.56 MeV. Spectroscopic factors for several final states have been obtained from observation of direct capture processes to them; they are in fair agreement with results from stripping reaction studies. The present data also provide information on partial and total widths of the states at Ex=8-9 MeV. The energy range investigated corresponds to the temperature range of T=(0.01-5)×109 K. The thermonuclear reaction rates deduced from the present results are compared with previously reported values. NUCLEAR REACTIONS 10B(p, γ), Ep=0.07-2.20 MeV; measured γ yield for 11C states up to Ex=10.7 MeV. Deduced resonance parameters, branching ratios, and direct capture contributions for proton-unbound states; deduced spectroscopic factors, ΓγΓtot, and Γtot for several α-unbound states. Calculated thermonuclear reaction rate for T=(0.01-5)×109 K.

  20. Syntheses and pharmacological evaluation of two potent antagonists for dopamine D4 receptors: [11C]YM-50001 and N-[2-[4-(4-Chlorophenyl)-piperizin-1-yl]ethyl]-3-[11C]methoxybenzamide.

    PubMed

    Zhang, Ming-Rong; Haradahira, Terushi; Maeda, Jun; Okauchi, Takashi; Kawabe, Kouichi; Noguchi, Junko; Kida, Takayo; Suzuki, Kazutoshi; Suhara, Tetsuya

    2002-02-01

    Two benzamide derivatives as dopamine D4 receptor antagonists, YM-50001(4) and N- [2-[4-(4-chlorophenyl]piperizin-1-yl]ethyl]-3-methoxybenzamide (9), were labeled by positron-emitter (11C), and their pharmacological specificities to dopamine D4 receptors were examined by quantitative autoradiography and positron emission tomography (PET). Radiosyntheses were accomplished by O-methylation of corresponding phenol precursors (5 and 10) with [11C]CH3I followed by HPLC purifications. In vitro binding on rat brain slices showed different distribution patterns and pharmacological properties between the two radioligands. The [11C]4 showed the highest binding in the striatum, which was inhibited not only by 10 microM 4 but also by 10 microM raclopride, a selective dopamine D2 receptor antagonist. In contrast, [11C]9 showed the highest binding in the cerebral cortex, which was inhibited by several D4 receptor antagonists (9, RBI-254, L-745,870), but not by any other receptor ligands (D1/D5, D2/D3, 5-HT1A, 5-HT2A, sigma1 and alpha1) tested. In vivo brain distribution of [11C]9 in rat showed the highest uptake in the frontal cortex, a region that has a high density of D4 receptors. These results indicate that the pharmacological property of [11C]9 matches the rat brain D4 receptors, but that of [11C]4 rather appears to match the rat brain D2 receptors. The results for the benzamide [11C]9 prompted us to further evaluate its potential as a PET radioligand for D4 receptors by employing PET on monkey brain. Unfortunately, in contrast to rats, neither specific binding nor differences in regional uptake of radioactivity were observed in monkey brain after intravenous 11C]9 injection. Based on that specific activities of radioligands might be critical in mapping the neurotransmitter receptors if they are only faintly expressed in the brain, 11C]9 with an extremely high specific activity (1810 GBq/micromol) was used for PET study. However, the effort to determine the specific binding

  1. Brain serotonin synthesis in MDMA (ecstasy) polydrug users: an alpha-[(11) C]methyl-l-tryptophan study.

    PubMed

    Booij, Linda; Soucy, Jean-Paul; Young, Simon N; Regoli, Martine; Gravel, Paul; Diksic, Mirko; Leyton, Marco; Pihl, Robert O; Benkelfat, Chawki

    2014-12-01

    3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) use may have long-term neurotoxic effects. In this study, positron emission tomography with the tracer alpha-[(11) C]methyl-l-tryptophan ((11) C-AMT) was used to compare human brain serotonin (5-HT) synthesis capacity in 17 currently drug-free MDMA polydrug users with that in 18 healthy matched controls. Gender differences and associations between regional (11) C-AMT trapping and characteristics of MDMA use were also examined. MDMA polydrug users exhibited lower normalized (11) C-AMT trapping in pre-frontal, orbitofrontal, and parietal regions, relative to controls. These differences were more widespread in males than in females. Increased normalized (11) C-AMT trapping in MDMA users was also observed, mainly in the brainstem and in frontal and temporal areas. Normalized (11) C-AMT trapping in the brainstem and pre-frontal regions correlated positively and negatively, respectively, with greater lifetime accumulated MDMA use, longer durations of MDMA use, and shorter time elapsed since the last MDMA use. Although the possibility of pre-existing 5-HT alterations pre-disposing people to use MDMA cannot be ruled out, regionally decreased 5-HT synthesis capacity in the forebrain could be interpreted as neurotoxicity of MDMA on distal (frontal) brain regions. On the other hand, increased 5-HT synthesis capacity in the raphe and adjacent areas could be due to compensatory mechanisms.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2016-06-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2013-12-01

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

  6. Radiosynthesis and Evaluation of [11C]EMPA as a potential PET Tracer for Orexin 2 Receptors

    PubMed Central

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

    2013-01-01

    EMPA is a selective antagonist of orexin 2 (OX2) receptors. Previous literature with [3H]-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 [11C]N-ethyl-2-(N-(6-methoxypyridin-3-yl)-2-methylphenylsulfonamido)-N-(pyridin-3-ylmethyl)acetamide ([11C]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 [11C]CH3I in the presence of cesium carbonate in DMSO at room temp afforded [11C]EMPA in 1.5–2.5% yield (non-decay corrected relative to trapped [11C]CH3I at EOS) with ≥95 % chemical and radiochemical purities. The total synthesis time was 34–36 min from EOB. Studies in rodent suggested that uptake in tissue was dominated by nonspecific binding. However, [11C]EMPA also showed poor uptake in both rats and baboon as measured with PET imaging. PMID:23601709

  7. Synthesis, Biodistribution and In vitro Evaluation of Brain Permeable High Affinity Type 2 Cannabinoid Receptor Agonists [11C]MA2 and [18F]MA3

    PubMed Central

    Ahamed, Muneer; van Veghel, Daisy; Ullmer, Christoph; Van Laere, Koen; Verbruggen, Alfons; Bormans, Guy M.

    2016-01-01

    The type 2 cannabinoid receptor (CB2) is a member of the endocannabinoid system and is known for its important role in (neuro)inflammation. A PET-imaging agent that allows in vivo visualization of CB2 expression may thus allow quantification of neuroinflammation. In this paper, we report the synthesis, radiosynthesis, biodistribution and in vitro evaluation of a carbon-11 ([11C]MA2) and a fluorine-18 ([18F]MA3) labeled analog of a highly potent N-arylamide oxadiazole CB2 agonist (EC50 = 0.015 nM). MA2 and MA3 behaved as potent CB2 agonist (EC50: 3 nM and 0.1 nM, respectively) and their in vitro binding affinity for hCB2 was found to be 87 nM and 0.8 nM, respectively. Also MA3 (substituted with a fluoro ethyl group) was found to have higher binding affinity and EC50 values when compared to the originally reported trifluoromethyl analog 12. [11C]MA2 and [18F]MA3 were successfully synthesized with good radiochemical yield, high radiochemical purity and high specific activity. In mice, both tracers were efficiently cleared from blood and all major organs by the hepatobiliary pathway and importantly these compounds showed high brain uptake. In conclusion, [11C]MA2 and [18F]MA3 are shown to be high potent CB2 agonists with good brain uptake, these favorable characteristics makes them potential PET probes for in vivo imaging of brain CB2 receptors. However, in view of its higher affinity and selectivity, further detailed evaluation of MA3 as a PET tracer for CB2 is warranted. PMID:27713686

  8. Polyinosinic-polycytidylic acid-mediated stimulation of human γδ T cells via CD11c+ dendritic cell-derived type I interferons

    PubMed Central

    Kunzmann, Volker; Kretzschmar, Eva; Herrmann, Thomas; Wilhelm, Martin

    2004-01-01

    The recognition of pathogen-associated molecular patterns (PAMPs) by the innate immune system is a crucial step in inducing effective immune responses. Double-stranded RNA [mimicked by polyinosinic-polycytidylic acid (poly(I:C)], synthesized by various types of viruses, represents one important member of these immunostimulatory microbial components. Here we report that poly(I:C) has potent γδ T-cell costimulatory capacity. Within peripheral blood mononuclear cells, poly(I:C)-stimulated γδ T cells expressed increased levels of CD69 and exhibited significantly enhanced antigen-mediated proliferation in response to isopentenylpyrophosphate (IPP). Among several recombinant cytokines tested, type I interferons (IFN-α, IFN-β) and interleukin-15 (IL-15) showed a similar activation pattern of γδ T cells. γδ T-cell clones and purified γδ T cells did not respond to poly(I:C), indicating indirect effects of this compound. Depletion of CD11c+ dendritic cells (DC), which express Toll-like receptor 3 (TLR3), known to recognize poly(I:C), abrogated poly(I:C)-mediated stimulation of γδ T cells. In addition, the supernatant of poly(I:C)-treated CD11c+ DC was able to mimic the stimulatory effects of poly(I:C) on γδ T cells. Experiments with neutralizing antibodies indicated that type I IFNs, but not IL-15, contributed to the poly(I:C)-mediated activation of γδ T cells. In conclusion, γδ T-cell activation by immunostimulatory double-stranded RNA, such as poly(I:C), is indirectly mediated via type I IFNs derived from TLR3-expressing CD11c+ DCs. These results suggest that upon confrontation with certain viruses, γδ T cells can be rapidly activated by type I interferons and may contribute to effective antiviral responses. PMID:15196204

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

    PubMed Central

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

    2015-01-01

    The aim of this study was to compare 111In-labeled leukocyte single-photon emission computed tomography (SPECT) and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) to PET with tracers that potentially could improve detection of osteomyelitis. We chose 11C-methionine, 11C-PK11195 and 68Ga-citrate and validated their diagnostic utility in a porcine haematogenous osteomyelitis model. Four juvenile 14-15 weeks old female pigs were scanned seven days after intra-arterial inoculation in the right femoral artery with a porcine strain of Staphylococcus aureus using a sequential scan protocol with 18F-FDG, 68Ga-citrate, 11C-methionine, 11C-PK11195, 99mTc-Nanocoll and 111In-labelled autologous leukocytes. This was followed by necropsy of the pigs and gross pathology, histopathology and microbial examination. The pigs developed a total of five osteomyelitis lesions, five lesions characterized as abscesses/cellulitis, arthritis in three joints and five enlarged lymph nodes. None of the tracers accumulated in joints with arthritis. By comparing the 10 infectious lesions, 18F-FDG accumulated in nine, 111In-leukocytes in eight, 11C-methionine in six, 68Ga-citrate in four and 11C-PK11195 accumulated in only one lesion. Overall, 18F-FDG PET was superior to 111In-leukocyte SPECT in marking infectious and proliferative, i.e. hyperplastic, lesions. However, leukocyte SPECT was performed as early scans, approximately 6 h after injection of the leukocytes, to match the requirements of the 18 h long scan protocol. 11C-methionine and possibly 68Ga-citrate may be useful for diagnosis of soft issue lesions. PMID:25973338

  10. 11C-Acetate PET/CT Imaging in Localized Prostate Cancer: A study with MRI and Histopathologic Correlation

    PubMed Central

    Mena, Esther; Turkbey, Baris; Mani, Haresh; Adler, Stephen; Valera, Vladimir A.; Bernardo, Marcelino; Shah, Vijay; Pohida, Thomas; McKinney, Yolanda; Kwarteng, Gideon; Daar, Dagane; Lindenberg, Maria L.; Eclarinal, Philip; Wade, Revia; Linehan, W. Marston; Merino, Maria J.; Pinto, Peter A.; Choyke, Peter L.; Kurdziel, Karen A.

    2012-01-01

    This work characterizes the uptake of 11C-Acetate in prostate cancer (PCa), benign prostate hyperplasia (BPH) and normal prostate tissue in comparison with multi-parametric MRI, whole mount histopathology and clinical markers, to evaluate its potential utility for delineating intra-prostatic tumors in a population of patients with localized PCa. METHODS 39 men with presumed localized PCa underwent dynamic/static abdomen-pelvic 11C-Acetate PET/CT for 30-minutes and 3T multi-parametric (MP) MRI prior to prostatectomy. PET/CT images were registered to MRI using pelvic bones for initial rotation-translation, followed by manual adjustments to account for prostate motion and deformation from the MRI endorectal coil. Whole-mount pathology specimens were sectioned using an MRI-based patient specific mold resulting in improved registration between the MRI, PET and pathology. 11C-Acetate PET standardized uptake values were compared with MP-MRI and pathology. RESULTS 11C-Acetate uptake was rapid but reversible, peaking at 3–5 minutes post-injection and reaching a relative plateau at ~10 minutes. The average SUVmax(10–12min) of tumors was significantly higher than that of normal prostate tissue (4.4±2.05, range 1.8–9.2 vs. 2.1±0.94, range 0.7–3.4; p<0.001); however it was not significantly different from benign prostatic hyperplasia (4.8±2.01; range 1.8–8.8). A sector-based comparison with histopathology, including all tumors > 0.5 cm, revealed a sensitivity and specificity of 61.6 % and 80.0 % for 11C-Acetate PET/CT, and 82.3% and 95.1% for MRI, respectively. Considering only tumors >0.9 cm the 11C-Acetate accuracy was comparable to that of MRI. In a small cohort (n=9), 11C-Acetate uptake was independent of fatty acid synthase expression based on immunohistochemistry. CONCLUSION 11C-Acetate PET/CT demonstrates higher uptake in tumor foci than normal prostate tissue; however 11C-Acetate uptake in tumors is similar to BPH nodules. While 11C-Acetate PET/CT is not

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

    PubMed Central

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

    2016-01-01

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

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

    SciTech Connect

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

    1995-05-01

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

  13. Promoting positive pediatric experiences for nursing students at the Children's Hospital of Pittsburgh of UPMC.

    PubMed

    Bagay, Joann Marie

    2014-01-01

    Challenges in professional nursing education today can be astonishing. Cognizant of the commitment to provide the most valuable learning experiences for our future nurses, academia and service organizations strive to meet this challenge. The escalation in nursing school enrollment, along with the increase in patient acuity and ongoing health care changes, requires hospitals and schools to continually review their practices to ensure positive outcomes. Providing pediatric nursing experiences to over 1,300 students annually, Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center (UPMC) implemented a process to meet this need. A Faculty Advisory Council was established to provide a venue for representative nursing instructors to meet with the Nursing Education Department at the hospital. The commonality of focus by nursing faculty and Children's Hospital continues to strengthen both academia and service. This well-defined process supports positive pediatric experiences for nursing students at Children's Hospital of Pittsburgh of UPCM.

  14. Promoting positive pediatric experiences for nursing students at the Children's Hospital of Pittsburgh of UPMC.

    PubMed

    Bagay, Joann Marie

    2014-01-01

    Challenges in professional nursing education today can be astonishing. Cognizant of the commitment to provide the most valuable learning experiences for our future nurses, academia and service organizations strive to meet this challenge. The escalation in nursing school enrollment, along with the increase in patient acuity and ongoing health care changes, requires hospitals and schools to continually review their practices to ensure positive outcomes. Providing pediatric nursing experiences to over 1,300 students annually, Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center (UPMC) implemented a process to meet this need. A Faculty Advisory Council was established to provide a venue for representative nursing instructors to meet with the Nursing Education Department at the hospital. The commonality of focus by nursing faculty and Children's Hospital continues to strengthen both academia and service. This well-defined process supports positive pediatric experiences for nursing students at Children's Hospital of Pittsburgh of UPCM. PMID:25134230

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

    PubMed Central

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

    2015-01-01

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

  16. Histone Deacetylase Inhibitor MS-275 Exhibits Poor Brain Penetration: Pharmacokinetic Studies of [11C]MS-275 using Positron Emission Tomography

    PubMed Central

    2009-01-01

    MS-275 (entinostat) is a histone deacetylase (HDAC) inhibitor currently in clinical trials for the treatment of several types of cancer. Recent reports have noted that MS-275 can cross the blood−brain barrier (BBB) and cause region-specific changes in rodent brain histone acetylation. To characterize the pharmacokinetics and distribution of MS-275 in the brain using positron emission tomography (PET), we labeled the carbamate carbon of MS-275 with carbon-11. Using PET, we determined that [11C]MS-275 has low uptake in brain tissue when administered intravenously to nonhuman primates. In rodent studies, we observed that pharmacokinetics and brain accumulation of [11C]MS-275 were not changed by the coadministration of large doses of unlabeled MS-275. These results, which both highlight the poor brain penetration of MS-275, clearly suggest its limitation as a therapeutic agent for the central nervous system (CNS). Moreover, our study demonstrates the effectiveness of PET at providing brain pharmacokinetic data for HDAC inhibitors. These data are important not only for the development of new compounds for peripheral cancer treatment (where CNS exclusion is often advantageous) but also for the treatment of neurological disorders (where CNS penetration is critical). PMID:20657706

  17. The effects of aging on dopaminergic neurotransmission: a microPET study of [11C]-raclopride binding in the aged rodent brain.

    PubMed

    Hoekzema, E; Herance, R; Rojas, S; Pareto, D; Abad, S; Jiménez, X; Figueiras, F P; Popota, F; Ruiz, A; Torrent, È; Fernández-Soriano, F J; Rocha, M; Rovira, M; Víctor, V M; Gispert, J D

    2010-12-29

    Rodent models are frequently used in aging research to investigate biochemical age effects and aid in the development of therapies for pathological and non-pathological age-related degenerative processes. In order to validate the use of animal models in aging research and pave the way for longitudinal intervention-based animal studies, the consistency of cerebral aging processes across species needs to be evaluated. The dopaminergic system seems particularly susceptible to the aging process, and one of the most consistent findings in human brain aging research is a decline in striatal D2-like receptor (D2R) availability, quantifiable by positron emission tomography (PET) imaging. In this study, we aimed to assess whether similar age effects can be discerned in rat brains, using in vivo molecular imaging with the radioactive compound [(11)C]-raclopride. We observed a robust decline in striatal [(11)C]-raclopride uptake in the aged rats in comparison to the young control group, comprising a 41% decrement in striatal binding potential. In accordance with human studies, these results indicate that substantial reductions in D2R availability can be measured in the aged striatal complex. Our findings suggest that rat and human brains exhibit similar biochemical alterations with age in the striatal dopaminergic system, providing support for the pertinence of rodent models in aging research.

  18. Histone Deacetylase Inhibitor MS-275 Exhibits Poor Brain Penetration: Pharmacokinetic Studies of [11C]MS-275 using Positron Emission Tomography

    SciTech Connect

    Hooker, J.M.; Hooker, J.M.; Kim, S.W.; Alexoff, D.; Xu, Y.; Shea, C.; Reid, A.; Volkow, N.D.; Fowler, J.S.

    2009-10-01

    MS-275 (entinostat) is a histone deacetylase (HDAC) inhibitor currently in clinical trials for the treatment of several types of cancer. Recent reports have noted that MS-275 can cross the blood-brain barrier (BBB) and cause region-specific changes in rodent brain histone acetylation. To characterize the pharmacokinetics and distribution of MS-275 in the brain using positron emission tomography (PET), we labeled the carbamate carbon of MS-275 with carbon-11. Using PET, we determined that [{sup 11}C]MS-275 has low uptake in brain tissue when administered intravenously to nonhuman primates. In rodent studies, we observed that pharmacokinetics and brain accumulation of [{sup 11}C]MS-275 were not changed by the coadministration of large doses of unlabeled MS-275. These results, which both highlight the poor brain penetration of MS-275, clearly suggest its limitation as a therapeutic agent for the central nervous system (CNS). Moreover, our study demonstrates the effectiveness of PET at providing brain pharmacokinetic data for HDAC inhibitors. These data are important not only for the development of new compounds for peripheral cancer treatment (where CNS exclusion is often advantageous) but also for the treatment of neurological disorders (where CNS penetration is critical).

  19. Dopamine D3 Receptor Alterations in Cocaine-Dependent Humans Imaged with [11C](+)PHNO

    PubMed Central

    Matuskey, David; Gallezot, Jean-Dominique; Pittman, Brian; Williams, Wendol; Wanyiri, Jane; Gaiser, Edward; Lee, Dianne E.; Hannestad, Jonas; Lim, Keunpoong; Zheng, Minq-Qiang; Lin, Shu-fei; Labaree, David; Potenza, Marc N.; Carson, Richard E.; Malison, Robert T.; Ding, Yu-Shin

    2014-01-01

    Background Evidence from animal models and postmortem human studies points to the importance of the dopamine D3 receptor (D3R) in cocaine dependence (CD). The objective of this pilot study was to use the D3R-preferring radioligand [11C](+)PHNO to compare receptor availability in groups with and without CD. Methods Ten medically healthy, non-treatment seeking CD subjects (mean age 41±8) in early abstinence were compared to 10 healthy control (HC) subjects (mean age 41±6) with no history of cocaine or illicit substance abuse. Binding potential (BPND), a measure of available receptors, was determined with parametric images, computed using the simplified reference tissue model (SRTM2) with the cerebellum as the reference region. Results BPND in CD subjects was higher in D3R-rich areas including the substantia nigra ((SN) 29%; P=0.03), hypothalamus (28%; P=0.02) and amygdala (35%, P=0.03). No between-group differences were observed in the striatum or pallidum. BPND values in the SN (r = + 0.83; p =0.008) and pallidum (r = + 0.67; p = 0.03) correlated with years of cocaine use. Conclusions Between-group differences suggest an important role for dopaminergic transmission in the SN, hypothalamus and amygdala in CD. Such findings also highlight the potential relevance of D3R as a medication development target in CD. PMID:24717909

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

    PubMed

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

    2014-11-01

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

  1. Activated MAO-B in the brain of Alzheimer patients, demonstrated by [11C]-L-deprenyl using whole hemisphere autoradiography.

    PubMed

    Gulyás, Balázs; Pavlova, Elena; Kása, Péter; Gulya, Károly; Bakota, Lidia; Várszegi, Szilvia; Keller, Eva; Horváth, Mónika Csilla; Nag, Sangram; Hermecz, István; Magyar, Kálmán; Halldin, Christer

    2011-01-01

    In the human brain the monoaminooxidase-B enzyme or MAO-B is highly abundant in astrocytes. As astrocyte activity and, consequently, the activity of the MAO-B enzyme, is up-regulated in neuroinflammatory processes, radiolabelled analogues of deprenyl may serve as an imaging biomarker in neuroinflammation and neurodegeneration, including Alzheimer's disease. In the present study [(11)C]-L-deprenyl, the PET radioligand version of L-deprenyl or selegiline®, a selective irreversible MAO-B inhibitor was used in whole hemisphere autoradiographic experiments in human brain sections in order to test the radioligand's binding to the MAO-B enzyme in human brain tissue, with an eye on exploring the radioligand's applicability as a molecular imaging biomarker in human PET studies, with special regard to diagnostic detection of reactive astrogliosis. Whole hemisphere brain sections obtained from Alzheimer patients and from age matched control subjects were examined. In control brains the binding of [(11)C]-L-deprenyl was the highest in the hippocampus, in the basal ganglia, the thalamus, the substantia nigra, the corpus geniculatum laterale, the nucleus accumbens and the periventricular grey matter. In Alzheimer brains significantly higher binding was observed in the temporal lobes and the white matter. Furthermore, in the Alzheimer brains in the hippocampus, temporal lobe and white matter the binding negatively correlated with Braak stages. The highest binding was observed in Braak I-II, whereas it decreased with increasing Braak grades. The increased regional binding in Alzheimer brains coincided with the presence of an increased number of activated astrocytes, as demonstrated by correlative immunohistochemical studies with GFAP in adjacent brain slices. Deprenyl itself as well as the MAO-B antagonist rasagiline did effectively block the binding of the radioligand, whereas the MAO-A antagonist pirlindole did not affect it. Compounds with high affinity for the PBR system did

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

    PubMed Central

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

    2015-01-01

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

  3. Mass size distributions and size resolved chemical composition of fine particulate matter at the Pittsburgh supersite

    NASA Astrophysics Data System (ADS)

    Cabada, Juan C.; Rees, Sarah; Takahama, Satoshi; Khlystov, Andrey; Pandis, Spyros N.; Davidson, Cliff I.; Robinson, Allen L.

    Size-resolved aerosol mass and chemical composition were measured during the Pittsburgh Air Quality Study. Daily samples were collected for 12 months from July 2001 to June 2002. Micro-orifice uniform deposit impactors (MOUDIs) were used to collect aerosol samples of fine particulate matter smaller than 10 μm. Measurements of PM 0.056, PM 0.10, PM 0.18, PM 0.32, PM 0.56, PM 1.0, PM 1.8 and PM 2.5 with the MOUDI are available for the full study period. Seasonal variations in the concentrations are observed for all size cuts. Higher concentrations are observed during the summer and lower during the winter. Comparison between the PM 2.5 measurements by the MOUDI and other integrated PM samplers reveals good agreement. Good correlation is observed for PM 10 between the MOUDI and an integrated sampler but the MOUDI underestimates PM 10 by 20%. Bouncing of particles from higher stages of the MOUDI (>PM 2.5) is not a major problem because of the low concentrations of coarse particles in the area. The main cause of coarse particle losses appears to be losses to the wall of the MOUDI. Samples were collected on aluminum foils for analysis of carbonaceous material and on Teflon filters for analysis of particle mass and inorganic anions and cations. Daily samples were analyzed during the summer (July 2001) and the winter intensives (January 2002). During the summer around 50% of the organic material is lost from the aluminum foils as compared to a filter-based sampler. These losses are due to volatilization and bounce-off from the MOUDI stages. High nitrate losses from the MOUDI are also observed during the summer (above 70%). Good agreement between the gravimetrically determined mass and the sum of the masses of the individual compounds is obtained, if the lost mass from organics and the aerosol water content are included for the summer. For the winter no significant losses of material are detected and there exists reasonable agreement between the gravimetrical mass and the

  4. Novel monoclonal antibody against alphaX subunit from horse CD11c/CD18 integrin.

    PubMed

    Espino-Solis, Gerardo Pavel; Quintero-Hernandez, Veronica; Olvera-Rodriguez, Alejandro; Calderon-Amador, Juana; Pedraza-Escalona, Martha; Licea-Navarro, Alexei; Flores-Romo, Leopoldo; Possani, Lourival Domingos

    2015-04-15

    The αX I-domain of the horse integrin CD11c was successfully expressed in Escherichia coli, purified, biochemically characterized and used as immunogen to generate murine monoclonal antibodies against horse CD11c, which are not yet commercially available. One monoclonal antibody mAb-1C4 against the αX I-domain, is an IgG2a able to interact with the recombinant I-domain, showing an EC50=2.4ng according to ELISA assays. By western blot with horse PBMCs lysates the mAb-1C4 recognized a protein of 150kDa which corresponds well with the CD11c molecule. Using immunohistochemistry in horse lymph node tissue sections, mAb-1C4 marked cells in situ, some with apparent dendritic morphology. Thus the mAb generated to a recombinant epitope from horse CD11c identified the molecule in intact cells within horse lymphoid tissue. By the labelling intensity, the histological location (paracortical and interfollicular areas) and the apparent morphology of the marked cells, we can say that these are putative horse dendritic cells (DCs). The development of a mAb to horse CD11c provides a new tool to better study the horse DC biology and opens other biotechnological avenues, such as DC targeting-based vaccines.

  5. How Roebling did it: Building the world's first wire-rope suspension aqueduct in 1840s Pittsburgh

    NASA Astrophysics Data System (ADS)

    Gibbon, Donald L.

    2006-05-01

    The noted bridge designed John Roebling introduced his wire-rope suspension concept in Pittsburgh on a wooden aqueduct. His design was later implemented in bridges in Pittsburgh and elsewhere, including New York's Brooklyn Bridge. This article describes Roebling's work based on reviews of his notes and other historical documents.

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

    PubMed Central

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

    2016-01-01

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

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

    SciTech Connect

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

    1984-07-01

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

  8. α-[11C]-Methyl-l-tryptophan–PET in 191 patients with tuberous sclerosis complex

    PubMed Central

    Luat, Aimee F.; Kumar, Ajay; Govindan, Rajkumar; Pawlik, Kathy; Asano, Eishi

    2013-01-01

    Objectives: This was an observational study done on a large cohort of patients with tuberous sclerosis complex (TSC) to determine whether i) the presence of α-[11C]-methyl-l-tryptophan (AMT) hotspots is related to the duration of seizure intractability, ii) the presence of AMT hotspots is related to specific TSC gene mutations, and iii) there is concordance between areas with an AMT hotspot and seizure lateralization/localization on scalp EEG. Methods: One hundred ninety-one patients (mean age: 6.7 years; median: 5 years; range: 3 months to 37 years) with TSC and intractable epilepsy were included. All patients underwent AMT-PET scan. AMT uptake in each tuber and normal-appearing cortex was measured and correlated with clinical, scalp EEG, and, if available, electrocorticographic data. Results: The longer the duration of seizure intractability, the greater the number of AMT hotspots (r = 0.2; p = 0.03). AMT hotspots were seen in both TSC1 and TSC2. There was excellent agreement in seizure focus lateralization between ictal scalp EEG and AMT-PET (Cohen κ 0.94) in 68 of 95 patients in whom both ictal video-EEG and AMT-PET showed lateralizing findings; in 28 of 68 patients (41%), AMT was more localizing. Furthermore, AMT-PET was localizing in 10 of 17 patients (58%) with nonlateralized ictal EEG. Conclusion: AMT-PET, when used together with video-EEG, provides additional lateralization/localization data, regardless of TSC mutation. The duration of seizure intractability may predict the multiplicity of areas with AMT hotspots. PMID:23851963

  9. Lack of endogenous opioid release during sustained visceral pain: a [11C]carfentanil PET study.

    PubMed

    Ly, Huynh Giao; Dupont, Patrick; Geeraerts, Brecht; Bormans, Guy; Van Laere, Koen; Tack, Jan; Van Oudenhove, Lukas

    2013-10-01

    Opioidergic neurotransmission in the central nervous system is involved in somatic pain, but its role in visceral pain remains unknown. We aimed to quantify endogenous opioid release in the brain during sustained painful gastric distension. Therefore, 2 dynamic [11C]carfentanil positron emission tomography scans were performed in 20 healthy subjects during 2 conditions: sustained (20 minutes) painful proximal gastric balloon distension at predetermined individual discomfort threshold (PAIN) and no distension (NO PAIN), in counterbalanced order. Pain levels were assessed during scanning using visual analogue scales and after scanning using the McGill Pain Questionnaire. Emotional state was rated after scanning using the Positive and Negative Affect Schedule. Distribution volume ratios in 21 volumes of interest in the pain matrix were used to quantify endogenous opioid release. During the PAIN compared to the NO PAIN condition, volunteers reported a significantly higher increase in negative affect (5.50±1.29 versus 0.10±1.08, P=.0147) as well as higher pain ratings (sensory: 74.05±9.23 versus 1.50±0.95, P<.0001; affective: 91.42±8.13 versus 4.33±6.56, P<.0001). No difference in endogenous opioid release was demonstrated in any of the volumes of interest. Thus, contrary to its somatic counterpart, no opioid release is detected in the brain during sustained visceral pain, despite similar pain intensities. Endogenous opioids may play a less important role in visceral compared to somatic pain.

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

    NASA Astrophysics Data System (ADS)

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

    2016-01-01

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

  11. Estimating the effect of endogenous dopamine on baseline [(11) C]-(+)-PHNO binding in the human brain.

    PubMed

    Caravaggio, Fernando; Kegeles, Lawrence S; Wilson, Alan A; Remington, Gary; Borlido, Carol; Mamo, David C; Graff-Guerrero, Ariel

    2016-11-01

    Endogenous dopamine (DA) levels at dopamine D2/3 receptors (D2/3 R) have been quantified in the living human brain using the agonist radiotracer [(11) C]-(+)-PHNO. As an agonist radiotracer, [(11) C]-(+)-PHNO is more sensitive to endogenous DA levels than antagonist radiotracers. We sought to determine the proportion of the variance in baseline [(11) C]-(+)-PHNO binding to D2/3 Rs which can be accounted for by variation in endogenous DA levels. This was done by computing the Pearson's coefficient for the correlation between baseline binding potential (BPND ) and the change in BPND after acute DA depletion, using previously published data. All correlations were inverse, and the proportion of the variance in baseline [(11) C]-(+)-PHNO BPND that can be accounted for by variation in endogenous DA levels across the striatal subregions ranged from 42-59%. These results indicate that lower baseline values of [(11) C]-(+)-PHNO BPND reflect greater stimulation by endogenous DA. To further validate this interpretation, we sought to examine whether these data could be used to estimate the dissociation constant (Kd) of DA at D2/3 R. In line with previous in vitro work, we estimated the in vivo Kd of DA to be around 20 nM. In summary, the agonist radiotracer [(11) C]-(+)-PHNO can detect the impact of endogenous DA levels at D2/3 R in the living human brain from a single baseline scan, and may be more sensitive to this impact than other commonly employed radiotracers. PMID:27341789

  12. Elevation of dopamine induced by cigarette smoking: novel insights from a [11C]-+-PHNO PET study in humans.

    PubMed

    Le Foll, Bernard; Guranda, Mihail; Wilson, Alan A; Houle, Sylvain; Rusjan, Pablo M; Wing, Victoria C; Zawertailo, Laurie; Busto, Usoa; Selby, Peter; Brody, Arthur L; George, Tony P; Boileau, Isabelle

    2014-01-01

    Positron emission tomography (PET) has convincingly provided in vivo evidence that psychoactive drugs increase dopamine (DA) levels in human brain, a feature thought critical to their reinforcing properties. Some controversy still exists concerning the role of DA in reinforcing smoking behavior and no study has explored whether smoking increases DA concentrations at the D3 receptor, speculated to have a role in nicotine's addictive potential. Here, we used PET and [(11)C]-(+)-PHNO ([(11)C]-(+)-4-propyl-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol) to test the hypothesis that smoking increases DA release (decreases [(11)C]-(+)-PHNO binding) in D2-rich striatum and D3-rich extra-striatal regions and is related to craving, withdrawal and smoking behavior. Ten participants underwent [(11)C]-(+)-PHNO scans after overnight abstinence and after smoking a cigarette. Motivation to smoke (smoking topography), mood, and craving were recorded. Smoking significantly decreased self-reported craving, withdrawal, and [(11)C]-(+)-PHNO binding in D2 and D3-rich areas (-12.0 and -15.3%, respectively). We found that motivation to smoke (puff rate) predicted magnitude of DA release in limbic striatum, and the latter was correlated with decreased craving and withdrawal symptoms. This is the first report suggesting that, in humans, DA release is increased in D3-rich areas in response to smoking. Results also support the preferential involvement of the limbic striatum in motivation to smoke, anticipation of pleasure from cigarettes and relief of withdrawal symptoms. We propose that due to the robust effect of smoking on [(11)C]-(+)-PHNO binding, this radiotracer represents an ideal translational tool to investigate novel therapeutic strategies targeting DA transmission.

  13. Kinetic brain analysis and whole-body imaging in monkey of [11C]MNPA: a dopamine agonist radioligand.

    PubMed

    Seneca, Nicholas; Skinbjerg, Mette; Zoghbi, Sami S; Liow, Jeih-San; Gladding, Robert L; Hong, Jinsoo; Kannan, Pavitra; Tuan, Edward; Sibley, David R; Halldin, Christer; Pike, Victor W; Innis, Robert B

    2008-09-01

    With a view to future extension of the use of the agonist radioligand [(11)C]MNPA ([O-methyl-(11)C]2-methoxy-N-propylnorapomorphine) from animals to humans, we performed two positron emission tomography (PET) studies in monkeys. First, we assessed the ability to quantify the brain uptake of [(11)C]MNPA with compartmental modeling. Second, we estimated the radiation exposure of [(11)C]MNPA to human subjects based on whole-body imaging in monkeys. Brain PET scans were acquired for 90 min and included concurrent measurements of the plasma concentration of unchanged radioligand. Time-activity data from striatum and cerebellum were quantified with two methods, a reference tissue model and distribution volume. Whole-body PET scans were acquired for 120 min using four bed positions from head to mid thigh. Regions of interest were drawn on compressed planar whole-body images to identify organs with the highest radiation exposures. After injection of [(11)C]MNPA, the highest concentration of radioactivity in brain was in striatum, with lowest levels in cerebellum. Distribution volume was well identified with a two-tissue compartmental model and was quite stable from 60 to 90 min. Whole-body PET scans showed the organ with the highest radiation burden (muSv/MBq) was the urinary bladder wall (26.0), followed by lungs (22.5), gallbladder wall (21.9), and heart wall (16.1). With a 2.4-h voiding interval, the effective dose was 6.4 muSv/MBq (23.5 mrem/mCi). In conclusion, brain uptake of [(11)C]MNPA reflected the density of D(2/3) receptors, quantified relative to serial arterial measurements, and caused moderate to low radiation exposure.

  14. Kinetic Analysis and Quantification of [11C]Martinostat for in vivo HDAC Imaging of the Brain

    PubMed Central

    Wey, Hsiao-Ying; Wang, Changning; Schroeder, Frederick A.; Logan, Jean; Price, Julie C.; Hooker, Jacob M.

    2015-01-01

    Epigenetic mechanisms mediated by histone deacetylases (HDACs) have been implicated in a wide-range of CNS disorders and may offer new therapeutic opportunities. In vivo evaluation of HDAC density and drug occupancy has become possible with [11C]Martinostat, which exhibits selectivity for a subset of class I/IIb HDAC enzymes. In this study, we characterize the kinetic properties of [11C]Martinostat in the nonhuman primate (NHP) brain in preparation for human neuroimaging studies. The goal of this work was to determine whether classic compartmental analysis techniques were appropriate and to further determine if arterial plasma is required for future NHP studies. Using an arterial plasma input function, several analysis approaches were evaluated for robust outcome measurements. [11C]Martinostat showed high baseline distribution volume (VT) ranging from 29.9–54.4 mL/cm3 in the brain and large changes in occupancy (up to 99%) with a blocking dose approaches full enzyme saturation. An averaged nondisplaceable tissue uptake (VND) of 8.6 ± 3.7 mL/cm3 suggests high specific binding of [11C]Martinostat. From a two-tissue compartment model, [11C]Martinostat exhibits a high K1 (averaged K1 of 0.65 mL/cm3/min) and a small k4 (average of 0.0085 min−1). Our study supports that [11C]Martinostat can be used to detect changes in HDAC density and occupancy in vivo and that simplified analysis not using arterial blood could be appropriate. PMID:25768025

  15. SPM analysis of parametric (R)-[11C]PK11195 binding images: plasma input versus reference tissue parametric methods.

    PubMed

    Schuitemaker, Alie; van Berckel, Bart N M; Kropholler, Marc A; Veltman, Dick J; Scheltens, Philip; Jonker, Cees; Lammertsma, Adriaan A; Boellaard, Ronald

    2007-05-01

    (R)-[11C]PK11195 has been used for quantifying cerebral microglial activation in vivo. In previous studies, both plasma input and reference tissue methods have been used, usually in combination with a region of interest (ROI) approach. Definition of ROIs, however, can be labourious and prone to interobserver variation. In addition, results are only obtained for predefined areas and (unexpected) signals in undefined areas may be missed. On the other hand, standard pharmacokinetic models are too sensitive to noise to calculate (R)-[11C]PK11195 binding on a voxel-by-voxel basis. Linearised versions of both plasma input and reference tissue models have been described, and these are more suitable for parametric imaging. The purpose of this study was to compare the performance of these plasma input and reference tissue parametric methods on the outcome of statistical parametric mapping (SPM) analysis of (R)-[11C]PK11195 binding. Dynamic (R)-[11C]PK11195 PET scans with arterial blood sampling were performed in 7 younger and 11 elderly healthy subjects. Parametric images of volume of distribution (Vd) and binding potential (BP) were generated using linearised versions of plasma input (Logan) and reference tissue (Reference Parametric Mapping) models. Images were compared at the group level using SPM with a two-sample t-test per voxel, both with and without proportional scaling. Parametric BP images without scaling provided the most sensitive framework for determining differences in (R)-[11C]PK11195 binding between younger and elderly subjects. Vd images could only demonstrate differences in (R)-[11C]PK11195 binding when analysed with proportional scaling due to intersubject variation in K1/k2 (blood-brain barrier transport and non-specific binding).

  16. Radiation dosimetry of N-([11C]methyl)benperidol as determined by whole-body PET imaging of primates

    PubMed Central

    Antenor-Dorsey, Jo Ann V.; Laforest, Richard; Moerlein, Stephen M.; Videen, Tom O.

    2010-01-01

    Purpose N-([11C]methyl)benperidol ([11C]NMB) can be used for positron emission tomography (PET) measurements of D2-like dopamine receptor binding in vivo. We report the absorbed radiation dosimetry of i.v.-administered 11C-NMB, a critical step before applying this radioligand to imaging studies in humans. Materials and methods Whole-body PET imaging with a CTI/Siemens ECAT 953B scanner was done in a male and a female baboon. After i.v. injection of 444–1221 MBq of 11C-NMB, sequential images taken from the head to the pelvis were collected for 3 h. Volumes of interest (VOIs) were identified that entirely encompassed small organs (whole brain, striatum, eyes, and myocardium). Large organs (liver, lungs, kidneys, lower large intestine, and urinary bladder) were sampled by drawing representative regions within the organ volume. Time–activity curves for each VOI were extracted from the PET, and organ residence times were calculated by analytical integration of a multi-exponential fit of the time–activity curves. Human radiation doses were estimated using OLINDA/EXM 1.0 and the standard human model. Results Highest retention was observed in the blood and liver, each with total residence times of 1.5 min. The highest absorbed radiation doses were to the heart (10.5 mGy/kBq) and kidney (9.19 mGy/kBq), making these the critical organs for [11C]NMB. A heart absorption of 50 mGy would result from an injected dose of 4,762 MBq [11C]NMB. Conclusions Thus, this study suggests that up to 4,762 MBq of [11C]NMB can be safely administered to human subjects for PET studies. Total body dose and effective dose for [11C] NMB are 2.82 mGy/kBq and 3.7 mSv/kBq, respectively. PMID:18071701

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

    PubMed

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

    2005-06-01

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

  18. The Nonprofit Clinic at the University of Pittsburgh: Preparing Students for Transition to Professional Settings

    ERIC Educational Resources Information Center

    Kearns, Kevin P.

    2014-01-01

    The Nonprofit Clinic at the University of Pittsburgh gives graduate students the opportunity to serve as management consultants to nonprofit organizations. This article describes the learning objectives, logistics, and outcomes of the Nonprofit Clinic. Bloom's 1956 taxonomy of learning objectives is employed to assess learning outcomes.

  19. Teacher Quality Roadmap: Improving Policies and Practices in Pittsburgh Public Schools

    ERIC Educational Resources Information Center

    Gonzalez, Angel; Kumar, Sudipti; Waymack, Nancy

    2014-01-01

    The Pittsburgh Public Schools study is the 12th district study since the National Council on Teacher Quality (NCTQ) began studying districts in-depth in 2009. The intent of these studies is to give select communities a comprehensive look at what is happening in their local school districts that may be either helping or hurting teacher quality, and…

  20. The Use of Research Libraries: A Comment about the Pittsburgh Study and Its Critics.

    ERIC Educational Resources Information Center

    Peat, W. Leslie

    1981-01-01

    Reviews the controversy surrounding the Pittsburgh study of library circulation and collection usage and proposes the use of citation analysis techniques as an acceptable method for measuring research use of a research library which will complement circulation studies. Five references are listed. (RAA)

  1. Higher Education Sustainability in Pittsburgh: Highlights from the AASHE 2011 Campus Tours

    ERIC Educational Resources Information Center

    Srinivasamohan, Ashwini; Walton, Judy; Wagner, Margo

    2012-01-01

    This quote by ecologist, "Silent Spring" author and Chatham University alum Rachel Carson reminds us of the everyday tenacity needed in working to advance a sustainable and just world. This publication celebrates that tenacity in the higher education sector, specifically among institutions in the Pittsburgh area. Historically known for its steel…

  2. The Effect of World War I on Black Occupational and Residential Segregation: The Case of Pittsburgh.

    ERIC Educational Resources Information Center

    Darden, Joe T.

    1988-01-01

    Study of census figures for Pittsburgh between 1900 and 1920 reveals that World War I had only a small measurable effect on reducing occupational segregation of Black men and White men and residential segregation by race. The war had no effect on reducing occupational segregation of Black women and White women. (BJV)

  3. Pittsburgh Area Preschool Association Publication: Selected Articles (Volume 8, No. 1-4).

    ERIC Educational Resources Information Center

    Frank, Mary, Ed.

    This compilation of short reports distributed to preschool teachers in the Pittsburgh area covers four main topics: (1) Adoption (2) Expressive Art Therapy, (3) The Infant, and (4) Learning Disorders in Young Children. The adoption section includes reports pertaining to the adoption process in Pennsylvania, adoptive parents' legal rights, medical…

  4. Pittsburgh Board of Public Education Task Force on Adolescent Pregnancy and Parenting: Minority Report.

    ERIC Educational Resources Information Center

    Kaleida, Phillip; And Others

    This minority report is a rebuttal to the recommendations made by the Task Force on Adolescent Pregnancy and Parenting of the Pittsburgh Board of Public Education. It takes issue with the way in which decisions were made and especially with the recommendation to establish school-based clinics (SBCs) in or near high risk schools. This minority…

  5. Newest Members of the Net Set: Pittsburgh's Carnegie Cashes in on Community Info.

    ERIC Educational Resources Information Center

    Hubbard, Bette Ann; And Others

    1996-01-01

    Describes the Electronic Information Network, a project created by the Carnegie Library of Pittsburgh in conjunction with public libraries in Pennsylvania's Allegheny County. The project uses the library's vision, funding, and librarian expertise to provide public access to community information on the Internet. Sidebars present steps and issues…

  6. Processing the CONSOL Energy, Inc. Mine Maps and Records Collection at the University of Pittsburgh

    ERIC Educational Resources Information Center

    Rougeux, Debora A.

    2011-01-01

    This article describes the efforts of archivists and student assistants at the University of Pittsburgh's Archives Service Center to organize, describe, store, and provide timely and efficient access to over 8,000 maps of underground coal mines in southwestern Pennsylvania, as well the records that accompanied them, donated by CONSOL Energy, Inc.…

  7. 77 FR 77016 - Foreign-Trade Zone 33 - Pittsburgh, Pennsylvania Notification of Proposed Export Production...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-31

    ... Export Production Activity Tsudis Chocolate Company (Chocolate Confectionery Bars) Pittsburgh, PA Tsudis Chocolate Company (Tsudis), an operator of FTZ 33, submitted a notification of proposed export production... production of chocolate confectionery bars for export (no shipments for U.S. consumption would occur)....

  8. 78 FR 22843 - Foreign-Trade Zone 33-Pittsburgh, Pennsylvania, Authorization of Export Production Activity...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-17

    ... 400), including notice in the Federal Register inviting public comment (77 FR 77016, 12-31-2012). The... Production Activity, Tsudis Chocolate Company (Chocolate Confectionery Bars), Pittsburgh, Pennsylvania On December 4, 2012, Tsudis Chocolate Company, submitted a notification of proposed export production...

  9. The Center on Race and Social Problems at the University of Pittsburgh

    ERIC Educational Resources Information Center

    Davis, Larry E.; Bangs, Ralph L.

    2007-01-01

    In 2002, the School of Social Work at the University of Pittsburgh established the Center on Race and Social Problems (CRSP). CRSP, which is the first race research center to be housed in a school of social work, has six foci: economic disparities; educational disparities; interracial group relations; mental health; youth, families, and elderly;…

  10. 76 FR 55471 - Pittsburgh & West Virginia Railroad-Abandonment Exemption-in Allegheny County, PA; Wheeling...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-07

    ... County, PA; Wheeling & Lake Erie Railway Company-- Discontinuance of Service Exemption--in Allegheny County, PA Pittsburgh & West Virginia Railroad (PWV) and Wheeling & Lake Erie Railway Company (WLE... Corp.--Acquisition & Operation Exemption--Lines of Norfolk & Western Railway, FD 31591 et al....

  11. 77 FR 62147 - Approval and Promulgation of Air Quality Implementation Plans; Pennsylvania; Pittsburgh-Beaver...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-12

    ... (hereafter referred to as ``the Pittsburgh Area'' or ``the Area''). First, EPA determines that the Area has... standard''), based on a 3-year average of annual mean PM 2.5 concentrations (62 FR 38652, July 18, 1997... annual PM 2.5 NAAQS based upon air quality monitoring data for calendar years 2001-2003 (70 FR...

  12. 77 FR 69591 - Expansion and Reorganization of Foreign-Trade Zone 33 Pittsburgh, PA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-20

    ... Register (76 FR 72673-72674, 11/25/11) and the application has been processed pursuant to the FTZ Act and... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF COMMERCE Foreign-Trade Zones Board Expansion and Reorganization of Foreign-Trade Zone 33 Pittsburgh, PA Pursuant...

  13. 75 FR 13488 - Expansion of Foreign-Trade Zone 33: Pittsburgh, PA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-22

    ...); Whereas, notice inviting public comment was given in the Federal Register (74 FR 17453, 4/15/09), and the... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF COMMERCE Foreign-Trade Zones Board Expansion of Foreign-Trade Zone 33: Pittsburgh, PA Pursuant to its...

  14. The automated radiosynthesis and purification of the opioid receptor antagonist, [6-O-methyl-11C]diprenorphine on the GE TRACERlab FXFE radiochemistry module.

    PubMed

    Fairclough, Michael; Prenant, Christian; Brown, Gavin; McMahon, Adam; Lowe, Jonathan; Jones, Anthony

    2014-05-15

    [6-O-Methyl-(11)C]diprenorphine ([(11)C]diprenorphine) is a positron emission tomography ligand used to probe the endogenous opioid system in vivo. Diprenorphine acts as an antagonist at all of the opioid receptor subtypes, that is, μ (mu), κ (kappa) and δ (delta). The radiosynthesis of [(11)C]diprenorphine using [(11)C]methyl iodide produced via the 'wet' method on a home-built automated radiosynthesis set-up has been described previously. Here, we describe a modified synthetic method to [(11)C]diprenorphine performed using [(11)C]methyl iodide produced via the gas phase method on a GE TRACERlab FXFE radiochemistry module. Also described is the use of [(11)C]methyl triflate as the carbon-11 methylating agent for the [(11)C]diprenorphine syntheses. [(11)C]Diprenorphine was produced to good manufacturing practice standards for use in a clinical setting. In comparison to previously reported [(11)C]diprenorphine radiosyntheisis, the method described herein gives a higher specific activity product which is advantageous for receptor occupancy studies. The radiochemical purity of [(11)C]diprenorphine is similar to what has been reported previously, although the radiochemical yield produced in the method described herein is reduced, an issue that is inherent in the gas phase radiosynthesis of [(11)C]methyl iodide. The yields of [(11)C]diprenorphine are nonetheless sufficient for clinical research applications. Other advantages of the method described herein are an improvement to both reproducibility and reliability of the production as well as simplification of the purification and formulation steps. We suggest that our automated radiochemistry route to [(11)C]diprenorphine should be the method of choice for routine [(11)C]diprenorphine productions for positron emission tomography studies, and the production process could easily be transferred to other radiochemistry modules such as the TRACERlab FX C pro.

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

    SciTech Connect

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

    1987-06-01

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

  16. Acute inhibition of cardiac monoamine oxidase A after tobacco smoke inhalation: validation study of [11C]befloxatone in rats followed by a positron emission tomography application in baboons.

    PubMed

    Valette, Héric; Bottlaender, Michel; Dollé, Frédéric; Coulon, Christine; Ottaviani, Michèle; Syrota, André

    2005-07-01

    The in vivo characteristics of [11C]befloxatone were assessed in myocardium of rats and monkeys. A complete multicompartmental model was developed to quantify monkey cardiac monoamine oxidase A (MAO-A) binding sites using positron emission tomography (PET) and was applied to assess the acute effects of inhalation of tobacco smoke. Unknown compounds contained in tobacco smoke inhibit brain MAO. In vitro, befloxatone inhibits selectively, competitively, and reversibly MAO-A in human tissues. [11C]Befloxatone (1.85 MBq) was i.v. injected into rats. Animals were sacrificed, dissected, and samples were assessed for radioactivity. Another group of rats was pretreated with clorgyline (10 mg/kg i.v.). Monkeys were injected with [11C]befloxatone (222-370 MBq), and the chest was imaged with PET for 2 h. Presaturation and displacement experiments were performed using unlabeled befloxatone. For quantification of myocardial binding sites (Bmax), [11C]befloxatone was first injected as a tracer dose (2.7-9.3 nmol) and 20 min later injected as a mixture of labeled and unlabeled befloxatone (labeled, 10.3-41.9 nmol; unlabeled, 407-765 nmol). In rodents, cardiac uptake was high (3.39 +/- 0.5% injected dose/g tissue) and strongly inhibited (80%) by clorgyline. In monkeys, administration of unlabeled befloxatone displaced 85% of cardiac radioactivity. Bmax was found to be 208 +/- 13 pmol ml(-1) tissue. Inhalation of tobacco smoke decreased Bmax: 150 +/- 6.2 pmol ml(-1), whereas nicotine did not. [11C]Befloxatone allows a good visualization of the heart. Cardiac MAO-A Bmax was quantified and a clear effect of acute inhalation of tobacco smoke was evidenced. Therefore, a single cigarette can interfere with the cardiac turnover of catecholamines.

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

    PubMed Central

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

    2016-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Lazzeroni, Marta; Brahme, Anders

    2015-09-01

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

  19. NK cells are necessary for recovery of corneal CD11c+ dendritic cells after epithelial abrasion injury

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mechanisms controlling CD11c(+) MHCII(+) DCs during corneal epithelial wound healing were investigated in a murine model of corneal abrasion. Selective depletion of NKp46(+) CD3- NK cells that normally migrate into the cornea after epithelial abrasion resulted in >85% reduction of the epithelial CD1...

  20. Automated synthesis of radiopharmaceuticals for positron emission tomography: an apparatus for labelling with [11C] methyl iodide (MIASA)

    PubMed Central

    Cork, D. G.; Yamato, H.; Yajima, K.; Hayashi, N.; Sugawara, T.; Kato, S.

    1994-01-01

    A fully automated apparatus for the routine synthesis and formulation of short-lived 11C (t1/2 = 20 min) labelled radiopharmaceuticals for positron emission tomography (PET) has been developed. [11C]Carbon dioxide is converted to [11C]methyl iodide, which can be used to label a wide variety of substrates by methylation at C, N, O, or S electron rich centres. The apparatus, MIASA (methyl iodide automated synthesis apparatus), was designed to operate as part of an automated labelling system in a shielded ‘hot’ laboratory. The apparatus was designed without the size constraints of typical instrumentation used in hot cells, although it is compact where necessary. Ample use of indicators and sensors, together with compact design of the reaction flasks for small dead space and efficient evaporation, led to good reliability and performance. The design of the hardware and software is described in this paper, together with a preparation of 3-N-[11C]methylspiperone as a sterile injectable solution in physiological saline. PMID:18924994

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

    NASA Astrophysics Data System (ADS)

    Leandre, Verida; Howell, Calvin

    2011-03-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  5. Downregulation of Brain Phosphodiesterase Type IV Measured with 11C-(R)-Rolipram Positron Emission Tomography in Major Depressive Disorder

    PubMed Central

    Fujita, Masahiro; Hines, Christina S.; Zoghbi, Sami S.; Mallinger, Alan G.; Dickstein, Leah P.; Liow, Jeih-San; Zhang, Yi; Pike, Victor W.; Drevets, Wayne C.; Innis, Robert B.; Zarate, Carlos A.

    2012-01-01

    Background Phosphodiesterase type IV (PDE4), an important component of the cyclic adenosine monophosphate (cAMP) cascade, selectively metabolizes cAMP in the brain to the inactive monophosphate. Basic studies suggest that PDE4 mediates the effects of several antidepressants. This study sought to quantify the binding of 11C-(R)-rolipram, a PDE4 inhibitor, as an indirect measure of this enzyme’s activity in the brain of individuals with major depressive disorder (MDD) compared with healthy control subjects. Methods 11C-(R)-Rolipram brain positron emission tomography scans were performed in 28 unmedicated MDD subjects and 25 age- and gender-matched healthy control subjects. Patients were moderately depressed and about one half were treatment-naive. 11C-(R)-Rolipram binding in the brain was measured using arterial 11C-(R)-rolipram levels to correct for the influence of cerebral blood flow. Results Major depressive disorder subjects showed a widespread, approximately 20% reduction in 11C-(R)-rolipram binding (p = .002), which was not caused by different volumes of gray matter. Decreased rolipram binding of similar magnitudes was observed in most brain areas. Rolipram binding did not correlate with the severity of depressive or anxiety symptoms. Conclusions This study is the first to demonstrate that brain levels of PDE4, a critical enzyme that regulates cAMP, are decreased in unmedicated individuals with MDD in vivo. These results are in line with human postmortem and rodent studies demonstrating downregulation of the cAMP cascade in MDD and support the hypothesis that agents such as PDE4 inhibitors, which increase activity within the cAMP cascade, may have antidepressant effects. PMID:22677471

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

    PubMed Central

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

    2016-01-01

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

  7. PET studies of binding competition between endogenous dopamine and the D1 radiotracer [11C]NNC 756.

    PubMed

    Abi-Dargham, A; Simpson, N; Kegeles, L; Parsey, R; Hwang, D R; Anjilvel, S; Zea-Ponce, Y; Lombardo, I; Van Heertum, R; Mann, J J; Foged, C; Halldin, C; Laruelle, M

    1999-05-01

    NNC 756 ((+)-8-chloro-5-(2,3-dihydrobenzofuran-7-yl)-7-hydroxy-3-methyl-2,3,4,5- tetrahydro-1H-3-benzazepine) is a new high affinity dopamine (DA) D1 receptor antagonist. Labeled with C-11, it has been used as a PET radiotracer to visualize D1 receptors both in striatal and extrastriatal areas, such as the prefrontal cortex. The goal of this study was to evaluate several methods for derivation of D1 receptor binding potential (BP) with [11C]NNC 756 in baboons, and to use these methods to assess the vulnerability of [11C]NNC 756 binding to competition by endogenous DA. A three-compartment model provided a good fit to PET data acquired following a single bolus injection. BP values obtained with this analysis were in good agreement with values derived from in vitro studies. BP values measured following injection of the potent DA releaser amphetamine (1 mg/kg, n=2) were similar to values measured under control conditions. Kinetic parameters derived from single bolus experiments were used to design a bolus plus continuous infusion administration protocol aimed at achieving a state of sustained binding equilibrium. Injection of amphetamine during sustained equilibrium did not affect [11C]NNC 756 binding. Similar results were observed with another D1 radiotracer, [11C]SCH 23390. Doses of amphetamine used in this study are known to reduce by 20-40% the binding potential of several D2 receptors radiotracers. Therefore, the absence of displacement of [11C]NNC 756 by an endogenous DA surge may indicate important differences between D1 and D2 receptors in vivo, such as differences in proportion of high affinity states not occupied by DA at baseline. These findings may also imply that a simple binding competition model is inadequate to account for the effects of manipulation of endogenous DA levels on the in vivo binding of radiolabeled antagonists.

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

    PubMed

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

    1992-03-24

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

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

    SciTech Connect

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

    1991-08-01

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

  10. Dopamine Transporter Correlates and Occupancy by Modafinil in Cocaine-Dependent Patients: A Controlled Study With High-Resolution PET and [(11)C]-PE2I.

    PubMed

    Karila, Laurent; Leroy, Claire; Dubol, Manon; Trichard, Christian; Mabondo, Audrey; Marill, Catherine; Dubois, Albertine; Bordas, Nadège; Martinot, Jean-Luc; Reynaud, Michel; Artiges, Eric

    2016-08-01

    Modafinil is a candidate compound for the treatment of cocaine addiction that binds to the dopamine transporter (DAT) in healthy humans, as observed by positron emission tomography (PET). This mechanism, analogous to that of cocaine, might mediate a putative therapeutic effect of modafinil on cocaine dependence, though the binding of modafinil to DAT has never been assessed in cocaine-dependent patients. We aimed at quantifying the DAT availability during a controlled treatment by modafinil, and its clinical and psychometric correlates in cocaine-dependent patients at the onset of abstinence initiation. Twenty-nine cocaine-dependent male patients were enrolled in a 3-month trial for cocaine abstinence. Modafinil was used in a randomized double-blind placebo-controlled design and was administered as follows: 400 mg/day for 26 days, then 300 mg/day for 30 days, and 200 mg/day for 31 days. Participants were examined twice during a 17-day hospitalization for their DAT availability using PET and [(11)C]-PE2I and for assessments of craving, depressive symptoms, working memory, and decision-making. Cocaine abstinence was further assessed during a 10-week outpatient follow-up period. Baseline [(11)C]-PE2I-binding potential covaried with risk taking and craving index in striatal and extrastriatal regions. A 65.6% decrease of binding potential was detected in patients receiving modafinil for 2 weeks, whereas placebo induced no significant change. During hospitalization, an equivalent improvement in clinical outcomes was observed in both treatment groups, and during the outpatient follow-up there were more therapeutic failures in the modafinil-treated group. Therefore, these results do not support the usefulness of modafinil to treat cocaine addiction. PMID:26892922

  11. Endotoxin-Induced Systemic Inflammation Activates Microglia: [11C]PBR28 Positron Emission Tomography in Nonhuman Primates

    PubMed Central

    Hannestad, Jonas; Gallezot, Jean-Dominique; Schafbauer, Thomas; Lim, Keunpoong; Kloczynski, Tracy; Morris, Evan D.; Carson, Richard E; Ding, Yu-Shin; Cosgrove, Kelly

    2013-01-01

    Microglia play an essential role in many brain diseases. Microglia are activated by local tissue damage or inflammation, but systemic inflammation can also activate microglia. An important clinical question is whether the effects of systemic inflammation on microglia mediates the deleterious effects of systemic inflammation in diseases such as Alzheimer's dementia, multiple sclerosis, and stroke. Positron Emission Tomography (PET) imaging with ligands that bind to Translocator Protein (TSPO) can be used to detect activated microglia. The aim of this study was to evaluate whether the effect of systemic inflammation on microglia could be measured with PET imaging in nonhuman primates, using the TSPO ligand [11C]PBR28. Methods Six female baboons (Papio anubis) were scanned before and at 1 h and/or 4h and/or 22h after intravenous administration of E. coli lipopolysaccharide (LPS; 0.1 mg/kg), which induces systemic inflammation. Regional time-activity data from regions of interest (ROIs) were fitted to the two-tissue compartmental model, using the metabolite-corrected arterial plasma curve as input function. Total volume of distribution (VT) of [11C]PBR28 was used as a measure of total ligand binding. The primary outcome was change in VT from baseline. Serum levels of tumor necrosis factor alpha (TNFα), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and interleukin-8 (IL-8) were used to assess correlations between systemic inflammation and microglial activation. In one baboon, immunohistochemistry was used to identify cells expressing TSPO. Results LPS administration increased [11C]PBR28 binding (F(3,6)=5.1, p=.043) with a 29±16 % increase at 1h (n = 4) and a 62±34% increase at 4h (n = 3) post-LPS. There was a positive correlation between serum IL-1β and IL-6 levels and the increase in [11C]PBR28 binding. TSPO immunoreactivity occurred almost exclusively in microglia and rarely in astrocytes. Conclusion In the nonhuman-primate brain, LPS-induced systemic

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

    PubMed Central

    Kil, Kun-Eek; Biegon, Anat; Ding, Yu-Shin; Fischer, Andre; Ferrieri, Richard A.; Kim, Sung Won; Pareto, Deborah; Schueller, Michael J.; Fowler, Joanna S.

    2011-01-01

    Introduction Aromatase, a member of the cytochrome P450 family, converts androgens such as androstenedione and testosterone to estrone and estradiol respectively. Letrozole (1-[bis-(4-cyanophenyl)methyl]-1H-1,2,4-triazole, Femara®) is a high affinity aromatase inhibitor (Ki=11.5 nM) which has FDA approval for breast cancer treatment. Here we report the synthesis of carbon-11 labeled letrozole and its assessment as a radiotracer for brain aromatase in the baboon. Methods Letrozole and its precursor (4-[(4-bromophenyl)-1H-1,2,4-triazol-1-ylmethyl]benzonitrile, 3) were prepared in two-step syntheses from 4-cyanobenzyl bromide and 4-bromobenzyl bromide, respectively. The [11C]cyano group was introduced via the tetrakis(triphenylphosphine)palladium(0) catalyzed coupling of [11C]cyanide with the bromo-precursor (3). PET studies in the baboon brain were carried out to assess regional distribution and kinetics, reproducibility of repeated measures and saturability. The free fraction of letrozole in the plasma, log D, and the [11C-cyano]letrozole fraction in the arterial plasma were also measured. Results [11C-cyano]Letrozole was synthesized in 60 min with a radiochemical yield of 79–80%, with a radiochemical purity greater than 98% and a specific activity of 4.16±2.21 Ci/μmol at the end of bombardment (n=4). PET studies in the baboon revealed initial rapid and high uptake and initial rapid clearance followed by slow clearance of carbon-11 from the brain with no difference between brain regions. The brain kinetics was not affected by co-injection of unlabeled letrozole (0.1 mg/kg). The free fraction of letrozole in plasma was 48.9% and log D was 1.84. Conclusion [11C-cyano]Letrozole is readily synthesized via a palladium catalyzed coupling reaction with [11C]cyanide. Although it is unsuitable as a PET radiotracer for brain aromatase as revealed by the absence of regional specificity and saturability in brain regions, such as amygdala, which are known to contain

  13. Deconvolution and Quantification of Primary and Oxygenated Organic Aerosols: Technique Development and Applications to the Pittsburgh AMS Datasets

    NASA Astrophysics Data System (ADS)

    Zhang, Q.; Jimenez, J.; Alfarra, R.; Allan, J.; Coe, H.; Worsnop, D.; Canagaratna, M.

    2004-12-01

    A new technique has been developed to deconvolve and quantify the mass concentrations of primary and oxygenated organic aerosol (POA and OOA) using highly time-resolved organic mass spectral data obtained with an Aerodyne Aerosol Mass Spectrometer (AMS). OOA may comprise secondary organic aerosol (SOA) as well as oxidized POA. This technique involves a series of multivariate linear regressions that use mass-to-charge ratios (m/z's) 57 (mostly C4H9+) and 44 (mostly CO2+), the identified AMS mass spectral tracers for POA and OOA, respectively, as the initial principal components followed by an iterative algorithm to evaluate and "purify" POA and OOA mass spectral tracers. We have applied this technique to the AMS organic aerosol data acquired at the EPA Pittsburgh Supersite during September 2002 and have observed excellent agreement between the reconstructed organic concentrations (= POA + OOA) and the measured values (r2 = 0.997, slope = 0.998). The reconstructed organic data matrix (size = 3199 time steps x 300 m/z's) explains 99% of the variance in the measured time series. The extracted mass spectrum of POA shows high similarity to those of diesel exhaust sampled during a chase study, lab-measured lubricating oil, and freshly emitted traffic aerosols measured in urban environments. The spectrum of OOA closely resembles those of aged organic aerosols sampled in remote areas and also shows similarity with the spectrum of fulvic acid-a humic-like substance that is ubiquitous in the environment and has previously been used as an analogue to represent polyacid compounds found in highly processed and oxidized atmospheric organic aerosols. Organic aerosols in Pittsburgh during Sept. 2002 are mainly oxygenated, on average consisting of ~ 70% OOA (likely mainly secondary in nature). Pronounced diurnal variations in the POA/OOA contributions to organic mass have been observed, with the contribution of POA peaking in the morning rush hours while that of OOA is largest in

  14. Pittsburgh as a High Risk Population: The Potential Savings of a Personalized Dental Care Plan.

    PubMed

    Ng, Andrew J; Vieira, Alexandre R

    2016-01-01

    Objectives. Little evidence exists for the current standard of two annual preventative care visits. The purpose of this study was investigate this claim by modeling the potential savings of implementing a personalized care plan for high risk individuals in the Pittsburgh region. Methods. Using radiographs from 39 patients in the University of Pittsburgh Dental Registry and DNA Repository database, two models were created to analyse the direct savings of implementing a more aggressive preventative treatment plan and to view the longitudinal cost of increased annual yearly visits. Results. There is a significant decrease (p < 0.001) between original and modeled treatment cost when treatment severity is reduced. In addition, there is a significant decrease in adult lifetime treatment cost (p < 0.001) for up to four annual visits. Conclusions. Patients in high risk populations may see significant cost benefits in treatment cost when a personalized care plan, or higher annual preventative care visits, is implemented. PMID:27006657

  15. Optimization of [(11)C]raclopride positron emission tomographic rat studies: comparison of methods for image quantification.

    PubMed

    Torrent, Elia; Farré, Magí; Abasolo, Ibane; Millan, Olga; Llop, Jordi; Gispert, Juan Domingo; Ruiz, Alba; Pareto, Deborah

    2013-06-01

    The goal of this study was to compare different quantification approaches and reconstruction methods to estimate the binding potential in [11C]raclopride studies in rats. The final aim was to determine if the results obtained with short-acquisition scanning were comparable to the results obtained with long-acquistion (conventional) scanning. We analyzed two rat data sets: a baseline versus a pretreatment study (with cold raclopride) and a young versus an old animal group comparison. The study results support the contention that optimization of [11C]raclopride positron emission tomographic studies in rats by shortening the acquisition time is feasible. In addition, filtered backprojection is recommended as a reconstruction algorithm, although iterative methods may be more sensitive to detect within-group differences.

  16. Changing fuel use behavior: the Pittsburgh smoke control movement, 1940-1950

    SciTech Connect

    Tarr, J.A.

    1981-12-01

    Local policy development in Pittsburgh brought about cleaner air by influencing change in the household use of fuel and combustion equipment. By a combination of media campaigns, voluntary organizations, technical advisers, and business and labor leaders, the public was convinced of the necessity to reduce air pollution. The unique aspect is that the public accepted the costs of a long-range policy decision through education and persuasion. 20 refs.

  17. COMPREHENSIVE INDEX TO THE MERRIMAN SCRAPBOOK COLLECTION OF MATERIALS ON PITTSBURGH AND NEW YORK THEATRE.

    ERIC Educational Resources Information Center

    BOWMAN, NED A.

    THIS INDEX TO A COLLECTION OF 10,800 ITEMS OF EPHEMERAL NATURE ON PITTSBURGH AND NEW YORK THEATRE FROM APPROXIMATELY 1880 TO THE SECOND WORLD WAR PROVIDES ENTRY INTO THE COLLECTION IN FIVE WAYS--(1) BY NAME OF ACTOR OR PERSON CONNECTED WITH THE THEATRE, (2) BY NAME OR PLAY, (3) BY NAME OF PRODUCING GROUP, (4) BY NAME OF THEATRE, AND (5) BY…

  18. New Whole-House Solutions Case Study: Evaluating Through-Wall Air Transfer Fans, Pittsburgh, Pennsylvania

    SciTech Connect

    2014-10-01

    In this project, Building America team IBACOS performed field testing in a new construction unoccupied test house in Pittsburgh, Pennsylvania, to evaluate heating, ventilating, and air conditioning (HVAC) distribution systems during heating, cooling, and midseason conditions. The team evaluated a market-available through-wall air transfer fan system that provides air to the bedrooms.The relative ability of this system was considered with respect to relevant Air Conditioning Contractors of America and ASHRAE standards for house temperature uniformity and stability.

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

    NASA Astrophysics Data System (ADS)

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

    2016-06-01

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

  20. Increased in vivo glial activation in patients with amyotrophic lateral sclerosis: Assessed with [11C]-PBR28

    PubMed Central

    Zürcher, Nicole R.; Loggia, Marco L.; Lawson, Robert; Chonde, Daniel B.; Izquierdo-Garcia, David; Yasek, Julia E.; Akeju, Oluwaseun; Catana, Ciprian; Rosen, Bruce R.; Cudkowicz, Merit E.; Hooker, Jacob M.; Atassi, Nazem

    2015-01-01

    Evidence from human post mortem, in vivo and animal model studies implicates the neuroimmune system and activated microglia in the pathology of amyotrophic lateral sclerosis. The study aim was to further evaluate in vivo neuroinflammation in individuals with amyotrophic lateral sclerosis using [11C]-PBR28 positron emission tomography. Ten patients with amyotrophic lateral sclerosis (seven males, three females, 38–68 years) and ten age- and [11C]-PBR28 binding affinity-matched healthy volunteers (six males, four females, 33–65 years) completed a positron emission tomography scan. Standardized uptake values were calculated from 60 to 90 min post-injection and normalized to whole brain mean. Voxel-wise analysis showed increased binding in the motor cortices and corticospinal tracts in patients with amyotrophic lateral sclerosis compared to healthy controls (pFWE < 0.05). Region of interest analysis revealed increased [11C]-PBR28 binding in the precentral gyrus in patients (normalized standardized uptake value = 1.15) compared to controls (1.03, p < 0.05). In patients those values were positively correlated with upper motor neuron burden scores (r = 0.69, p < 0.05), and negatively correlated with the amyotrophic lateral sclerosis functional rating scale (r = –0.66, p < 0.05). Increased in vivo glial activation in motor cortices, that correlates with phenotype, complements previous histopathological reports. Further studies will determine the role of [11C]-PBR28 as a marker of treatments that target neuroinflammation. PMID:25685708

  1. Expression of CD11c and EMR2 on neutrophils: potential diagnostic biomarkers for sepsis and systemic inflammation.

    PubMed

    Lewis, S M; Treacher, D F; Edgeworth, J; Mahalingam, G; Brown, C S; Mare, T A; Stacey, M; Beale, R; Brown, K A

    2015-11-01

    There is a need for cellular biomarkers to differentiate patients with sepsis from those with the non-infectious systemic inflammatory response syndrome (SIRS). In this double-blind study we determined whether the expression of known (CD11a/b/c, CD62L) and putative adhesion molecules [CD64, CD97 and epidermal growth factor (EGF)-like molecule containing mucin-like hormone receptor (EMR2)] on blood neutrophils could serve as useful biomarkers of infection and of non-infectious SIRS in critically ill patients. We studied 103 patients with SIRS, 83 of whom had sepsis, and 50 healthy normal subjects, using flow cytometry to characterize neutrophils phenotypically in whole blood samples. Patients with SIRS had an increased prevalence of neutrophils expressing CD11c, CD64 and EMR2 in comparison with healthy subjects (P < 0.001), but normal expression of CD11a, CD11b, CD62L and CD97. An increase in the percentage of neutrophils bearing CD11c was associated with sepsis, EMR2 with SIRS and CD64 with sepsis and SIRS. Neutrophils expressing CD11c had the highest sensitivity (81%) and specificity (80%) for the detection of sepsis, and there was an association between the percentage of neutrophils expressing EMR2 and the extent of organ failure (P < 0.05). Contrary to other reports, we did not observe an abnormal expression of CD11b or CD62L on neutrophils from patients with SIRS, and suggest that this discrepancy is due to differences in cell processing protocols. We propose that blood neutrophils expressing CD11c and EMR2 be considered as potential biomarkers for sepsis and SIRS, respectively.

  2. Serotonin 2A Receptors in Obsessive-Compulsive Disorder: a Positron Emission Tomography Study with [11C]MDL 100907

    PubMed Central

    Simpson, H. Blair; Slifstein, Mark; Bender, James; Xu, Xiaoyan; Hackett, Elizabeth; Maher, Michael J.; Abi-Dargham, Anissa

    2014-01-01

    Background Serotonergic abnormalities are hypothesized to contribute to obsessive-compulsive disorder (OCD). This study used positron emission tomography (PET) with the radioligand [11C]MDL 100907 to examine whether the distribution of one of the serotonin receptors, the 5-HT2A receptor, is altered in OCD. Methods Nineteen OCD subjects, free of psychiatric medications and depression, and 19 matched healthy controls underwent PET scans following injection of [11C]MDL 100907. Total distribution volumes (VT) were derived by kinetic analysis using the arterial input function. Two measures of 5-HT2A availability were computed (BPND and BPP). Groups were compared using a region of interest (ROI) analysis and voxelwise analysis of spatially normalized parametric maps. ROIs included cortical regions (orbitofrontal, dorsolateral prefrontal, medial prefrontal, anterior cingulate, temporal, parietal, occipital, and insular cortex) and limbic regions (entorhinal cortex, parahippocampal gyrus, and medial temporal lobe). Results No significant group differences were observed in [11C]MDL 100907 BPND or BPP in the ROIs or in the voxelwise analysis of BPND maps. There was a significant correlation in the orbitofrontal cortex between [11C] MDL 100907 binding and age of onset, with earlier age of onset associated with higher binding. Conclusions In contrast to prior reports, people with OCD (free of psychiatric medications and depression) are not characterized as a group by major changes in 5-HT2A availability in cortical or limbic brain regions. Further research is warranted to examine potential differences in 5-HT2A availability between early and late onset OCD and to assess 5-HT2A function in relation to other neurotransmitter systems implicated in OCD. PMID:21855857

  3. Increased in vivo glial activation in patients with amyotrophic lateral sclerosis: assessed with [(11)C]-PBR28.

    PubMed

    Zürcher, Nicole R; Loggia, Marco L; Lawson, Robert; Chonde, Daniel B; Izquierdo-Garcia, David; Yasek, Julia E; Akeju, Oluwaseun; Catana, Ciprian; Rosen, Bruce R; Cudkowicz, Merit E; Hooker, Jacob M; Atassi, Nazem

    2015-01-01

    Evidence from human post mortem, in vivo and animal model studies implicates the neuroimmune system and activated microglia in the pathology of amyotrophic lateral sclerosis. The study aim was to further evaluate in vivo neuroinflammation in individuals with amyotrophic lateral sclerosis using [(11)C]-PBR28 positron emission tomography. Ten patients with amyotrophic lateral sclerosis (seven males, three females, 38-68 years) and ten age- and [(11)C]-PBR28 binding affinity-matched healthy volunteers (six males, four females, 33-65 years) completed a positron emission tomography scan. Standardized uptake values were calculated from 60 to 90 min post-injection and normalized to whole brain mean. Voxel-wise analysis showed increased binding in the motor cortices and corticospinal tracts in patients with amyotrophic lateral sclerosis compared to healthy controls (p FWE < 0.05). Region of interest analysis revealed increased [(11)C]-PBR28 binding in the precentral gyrus in patients (normalized standardized uptake value = 1.15) compared to controls (1.03, p < 0.05). In patients those values were positively correlated with upper motor neuron burden scores (r = 0.69, p < 0.05), and negatively correlated with the amyotrophic lateral sclerosis functional rating scale (r = -0.66, p < 0.05). Increased in vivo glial activation in motor cortices, that correlates with phenotype, complements previous histopathological reports. Further studies will determine the role of [(11)C]-PBR28 as a marker of treatments that target neuroinflammation.

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

    PubMed

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

    2009-05-01

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

  5. In vivo imaging of brain aromatase in female baboons: [11C]vorozole kinetics and effect of the menstrual cycle.

    PubMed

    Pareto, Deborah; Biegon, Anat; Alexoff, David; Carter, Pauline; Shea, Coreen; Muench, Lisa; Xu, Youwen; Fowler, Joanna S; Kim, Sunny W; Logan, Jean

    2013-01-01

    The aim of this work was to quantify the brain distribution of the enzyme aromatase in the female baboon with positron emission tomography and the tracer [11C]vorozole using three different quantification methods for estimating the total distribution volume (V(T)): a graphical method, compartment modeling, and a tissue to plasma ratio. The graphical model and the compartment modeling gave similar estimates to the data and similar values (correlation R  =  .988; p  =  .0001). [11C]Vorozole shows a rapid uptake by the brain followed by a relatively constant accumulation, suggesting the possibility of using the tissue to plasma ratio as an estimate of V(T). The highest uptake of [11C]vorozole in the baboon brain was measured in the amygdala, followed by the preoptic area and hypothalamus, basal ganglia, and cortical areas. Pretreatment studies with vorozole or letrozole showed a generalized decrease in brain accumulation and V(T). The results suggested that the physiologic changes in gonadal hormone levels accompanying the menstrual cycle had a significant effect on brain aromatase V(T).

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

    SciTech Connect

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

    1994-12-31

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

  7. Air Quality from Early Pittsburgh to the Present: The Science of Change

    NASA Astrophysics Data System (ADS)

    Davidson, Cliff

    2009-03-01

    Throughout Pittsburgh's history over the past 250 years, coal reserves in the city and nearby have influenced its economy, demographics, and environmental quality. They have also played a major role in determining air quality in the region. For example, Pittsburgh became famous for its high particle loadings as early as the beginning of the nineteenth century, when the first complaints about air quality in the city were recorded. Nevertheless, residents tolerated the high coal smoke levels since jobs depended on the iron works, steel mills, and other industries. When natural gas was discovered just east of the city in the 1870's and replaced coal for some applications, particle concentrations decreased. But the local supplies of natural gas ran short several years later, and as industry continued to expand in the 1890's the city went back to the use of coal as its primary fuel. The return to smoky air was met with resistance that marked the beginning of sustained public outcry and initiation of several air pollution studies. The next half century was marked by periods of occasional high and low concentration, the latter due to events such as the financial panic of 1907 and the depression of the 1930's. It was not until the 1940's that effective regulations were passed to reduce smoky conditions. Particle levels fell throughout the 1950's and 1960's, and eventually the decline of heavy industry in Pittsburgh led to relatively clean air in many parts of the city. Over the past few decades, airborne particle concentrations averaged across the Pittsburgh region have remained below their earlier levels. However, there are still ``hot spots'' of high concentration resulting from regional background coming from upwind areas and emissions of some large sources that have continued to operate in the Pittsburgh region. Furthermore, the composition of airborne particles in the city has changed from earlier times. Such particles are now the result of emissions from sources in

  8. CD11c gene expression in hairy cell leukemia is dependent upon activation of the proto-oncogenes ras and junD.

    PubMed

    Nicolaou, Fotini; Teodoridis, Jens M; Park, Heiyoung; Georgakis, Alexander; Farokhzad, Omid C; Böttinger, Erwin P; Da Silva, Nicolas; Rousselot, Philippe; Chomienne, Christine; Ferenczi, Katalin; Arnaout, M Amin; Shelley, C Simon

    2003-05-15

    Hairy cell leukemia (HCL) is a chronic lymphoproliferative disease, the cause of which is unknown. Diagnostic of HCL is abnormal expression of the gene that encodes the beta2 integrin CD11c. In order to determine the cause of CD11c gene expression in HCL the CD11c gene promoter was characterized. Transfection of the CD11c promoter linked to a luciferase reporter gene indicated that it is sufficient to direct expression in hairy cells. Mutation analysis demonstrated that of predominant importance to the activity of the CD11c promoter is its interaction with the activator protein-1 (AP-1) family of transcription factors. Comparison of nuclear extracts prepared from hairy cells with those prepared from other cell types indicated that hairy cells exhibit abnormal constitutive expression of an AP-1 complex containing JunD. Functional inhibition of AP-1 expressed by hairy cells reduced CD11c promoter activity by 80%. Inhibition of Ras, which represents an upstream activator of AP-1, also significantly inhibited the CD11c promoter. Furthermore, in the hairy cell line EH, inhibition of Ras signaling through mitogen-activated protein kinase/extracellular signal-regulated kinase kinases 1 and 2 (MEK1/2) reduced not only CD11c promoter activity but also reduced both CD11c surface expression and proliferation. Expression in nonhairy cells of a dominant-positive Ras mutant activated the CD11c promoter to levels equivalent to those in hairy cells. Together, these data indicate that the abnormal expression of the CD11c gene characteristic of HCL is dependent upon activation of the proto-oncogenes ras and junD.

  9. [18F]- and [11C]-Labeled N-benzyl-isatin sulfonamide analogues as PET tracers for apoptosis: synthesis, radiolabeling mechanism, and in vivo imaging of apoptosis in Fas-treated mice

    PubMed Central

    Zhou, Dong; Chu, Wenhua; Chen, Delphine L.; Wang, Qi; Reichert, David E.; Rothfuss, Justin; D'Avignon, Andre; Welch, Michael J.; Mach, Robert H.

    2011-01-01

    Summary The radiolabeled isatin sulfonamide caspase-3 inhibitor, [18F]2 (WC-II-89), is a potential PET radiotracer for noninvasive imaging of apoptosis. The radiolabeling mechanism was studied by 13C NMR, ESI/MS, and computational calculations. It was found that the high electrophilicity of the C3 carbonyl group in the isatin ring, which served as a trap for [18F]fluoride, was responsible for the failure of the radiolabeling via nucleophilic substitution of the mesylate group in 7a by [18F]fluoride. Once treated with a strong base, 7a opened the isatin ring completely to form an isatinate intermediate 16, which lost the ability to trap [18F]fluoride, thereby allowing the displacement of the mesylate group to afford the 18F-labeled isatinate 17. [18F]17 can be converted to isatin [18F]2 efficiently under acidic conditions. The ring-opening and re-closure of the isatin ring under basic and acidic conditions were confirmed by reversed phase HPLC analysis, ESI/MS and 13C NMR studies. Computational studies of model compounds also support the above proposed mechanism. Similarly, the ring-opening and re-closure method was used successfully in the synthesis of the 11C labeled isatin sulfonamide analogue [11C]4 (WC-98). A microPET imaging study using [11C]4 in the Fas liver apoptosis model demonstrated retained activity in the target organ (liver) of the treated mice. Increased caspase-3 activation in the liver was verified by the fluorometric caspase-3 enzyme assay. Therefore, this study provides a useful method for radio-synthesis of isatin derivative radiotracers for PET and SPECT studies, and [11C]4 is a potential PET radiotracer for noninvasive imaging of apoptosis. PMID:19300818

  10. The relationship between the University of Pittsburgh School of Medicine and the University of Pittsburgh Medical Center--a profile in synergy.

    PubMed

    Levine, Arthur S; Detre, Thomas P; McDonald, Margaret C; Roth, Loren H; Huber, George A; Brignano, Mary Germann; Danoff, Sandra N; Farner, David M; Masnick, Jeffrey L; Romoff, Jeffrey A

    2008-09-01

    In the synergistic evolution of their research, educational, and clinical programs, the University of Pittsburgh (Pitt) School of Medicine (SOM) and the University of Pittsburgh Medical Center (UPMC) have followed one core principle: What is good for one is good for both. The collaboration is underpinned by UPMC's commitment to its community mission, including support for the academic and research objectives of the SOM. UPMC's conceptual origin was fostered by its experience with Western Psychiatric Institute and Clinic in the 1970s. Over time, UPMC acquired other hospitals through merger and negotiation and, by 2008, had grown into a $7 billion global health enterprise. From the outset, the senior leaders of both UPMC and Pitt committed to collaborative decision making on all key issues. Under this coordinated decision-making model, UPMC oversees all clinical activity, including that from a consolidated physicians' practice plan. Pitt remains the guardian of all academic priorities, particularly faculty-based research. UPMC's steady financial success underpins the model. A series of interrelated agreements formally defines the relationship between Pitt and UPMC, including shared board seats and UPMC's committed ongoing financial support of the SOM. In addition, the two institutions have jointly made research growth a priority. The payoff from this dynamic has been a steadily growing Pitt research portfolio; enhanced growth, visibility, and stature for UPMC, the SOM, and Pitt as a whole; and the sustained success of UPMC's clinical enterprise, which now has an international scope. Given the current stagnation in the National Institutes of Health budget, the Pitt-UPMC experience may be instructive to other academic health centers. PMID:18728434

  11. NK-CD11c+ Cell Crosstalk in Diabetes Enhances IL-6-Mediated Inflammation during Mycobacterium tuberculosis Infection

    PubMed Central

    Cheekatla, Satyanarayana Swamy; Tripathi, Deepak; Venkatasubramanian, Sambasivan; Nathella, Pavan Kumar; Paidipally, Padmaja; Ishibashi, Munenori; Welch, Elwyn; Tvinnereim, Amy R.; Ikebe, Mitsuo; Valluri, Vijaya Lakshmi; Babu, Subash; Kornfeld, Hardy; Vankayalapati, Ramakrishna

    2016-01-01

    In this study, we developed a mouse model of type 2 diabetes mellitus (T2DM) using streptozotocin and nicotinamide and identified factors that increase susceptibility of T2DM mice to infection by Mycobacterium tuberculosis (Mtb). All Mtb-infected T2DM mice and 40% of uninfected T2DM mice died within 10 months, whereas all control mice survived. In Mtb-infected mice, T2DM increased the bacterial burden and pro- and anti-inflammatory cytokine and chemokine production in the lungs relative to those in uninfected T2DM mice and infected control mice. Levels of IL-6 also increased. Anti-IL-6 monoclonal antibody treatment of Mtb-infected acute- and chronic-T2DM mice increased survival (to 100%) and reduced pro- and anti-inflammatory cytokine expression. CD11c+ cells were the major source of IL-6 in Mtb-infected T2DM mice. Pulmonary natural killer (NK) cells in Mtb-infected T2DM mice further increased IL-6 production by autologous CD11c+ cells through their activating receptors. Anti-NK1.1 antibody treatment of Mtb-infected acute-T2DM mice increased survival and reduced pro- and anti-inflammatory cytokine expression. Furthermore, IL-6 increased inflammatory cytokine production by T lymphocytes in pulmonary tuberculosis patients with T2DM. Overall, the results suggest that NK-CD11c+ cell interactions increase IL-6 production, which in turn drives the pathological immune response and mortality associated with Mtb infection in diabetic mice. PMID:27783671

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

    PubMed

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

    2011-12-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2013-12-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2013-03-01

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

  16. Determination of [11C]PBR28 binding potential in vivo: a first human TSPO blocking study

    PubMed Central

    Owen, David R; Guo, Qi; Kalk, Nicola J; Colasanti, Alessandro; Kalogiannopoulou, Dimitra; Dimber, Rahul; Lewis, Yvonne L; Libri, Vincenzo; Barletta, Julien; Ramada-Magalhaes, Joaquim; Kamalakaran, Aruloly; Nutt, David J; Passchier, Jan; Matthews, Paul M; Gunn, Roger N; Rabiner, Eugenii A

    2014-01-01

    Positron emission tomography (PET) targeting the 18 kDa translocator protein (TSPO) is used to quantify neuroinflammation. Translocator protein is expressed throughout the brain, and therefore a classical reference region approach cannot be used to estimate binding potential (BPND). Here, we used blockade of the TSPO radioligand [11C]PBR28 with the TSPO ligand XBD173, to determine the non-displaceable volume of distribution (VND), and hence estimate the BPND. A total of 26 healthy volunteers, 16 high-affinity binders (HABs) and 10 mixed affinity binders (MABs) underwent a [11C]PBR28 PET scan with arterial sampling. Six of the HABs received oral XBD173 (10 to 90 mg), 2 hours before a repeat scan. In XBD173-dosed subjects, VND was estimated via the occupancy plot. Values of BPND for all subjects were calculated using this VND estimate. Total volume of distribution (VT) of MABs (2.94±0.31) was lower than VT of HABs (4.33±0.29) (P<0.005). There was dose-dependent occupancy of TSPO by XBD173 (ED50=0.34±0.13 mg/kg). The occupancy plot provided a VND estimate of 1.98 (1.69, 2.26). Based on these VND estimates, BPND for HABs is approximately twice that of MABs, consistent with predictions from in vitro data. Our estimates of [11C]PBR28 VND and hence BPND in the healthy human brain are consistent with in vitro predictions. XBD173 blockade provides a practical means of estimating VND for TSPO targeting radioligands. PMID:24643083

  17. Clinically different stages of Alzheimer's disease associated by amyloid deposition with [11C]-PIB PET imaging.

    PubMed

    Hatashita, Shizuo; Yamasaki, Hidetomo

    2010-01-01

    We investigated whether [11C]-PIB PET detects underlying amyloid deposition at clinically different stages of Alzheimer's disease (AD) and preclinical dementia. The Japanese cohort of 214 subjects underwent cognitive testing and 60-min dynamic [11C]-PIB PET. [11C]-PIB data were acquired from 35-60 min after injection. Regions of interest were defined on co-registered MRI. Distribution volume ratios (DVR) of PIB retention were determined using Logan graphical analysis. All 56 patients with AD showed a robust increase in PIB retention in cortical areas (typical PIB AD-pattern). A mean DVR value in 11 patients with moderate AD (CDR: 2.1 ± 0.4) showed significantly higher PIB retention (2.38 ± 0.42, p < 0.01) than amyloid-negative healthy control (HC) subjects. The DVR values in 23 patients with very mild AD (CDR: 0.5) and 22 patients with mild AD (CDR: 1.0) were 2.32 ± 0.45 and 2.34 ± 0.42, respectively, similar to moderate AD. In contrast, 28 (48%) of the 58 mild cognitive impairment (MCI) patients (MMSE: 27.3 ± 1.7) showed a typical AD-like pattern with a DVR value of 2.07 ± 0.34. Further, 17 (18%) of 91 HC subjects had a typical AD-like pattern with a DVR value of 2.06 ± 0.28. They did not significantly differ from very mild AD. The prevalence of AD among the 53 amyloid positive patients aged 75 years or older increased greatly to 74% whereas that of amyloid positive HC decreased by only 9% and amyloid positive MCI by 17%. Prodromal AD and AD dementia is identified, based on cognitive function and amyloid deposition by PIB PET imaging. Further, the cortical amyloid deposition could be detected at preclinical stage of AD.

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

    PubMed

    Klein, A T; Holschbach, M

    2001-09-01

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

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

    NASA Astrophysics Data System (ADS)

    Elmekawy, Ahmed Farouk

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

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

    PubMed

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

    2015-01-01

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

  1. Time of travel of water in the Ohio River, Pittsburgh to Cincinnati

    USGS Publications Warehouse

    Steacy, Robert E.

    1961-01-01

    This report presents a procedure for estimating the time of travel of water in the Ohio River from Pittsburgh, Pa., to Cincinnati, Ohio, under various river stage conditions. This information is primarily for use by civil defense officials and by others concerned with problems involving travel time of river water. Tables and charts are presented to show, for a particular stage or discharge at Cincinnati, the average time it would take for water to travel through the entire reach from Pittsburgh, or through successive intermediate segments of the reach. For example, when the discharge at Cincinnati is 200,000 cfs, travel time from Pittsburgh to Cincinnati, a distance of 470 miles, averages about 7 days; and for discharges of more than 200,000 cfs, the travel time decreases very slowly with increasing discharge. When the discharge is 30,000 cfs, travel time is about 28 days; and for discharges of less than 30,000 cfs, the travel time increases very rapidly with decreasing discharge. Estimates of travel time at low discharge are subject to large errors. Statistical analysis of the possible variations of upstream discharge for a given discharge at Cincinnati indicates that the shortest probable travel time from Pittsburgh to Cincinnati ranges from 56 percent of that under average conditions when the discharge at Cincinnati is 15,000 cfs to 93 percent of that under average conditions when the discharge at Cincinnati is 894,000 cfs. A chart showing the time distribution of flow at Cincinnati is presented so that the probable travel time of Ohio River water can be determined for any time of the year. This chart provides information which, when applied to the time-of-travel chart, shows that the most probable travel time of water from Pittsburgh to Cincinnati ranges from 160 hours in February to 1,250 hours in September. Also presented is a flow-duration curve that can be used to predict future discharges and, subsequently, times of travel, for use in long-range planning

  2. Indoor allergen sensitization and the risk of asthma and eczema in children in Pittsburgh.

    PubMed

    McHugh, Brook M; MacGinnitie, Andrew J

    2011-01-01

    Several studies have shown that sensitization to cockroach and mouse allergens is correlated with presence and severity of asthma, especially among children living in inner cities. This study evaluated the prevalence of positive skin testing to indoor allergens in the Pittsburgh area and the association with asthma and eczema. A retrospective analysis was performed of 540 children from the Pittsburgh area who underwent skin testing to indoor allergens. Presence of asthma and eczema were determined by parent and/or physician report. Asthma and eczema are not significantly more frequent among children who had positive skin testing to cockroaches or mice. However, asthma was more common among children who had positive skin testing to dogs (odds ratio [OR], 1.4; 95% CI, 1.23-1.65), cats (OR, 1.4; 95% CI, 1.21-1.58), and dust mites (OR, 1.2; 95% CI, 1.03-1.37). Eczema was more common in children who had positive skin testing to cats (OR, 1.5; 95% CI, 1.14-2.02). Both asthma (OR, 1.4; 95% CI, 1.18-1.58) and eczema (OR, 1.4; 95% CI, 1.07-1.92) were more prevalent among children with any positive skin test. We did not find that sensitization to cockroaches or mice was correlated with the diagnosis or asthma or eczema in the Pittsburgh area. However, sensitization to any allergen, and to cats and/or dogs specifically, was associated with diagnosis of both asthma and eczema. Our result suggests that allergic sensitization is associated with these diseases, but the implicated allergens may vary.

  3. Building America Case Study: Evaluating Through-Wall Air Transfer Fans, Pittsburgh, Pennsylvania (Fact Sheet)

    SciTech Connect

    Not Available

    2014-10-01

    In this project, Building America team IBACOS performed field testing in a new construction unoccupied test house in Pittsburgh, Pennsylvania to evaluate heating, ventilating, and air conditioning (HVAC) distribution systems during heating, cooling, and midseason conditions. Four air-based HVAC distribution systems were assessed:-a typical airflow ducted system to the bedrooms, a low airflow ducted system to the bedrooms, a system with transfer fans to the bedrooms, and a system with no ductwork to the bedrooms. The relative ability of each system was considered with respect to relevant Air Conditioning Contractors of America and ASHRAE standards for house temperature uniformity and stability, respectively.

  4. Reclaim Northside: An Environmental Justice Approach to Address Vacant Land in Pittsburgh.

    PubMed

    Teixeira, Samantha; Sing, Evaine

    2016-01-01

    Urban decline, disinvestment, and blight have not traditionally been addressed by the environmental conservation movement. In this article, we describe an environmental justice-focused intervention located in Pittsburgh, Pennsylvania, that aimed to increase community empowerment to address urban environmental injustices by training residents to reclaim vacant land. We use a case study approach to illustrate resident perceptions of the impact of vacant land and urban decay. The results suggest that these residents viewed vacancy as an important indicator of community well-being and social inequality. We use a social and environmental justice framework to describe results and implications for practitioners and researchers.

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

    NASA Astrophysics Data System (ADS)

    Rybicki, Maciej; Krzykawski, Tomasz

    2014-09-01

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

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

    NASA Astrophysics Data System (ADS)

    Rybicki, Maciej; Krzykawski, Tomasz

    2014-09-01

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

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

    PubMed Central

    Lan, Jian-yi; Zhou, Ying

    2014-01-01

    The prediction of mine accident is the basis of aviation safety assessment and decision making. Gray prediction is suitable for such kinds of system objects with few data, short time, and little fluctuation, and Markov chain theory is just suitable for forecasting stochastic fluctuating dynamic process. Analyzing the coal mine accident human error cause, combining the advantages of both Gray prediction and Markov theory, an amended Gray Markov SCGM(1,1)c model is proposed. The gray SCGM(1,1)c model is applied to imitate the development tendency of the mine safety accident, and adopt the amended model to improve prediction accuracy, while Markov prediction is used to predict the fluctuation along the tendency. Finally, the new model is applied to forecast the mine safety accident deaths from 1990 to 2010 in China, and, 2011–2014 coal accidents deaths were predicted. The results show that the new model not only discovers the trend of the mine human error accident death toll but also overcomes the random fluctuation of data affecting precision. It possesses stronger engineering application. PMID:27419203

  8. Elements related to attrition of women faculty at the University of Pittsburgh, School of Medicine: A case study

    NASA Astrophysics Data System (ADS)

    Gandhi, Pooja

    Recent studies have shown that the number of women faculty in academic medicine is much lesser than the number of women that are graduating from medical schools. Many academic institutes face the challenge of retaining talented faculty and this attrition from academic medicine prevents career advancement of women faculty. This case study attempts to identify some of the reasons for dissatisfaction that may be related to the attrition of women medical faculty at the University of Pittsburgh, School of Medicine. Data was collected using a job satisfaction survey, which consisted of various constructs that are part of a faculty's job and proxy measures to gather the faculty's intent to leave their current position at the University of Pittsburgh or academic medicine in general. The survey results showed that although women faculty were satisfied with their job at the University of Pittsburgh, there are some important factors that influenced their decision of potentially dropping out. The main reasons cited by the women faculty were related to funding pressures, work-life balance, mentoring of junior faculty and the amount of time spent on clinical responsibilities. The analysis of proxy measures showed that if women faculty decided to leave University of Pittsburgh, it would most probably be due to better opportunity elsewhere followed by pressure to get funding. The results of this study aim to provide the School of Medicine at the University of Pittsburgh with information related to attrition of its women faculty and provide suggestions for implications for policy to retain their women faculty.

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

    SciTech Connect

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

    2011-11-25

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2014-10-01

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

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

    SciTech Connect

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

    1990-05-01

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

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

    PubMed

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

    2016-05-15

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

  14. [11C]Doxepin binding to histamine H1 receptors in living human brain: reproducibility during attentive waking and circadian rhythm

    PubMed Central

    Shibuya, Katsuhiko; Funaki, Yoshihito; Hiraoka, Kotaro; Yoshikawa, Takeo; Naganuma, Fumito; Miyake, Masayasu; Watanuki, Shoichi; Sato, Hirotoshi; Tashiro, Manabu; Yanai, Kazuhiko

    2012-01-01

    Molecular imaging in neuroscience is a new research field that enables visualization of the impact of molecular events on brain structure and function in humans. While magnetic resonance-based imaging techniques can provide complex information at the level of system, positron emission tomography (PET) enables determination of the distribution and density of receptor and enzyme in the human brain. Previous studies using [11C]raclopride and [11C]FLB457 revealed that the release of neuronal dopamine was increased in human brain by psychostimulants or reward stimuli. Following on from these previous [11C]raclopride studies, we examined whether the levels of neuronal release of histamine might change [11C]doxepin binding to the H1 receptors under the influence of physiological stimuli. The purpose of the present study was to evaluate the test–retest reliability of quantitative measurement of [11C]doxepin binding between morning and afternoon and between resting and attentive waking conditions in healthy human subjects. There was a trend for a decrease in [11C]doxepin binding during attentive calculation tasks compared with that in resting conditions, but the difference (less than 10%) was not significant. Similarly, the binding potential of [11C]doxepin in the cerebral cortex was slightly higher in the morning than that in the afternoon, but it was also insignificant. These data suggest that higher histamine release during wakefulness could not decrease the [11C]doxepin binding in the brain. This study confirmed the reproducibility and reliability of [11C]doxepin in the previous imaging studies to measure the H1 receptor. PMID:22701403

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

    PubMed Central

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

    2016-01-01

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

  16. Sustained Recreational Use of Ecstasy Is Associated with Altered Pre and Postsynaptic Markers of Serotonin Transmission in Neocortical Areas: A PET Study with [11C]DASB and [11C]MDL 100907

    PubMed Central

    Urban, Nina BL; Girgis, Ragy R; Talbot, Peter S; Kegeles, Lawrence S; Xu, X; Frankle, W Gordon; Hart, Carl L; Slifstein, Mark; Abi-Dargham, Anissa; Laruelle, Marc

    2012-01-01

    3,4-Methylenedioxymethamphetamine (MDMA), the main psychoactive component of the recreational drug ecstasy, is a potent serotonin (5-HT) releaser. In animals, MDMA induces 5-HT depletion and toxicity in 5-HT neurons. The aim of this study was to investigate both presynaptic (5-HT transporter, SERT) and postsynaptic (5-HT2A receptor) markers of 5-HT transmission in recently abstinent chronic MDMA users compared with matched healthy controls. We hypothesized that MDMA use is associated with lower SERT density and concomitant upregulation of 5-HT2A receptors. Positron emission tomography studies using the SERT ligand [11C]DASB and the 5-HT2A receptor ligand [11C]MDL 100907 were evaluated in 13 current and recently detoxified MDMA users and 13 matched healthy controls. MDMA users reported a mean duration of ecstasy use of 8 years, regular exposure, and at least 2 weeks of abstinence before the scans. SERT and 5-HT2A receptor availability (binding potential, BPND) were analyzed with a two-tissue compartment model with arterial input function. Current recreational MDMA use was significantly associated with lower SERT BPND and higher 5-HT2A receptor BPND in cortical, but not subcortical regions. Decreased SERT BPND was regionally associated with upregulated 5-HT2A receptor BPND. In light of the animal literature, the most parsimonious interpretation is that repeated exposure to MDMA in humans, even in moderate amounts, leads to damage in 5-HT neuron terminals innervating the cortex. Alterations in mood, cognition, and impulse control associated with these changes might contribute to sustain MDMA use. The reversibility of these changes upon abstinence remains to be firmly established. PMID:22353758

  17. Validation of the French version of the Pittsburgh Sleep Quality Index Addendum for posttraumatic stress disorder

    PubMed Central

    Ait-Aoudia, Malik; Levy, Pierre P.; Bui, Eric; Insana, Salvatore; de Fouchier, Capucine; Germain, Anne; Jehel, Louis

    2013-01-01

    Background Sleep disturbances are one of the main complaints of patients with trauma-related disorders. The original Pittsburgh Sleep Quality Index Addendum for PTSD (PSQI-A) is self-report instrument developed to evaluate posttraumatic stress disorder (PTSD)-specific sleep disturbances in trauma-exposed individuals. However, to date, the PSQI-A has not yet been translated nor validated in French. Objective The present study aims to: a) translate the PSQI-A into French, and b) examine its psychometric properties. Method Seventy-three adult patients (mean age=40.3 [SD=15.0], 75% females) evaluated in a specialized psychotraumatology unit completed the French versions of the PSQI-A, Pittsburgh Sleep Quality Index (PSQI), Hospital Anxiety and Depression Scale (HADS), and Impact Event Scale-Revised (IES-R). Results The French version of the PSQI-A showed satisfactory internal consistency, inter-item correlations, item correlations with the total score, convergent validity with PTSD and anxiety measures, and divergent validity with a depression measure. Conclusion Our findings support the use of the French version of the PSQI-A for both clinical care and research. The French version of the PSQI-A is an important addition to the currently available instruments that can be used to examine trauma-related sleep disturbances among French-speaking individuals. PMID:24044071

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

    PubMed Central

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

    2013-01-01

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

  19. Imaging Serotonergic Transmission with [11C]DASB-PET in Depressed and Non-Depressed Patients Infected with HIV

    PubMed Central

    Hammoud, Dima A.; Endres, Christopher J.; Hammond, Edward; Uzuner, Ovsev; Brown, Amanda; Nath, Avindra; Kaplin, Adam I.; Pomper, Martin G.

    2009-01-01

    Introduction Site-selective imaging can provide significant insight into the mechanism of HIV-associated neurological disease. The goal of this study was to evaluate the involvement of serotonergic transmission in HIV-associated depression using [11C]DASB, a serotonin transporter (5-HTT)-specific radiopharmaceutical for positron emission tomography (PET). Methods 9 depressed HIV+ subjects (HIV-D), 9 nondepressed HIV+ subjects (HIV-ND) and 7 healthy controls (HC) underwent an MRI scan and a [11C]DASB-PET scan. The outcome measure was 5-HTT binding potential normalized to nondisplaceable tissue radioligand (BPND). Results HIV-ND subjects had lower mean regional 5-HTT BPND estimates across regions, compared to HC, while HIV-D subjects demonstrated higher mean regional binding values than HIV-ND subjects in most regions. Prior to correction for the false discovery rate, HIV-ND had significantly lower BPND values compared to HC subjects in two regions (insula and anterior cingulate) and all HIV+ patients had significantly lower binding than HC in all regions except for the midbrain, thalamus and pons. After correction for the false discovery rate, only the insula showed significantly lower binding in HIV+ subjects compared to HC (P < 0.0045). Despite a significant difference in the duration of illness between the HIV-D and HIV-ND groups, there was no definite correlation between the duration of illness and BPND. Conclusion Lower [11C]DASB binding in HIV+ patients compared to HC may reflect serotonergic neuronal loss as a component of generalized HIV-associated neurodegeneration. Higher mean regional BPND values in HIV-D compared to HIV-ND subjects could reflect increased density of 5-HTT, leading to increased clearance of serotonin from the synapse, which could account, in part, for symptoms of depression. The lack of correlation between duration of illness and binding argues against these findings being the result of differential neurodegeneration only. Our findings

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

    PubMed

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

    2014-01-01

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

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

    PubMed

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

    2015-05-01

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

  2. Fate of xylem-transported 11C- and 13C-labeled CO2 in leaves of poplar.

    PubMed

    Bloemen, Jasper; Bauweraerts, Ingvar; De Vos, Filip; Vanhove, Christian; Vandenberghe, Stefaan; Boeckx, Pascal; Steppe, Kathy

    2015-04-01

    In recent studies, assimilation of xylem-transported CO2 has gained considerable attention as a means of recycling respired CO2 in trees. However, we still lack a clear and detailed picture on the magnitude of xylem-transported CO2 assimilation, in particular within leaf tissues. To this end, detached poplar leaves (Populus × canadensis Moench 'Robusta') were allowed to take up a dissolved (13)CO2 label serving as a proxy of xylem-transported CO2 entering the leaf from the branch. The uptake rate of the (13)C was manipulated by altering the vapor pressure deficit (VPD) (0.84, 1.29 and 1.83 kPa). Highest tissue enrichments were observed under the highest VPD. Among tissues, highest enrichment was observed in the petiole and the veins, regardless of the VPD treatment. Analysis of non-labeled leaves showed that some (13)C diffused from the labeled leaves and was fixed in the mesophyll of the non-labeled leaves. However, (13)C leaf tissue enrichment analysis with elemental analysis coupled to isotope ratio mass spectrometry was limited in spatial resolution at the leaf tissue level. Therefore, (11)C-based CO2 labeling combined with positron autoradiography was used and showed a more detailed spatial distribution within a single tissue, in particular in secondary veins. Therefore, in addition to (13)C, (11) C-based autoradiography can be used to study the fate of xylem-transported CO2 at leaf level, allowing the acquisition of data at a yet unprecedented resolution.

  3. A General Tank Test of NACA Model 11-C Flying-boat Hull, Including the Effect of Changing the Plan Form of the Step

    NASA Technical Reports Server (NTRS)

    Dawson, John R

    1935-01-01

    The results of a general tank test model 11-C, a conventional pointed afterbody type of flying-boat hull, are given in tables and curves. These results are compared with the results of tests on model 11-A, from which model 11-C was derived, and it is found that the resistance of model 11-C is somewhat greater. The effect of changing the plan form of the step on model 11-C is shown from the results of tests made with three swallow-tail and three pointed steps formed by altering the original step of the model. These results show only minor differences from the results obtained with the original model.

  4. Evaluation of Oatp and Mrp2 activities in hepatobiliary excretion using newly developed positron emission tomography tracer [11C]dehydropravastatin in rats.

    PubMed

    Shingaki, Tomotaka; Takashima, Tadayuki; Ijuin, Ryosuke; Zhang, Xuan; Onoue, Tomohiro; Katayama, Yumiko; Okauchi, Takashi; Hayashinaka, Emi; Cui, Yilong; Wada, Yasuhiro; Suzuki, Masaaki; Maeda, Kazuya; Kusuhara, Hiroyuki; Sugiyama, Yuichi; Watanabe, Yasuyoshi

    2013-10-01

    We developed a pravastatin derivative, sodium (3R,5R)-3,5-dihydroxy-7-((1S,2S,6S,8S)-6-hydroxy-2-methyl-8-((1-[(11)C]-(E)-2-methyl-but-2-enoyl)oxy)-1,2,6,7,8,8a-hexahydronaphthalen-1-yl)heptanoate ([(11)C]DPV), as a positron emission tomography (PET) probe for noninvasive measurement of hepatobiliary transport, and conducted pharmacokinetic analysis in rats as a feasibility study for future clinical study. Transport activities of DPV in freshly isolated rat hepatocytes and rodent multidrug resistance-associated protein 2 (rMrp2; human, MRP2)-expressing membrane vesicles were similar to those of pravastatin. Rifampicin diminished the uptake of DPV and pravastatin by the hepatocytes, with similar inhibition potency. [(11)C]DPV underwent biotransformation to produce at least two metabolites in rat, but metabolism of [(11)C]DPV occurred negligibly in human hepatocytes during a 90-minute incubation. After intravenous injection, [(11)C]DPV was mainly distributed to the liver and kidneys, where the tissue uptake clearances (CLuptake,liver and CLuptake,kidney) were blood-flow-limited (73.6 ± 4.8 and 24.6 ± 0.6 ml/min per kilogram, respectively). Systemic elimination of [(11)C]DPV was delayed in rifampicin-treated rat and an Mrp2-deficient mutant rat, Eisai hyperbilirubinemic mutant rat (EHBR). Rifampicin treatment decreased both CLuptake,liver and CLuptake,kidney of [(11)C]DPV by 30% (P < 0.05), whereas these parameters were unchanged in EHBR. Meanwhile, the canalicular efflux clearance (CLint,bile) of [(11)C]DPV, which was 12.2 ± 1.5 ml/min per kilogram in the control rat, decreased by 60% and 89% in rifampicin-treated rat and EHBR (P < 0.05), respectively. These results indicate that [(11)C]DPV is taken up into the liver by organic anion-transporting polypeptides (rodent, Oatps; human, OATP) and excreted into bile by Mrp2 in rat, and that rifampicin may inhibit Mrp2 as well as Oatps, and consequently increase systemic exposure of [(11)C]DPV. PET using [(11)C]DPV is

  5. CD11c/CD18 Dominates Adhesion of Human Monocytes, Macrophages and Dendritic Cells over CD11b/CD18

    PubMed Central

    Ungai-Salánki, Rita; Orgován, Norbert; Szabó, Bálint; Horváth, Róbert; Erdei, Anna; Bajtay, Zsuzsa

    2016-01-01

    Complement receptors CR3 (CD11b/CD18) and CR4 (CD11c/CD18) belong to the family of beta2 integrins and are expressed mainly by myeloid cell types in humans. Previously, we proved that CR3 rather than CR4 plays a key role in phagocytosis. Here we analysed how CD11b and CD11c participate in cell adhesion to fibrinogen, a common ligand of CR3 and CR4, employing human monocytes, monocyte-derived macrophages (MDMs) and monocyte-derived dendritic cells (MDDCs) highly expressing CD11b as well as CD11c. We determined the exact numbers of CD11b and CD11c on these cell types by a bead-based technique, and found that the ratio of CD11b/CD11c is 1.2 for MDDCs, 1.7 for MDMs and 7.1 for monocytes, suggesting that the function of CD11c is preponderant in MDDCs and less pronounced in monocytes. Applying state-of-the-art biophysical techniques, we proved that cellular adherence to fibrinogen is dominated by CD11c. Furthermore, we found that blocking CD11b significantly enhances the attachment of MDDCs and MDMs to fibrinogen, demonstrating a competition between CD11b and CD11c for this ligand. On the basis of the cell surface receptor numbers and the measured adhesion strength we set up a model, which explains the different behavior of the three cell types. PMID:27658051

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

    SciTech Connect

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

    2012-11-12

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

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

    SciTech Connect

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

    2012-11-20

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  10. Using a Merit-Based Scholarship Program to Increase Rates of College Enrollment in an Urban School District: The Case of the Pittsburgh Promise

    ERIC Educational Resources Information Center

    Bozick, Robert; Gonzalez, Gabriella; Engberg, John

    2015-01-01

    The Pittsburgh Promise is a scholarship program that provides $5,000 per year toward college tuition for public high school graduates in Pittsburgh, Pennsylvania who earned a 2.5 GPA and a 90% attendance record. This study used a difference-in-difference design to assess whether the introduction of the Promise scholarship program directly…

  11. Partners in Pittsburgh Public Schools' Excellence for All Initiative: Findings from the First Year of Implementation. Documented Briefing. DB-544-FFE

    ERIC Educational Resources Information Center

    Tharp-Taylor, Shannah; Nelson, Catherine Awsumb; Dembosky, Jacob W.; Gill, Brian

    2007-01-01

    The Pittsburgh Public School District asked the RAND Corporation to monitor the first year's implementation (2006-2007) of Excellence for All (EFA) and provide feedback to district staff, the board, and other stakeholders. The Pittsburgh Public School District leadership developed EFA with the aim of increasing student achievement by improving…

  12. (11) C-labeled and (18) F-labeled PET ligands for subtype-specific imaging of histamine receptors in the brain.

    PubMed

    Funke, Uta; Vugts, Danielle J; Janssen, Bieneke; Spaans, Arnold; Kruijer, Perry S; Lammertsma, Adriaan A; Perk, Lars R; Windhorst, Albert D

    2013-01-01

    The signaling molecule histamine plays a key role in the mediation of immune reactions, in gastric secretion, and in the sensory system. In addition, it has an important function as a neurotransmitter in the central nervous system, acting in pituitary hormone secretion, wakefulness, motor and cognitive functions, as well as in itch and nociception. This has raised interest in the role of the histaminergic system for the treatment and diagnosis of various pathologies such as allergy, sleeping and eating disorders, neurodegeneration, neuroinflammation, mood disorders, and pruritus. In the past 20 years, several ligands targeting the four different histamine receptor subtypes have been explored as potential radiotracers for positron emission tomography (PET). This contribution provides an overview of the developments of subtype-selective carbon-11-labeled and fluorine-18-labeled compounds for imaging in the brain. Using specific radioligands, the H1 R expression in human brain could be examined in diseases such as schizophrenia, depression, and anorexia nervosa. In addition, the sedative effects of antihistamines could be investigated in terms of H1 R occupancy. The H3 R is of special interest because of its regulatory role in the release of various other neurotransmitters, and initial H3 R PET imaging studies in humans have been reported. The H4 R is the youngest member of the histamine receptor family and is involved in neuroinflammation and various sensory pathways. To date, two H4 R-specific (11) C-labeled ligands have been synthesized, and the imaging of the H4 R in vivo is in the early stage.

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

    PubMed Central

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

    2014-01-01

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

  14. Brain and whole-body imaging in nonhuman primates with [11C]MeS-IMPY, a candidate radioligand for beta-amyloid plaques.

    PubMed

    Seneca, Nicholas; Cai, Lisheng; Liow, Jeih-San; Zoghbi, Sami S; Gladding, Robert L; Hong, Jinsoo; Pike, Victor W; Innis, Robert B

    2007-08-01

    [(11)C]MeS-IMPY ([S-methyl-(11)C]N,N-dimethyl-4-(6-(methylthio)imidazo[1,2-a]pyridine-2-yl)aniline) is a potential radioligand for imaging beta-amyloid plaques with positron emission tomography (PET). The aims of this study were to evaluate [(11)C]MeS-IMPY uptake in nonhuman primate brain and to estimate radiation exposure from serial whole-body images. Eight PET studies were performed in rhesus monkeys to measure the brain uptake and washout of [(11)C]MeS-IMPY. Time-activity data were analyzed with one-tissue and two-tissue compartmental models using radiometabolite-corrected plasma input function. In addition, two whole-body PET scans were acquired for 120 min to determine the biodistribution of [(11)C]MeS-IMPY. Tomographic PET images were compressed into a single planar image to identify organs with the highest radiation exposures. Estimates of the absorbed dose of radiation were calculated using OLINDA 1.0. Injection of [(11)C]MeS-IMPY caused little change in pulse rate, blood pressure, respiratory rate and temperature. [(11)C]MeS-IMPY showed high standardized brain uptake values of approximately 500% and 600% between 2 and 3 min in cortical regions and the cerebellum, respectively. The brain uptake of [(11)C]MeS-IMPY was widespread and quite uniform across all cortical regions. Activity rapidly washed out of the brain, with 20% of peak activity remaining at 40 min. Thus, all brain regions showed minimal retention of radioactivity, consistent with these healthy young animals having negligible amyloid plaques. Regional brain activity fitted well into a one-tissue compartment model. The average volume of distribution in all brain regions was 7.66+/-2.14 ml/cm(3) (n=4). The organs with the highest radiation exposure (muSv/MBq) were the gallbladder wall (33.4), urinary bladder (17) and lungs (12.9), with a resulting effective dose of 4.9 microSv/MBq (18 mrem/mCi). The high brain uptake, rapid washout and quantifiable volume of distribution in nonhuman primate brain

  15. 2003 Environmental Monitoring Report for the Bettis Atomic Power Laboratory Pittsburgh Site

    SciTech Connect

    2003-12-31

    The 2003 results for the Bettis-Pittsburgh radiological and nonradiological environmental monitoring programs are presented. The results demonstrate that the existing procedures ensured that releases to the environment during 2003 were in accordance with applicable Federal, State, County, and local regulations. Evaluation of the environmental data indicates that current operations at the Site continue to have no adverse effect on human health and the quality of the environment. A conservative assessment of radiation exposure to the general public as a result of Site operations demonstrates that the dose received by any member of the public was well below the most restrictive dose limits established by the Environmental Protection Agency, the Nuclear Regulatory Commission, and the U.S. Department of Energy. A risk assessment of potentially exposed populations to chemical residues in the environment at the Site demonstrates that any potential risk posed by these residues in much less than the risks encountered in normal everyday life.

  16. Innovative approaches to interprofessional care at the University of Pittsburgh Medical Center.

    PubMed

    Driessen, Julia; Bellon, Johanna E; Stevans, Joel; James, A Everette; Minnier, Tami; Reynolds, Benjamin R; Zhang, Yuting

    2015-01-01

    The enactment of the Affordable Care Act expands coverage to millions of uninsured Americans and creates a new workforce landscape. Interprofessional Collaborative Practice (ICP) is no longer a choice but a necessity. In this paper, we describe four innovative approaches to interprofessional practice at the University of Pittsburgh Medical Center. These models demonstrate innovative applications of ICP to inpatient and outpatient care, relying on non-physician providers, training programs, and technology to deliver more appropriate care to specific patient groups. We also discuss the ongoing evaluation plans to assess the effects of these interprofessional practices on patient health, quality of care, and healthcare costs. We conclude that successful implementation of interprofessional teams involves more than just a reassignment of tasks, but also depends on structuring the environment and workflow in a way that facilitates team-based care.

  17. 1992 Effluent and environmental monitoring report for the Bettis Atomic Power Laboratory Pittsburgh Site

    SciTech Connect

    Not Available

    1992-12-31

    The results of the radiological and non-radiological environmental monitoring programs for 1992 at the Bettis-Pittsburgh Site are presented. The results obtained from the monitoring programs demonstrate that the existing procedures ensured that environmental releases during 1992 were in accordance with applicable Federal and State regulations. Evaluation of the environmental data indicates that operation of the Laboratory continues to have no adverse effect on the quality of the environment. A conservative assessment of radiation exposure to the general public as a result of Laboratory operations demonstrated that the dose received by any member of the public was well below the most restrictive dose limits established by the Environmental Protection Agency and the Department of Energy.

  18. Prevalence of Clostridium difficile in uncooked ground meat products from Pittsburgh, Pennsylvania.

    PubMed

    Curry, Scott R; Marsh, Jane W; Schlackman, Jessica L; Harrison, Lee H

    2012-06-01

    The prevalence of Clostridium difficile in retail meat samples has varied widely. The food supply may be a source for C. difficile infections. A total of 102 ground meat and sausage samples from 3 grocers in Pittsburgh, PA, were cultured for C. difficile. Brand A pork sausages were resampled between May 2011 and January 2012. Two out of 102 (2.0%) meat products initially sampled were positive for C. difficile; both were pork sausage from brand A from the same processing facility (facility A). On subsequent sampling of brand A products, 10/19 samples from processing facility A and 1/10 samples from 3 other facilities were positive for C. difficile. The isolates recovered were inferred ribotype 078, comprising 6 genotypes. The prevalence of C. difficile in retail meat may not be as high as previously reported in North America. When contamination occurs, it may be related to events at processing facilities.

  19. 1993 Effluent and environmental monitoring report for the Bettis Atomic Power Laboratory, Pittsburgh Site

    SciTech Connect

    Not Available

    1993-12-31

    The results of the radiological and non-radiological environmental monitoring programs for 1993 at the Bettis-Pittsburgh Site are presented. The results obtained from the monitoring programs demonstrate that the existing procedures ensured that environmental releases during 1993 were in accordance with applicable Federal and State regulations. Evaluation of the environmental data indicates that the current operations at the Site continue to have no adverse effect on the quality of the environment. A conservative assessment of radiation exposure to the general public as a result of Site operations demonstrated that the dose received by any member of the public was well below the most restrictive dose limits established by the US Environmental Protection Agency and the US Department of Energy.

  20. 1997 environmental monitoring report for the Bettis Atomic Power Laboratory, Pittsburgh Site

    SciTech Connect

    1997-12-31

    The 1997 results for the Bettis-Pittsburgh radiological and nonradiological environmental monitoring programs are presented. The results demonstrate that the existing procedures ensured that releases to the environment during 1997 were in accordance with applicable Federal, State, County, and local regulations. Evaluation of the environmental data indicates tat current operations at the Site continue to have no adverse effect on human health and the quality of the environment. A conservative assessment of radiation exposure to the general public as a result of Site operations demonstrates that the dose received by any member of the public was well below the most restrictive dose limits established by the Environmental Protection Agency, the Nuclear Regulatory Commission, and the US Department of Energy. A risk assessment of potentially exposed populations to chemical residues in the environment at the Site demonstrates that these residues do not pose any significant risk to human health or the environment.

  1. The Pittsburgh Reference Laboratory Alliance: a model for laboratory medicine in the 21st century.

    PubMed

    Gilbertson, J; Mango, P; McLinden, S; Becich, M J; Triulzi, D

    1997-04-01

    The Pittsburgh Reference Library Alliance (RLA) represents a successful response by hospital laboratories to the new realities of medical economics and practice. By using informatics technology to integrate the laboratory resources of community hospitals and academic medical centers across western Pennsylvania, the RLA has created a large virtual laboratory that can compete for price with large national referral laboratories. More significantly, the combination of medical expertise, the ties to academic and community centers, and the regional medical database of the RLAs allows laboratory medicine to be practiced in a new proactive way. This should provide better and more cost-effective patient care. The success of the RLA is a model for regional cooperation in pathology and potentially in other medical specialties and demonstrates the importance of informatics in the future of medical practice. PMID:9124206

  2. 1999 environmental monitoring report for the Bettis Atomic Power Laboratory, Pittsburgh Site

    SciTech Connect

    2000-12-01

    The 1999 results for the Bettis-Pittsburgh radiological and nonradiological environmental monitoring programs are presented. The results demonstrate that the existing procedures ensured that releases to the environment during 1999 were in accordance with applicable Federal, State, County, and local regulations. Evaluation of the environmental data indicates that current operations at the Site continue to have no adverse effect on human health and the quality of the environment. A conservative assessment of radiation exposure to the general public as a result of Site operations demonstrates that the dose received by any member of the public was well below the most restrictive dose limits established by the Environmental Protection Agency, the Nuclear Regulatory Commission, and the US Department of Energy. A risk assessment of potentially exposed populations to chemical residues in the environment at the Site demonstrates that these residues do not pose any significant risk to human health or the environment.

  3. Structural Validity of the Pittsburgh Sleep Quality Index in Chinese Undergraduate Students

    PubMed Central

    Guo, Suran; Sun, Wenmei; Liu, Chang; Wu, Siwei

    2016-01-01

    The purpose of this study was to examine the structural validity of the Pittsburgh Sleep Quality Index (PSQI) in Chinese undergraduate students. A cross-sectional questionnaire survey with 631 Chinese undergraduate students was conducted, and the questionnaire package included a measure of demographic characteristics, PSQI, Chinese editions of Center for Epidemiologic Studies-Depression, State- Trait Anxiety Inventory, Rumination Response Scale, and Perceived Social Support Scale. Results showed that the item “use of sleep medicine” was not suitable for use with this population, that a two-factor model provided the best fit to the data as assessed through confirmatory factor analysis, and that other indices were consistently correlated with the sleep quality but not the sleep efficiency factor. PMID:27551270

  4. Structural Validity of the Pittsburgh Sleep Quality Index in Chinese Undergraduate Students.

    PubMed

    Guo, Suran; Sun, Wenmei; Liu, Chang; Wu, Siwei

    2016-01-01

    The purpose of this study was to examine the structural validity of the Pittsburgh Sleep Quality Index (PSQI) in Chinese undergraduate students. A cross-sectional questionnaire survey with 631 Chinese undergraduate students was conducted, and the questionnaire package included a measure of demographic characteristics, PSQI, Chinese editions of Center for Epidemiologic Studies-Depression, State- Trait Anxiety Inventory, Rumination Response Scale, and Perceived Social Support Scale. Results showed that the item "use of sleep medicine" was not suitable for use with this population, that a two-factor model provided the best fit to the data as assessed through confirmatory factor analysis, and that other indices were consistently correlated with the sleep quality but not the sleep efficiency factor. PMID:27551270

  5. [Proceedings of the] International Conference on Educational Data Mining (EDM) (3rd, Pittsburgh, PA, July 11-13, 2010)

    ERIC Educational Resources Information Center

    Baker, Ryan S. J. d., Ed.; Merceron, Agathe, Ed.; Pavlik, Philip I., Jr., Ed.

    2010-01-01

    The Third International Conference on Data Mining (EDM 2010) was held in Pittsburgh, PA, USA. It follows the second conference at the University of Cordoba, Spain, on July 1-3, 2009 and the first edition of the conference held in Montreal in 2008, and a series of workshops within the AAAI, AIED, EC-TEL, ICALT, ITS, and UM conferences. EDM 2011…

  6. Findings From the Pittsburgh Youth Study: Cognitive Impulsivity and Intelligence as Predictors of the Age-Crime Curve

    ERIC Educational Resources Information Center

    Loeber, Rolf; Menting, Barbara; Lynam, Donald R.; Moffitt, Terri E.; Stouthamer-Loeber, Magda; Stallings, Rebecca; Farrington, David P.; Pardini, Dustin

    2012-01-01

    Objective: This article first summarizes key research findings from the Pittsburgh Youth Study from 1987 to the present, and focuses on delinquency in 1,517 young men who have been followed up from late childhood into their 20s. Second, the article addresses how indicators of self-control prospectively predict later offending, and whether the…

  7. Creating Social Connections in Higher Education: Insights from the Campus Canines Program at the University of Pittsburgh

    ERIC Educational Resources Information Center

    Camaioni, Nicole

    2013-01-01

    The overall purpose of this study was to capture the relationships made during the Campus Canines Program, an animal-assisted activity program, at the University of Pittsburgh. Meaningful social relationships create greater educational satisfaction. These social relationships are an important piece to creating and sustaining student involvement,…

  8. An Analysis of Two Beginning Reading Programs: Scott Foresman's "Reading Unlimited" and Pittsburgh LRDC's "New Primary Grades Reading Systems."

    ERIC Educational Resources Information Center

    Popp, Helen Mitchell

    The two reading programs discussed in this paper, "Reading Unlimited" (RU) published by Scott Foresman and "New Primary Grades Reading Systems" (RS) by the University of Pittsburgh Learning Research and Development Center, provide maximal contrasts in materials and teaching strategies. The instructional strategies in RU are analytic and inductive,…

  9. The Use of Information Theory to Study Human Learning. Project on the Information Memory Model, University of Pittsburgh.

    ERIC Educational Resources Information Center

    Moser, Gene W.

    As the proceedings of a symposium held at the 1973 Annual Meeting of the National Association for Research in Science Teaching, theoretical and experimental results from research in the use of information theory to study human learning are presented in this volume to reflect the efforts made at the University of Pittsburgh over the past four…

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

    SciTech Connect

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

    1989-06-01

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

  11. Psychometric Properties of the Pittsburgh Sleep Quality Index (PSQI) in a Cohort of Peruvian Pregnant Women

    PubMed Central

    Zhong, Qiu-Yue; Gelaye, Bizu; Sánchez, Sixto E.; Williams, Michelle A.

    2015-01-01

    Study Objectives: We sought to evaluate the construct validity and factor structure of the Spanish-language version of the Pittsburgh Sleep Quality Index (PSQI) among pregnant Peruvian women. Methods: A cohort of 642 women were interviewed at ≤ 16 weeks of gestation. During interview, we ascertained information about lifestyles, demographics, sleep characteristics, and mood symptoms. Stress induced sleep disturbance, depressive symptoms, and anxiety symptoms were evaluated using the Ford Insomnia Response to Stress Test (FIRST), Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder-7 (GAD-7) assessment scales, respectively. Consistency indices, exploratory and confirmatory factor analyses, correlations, and logistic regressions were used. Results: Both exploratory and confirmatory factor analyses indicated a three-factor solution: sleep quality, sleep efficiency, and sleep medication. We observed significantly positive correlations of the PSQI with the FIRST (0.42), the PHQ-9 (0.49), and the GAD-7 (0.46). Poor sleepers (PSQI global score > 5) had significantly increased odds of experiencing stress-induced sleep disturbance (odds ratio, OR = 3.57; 95% CI: 2.40, 5.31), depression (OR = 5.48; 95% CI: 3.58, 8.37), and generalized anxiety disorder (OR = 4.57; 95% CI: 3.08, 6.76). Conclusions: The Spanish-language version of the PSQI instrument was found to have good construct validity among pregnant Peruvian women. Consistent with some other studies, the PSQI was found to have a three-factor structure. Further assessment and validation studies are needed to determine whether the three, factor-specific scoring of the PSQI is favored over the PSQI global score in diverse populations. Citation: Zhong QY, Gelaye B, Sánchez SE, Williams MA. Psychometric properties of the Pittsburgh Sleep Quality Index (PSQI) in a cohort of Peruvian pregnant women. J Clin Sleep Med 2015;11(8):869–877. PMID:25845902

  12. A geostatistical approach to predicting sulfur content in the Pittsburgh coal bed

    USGS Publications Warehouse

    Watson, W.D.; Ruppert, L.F.; Bragg, L.J.; Tewalt, S.J.

    2001-01-01

    The US Geological Survey (USGS) is completing a national assessment of coal resources in the five top coal-producing regions in the US. Point-located data provide measurements on coal thickness and sulfur content. The sample data and their geologic interpretation represent the most regionally complete and up-to-date assessment of what is known about top-producing US coal beds. The sample data are analyzed using a combination of geologic and Geographic Information System (GIS) models to estimate tonnages and qualities of the coal beds. Traditionally, GIS practitioners use contouring to represent geographical patterns of "similar" data values. The tonnage and grade of coal resources are then assessed by using the contour lines as references for interpolation. An assessment taken to this point is only indicative of resource quantity and quality. Data users may benefit from a statistical approach that would allow them to better understand the uncertainty and limitations of the sample data. To develop a quantitative approach, geostatistics were applied to the data on coal sulfur content from samples taken in the Pittsburgh coal bed (located in the eastern US, in the southwestern part of the state of Pennsylvania, and in adjoining areas in the states of Ohio and West Virginia). Geostatistical methods that account for regional and local trends were applied to blocks 2.7 mi (4.3 km) on a side. The data and geostatistics support conclusions concerning the average sulfur content and its degree of reliability at regional- and economic-block scale over the large, contiguous part of the Pittsburgh outcrop, but not to a mine scale. To validate the method, a comparison was made with the sulfur contents in sample data taken from 53 coal mines located in the study area. The comparison showed a high degree of similarity between the sulfur content in the mine samples and the sulfur content represented by the geostatistically derived contours. Published by Elsevier Science B.V.

  13. Ablation of CD11c(hi) dendritic cells exacerbates Japanese encephalitis by regulating blood-brain barrier permeability and altering tight junction/adhesion molecules.

    PubMed

    Kim, Jin Hyoung; Hossain, Ferdaus Mohd Altaf; Patil, Ajit Mahadev; Choi, Jin Young; Kim, Seong Bum; Uyangaa, Erdenebelig; Park, Sang-Youel; Lee, John-Hwa; Kim, Bumseok; Kim, Koanhoi; Eo, Seong Kug

    2016-10-01

    Japanese encephalitis (JE), characterized by extensive neuroinflammation following infection with neurotropic JE virus (JEV), is becoming a leading cause of viral encephalitis due to rapid changes in climate and demography. The blood-brain barrier (BBB) plays an important role in restricting neuroinvasion of peripheral leukocytes and virus, thereby regulating the progression of viral encephalitis. In this study, we explored the role of CD11c(hi) dendritic cells (DCs) in regulating BBB integrity and JE progression using a conditional depletion model of CD11c(hi) DCs. Transient ablation of CD11c(hi) DCs resulted in markedly increased susceptibility to JE progression along with highly increased neuro-invasion of JEV. In addition, exacerbated JE progression in CD11c(hi) DC-ablated hosts was closely associated with increased expression of proinflammatory cytokines (IFN-β, IL-6, and TNF-α) and CC chemokines (CCL2, CCL3, CXCL2) in the brain. Moreover, our results revealed that the exacerbation of JE progression in CD11c(hi) DC-ablated hosts was correlated with enhanced BBB permeability and reduced expression of tight junction and adhesion molecules (claudin-5, ZO-1, occluding, JAMs). Ultimately, our data conclude that the ablation of CD11c(hi) DCs provided a subsidiary impact on BBB integrity and the expression of tight junction/adhesion molecules, thereby leading to exacerbated JE progression. These findings provide insight into the secondary role of CD11c(hi) DCs in JE progression through regulation of BBB integrity and the expression of tight junction/adhesion molecules. PMID:27638116

  14. Ablation of CD11c(hi) dendritic cells exacerbates Japanese encephalitis by regulating blood-brain barrier permeability and altering tight junction/adhesion molecules.

    PubMed

    Kim, Jin Hyoung; Hossain, Ferdaus Mohd Altaf; Patil, Ajit Mahadev; Choi, Jin Young; Kim, Seong Bum; Uyangaa, Erdenebelig; Park, Sang-Youel; Lee, John-Hwa; Kim, Bumseok; Kim, Koanhoi; Eo, Seong Kug

    2016-10-01

    Japanese encephalitis (JE), characterized by extensive neuroinflammation following infection with neurotropic JE virus (JEV), is becoming a leading cause of viral encephalitis due to rapid changes in climate and demography. The blood-brain barrier (BBB) plays an important role in restricting neuroinvasion of peripheral leukocytes and virus, thereby regulating the progression of viral encephalitis. In this study, we explored the role of CD11c(hi) dendritic cells (DCs) in regulating BBB integrity and JE progression using a conditional depletion model of CD11c(hi) DCs. Transient ablation of CD11c(hi) DCs resulted in markedly increased susceptibility to JE progression along with highly increased neuro-invasion of JEV. In addition, exacerbated JE progression in CD11c(hi) DC-ablated hosts was closely associated with increased expression of proinflammatory cytokines (IFN-β, IL-6, and TNF-α) and CC chemokines (CCL2, CCL3, CXCL2) in the brain. Moreover, our results revealed that the exacerbation of JE progression in CD11c(hi) DC-ablated hosts was correlated with enhanced BBB permeability and reduced expression of tight junction and adhesion molecules (claudin-5, ZO-1, occluding, JAMs). Ultimately, our data conclude that the ablation of CD11c(hi) DCs provided a subsidiary impact on BBB integrity and the expression of tight junction/adhesion molecules, thereby leading to exacerbated JE progression. These findings provide insight into the secondary role of CD11c(hi) DCs in JE progression through regulation of BBB integrity and the expression of tight junction/adhesion molecules.

  15. MBP-Positive and CD11c-Positive Cells Are Associated with Different Phenotypes of Korean Patients with Non-Asthmatic Chronic Rhinosinusitis

    PubMed Central

    Chang, Dong-Yeop; Eun, Kyung Mi; Shin, Hyun-Woo; Mo, Ji-Hun; Shin, Eui-Cheol; Jin, Hong Ryul; Shin, Sue; Roh, Eun Youn; Han, Doo Hee; Kim, Dae Woo

    2014-01-01

    Background Asthmatic nasal polyps primarily exhibit eosinophilic infiltration. However, the identities of the immune cells that infiltrate non-asthmatic nasal polyps remain unclear. Thus, we thought to investigate the distribution of innate immune cells and its clinical relevance in non-asthmatic chronic rhinosinusitis (CRS) in Korea. Methods Tissues from uncinate process (UP) were obtained from controls (n = 18) and CRS without nasal polyps (CRSsNP, n = 45). Nasal polyps (NP) and UP were obtained from CRS with nasal polyps (CRSwNP, n = 56). The innate immune cells was evaluated by immunohistochemistry such as, eosinophil major basic protein (MBP), tryptase, CD68, CD163, CD11c, 2D7, human neutrophil elastase (HNE) and its distribution was analyzed according to clinical parameters. Results In comparisons between UP from each group, CRSwNP had a higher number of MPB+, CD68+, and CD11c+ cells relative to CRSsNP. Comparisons between UP and NP from CRSwNP indicated that NP have a higher infiltrate of MBP+, CD163+, CD11c+, 2D7+ and HNE+ cells, whereas fewer CD68+ cells were found in NP. In addition, MBP+ and CD11c+ cells were increased from UP of CRSsNP, to UP of CRSwNP, and to NP of CRSwNP. Moreover, in UP from CRSwNP, the number of MBP+ and CD11c+ cells positively correlated with CT scores. In the analysis of CRSwNP phenotype, allergic eosinophilic polyps had a higher number of MBP+, tryptase+, CD11c+, 2D7+ cells than others, whereas allergic non-eosinophilic polyps showed mainly infiltration of HNE+ and 2D7+ cells. Conclusions The infiltration of MBP+ and CD11c+ innate immune cells show a significant association with phenotype and disease extent of CRS and allergic status also may influences cellular phenotype in non-asthmatic CRSwNP in Korea. PMID:25361058

  16. Evaluation of a novel PDE10A PET radioligand, [(11) C]T-773, in nonhuman primates: brain and whole body PET and brain autoradiography.

    PubMed

    Takano, Akihiro; Stepanov, Vladimir; Gulyás, Balázs; Nakao, Ryuji; Amini, Nahid; Miura, Shotaro; Kimura, Haruhide; Taniguchi, Takahiko; Halldin, Christer

    2015-07-01

    Phosphodiesterase 10A (PDE10A) is considered to be a key target for the treatment of several neuropsychiatric diseases. The characteristics of [(11) C]T-773, a novel positron emission tomography (PET) radioligand with high binding affinity and selectivity for PDE10A, were evaluated in autoradiography and in nonhuman primate (NHP) PET. Brain PET measurements were performed under baseline conditions and after administration of a selective PDE10A inhibitor, MP-10. Total distribution volume (VT ) and binding potential (BPND ) were calculated using various kinetic models. Whole body PET measurements were performed to calculate the effective dose of [(11) C]T-773. Autoradiography studies in postmortem human and monkey brain sections showed high accumulation of [(11) C]T-773 in the striatum and substantia nigra which was blocked by MP-10. Brain PET showed high accumulation of [(11) C]T-773 in the striatum, and the data could be fitted using a two tissue compartment model. BPND was approximately 1.8 in the putamen when the cerebellum was used as the reference region. Approximately 70% of PDE10A binding was occupied by 1.8 mg/kg of MP-10. Whole body PET showed high accumulation of [(11) C]T-773 in the liver, kidney, heart, and brain in the initial phase. The radioligand was partly excreted via bile and the gastrointestinal tract, and partly excreted through the urinary tract. The calculated effective dose was 0.007 mSv/MBq. In conclusion, [(11) C]T-773 was demonstrated to be a promising PET radioligand for PDE10A with favorable brain kinetics. Dosimetry results support multiple PET measurements per person in human studies. Further research is required with [(11) C]T-773 in order to test the radioligand's potential clinical applications.

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

    PubMed Central

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

    2013-01-01

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

  18. No effect of dopamine depletion on the binding of the high-affinity D 2/3 radiotracer [11C]FLB 457 in the human cortex.

    PubMed

    Frankle, W Gordon; Mason, N Scott; Rabiner, Eugenii A; Ridler, Khanum; May, Maureen A; Asmonga, Deanna; Chen, Chi-Min; Kendro, Steve; Cooper, Thomas B; Mathis, Chester A; Narendran, Rajesh

    2010-12-01

    The use of PET and SPECT endogenous competition-binding techniques has contributed to the understanding of the role of dopamine (DA) in several neuropsychiatric disorders. An important limitation of these imaging studies is the fact that measurements of changes in synaptic DA have been restricted to the striatum. The ligands previously used, such as [(11)C]raclopride and [(123)I]IBZM, do not provide sufficient signal-to-noise ratio to quantify D(2) receptors in extrastriatal areas, such as cortex, where the concentration of D(2) receptors is much lower than that in the striatum. Recently, we published a comparison study of the ability of two high-affinity DA D(2) radioligands [(11)C]FLB 457 and [(11)C]fallypride to measure amphetamine-induced changes in DA transmission in the human cortex. Our findings support the use of [(11)C]FLB 457 to measure changes in cortical synaptic DA induced by amphetamine. The goal of this study is to examine the effects of DA depletion with α-methyl-para-tyrosine (α-MPT) on [(11)C]FLB 457 binding in the cortex. Six healthy volunteers underwent two PET scans, first under control conditions and subsequently after DA depletion. The simplified reference tissue model as well as kinetic modeling with an arterial input function was used to derive the binding potential (BP(ND)) in seven cortical regions. We found no effect of DA depletion with α-MPT on [(11)C]FLB 457 binding in any of the regions examined. In contrast to the measurement of DA release, the combination of low D(2) receptor density and low basal DA levels in the cortex greatly reduce the power to detect alterations in [(11)C]FLB 457 binding secondary to DA depletion.

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

    SciTech Connect

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

    1990-03-01

    Several groups have reported increased densities of D2 dopamine receptors in the basal ganglia of schizophrenic brains postmortem. The significance of this finding has been questioned, since an upregulation of receptor number may be a neuronal response to neuroleptic drug treatment. We have used positron emission tomography and ({sup 11}C)raclopride to examine central D2 dopamine receptor binding in 20 healthy subjects and 18 newly admitted, young, neuroleptic-naive patients with schizophrenia. An in vivo saturation procedure was applied for quantitative determination of D2 dopamine receptor density (Bmax) and affinity (Kd). When the two groups were compared, no significant difference in Bmax or Kd values was found in the putamen or the caudate nucleus. The hypothesis of generally elevated central D2 dopamine receptor densities in schizophrenia was thus not supported by the present findings. In the patients but not in the healthy controls, significantly higher densities were found in the left than in the right putamen but not in the caudate nucleus.

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

    NASA Astrophysics Data System (ADS)

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

    2016-06-01

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

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

    PubMed

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

    2013-01-01

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

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

    SciTech Connect

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

    1984-01-01

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

  3. 11C-Methionine-PET: a novel and sensitive tool for monitoring of early response to treatment in multiple myeloma.

    PubMed

    Lückerath, Katharina; Lapa, Constantin; Albert, Christa; Herrmann, Ken; Jörg, Gerhard; Samnick, Samuel; Einsele, Herrmann; Knop, Stefan; Buck, Andreas K

    2015-04-10

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

  4. A comparison study of 11C-methionine and 18F-fluorodeoxyglucose positron emission tomography-computed tomography scans in evaluation of patients with recurrent brain tumors

    PubMed Central

    Sharma, Rajnish; D’Souza, Maria; Jaimini, Abhinav; Hazari, Puja Panwar; Saw, Sanjeev; Pandey, Santosh; Singh, Dinesh; Solanki, Yachna; Kumar, Nitin; Mishra, Anil K.; Mondal, Anupam

    2016-01-01

    Introduction: 11C-methonine ([11C]-MET) positron emission tomography-computed tomography (PET-CT) is a well-established technique for evaluation of tumor for diagnosis and treatment planning in neurooncology. [11C]-MET reflects amino acid transport and has been shown to be more sensitive than magnetic resonance imaging (MRI) in stereotactic biopsy planning. This study compared fluorodeoxyglucose (FDG) PET-CT and MET PET-CT in the detection of various brain tumors. Materials and Methods: Sixty-four subjects of brain tumor treated by surgery, chemotherapy, and/or radiotherapy were subjected to [18F]-FDG, [11C]-MET, and MRI scan. The lesion was analyzed semiquantitatively using tumor to normal contralateral ratio. The diagnosis was confirmed by surgery, stereotactic biopsy, clinical follow-up, MRI, or CT scans. Results: Tumor recurrence was found in 5 out of 22 patients on [F-18] FDG scan while [11C]-MET was able to detect recurrence in 18 out of 22 patients in low-grade gliomas. Two of these patients were false positive for the presence of recurrence of tumor and later found to be harboring necrosis. Among oligodendroglioma, medulloblastoma and high-grade glioma out of 42 patients 39 were found to be concordant MET and FDG scans. On semiquantitative analysis, mean T/NT ratio was found to be 2.96 ± 0.94 for lesions positive for recurrence of tumors and 1.18 ± 0.74 for lesions negative for recurrence of tumor on [11C]-MET scan. While the ratio for FDG scan on semiquantitative analysis was found to be 2.05 ± 1.04 for lesions positive for recurrence of tumors and 0.52 ± 0.15 for lesions negative for recurrence of tumors. Conclusion: The study highlight that [11C]-MET is superior to [18F]-FDG PET scans to detect recurrence in low-grade glioma. A cut-off value of target to nontarget value of 1.47 is a useful parameter to distinguish benign from malignant lesion on an [11C]-MET Scan. Both [18F]-FDG and [11C]-MET scans were found to be useful in high-grade astrocytoma

  5. Automated Measurements of Ambient Aerosol Chemical Composition and its Dry and Wet Size Distributions at Pittsburgh Supersite

    NASA Astrophysics Data System (ADS)

    Khlystov, A. Y.; Stanier, C.; Chun, W.; Vayenas, D.; Mandiro, M.; Pandis, S. N.

    2001-12-01

    Ambient aerosol particles change size with changes in ambient relative humidity. The magnitude of the size change depends on the hygroscopic properties of the particles, which is determined by their chemical composition. Hygroscopic properties of particles influence many environmentally important aerosol qualities, such as light scattering and partitioning between the gas and particle phases of semivolitile compounds. Studying the hygroscopic growth of ambient particles is thus of paramount importance. The highroscopic growth of ambient particles and their chemical composition are measured continuously within the Pittsburgh Air Quality Study (EPA supersite program). The hygroscopic size changes are measured using an automated system built for this study. The system consists of two Scanning Mobility Particle Sizers (SMPS, TSI Inc.) and an Aerodynamic Particle Sizer (APS, TSI Inc.). The three instruments measure aerosol size distribution between 5 nanometers and 10 micrometers in diameter. The inlets of the instruments and the sheath air lines of the SMPS systems are equipped with computer controlled valves that direct air through Nafion dryers (PermaPure Inc.) or bypass them. The Nafion dryers are drying the air stream below 40% RH at which point ambient particles are expected to lose most or all water and thus be virtually dry. To avoid changes in relative humidity and evaporation of volatile particles due to temperature differences the system is kept at ambient temperature. The system measures alternatively dry (below 40% RH) and wet (actual ambient RH) aerosol size distributions every 6 minutes. The hygroscopic growth observed with the size-spectrometer system is compared with theoretic predictions based on the chemical composition of aerosol particles. A modified semi-continuous Steam-Jet Aerosol Collector provides the total available budget (particles and gas) of water-soluble species, which is used as an input to the thermodynamic model. The model calculates

  6. Characterisation of [11C]PR04.MZ in Papio anubis baboon: A selective high-affinity radioligand for quantitative imaging of the dopamine transporter

    SciTech Connect

    Riss P. J.; Fowler J.; Riss, P.J.; Hooker, J.M.; Shea, C.; Xu, Y.; Carter, P.; Warner, D.; Ferrari V.; Kim, S.W.; Aigbirhio, F.I.; Fowler, J.S.; Roesch, F.

    2011-10-25

    N-(4-fluorobut-2-yn-1-yl)-2{beta}-carbomethoxy-3{beta}-(4{prime}-tolyl)nortropane (PR04.MZ, 1) is a PET radioligand for the non-invasive exploration of the function of the cerebral dopamine transporter (DAT). A reliable automated process for routine production of the carbon-11 labelled analogue [{sup 11}C]PR04.MZ ([{sup 11}C]-1) has been developed using GMP compliant equipment. An adult female Papioanubis baboon was studied using a test-retest protocol with [{sup 11}C]-1 in order to assess test-retest reliability, metabolism and CNS distribution profile of the tracer in non-human primates. Blood sampling was performed throughout the studies for determination of the free fraction in plasma (fP), plasma input functions and metabolic degradation of the radiotracer [{sup 11}C]-1. Time-activity curves were derived for the putamen, the caudate nucleus, the ventral striatum, the midbrain and the cerebellum. Distribution volumes (VT) and non-displaceable binding potentials (BPND) for various brain regions and the blood were obtained from kinetic modelling. [{sup 11}C]-1 shows promising results as aselective marker of the presynaptic dopamine transporter. With the reliable visualisation of the extra-striatal dopaminergic neurons and no indication on labelled metabolites, the tracer provides excellent potential for translation into man.

  7. Quantification of [(11)C]PIB PET for imaging myelin in the human brain: a test-retest reproducibility study in high-resolution research tomography.

    PubMed

    Veronese, Mattia; Bodini, Benedetta; García-Lorenzo, Daniel; Battaglini, Marco; Bongarzone, Salvatore; Comtat, Claude; Bottlaender, Michel; Stankoff, Bruno; Turkheimer, Federico E

    2015-11-01

    An accurate in vivo measure of myelin content is essential to deepen our insight into the mechanisms underlying demyelinating and dysmyelinating neurological disorders, and to evaluate the effects of emerging remyelinating treatments. Recently [(11)C]PIB, a positron emission tomography (PET) tracer originally conceived as a beta-amyloid marker, has been shown to be sensitive to myelin changes in preclinical models and humans. In this work, we propose a reference-region methodology for the voxelwise quantification of brain white-matter (WM) binding for [(11)C]PIB. This methodology consists of a supervised procedure for the automatic extraction of a reference region and the application of the Logan graphical method to generate distribution volume ratio (DVR) maps. This approach was assessed on a test-retest group of 10 healthy volunteers using a high-resolution PET tomograph. The [(11)C]PIB PET tracer binding was shown to be up to 23% higher in WM compared with gray matter, depending on the image reconstruction. The DVR estimates were characterized by high reliability (outliers <1%) and reproducibility (intraclass correlation coefficient (ICC) >0.95). [(11)C]PIB parametric maps were also found to be significantly correlated (R(2)>0.50) to mRNA expressions of the most represented proteins in the myelin sheath. On the contrary, no correlation was found between [(11)C]PIB imaging and nonmyelin-associated proteins.

  8. Estimating endogenous dopamine levels at D2 and D3 receptors in humans using the agonist radiotracer [(11)C]-(+)-PHNO.

    PubMed

    Caravaggio, Fernando; Nakajima, Shinichiro; Borlido, Carol; Remington, Gary; Gerretsen, Philip; Wilson, Alan; Houle, Sylvain; Menon, Mahesh; Mamo, David; Graff-Guerrero, Ariel

    2014-11-01

    Using positron emission tomography (PET) and an acute dopamine depletion challenge it is possible to estimate endogenous dopamine levels occupying dopamine D2/3 receptors (D2/3R) in humans in vivo. Our group has developed [(11)C]-(+)-PHNO, the first agonist radiotracer with preferential in vivo affinity for D3R. Thus, the use of [(11)C]-(+)-PHNO offers the novel possibility of (i) estimating in vivo endogenous dopamine levels at D2/3R using an agonist radiotracer, and (ii) estimating endogenous dopamine levels at D3R in extrastriatal regions such as the substantia nigra, hypothalamus, and ventral pallidum. Ten healthy participants underwent a [(11)C]-(+)-PHNO PET scan under baseline conditions and another under acute endogenous dopamine depletion achieved via oral administration of alpha-methyl-para-tyrosine (64 mg/kg). [(11)C]-(+)-PHNO binding was sensitive to acute dopamine depletion, allowing in vivo estimates of endogenous dopamine in D2R-rich regions (caudate and putamen), mixed D2/3R-rich regions (ventral striatum and globus pallidus), and extrastriatal D3R-rich regions (hypothalamus and ventral pallidum). Dopamine depletion decreased self-reported vigor, which was correlated with the reduction in dopamine levels in the globus pallidus. [(11)C]-(+)-PHNO is a suitable radiotracer for use in estimating endogenous dopamine levels at D2R and D3R in neuropsychiatric populations.

  9. Estimating Endogenous Dopamine Levels at D2 and D3 Receptors in Humans using the Agonist Radiotracer [11C]-(+)-PHNO

    PubMed Central

    Caravaggio, Fernando; Nakajima, Shinichiro; Borlido, Carol; Remington, Gary; Gerretsen, Philip; Wilson, Alan; Houle, Sylvain; Menon, Mahesh; Mamo, David; Graff-Guerrero, Ariel

    2014-01-01

    Using positron emission tomography (PET) and an acute dopamine depletion challenge it is possible to estimate endogenous dopamine levels occupying dopamine D2/3 receptors (D2/3R) in humans in vivo. Our group has developed [11C]-(+)-PHNO, the first agonist radiotracer with preferential in vivo affinity for D3R. Thus, the use of [11C]-(+)-PHNO offers the novel possibility of (i) estimating in vivo endogenous dopamine levels at D2/3R using an agonist radiotracer, and (ii) estimating endogenous dopamine levels at D3R in extrastriatal regions such as the substantia nigra, hypothalamus, and ventral pallidum. Ten healthy participants underwent a [11C]-(+)-PHNO PET scan under baseline conditions and another under acute endogenous dopamine depletion achieved via oral administration of alpha-methyl-para-tyrosine (64 mg/kg). [11C]-(+)-PHNO binding was sensitive to acute dopamine depletion, allowing in vivo estimates of endogenous dopamine in D2R-rich regions (caudate and putamen), mixed D2/3R-rich regions (ventral striatum and globus pallidus), and extrastriatal D3R-rich regions (hypothalamus and ventral pallidum). Dopamine depletion decreased self-reported vigor, which was correlated with the reduction in dopamine levels in the globus pallidus. [11C]-(+)-PHNO is a suitable radiotracer for use in estimating endogenous dopamine levels at D2R and D3R in neuropsychiatric populations. PMID:24874713

  10. Inhibition of acetylcholinesterase in CSF versus brain assessed by 11C-PMP PET in AD patients treated with galantamine.

    PubMed

    Darreh-Shori, T; Kadir, A; Almkvist, O; Grut, M; Wall, A; Blomquist, G; Eriksson, B; Långström, B; Nordberg, A

    2008-02-01

    The relationship between acetylcholinesterase (AChE) activity in the CSF and brain of patients with Alzheimer's disease (AD) was investigated in 18 mild AD patients following galantamine treatment. The first 3 months of the study had a randomized double-blind placebo-controlled design, during which 12 patients received galantamine (16-24 mg/day) and six patients placebo. This was followed by 9 months galantamine treatment in all patients. Activities and protein levels of both the "read-through" AChE (AChE-R) and the synaptic (AChE-S) variants in CSF were assessed in parallel together with the regional brain AChE activity by (11)C-PMP and PET. The AChE-S inhibition was 30-36% in CSF, which correlated well with the in vivo AChE inhibition in the brain. No significant AChE inhibition was observed in the placebo group. The increased level of the AChE-R protein was 16% higher than that of AChE-S. Both the AChE inhibition and the increased level of AChE-R protein positively correlated with the patient's performance in cognitive tests associated with visuospatial ability and attention. In conclusion, AChE levels in CSF closely mirror in vivo brain AChE levels prior to and after treatment with the cholinesterase inhibitors. A positive cognitive response seems to dependent on the AChE inhibition level, which is balanced by an increased protein level of the AChE-R variant in the patients.

  11. {sup 11}C-methionine PET improves the target volume delineation of meningiomas treated with stereotactic fractionated radiotherapy

    SciTech Connect

    Grosu, Anca-Ligia . E-mail: anca-ligia.grosu@lrz.tum.de; Weber, Wolfgang A.; Astner, Sabrina T.; Adam, Markus; Krause, Bernd J.; Schwaiger, Markus; Molls, Michael; Nieder, Carsten

    2006-10-01

    Purpose: To evaluate the role of {sup 11}C-methionine positron emission tomography (MET-PET) in target volume delineation for meningiomas and to determine the interobserver variability. Methods and Materials: Two independent observers performed treatment planning in 10 patients according to a prospective written protocol. In the first step, they used coregistered computed tomography (CT) and magnetic resonance imaging (MRI). In the second step, MET-PET was added to CT/MRI (image fusion based on mutual information). Results: The correlation between gross tumor volume (GTVs) delineated by the two observers based on CT/MRI was r = 0.855 (Spearman's correlation coefficient, p = 0.002) and r = 0.988 (p = 0.000) when MET-PET/CT/MRI were used. The number of patients with agreement in more then 80% of the outlined volume increased with the availability of MET-PET from 1 in 10 to 5 in 10. The median volume of intersection between the regions delineated by two observers increased significantly from 69% (from the composite volume) to 79%, by the addition of MET-PET (p = 0.005). The information of MET-PET was useful to delineate GTV in the area of cavernous sinus, orbit, and base of the skull. Conclusions: The hypothesis-generating findings of potential normal tissue sparing and reduced interobserver variability provide arguments for invasive studies of the correlation between MET-PET images and histologic tumor extension and for prospective trials of target volume delineation with CT/MRI/MET-PET image fusion.

  12. Postpartum and Depression Status are Associated With Lower [11C]raclopride BPND in Reproductive-Age Women

    PubMed Central

    Moses-Kolko, Eydie L; Price, Julie C; Wisner, Katherine L; Hanusa, Barbara H; Meltzer, Carolyn C; Berga, Sarah L; Grace, Anthony A; di Scalea, Teresa Lanza; Kaye, Walter H; Becker, Carl; Drevets, Wayne C

    2012-01-01

    The early postpartum period is associated with increased risk for affective and psychotic disorders. Because maternal dopaminergic reward system function is altered with perinatal status, dopaminergic system dysregulation may be an important mechanism of postpartum psychiatric disorders. Subjects included were non-postpartum healthy (n=13), postpartum healthy (n=13), non-postpartum unipolar depressed (n=10), non-postpartum bipolar depressed (n=7), postpartum unipolar (n=13), and postpartum bipolar depressed (n=7) women. Subjects underwent 60 min of [11C]raclopride–positron emission tomography imaging to determine the nondisplaceable striatal D2/3 receptor binding potential (BPND). Postpartum status and unipolar depression were associated with lower striatal D2/3 receptor BPND in the whole striatum (p=0.05 and p=0.02, respectively) that reached a maximum of 7–8% in anteroventral striatum for postpartum status (p=0.02). Unipolar depression showed a nonsignificant trend toward being associated with 5% lower BPND in dorsal striatum (p=0.06). D2/3 receptor BPND did not differ significantly between unipolar depressed and healthy postpartum women or between bipolar and healthy subjects; however, D2/3 receptor BPND was higher in dorsal striatal regions in bipolar relative to unipolar depressives (p=0.02). In conclusion, lower striatal D2/3 receptor BPND in postpartum and unipolar depressed women, primarily in ventral striatum, and higher dorsal striatal D2/3 receptor BPND in bipolar relative to unipolar depressives reveal a potential role for the dopamine (DA) system in the physiology of these states. Further studies delineating the mechanisms underlying these differences in D2/3 receptor BPND, including study of DA system responsivity to rewarding stimuli, and increasing power to assess unipolar vs bipolar-related differences, are needed to better understand the affective role of the DA system in postpartum and depressed women. PMID:22257897

  13. Nonuniform Cardiac Denervation Observed by 11C-meta-Hydroxyephedrine PET in 6-OHDA-Treated Monkeys

    PubMed Central

    Joers, Valerie; Seneczko, Kailie; Goecks, Nichole C.; Kamp, Timothy J.; Hacker, Timothy A.; Brunner, Kevin G.; Engle, Jonathan W.; Barnhart, Todd E.; Nickles, R. Jerome; Holden, James E.; Emborg, Marina E.

    2012-01-01

    Parkinson's disease presents nonmotor complications such as autonomic dysfunction that do not respond to traditional anti-parkinsonian therapies. The lack of established preclinical monkey models of Parkinson's disease with cardiac dysfunction hampers development and testing of new treatments to alleviate or prevent this feature. This study aimed to assess the feasibility of developing a model of cardiac dysautonomia in nonhuman primates and preclinical evaluations tools. Five rhesus monkeys received intravenous injections of 6-hydroxydopamine (total dose: 50 mg/kg). The animals were evaluated before and after with a battery of tests, including positron emission tomography with the norepinephrine analog 11C-meta-hydroxyephedrine. Imaging 1 week after neurotoxin treatment revealed nearly complete loss of specific radioligand uptake. Partial progressive recovery of cardiac uptake found between 1 and 10 weeks remained stable between 10 and 14 weeks. In all five animals, examination of the pattern of uptake (using Logan plot analysis to create distribution volume maps) revealed a persistent region-specific significant loss in the inferior wall of the left ventricle at 10 (P<0.001) and 14 weeks (P<0.01) relative to the anterior wall. Blood levels of dopamine, norepinephrine (P<0.05), epinephrine, and 3,4-dihydroxyphenylacetic acid (P<0.01) were notably decreased after 6-hydroxydopamine at all time points. These results demonstrate that systemic injection of 6-hydroxydopamine in nonhuman primates creates a nonuniform but reproducible pattern of cardiac denervation as well as a persistent loss of circulating catecholamines, supporting the use of this method to further develop a monkey model of cardiac dysautonomia. PMID:22539969

  14. Nanostructured copper, chromium, and tin oxide multicomponent materials as catalysts for methanol decomposition: 11C-radiolabeling study.

    PubMed

    Tsoncheva, Tanya; Sarkadi-Priboczki, Eva; Dimitrov, Momtchil; Genova, Izabela

    2013-01-01

    Copper and chromium modified tin oxide nanocomposites were obtained via incipient wetness impregnation of high surface area nanosized SnO(2) with the corresponding metal acetylacetonates and their further decomposition in air. Powder X-ray diffraction (XRD), Nitrogen physisorption, UV-Vis, and Temperature-programmed reduction (TPR) with hydrogen were applied for the samples characterization. The catalytic activity of the obtained materials was tested in methanol conversion. A new approach based on the selective coverage of the surface with (11)C-methanol was used for the characterization of the catalytic sites. It was demonstrated that the products distribution could be controlled by the surface coverage with methanol and the role of different active sites was discussed. The modification of SnO(2) with copper oxide increased the activity in methanol decomposition to CO(2)via dioxymethylene intermediates, but the catalyst suffered considerable loss of activity due to the reduction transformations by the reaction medium and formation of an inactive intermetallic alloy. The modification with chromium changed the acid-basic properties of SnO(2) by the formation of Cr(2)O(3) nanoparticles as well as anchored to the support chromate species. The former particles facilitated the formation of dimethyl ether (DME), while the latter species converted methanol predominantly to hydrocarbons. The fraction of chromate species increased in Cu-Cr-Sn oxide multicomponent nanocomposites and promoted the formation of hydrocarbons over DME at low temperatures, while at higher temperatures, the activity of the copper species leading to CO(2) formation was more pronounced. PMID:23031492

  15. Examining Endogenous Dopamine in Treated Schizophrenia using [11C]-(+)-PHNO Positron Emission Tomography: A Pilot study

    PubMed Central

    Caravaggio, Fernando; Borlido, Carol; Wilson, Alan; Graff-Guerrero, Ariel

    2015-01-01

    Background Using positron emission tomography (PET) it is possible to estimate endogenous dopamine (DA) occupying D2/3 receptors (D2/3R) in the living human brain. Persons with schizophrenia (SZ) (previously medicated and naïve) have increased endogenous DA occupying D2/3R in the caudate. It is unknown whether currently medicated patients demonstrate increased DA levels at D2/3R. Moreover, DA levels have not been estimated in SZ using agonist radiotracers, which may offer a more sensitive quantification over antagonists. Methods Using the agonist radiotracer [11C]-(+)-PHNO, DA levels were estimated at D2/3R (ΔBPND) in three patients with SZ (Male, Mage=30±16). Patients were currently being treated long-term with Olanzapine (147±88 nmol/L). Results were compared to ten healthy controls (HC’s). Results Medicated persons with SZ had greater ΔBPND in the left caudate (U=2, Z=−2.20, p=.03) and right putamen (U=2, Z=−2.20, p=.03). No differences were observed in the ventral striatum or globus pallidus. Conclusions It is possible to estimate endogenous DA at D2/3R in SZ patients currently taking antipsychotics. Despite medication, patients continue to have increased endogenous DA at D2/3R. This lends more biological support to the clinical observation that relapses in symptoms can occur in the face of complete antipsychotic discontinuation. Future studies with larger samples are warranted. PMID:25814099

  16. Radiosynthesis of [11C]SNAP-7941—the first PET-tracer for the melanin concentrating hormone receptor 1 (MCHR1)

    PubMed Central

    Philippe, C.; Schirmer, E.; Mitterhauser, M.; Shanab, K.; Lanzenberger, R.; Karanikas, G.; Spreitzer, H.; Viernstein, H.; Wadsak, W.

    2012-01-01

    The melanin concentrating hormone (MCH) system is a new target to treat human disorders. Our aim was the preparation of the first PET-tracer for the MCHR1. [11C]SNAP-7941 is a carbon-11 labeled analog of the published MCHR1 antagonist SNAP-7941. The optimum reaction conditions were 2 min reaction time, ≤25 °C reaction temperature, and 2 mg/mL precursor (SNAP-acid) in acetonitrile, using [11C]CH3OTf as methylation agent. [11C]SNAP-7941 was prepared in a reliable and feasible manner with high radiochemical yields (2.9±1.6 GBq; 11.5±6.4% EOB, n=15). PMID:22858577

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

    PubMed

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

    2015-12-02

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

  18. Visualization of angiogenesis during cancer development in the polyoma middle T breast cancer model: molecular imaging with (R)-[11C]PAQ

    PubMed Central

    2014-01-01

    Background Vascular endothelial growth factor receptor 2 (VEGFR2) is a crucial mediator of tumour angiogenesis. High expression levels of the receptor have been correlated to poor prognosis in cancer patients. Reliable imaging biomarkers for stratifying patients for anti-angiogenic therapy could therefore be valuable for increasing treatment success rates. The aim of this study was to investigate the pharmacokinetics and angiogenesis imaging abilities of the VEGFR2-targeting positron emission tomography (PET) tracer (R)-[11C]PAQ. Methods (R)-[11C]PAQ was evaluated in the mouse mammary tumour virus-polyoma middle T (MMTV-PyMT) model of metastatic breast cancer. Mice at different stages of disease progression were imaged with (R)-[11C]PAQ PET, and results were compared to those obtained with [18 F]FDG PET and magnetic resonance imaging. (R)-[11C]PAQ uptake levels were also compared to ex vivo immunofluorescence analysis of tumour- and angiogenesis-specific biomarkers. Additional pharmacokinetic studies were performed in rat and mouse. Results A heterogeneous uptake of (R)-[11C]PAQ was observed in the tumorous mammary glands. Ex vivo analysis confirmed the co-localization of areas with high radioactivity uptake and areas with elevated levels of VEGFR2. In some animals, a high focal uptake was observed in the lungs. The lung uptake correlated to metastatic and angiogenic activity, but not to uptake of [18 F]FDG PET. The pharmacokinetic studies revealed a limited metabolism and excretion during the 1-h scan and a distribution of radioactivity mainly to the liver, kidneys and lungs. In rat, a high uptake was additionally observed in adrenal and parathyroid glands. Conclusion The results indicate that (R)-[11C]PAQ is a promising imaging biomarker for visualization of angiogenesis, based on VEGFR2 expression, in primary tumours and during metastasis development. PMID:24670127

  19. Imaging brain inflammation with [(11)C]PK11195 by PET and induction of the peripheral-type benzodiazepine receptor after transient focal ischemia in rats.

    PubMed

    Rojas, Santiago; Martín, Abraham; Arranz, Maria J; Pareto, Deborah; Purroy, Jesús; Verdaguer, Esther; Llop, Jordi; Gómez, Vanessa; Gispert, Joan D; Millán, Olga; Chamorro, Angel; Planas, Anna M

    2007-12-01

    [(11)C]PK11195 is used in positron emission tomography (PET) studies for imaging brain inflammation in vivo as it binds to the peripheral-type benzodiazepine receptor (PBR) expressed by reactive glia and macrophages. However, features of the cellular reaction required to induce a positive [(11)C]PK11195 signal are not well characterized. We performed [(11)C]PK11195 PET and autoradiography in rats after transient focal cerebral ischemia. We determined [(3)H]PK11195 binding and PBR expression in brain tissue and examined the lesion with several markers. [(11)C]PK11195 standard uptake value increased at day 4 and grew further at day 7 within the ischemic core. Accordingly, ex vivo [(3)H]PK11195 binding increased at day 4, and increases further at day 7. The PET signal also augmented in peripheral regions, but to a lesser extent than in the core. Binding in the region surrounding infarction was supported by [(11)C]PK11195 autoradiography at day 7 showing that the radioactive signal extended beyond the infarcted core. Enhanced binding was preceded by increases in PBR mRNA expression in the ipsilateral hemisphere, and a 18-kDa band corresponding to PBR protein was detected. Peripheral-type benzodiazepine receptor immunohistochemistry showed subsets of ameboid microglia/macrophages within the infarcted core showing a distinctive strong PBR expression from day 4. These cells were often located surrounding microhemorrhages. Reactive astrocytes forming a rim surrounding infarction at day 7 also showed some PBR immunostaining. These results show cellular heterogeneity in the level of PBR expression, supporting that PBR is not a simple marker of inflammation, and that the extent of [(11)C]PK11195 binding depends on intrinsic features of the inflammatory cells.

  20. A digital resource model of the Upper Pennsylvanian Pittsburgh coal bed, Monongahela Group, northern Appalachian basin coal region, USA

    USGS Publications Warehouse

    Ruppert, L.F.; Tewalt, S.J.; Bragg, L.J.; Wallack, R.N.

    1999-01-01

    The U.S. Geological Survey is currently conducting a coal resource assessment of the coal beds and zones that are expected to provide the bulk of the Nation's coal resources for the next few decades. The Pittsburgh coal bed is the first bed in the northern and central Appalachian basin coal region to undergo a fully-digital assessment. The bed-specific assessment is being carried out in partnership with the state geologic surveys of West Virginia (WV), Pennsylvania (PA), Ohio (OH), and Maryland (MD). Comprehensive stratigraphic and geochemical databases have been developed for the Pittsburgh coal bed, and areal extent, mined areas, structure contour, isopach, overburden thickness maps of the bed have been released as United States Geological Survey (USGS) Open-File Reports. The resulting resource model indicates that of the original 34 billion short tons (31 billion tonnes) of Pittsburgh coal, 16 billion short tons (14 billion tonnes) remain. Although most of the remaining coal is thinner, deeper, and higher in ash and sulfur (S) than the original resource, there are blocks of extensive thick (6-8 ft or 1.8-2.4 m) coal in southwestern PA and the northern panhandle of WV.The U.S. Geological Survey is currently conducting a coal resource assessment of the coal beds and zones that are expected to provide the bulk of the Nation's coal resources for the next few decades. The Pittsburgh coal bed is the first bed in the northern and central Appalachian basin coal region to undergo a fully-digital assessment. The bed-specific assessment is being carried out in partnership with the state geologic surveys of West Virginia (WV), Pennsylvania (PA), Ohio (OH), and Maryland (MD). Comprehensive stratigraphic and geochemical databases have been developed for the Pittsburgh coal bed, and areal extent, mined areas, structure contour, isopach, overburden thickness maps of the bed have been released as United States Geological Survey (USGS) Open-File Reports. The resulting resource

  1. Sea surface temperature and salinity patterns in the northern North Atlantic and the Arctic during interglacial MIS 11c: Implications for oceanic circulation reconstruction

    NASA Astrophysics Data System (ADS)

    Kandiano, E.; van der Meer, M.; Schouten, S.; Fahl, K.; Polyak, L. V.; Cronin, T. M.; Bauch, H. A.; Sinninghe Damste, J. S.

    2013-12-01

    Sea surface temperature (SST) patterns in the northern North Atlantic, the Nordic seas, and the western Arctic Ocean (AO) were reconstructed across the MIS 11c interglacial, a potential future climate analogue, using planktic foraminiferal abundances, alkenone-based Uk'37 and glycerol dialkyl glycerol tetraether (GDGT)-based TEX86 analyses. Foraminiferal SST reconstructions were supported by foraminiferal counts of small-sized fractions and rare foraminiferal species, stable oxygen isotope measurements on benthic and planktic foraminifers, and ice rafted debris records. Additionally, the hydrogen isotopic (δD) compositions of long chain alkenones were determined to assess variations in paleo sea surface salinity in the North Atlantic. In the North Atlantic our newly produced TEX86 -based SSTs range between 14 and 19 °C in agreement with summer foraminiferal SST (13 and 18 °C) and alkenone SSTs (13 and 16 °C). However, the former showed higher fluctuations than SSTs based on foraminiferal abundances. In concordance with δ18O records TEX86 SSTs demonstrate notable variability in the middle of MIS 11c, between 400 and 410 ka, which is consistent with the intra-MIS 11c cold event in the Arctic indicated by planktic foraminifers. This pattern implies that the interglacial MIC 11c climate was probably not as stable as it widely believed. The preliminary alkenone δD data show that during MIS 11c salinity values in the North Atlantic were similar to Holocene values. Foraminiferal SST records imply that during MIS 11c at least parts of the AO experienced unusually warm and probably ice free conditions, whereas the Nordic seas remained rather cold, especially during the early phase of this period, as it is inferred from foraminiferal and alkenone SSTs. At the same time all our SST records show that the North Atlantic was 1-2°C warmer than present during MIS 11c. This pattern suggests that during MIS 11c the North Atlantic Current was deflected to the west, which

  2. Distribution of Intravenously Administered Acetylcholinesterase Inhibitor and Acetylcholinesterase Activity in the Adrenal Gland: 11C-Donepezil PET Study in the Normal Rat

    PubMed Central

    Watabe, Tadashi; Naka, Sadahiro; Ikeda, Hayato; Horitsugi, Genki; Kanai, Yasukazu; Isohashi, Kayako; Ishibashi, Mana; Kato, Hiroki; Shimosegawa, Eku; Watabe, Hiroshi; Hatazawa, Jun

    2014-01-01

    Purpose Acetylcholinesterase (AChE) inhibitors have been used for patients with Alzheimer's disease. However, its pharmacokinetics in non-target organs other than the brain has not been clarified yet. The purpose of this study was to evaluate the relationship between the whole-body distribution of intravenously administered 11C-Donepezil (DNP) and the AChE activity in the normal rat, with special focus on the adrenal glands. Methods The distribution of 11C-DNP was investigated by PET/CT in 6 normal male Wistar rats (8 weeks old, body weight  = 220±8.9 g). A 30-min dynamic scan was started simultaneously with an intravenous bolus injection of 11C-DNP (45.0±10.7 MBq). The whole-body distribution of the 11C-DNP PET was evaluated based on the Vt (total distribution volume) by Logan-plot analysis. A fluorometric assay was performed to quantify the AChE activity in homogenized tissue solutions of the major organs. Results The PET analysis using Vt showed that the adrenal glands had the 2nd highest level of 11C-DNP in the body (following the liver) (13.33±1.08 and 19.43±1.29 ml/cm3, respectively), indicating that the distribution of 11C-DNP was the highest in the adrenal glands, except for that in the excretory organs. The AChE activity was the third highest in the adrenal glands (following the small intestine and the stomach) (24.9±1.6, 83.1±3.0, and 38.5±8.1 mU/mg, respectively), indicating high activity of AChE in the adrenal glands. Conclusions We demonstrated the whole-body distribution of 11C-DNP by PET and the AChE activity in the major organs by fluorometric assay in the normal rat. High accumulation of 11C-DNP was observed in the adrenal glands, which suggested the risk of enhanced cholinergic synaptic transmission by the use of AChE inhibitors. PMID:25225806

  3. 11C-choline vs. 18F-FDG PET/CT in assessing bone involvement in patients with multiple myeloma

    PubMed Central

    Nanni, Cristina; Zamagni, Elena; Cavo, Michele; Rubello, Domenico; Tacchetti, Paola; Pettinato, Cinzia; Farsad, Mohsen; Castellucci, Paolo; Ambrosini, Valentina; Montini, Gian Carlo; Al-Nahhas, Adil; Franchi, Roberto; Fanti, Stefano

    2007-01-01

    Background Multiple Myeloma (MM) is a B cell neoplasm causing lytic or osteopenic bone abnormalities. Whole body skeletal survey (WBSS), Magnetic resonance (MR) and 18F-FDG PET/CT are imaging techniques routinely used for the evaluation of bone involvement in MM patients. Aim As MM bone lesions may present low 18F-FDG uptake; the aim of this study was to assess the possible added value and limitations of 11C-Choline to that of 18F-FDG PET/CT in patients affected with MM. Methods Ten patients affected with MM underwent a standard 11C-Choline PET/CT and an 18F-FDG PET/CT within one week. The results of the two scans were compared in terms of number, sites and SUVmax of lesions. Results Four patients (40%) had a negative concordant 11C-Choline and 18F-FDG PET/CT scans. Two patients (20%) had a positive 11C-Choline and 18F-FDG PET/CT scans that identified the same number and sites of bone lesions. The remaining four patients (40%) had a positive 11C-Choline and 18F-FDG PET/CT scan, but the two exams identified different number of lesions. Choline showed a mean SUVmax of 5 while FDG showed a mean SUVmax of 3.8 (P = 0.042). Overall, 11C-Choline PET/CT scans detected 37 bone lesions and 18F-FDG PET/CT scans detected 22 bone lesions but the difference was not significant (P = 0.8). Conclusion According to these preliminary data, 11C-Choline PET/CT appears to be more sensitive than 18F-FDG PET/CT for the detection of bony myelomatous lesions. If these data are confirmed in larger series of patients, 11C-Choline may be considered a more appropriate functional imaging in association with MRI for MM bone staging. PMID:17584499

  4. Comparison of [11C]cocaine binding at tracer and pharmacological doses of baboon brain: A PET study

    SciTech Connect

    Volkow, N.D.; Fowler, J.S.; Logan, J.

    1994-05-01

    In vitro studies have shown that cocaine (C) binds to both high and low affinity sites on the dopamine transporter (DAT). We have previously characterized the binding of tracer doses of [{sup 11}C]cocaine (C*)to a high affinity site on the DAT. To assess if in vivo C also binds to low affinity sites we used PET to compare binding of tracer doses (17.8{plus_minus}12.2 {mu}g C) of C* to pharmacological doses (8 mg of C coadministered with C*). Sixteen paired studies were done to assess test/retest variability, specific versus non specific binding and to characterize binding profile. Dynamic scans were started immediately after injection of C* (5-8 mCi) for 50 min on the CTI-931 (6 x 6 x 6.5 mm FWHM). Time activity curves for tissue concentration and for unchanged tracer in plasma were used to calculate the transport constant between plasma and tissue (K1) and to obtain the distribution volume (DV). The ratio of the DV in striatum (ST) to that in cerebellum (CB) (which corresponds to Bmax/Kd-1) was used as model parameter. Peak brain uptake of C* was significantly higher for tracer than for pharmacological doses (0.041 versus 0.033 % dose/cc), as were the values for K1 (1.07{plus_minus}0.21 versus 0.68{plus_minus}0.26 (t=3.0 p<0.01)). Repeated measures were reproducible for tracer ({plus_minus}2%) and pharmacological doses of C* ({plus_minus}4%). Tracer dose C* showed highest binding and slowest clearance in ST which was reduced by C (0.5-2.0 mg/kg iv, -25 to -30%) and by drugs that inhibit DAT (2mg/kg nomifensine - 21%, 0.5 mg/kg methylphenidate -12%) and was increased by serotonin transporter inhibitors (5HT-Ti) (2 mg/kg citalopram +11%, 0.5 mg/kg fluoxetine +6%) and not changed by NE transporter inhibitors (0.5 mg/kg desipramine or 2 mg/kg tomoxetine). The increase with (5HT-Ti) may reflect neurotransmitter interactions or changes in bioavailability. At pharmacological doses C* showed homogeneous distribution and was not changed by C nor by any of the above drugs.

  5. 1996 environmental monitoring report for the Bettis Atomic Power Laboratory, Pittsburgh Site

    SciTech Connect

    1996-12-31

    The 1996 results for the Bettis-Pittsburgh radiological and non-radiological environmental monitoring programs are presented. The primary mission of the Bettis Laboratory has been directed toward the design, development, testing, and operation of nuclear reactor propulsion plants for naval surface and submarine vessels. The results obtained from the monitoring programs demonstrate that the existing procedures ensured that releases to the environment during 1996 were in accordance with applicable federal, state, county, and local regulations. Evaluation of the environmental data indicated that the current operations at the Site continue to have no adverse effect on the quality of the environment. A conservative assessment of radiation exposure to the general public as a result of Site operations demonstrated that the dose received by any member of the public was well below the most restrictive dose limits established by the Environmental Protection Agency, the Nuclear Regulatory Commission and the US Department of Energy. A risk assessment of potentially exposed populations to chemical residues in the environment at the Site demonstrated that these residues do not pose any significant health risk.

  6. Reconstruction of the 1994 Pittsburgh Airplane Accident Using a Computer Simulation

    NASA Technical Reports Server (NTRS)

    Parks, Edwin K.; Bach, Ralph E., Jr.; Shin, Jae Ho

    1998-01-01

    On September 8, 1994, a Boeing 737-300 passenger airplane was on a downwind approach to the Pittsburgh International Airport at an altitude of 5000 feet above ground level (6000 feet MSL). While in a shallow left turn onto a downwind approach heading, the airplane crossed into the vortex trail of a Boeing 727 flying in the same approach pattern about 4 miles ahead. The B-737 airplane rolled and turned sharply to the left, exited the vortex wake and plunged into the ground. Weather was not a factor in the accident. The airplane was equipped with a 11+ channel digital Flight Data Recorder (FDR) and a multiple channel Cockpit Voice Recorder (CVR). Both recorders were recovered from the crash site and provided excellent data for the development of an accident scenario. Radar tracking of the two airplanes as well as the indicated air speed (IAS) perturbations clearly visible on the B-737 FDR recordings indicate that the upset was apparently initiated by the airplane's crossing into the wake of the B-727 flying ahead in the same traffic pattern. A 6 degree-of-freedom simulation program for the B-737 airplane using MATLAB and SIMULINK was constructed. The simulation was initialized at the stabilized flight conditions of the airplane about 13 seconds prior to its entry into the vortex trail of the B-727 airplane. By assuming a certain combination of control inputs, it was possible to produce a simulated motion that closely matched that recorded on the FDR.

  7. Social Contact Networks and Mixing among Students in K-12 Schools in Pittsburgh, PA

    PubMed Central

    Guclu, Hasan; Read, Jonathan; Vukotich, Charles J.; Galloway, David D.; Gao, Hongjiang; Rainey, Jeanette J.; Uzicanin, Amra; Zimmer, Shanta M.; Cummings, Derek A. T.

    2016-01-01

    Students attending schools play an important role in the transmission of influenza. In this study, we present a social network analysis of contacts among 1,828 students in eight different schools in urban and suburban areas in and near Pittsburgh, Pennsylvania, United States of America, including elementary, elementary-middle, middle, and high schools. We collected social contact information of students who wore wireless sensor devices that regularly recorded other devices if they are within a distance of 3 meters. We analyzed these networks to identify patterns of proximal student interactions in different classes and grades, to describe community structure within the schools, and to assess the impact of the physical environment of schools on proximal contacts. In the elementary and middle schools, we observed a high number of intra-grade and intra-classroom contacts and a relatively low number of inter-grade contacts. However, in high schools, contact networks were well connected and mixed across grades. High modularity of lower grades suggests that assumptions of homogeneous mixing in epidemic models may be inappropriate; whereas lower modularity in high schools suggests that homogenous mixing assumptions may be more acceptable in these settings. The results suggest that interventions targeting subsets of classrooms may work better in elementary schools than high schools. Our work presents quantitative measures of age-specific, school-based contacts that can be used as the basis for constructing models of the transmission of infections in schools. PMID:26978780

  8. Vulnerability studies and integrated assessments for hazard risk reduction in Pittsburgh, PA (Invited)

    NASA Astrophysics Data System (ADS)

    Klima, K.

    2013-12-01

    Today's environmental problems stretch beyond the bounds of most academic disciplines, and thus solutions require an interdisciplinary approach. For instance, the scientific consensus is changes in the frequency and severity of many types of extreme weather events are increasing (IPCC 2012). Yet despite our efforts to reduce greenhouse gases, we continue to experience severe weather events such as Superstorm Sandy, record heat and blizzards, and droughts. These natural hazards, combined with increased vulnerability and exposure, result in longer-lasting disruptions to critical infrastructure and business continuity throughout the world. In order to protect both our lives and the economy, we must think beyond the bounds of any one discipline to include an integrated assessment of relevant work. In the wake of recent events, New York City, Washington, DC, Chicago, and a myriad of other cities have turned to their academic powerhouses for assistance in better understanding their vulnerabilities. This talk will share a case study of the state of integrated assessments and vulnerability studies of energy, transportation, water, real estate, and other main sectors in Pittsburgh, PA. Then the talk will use integrated assessment models and other vulnerability studies to create coordinated sets of climate projections for use by the many public agencies and private-sector organizations in the region.

  9. Stream reconnaissance for nutrients and other water-quality parameters, Greater Pittsburgh Region, Pennsylvania

    USGS Publications Warehouse

    Beall, Robert M.

    1975-01-01

    Eighty-five stream sites in and near the six-county Greater Pittsburgh Region were sampled in mid-June 1971 in mid-October 1972. Data are reported for 89 sites because 4 substitute sites were sampled in the second period. Drainage areas of the basins sampled ranged from 4.1 to 19,5000 square miles (10.6 to 50,500 square kilometres). The chemical analyses included constituents of three general classes: (1) nutrients, (2) activity indicators, and (3) dominant anions. Modification of the natural chemical and physical characteristics of the surface waters by man's activities is evident in some of the data. However, the activities are so diverse in type and in areal extent that their influence in terms of cause and effect is often obscure. Nutrient concentrations were high enough to indicate potential problems at about a quarter of the sampling sites. Temperature, dissolved oxygen, and pH values indicated a generally favorable capacity for regeneration or recovery from degradation, although a number a streams east of the Allegheny and Monongahela Rivers are marginal or lacking in the capacity. Regionally, sulfate is the dominant ion and was observed in concentrations of 40 milligrams per litre or more at 90 percent of the sites. Bicarbonate exceeded 100 milligrams per litre at 22 sites. A moderate to high degree of mineralization, as indicated by conductance readings of more than 500 micromhos per cetrimetre at half of the sampling sites, is a characteristic of the region's surface waters.

  10. Nonstandard Programs: the University of Pittsburgh Medical Center's next frontier in graduate medical education.

    PubMed

    Kroboth, Frank J; Zerega, W Dennis; Patel, Rita M; Barnes, Barbara E; Webster, Marshall W

    2011-02-01

    The University of Pittsburgh Medical Center has seen continuous growth in the number and types of graduate training programs not accredited by the Accreditation Council for Graduate Medical Education (ACGME), the American Board of Medical Specialties, or the American Osteopathic Association. For the purposes of ensuring best educational products and of controlling unrecognized competition with our accredited programs, a sequential process of centralized oversight of these nonstandard programs was undertaken. The first step involved programs whose fellows were hired and tracked like accredited fellows (i.e., not instructors). The basic process began with consensus among leadership, writing of policy with consultation as necessary, establishment of a registry of programs and graduates, and a committee to allow sharing of best practices and dissemination of policy. The second step applied the same process to instructor-level programs. Whereas the previous group of programs was made subject to ACGME regulations, more latitude in duty hours and progressive responsibility were allowed for instructor programs. The final step, in progress, is extending a similar but modified approach to short-duration clinical experiences and observerships. The outcomes of these efforts have been the creation of a centralized organizational structure, policies to guide this structure, an accurate registry of a surprising number of training programs, and a rolling record of all graduates from these programs. Included in the process is a mechanism that ensures that core program directors and department chairs specifically review the impact of new programs on core programs before allowing their creation.

  11. Continued development of the Nimbus/University of Pittsburgh (UOP) axial flow left ventricular assist system.

    PubMed

    Thomas, D C; Butler, K C; Taylor, L P; Le Blanc, P; Griffith, B P; Kormos, R L; Borovetz, H S; Litwak, P; Kameneva, M V; Choi, S; Burgreen, G W; Wagner, W R; Wu, Z; Antaki, J F

    1997-01-01

    Nimbus and the University of Pittsburgh (UOP) have continued the development of a totally implanted axial flow blood pump under the National Institutes of Health (NIH) Innovative Ventricular Assist System (IVAS) program. This 62 cc device has an overall length of 84 mm and an outer diameter of 34.5 mm. The inner diameter of the blood pump is 12 mm. It is being designed to be a totally implanted permanent device. A key achievement during the past year was the completion of the Model 2 pump design. Ten of these pumps have been fabricated and are being used to conduct in vitro and in vivo experiments to evaluate the performance of different materials and hydraulic components. Efforts for optimizing the closed loop speed control have continued using mathematical modeling, computer simulations, and in vitro and in vivo testing. New hydraulic blade designs have been tested using computational fluid dynamics (CFD) and flow visualization. A second generation motor was designed with improved efficiency. To support the new motor, a new motor controller fabricated as a surface mount PC board has been completed. The program is now operating under a formal QA system.

  12. Social Contact Networks and Mixing among Students in K-12 Schools in Pittsburgh, PA.

    PubMed

    Guclu, Hasan; Read, Jonathan; Vukotich, Charles J; Galloway, David D; Gao, Hongjiang; Rainey, Jeanette J; Uzicanin, Amra; Zimmer, Shanta M; Cummings, Derek A T

    2016-01-01

    Students attending schools play an important role in the transmission of influenza. In this study, we present a social network analysis of contacts among 1,828 students in eight different schools in urban and suburban areas in and near Pittsburgh, Pennsylvania, United States of America, including elementary, elementary-middle, middle, and high schools. We collected social contact information of students who wore wireless sensor devices that regularly recorded other devices if they are within a distance of 3 meters. We analyzed these networks to identify patterns of proximal student interactions in different classes and grades, to describe community structure within the schools, and to assess the impact of the physical environment of schools on proximal contacts. In the elementary and middle schools, we observed a high number of intra-grade and intra-classroom contacts and a relatively low number of inter-grade contacts. However, in high schools, contact networks were well connected and mixed across grades. High modularity of lower grades suggests that assumptions of homogeneous mixing in epidemic models may be inappropriate; whereas lower modularity in high schools suggests that homogenous mixing assumptions may be more acceptable in these settings. The results suggest that interventions targeting subsets of classrooms may work better in elementary schools than high schools. Our work presents quantitative measures of age-specific, school-based contacts that can be used as the basis for constructing models of the transmission of infections in schools.

  13. Social Contact Networks and Mixing among Students in K-12 Schools in Pittsburgh, PA.

    PubMed

    Guclu, Hasan; Read, Jonathan; Vukotich, Charles J; Galloway, David D; Gao, Hongjiang; Rainey, Jeanette J; Uzicanin, Amra; Zimmer, Shanta M; Cummings, Derek A T

    2016-01-01

    Students attending schools play an important role in the transmission of influenza. In this study, we present a social network analysis of contacts among 1,828 students in eight different schools in urban and suburban areas in and near Pittsburgh, Pennsylvania, United States of America, including elementary, elementary-middle, middle, and high schools. We collected social contact information of students who wore wireless sensor devices that regularly recorded other devices if they are within a distance of 3 meters. We analyzed these networks to identify patterns of proximal student interactions in different classes and grades, to describe community structure within the schools, and to assess the impact of the physical environment of schools on proximal contacts. In the elementary and middle schools, we observed a high number of intra-grade and intra-classroom contacts and a relatively low number of inter-grade contacts. However, in high schools, contact networks were well connected and mixed across grades. High modularity of lower grades suggests that assumptions of homogeneous mixing in epidemic models may be inappropriate; whereas lower modularity in high schools suggests that homogenous mixing assumptions may be more acceptable in these settings. The results suggest that interventions targeting subsets of classrooms may work better in elementary schools than high schools. Our work presents quantitative measures of age-specific, school-based contacts that can be used as the basis for constructing models of the transmission of infections in schools. PMID:26978780

  14. Mapping of serotonin transporters by positron emission tomography with [11C]DASB in conscious common marmosets: comparison with rhesus monkeys.

    PubMed

    Yokoyama, Chihiro; Yamanaka, Hajime; Onoe, Kayo; Kawasaki, Akihiro; Nagata, Hiroko; Shirakami, Keiko; Doi, Hisashi; Onoe, Hirotaka

    2010-08-01

    The common marmoset (Callithrix jacchus) is unique among the primates in its small body size, reproductive efficacy, and characteristic social behavior, making it useful as an animal model in neuroscientific research. To assess the brain serotonergic systems, we investigated the binding of [(11)C]-3-amino-4-(2-dimetylaminomethyl-phenylsulfanyl)-benzonitrile ([(11)C]DASB) to brain serotonin transporter (SERT) in conscious common marmosets using positron emission tomography (PET), and compared with findings for rhesus monkeys. Both species showed globally similar distribution patterns of [(11)C]DASB uptake in the brain, with highest activity in the midline of the brain and lowest in the cerebellum, and higher activity in some subcortical regions than in surrounding cortex, while the common marmoset brain showed almost equal or rather higher binding potential (BP) values (BP(ND)) in cortical regions and hippocampus, and lower BP(ND) than the rhesus monkey brain in some subcortical regions. Test-retest reproducibility of BP(ND) at an interval of several months was high, indicating reliable and stable measurements of serotonin transporters in both species. These results suggest that SERT imaging by PET with [(11)C]DASB under conscious state is valuable for investigating the physiological serotonergic functions in common marmosets (182).

  15. Compartmental analysis of (11C)flumazenil kinetics for the estimation of ligand transport rate and receptor distribution using positron emission tomography

    SciTech Connect

    Koeppe, R.A.; Holthoff, V.A.; Frey, K.A.; Kilbourn, M.R.; Kuhl, D.E. )

    1991-09-01

    The in vivo kinetic behavior of (11C)flumazenil ((11C)FMZ), a non-subtype-specific central benzodiazepine antagonist, is characterized using compartmental analysis with the aim of producing an optimized data acquisition protocol and tracer kinetic model configuration for the assessment of (11C)FMZ binding to benzodiazepine receptors (BZRs) in human brain. The approach presented is simple, requiring only a single radioligand injection. Dynamic positron emission tomography data were acquired on 18 normal volunteers using a 60- to 90-min sequence of scans and were analyzed with model configurations that included a three-compartment, four-parameter model, a three-compartment, three-parameter model, with a fixed value for free plus nonspecific binding; and a two-compartment, two-parameter model. Statistical analysis indicated that a four-parameter model did not yield significantly better fits than a three-parameter model. Goodness of fit was improved for three- versus two-parameter configurations in regions with low receptor density, but not in regions with moderate to high receptor density. Thus, a two-compartment, two-parameter configuration was found to adequately describe the kinetic behavior of (11C)FMZ in human brain, with stable estimates of the model parameters obtainable from as little as 20-30 min of data. Pixel-by-pixel analysis yields functional images of transport rate (K1) and ligand distribution volume (DV), and thus provides independent estimates of ligand delivery and BZR binding.

  16. Cutting Edge: IL-4, IL-21, and IFN-γ Interact To Govern T-bet and CD11c Expression in TLR-Activated B Cells.

    PubMed

    Naradikian, Martin S; Myles, Arpita; Beiting, Daniel P; Roberts, Kenneth J; Dawson, Lucas; Herati, Ramin Sedaghat; Bengsch, Bertram; Linderman, Susanne L; Stelekati, Erietta; Spolski, Rosanne; Wherry, E John; Hunter, Christopher; Hensley, Scott E; Leonard, Warren J; Cancro, Michael P

    2016-08-15

    T-bet and CD11c expression in B cells is linked with IgG2c isotype switching, virus-specific immune responses, and humoral autoimmunity. However, the activation requisites and regulatory cues governing T-bet and CD11c expression in B cells remain poorly defined. In this article, we reveal a relationship among TLR engagement, IL-4, IL-21, and IFN-γ that regulates T-bet expression in B cells. We find that IL-21 or IFN-γ directly promote T-bet expression in the context of TLR engagement. Further, IL-4 antagonizes T-bet induction. Finally, IL-21, but not IFN-γ, promotes CD11c expression independent of T-bet. Using influenza virus and Heligmosomoides polygyrus infections, we show that these interactions function in vivo to determine whether T-bet(+) and CD11c(+) B cells are formed. These findings suggest that T-bet(+) B cells seen in health and disease share the common initiating features of TLR-driven activation within this circumscribed cytokine milieu.

  17. 76 FR 16851 - Notice of Intent To Rule on Passenger Facility Charge (PFC) Application 11-11-C-00-BUR, To Impose...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-25

    ...-11-C-00-BUR, To Impose and Use PFC Revenue at Bob Hope Airport, Burbank, CA AGENCY: Federal Aviation... invites public comment on the application to impose and use PFC revenue at Bob Hope Airport, under the... rule and invites public comment on the application to impose and use PFC revenue at Bob Hope...

  18. Salmonella inhibits monocyte differentiation into CD11c hi MHC-II hi cells in a MyD88-dependent fashion.

    PubMed

    Rydström, Anna; Wick, Mary Jo

    2010-05-01

    Monocytes and DCs originate from a shared precursor in the bone marrow, and steady-state DCs in lymphoid organs develop directly from the precursor rather than via a monocyte intermediate. However, monocytes can differentiate into DCs in tissues such as the lung and gut mucosa and into macrophages in most tissues. As Ly6C hi monocytes accumulate in lymphoid organs during oral Salmonella infection, we investigated their ability to develop into potential DCs, identified as CD11c hi MHC-II hi cells, in infected hosts. Ly6C hi monocytes, isolated from the blood of Salmonella-infected mice, developed into CD11c hi MHC-II hi cells after culture with GM-CSF or Flt3L. In contrast, the same monocytes cultured in the presence of GM-CSF and heat-killed Salmonella did not differentiate into CD11c hi MHC-II hi cells. The bacteria-induced differentiation block was dependent on TLRs, as monocytes from MyD88-/- mice converted into CD11c hi MHC-II hi cells even in the presence of bacteria. We hypothesized that Salmonella-activated wild-type monocytes secreted mediators that inhibited differentiation of MyD88-/--derived monocytes. However, IL-6, IL-10, TNF-alpha, or IL-12p70 did not account for the inhibition. Finally, monocyte-derived CD11c hi MHC-II hi cells pulsed with OVA peptide or protein did not induce proliferation of antigen-specific CD4+ T cells but rather, suppressed the ability of DCs to activate CD4+ T cells. Overall, the data show that Ly6C hi monocytes from Salmonella-infected mice develop into CD11c hi MHC-II hi cells with poor antigen-presentation capacity when cultured ex vivo, and that monocyte exposure to Salmonella inhibits their differentiation into CD11c hi MHC-II hi cells in a MyD88-dependent fashion.

  19. Synthesis and in vivo evaluation of [11C]tariquidar, a positron emission tomography radiotracer based on a third-generation P-glycoprotein inhibitor

    PubMed Central

    Bauer, Florian; Kuntner, Claudia; Bankstahl, Jens P.; Wanek, Thomas; Bankstahl, Marion; Stanek, Johann; Mairinger, Severin; Dörner, Bernd; Löscher, Wolfgang; Müller, Markus; Erker, Thomas; Langer, Oliver

    2013-01-01

    The aim of this study was to develop a positron emission tomography (PET) tracer based on the dual P-glycoprotein (P-gp) breast cancer resistance protein (BCRP) inhibitor tariquidar (1) to study the interaction of 1 with P-gp and BCRP in the blood-brain barrier (BBB) in vivo. O-desmethyl-1 was synthesized and reacted with [11C]methyl triflate to afford [11C]-1. Small-animal PET imaging of [11C]-1 was performed in naïve rats, before and after administration of unlabeled 1 (15 mg/kg, n=3) or the dual P-gp/BCRP inhibitor elacridar (5 mg/kg, n=2), as well as in wild-type, Mdr1a/b(−/−), Bcrp1(−/−) and Mdr1a/b(−/−)Bcrp1(−/−) mice (n=3). In vitro autoradiography was performed with [11C]-1 using brain sections of all 4 mouse types, with and without co-incubation with unlabeled 1 or elacridar (1 μM). In PET experiments in rats, administration of unlabeled 1 or elacridar increased brain activity uptake by a factor of 3-4, whereas blood activity levels remained unchanged. In Mdr1a/b(−/−), Bcrp1(−/−) and Mdr1a/b(−/−)Bcrp1(−/−) mice, brain-to-blood ratios of activity at 25 min after tracer injection were 3.4, 1.8 and 14.5 times higher, respectively, as compared to wild-type animals. Autoradiography showed approximately 50% less [11C]-1 binding in transporter knockout mice compared to wild-type mice and significant displacement by unlabeled elacridar in wild-type and Mdr1a/b(−/−) mouse brains. Our data suggest that [11C]-1 interacts specifically with P-gp and BCRP in the BBB. However, further investigations are needed to assess if [11C]-1 behaves in vivo as a transported or a non-transported inhibitor. PMID:20621487

  20. A case of mistaken identity: CD11c-eYFP(+) cells in the normal mouse brain parenchyma and neural retina display the phenotype of microglia, not dendritic cells.

    PubMed

    Dando, Samantha J; Naranjo Golborne, Cecilia; Chinnery, Holly R; Ruitenberg, Marc J; McMenamin, Paul G

    2016-08-01

    Under steady-state conditions the central nervous system (CNS) is traditionally thought to be devoid of antigen presenting cells; however, putative dendritic cells (DCs) expressing enhanced yellow fluorescent protein (eYFP) are present in the retina and brain parenchyma of CD11c-eYFP mice. We previously showed that these mice carry the Crb1(rd8) mutation, which causes retinal dystrophic lesions; therefore we hypothesized that the presence of CD11c-eYFP(+) cells within the CNS may be due to pathology associated with the Crb1(rd8) mutation. We generated CD11c-eYFP Crb1(wt/wt) mice and compared the distribution and immunophenotype of CD11c-eYFP(+) cells in CD11c-eYFP mice with and without the Crb1(rd8) mutation. The number and distribution of CD11c-eYFP(+) cells in the CNS was similar between CD11c-eYFP Crb1(wt/wt) and CD11c-eYFP Crb1(rd8/rd8) mice. CD11c-eYFP(+) cells were distributed throughout the inner retina, and clustered in brain regions that receive input from the external environment or lack a blood-brain barrier. CD11c-eYFP(+) cells within the retina and cerebral cortex of CD11c-eYFP Crb1(wt/wt) mice expressed CD11b, F4/80, CD115 and Iba-1, but not DC or antigen presentation markers, whereas CD11c-eYFP(+) cells within the choroid plexus and pia mater expressed CD11c, I-A/I-E, CD80, CD86, CD103, DEC205, CD8α and CD135. The immunophenotype of CD11c-eYFP(+) cells and microglia within the CNS was similar between CD11c-eYFP Crb1(wt/wt) and CD11c-eYFP Crb1(rd8/rd8) mice; however, CD11c and I-A/I-E expression was significantly increased in CD11c-eYFP Crb1(rd8/rd8) mice. This study demonstrates that the overwhelming majority of CNS CD11c-eYFP(+) cells do not display the phenotype of DCs or their precursors and are most likely a subpopulation of microglia. GLIA 2016. GLIA 2016;64:1331-1349.

  1. Combining [11C]-AnxA5 PET Imaging with Serum Biomarkers for Improved Detection in Live Mice of Modest Cell Death in Human Solid Tumor Xenografts

    PubMed Central

    Cheng, Qing; Lu, Li; Grafström, Jonas; Olofsson, Maria Hägg; Thorell, Jan-Olov; Samén, Erik; Johansson, Katarina; Ahlzén, Hanna-Stina; Stone-Elander, Sharon; Linder, Stig; Arnér, Elias S. J.

    2012-01-01

    Background In vivo imaging using Annexin A5-based radioligands is a powerful technique for visualizing massive cell death, but has been less successful in monitoring the modest cell death typically seen in solid tumors after chemotherapy. Here we combined dynamic positron emission tomography (PET) imaging using Annexin A5 with a serum-based apoptosis marker, for improved sensitivity and specificity in assessment of chemotherapy-induced cell death in a solid tumor model. Methodology/Principal Findings Modest cell death was induced by doxorubicin in a mouse xenograft model with human FaDu head and neck cancer cells. PET imaging was based on 11C-labeled Sel-tagged Annexin A5 ([11C]-AnxA5-ST) and a size-matched control. 2-deoxy-2-[18F]fluoro-D-glucose ([18F]-FDG) was utilized as a tracer of tissue metabolism. Serum biomarkers for cell death were ccK18 and K18 (M30 Apoptosense® and M65). Apoptosis in tissue sections was verified ex vivo for validation. Both PET imaging using [11C]-AnxA5-ST and serum ccK18/K18 levels revealed treatment-induced cell death, with ccK18 displaying the highest detection sensitivity. [18F]-FDG uptake was not affected by this treatment in this tumor model. [11C]-AnxA5-ST gave robust imaging readouts at one hour and its short half-life made it possible to perform paired scans in the same animal in one imaging session. Conclusions/Significance The combined use of dynamic PET with [11C]-AnxA5-ST, showing specific increases in tumor binding potential upon therapy, with ccK18/K18 serum measurements, as highly sensitive markers for cell death, enabled effective assessment of modest therapy-induced cell death in this mouse xenograft model of solid human tumors. PMID:22870292

  2. Heightened D3 Dopamine Receptor Levels in Cocaine Dependence and Contributions to the Addiction Behavioral Phenotype: A Positron Emission Tomography Study with [11C]-(+)-PHNO

    PubMed Central

    Payer, Doris E; Behzadi, Arian; Kish, Stephen J; Houle, Sylvain; Wilson, Alan A; Rusjan, Pablo M; Tong, Junchao; Selby, Peter; George, Tony P; McCluskey, Tina; Boileau, Isabelle

    2014-01-01

    The dopamine system is a primary treatment target for cocaine dependence (CD), but research on dopaminergic abnormalities (eg, D2 receptor system deficiencies) has so far failed to translate into effective treatment strategies. The D3 receptor system has recently attracted considerable clinical interest, and D3 antagonism is now under investigation as a novel avenue for addiction treatment. The objective here was to evaluate the status and behavioral relevance of the D3 receptor system in CD, using the positron emission tomography (PET) radiotracer [11C]-(+)-PHNO. Fifteen CD subjects (many actively using, but all abstinent 7–240 days on scan day) and fifteen matched healthy control (HC) subjects completed two PET scans: one with [11C]-(+)-PHNO to assess D3 receptor binding (BPND; calculated regionally using the simplified reference tissue model), and for comparison, a second scan with [11C]raclopride to assess D2/3 binding. CD subjects also completed a behavioral battery to characterize the addiction behavioral phenotype. CD subjects showed higher [11C]-(+)-PHNO BPND than HC in the substantia nigra, which correlated with behavioral impulsiveness and risky decision making. In contrast, [11C]raclopride BPND was lower across the striatum in CD, consistent with previous literature in ⩾2 week abstinence. The data suggest that in contrast to a D2 deficiency, CD individuals may have heightened D3 receptor levels, which could contribute to addiction-relevant traits. D3 upregulation is emerging as a biomarker in preclinical models of addiction, and human PET studies of this receptor system can help guide novel pharmacological strategies for treatment. PMID:23921256

  3. Quantification of human opiate receptor concentration and affinity using high and low specific activity ( sup 11 C)diprenorphine and positron emission tomography

    SciTech Connect

    Sadzot, B.; Price, J.C.; Mayberg, H.S.; Douglass, K.H.; Dannals, R.F.; Lever, J.R.; Ravert, H.T.; Wilson, A.A.; Wagner, H.N. Jr.; Feldman, M.A. )

    1991-03-01

    (11C)Diprenorphine, a weak partial opiate agonist, and positron emission tomography were used to obtain noninvasive regional estimates of opiate receptor concentration (Bmax) and affinity (Kd) in human brain. Different compartmental models and fitting strategies were compared statistically to establish the most reliable method of parameter estimation. Paired studies were performed in six normal subjects using high (769-5,920 Ci/mmol) and low (27-80 Ci/mmol) specific activity (SA) (11C)diprenorphine. Two subjects were studied a third time using high SA (11C)diprenorphine after a pretreatment with 1-1.5 mg/kg of the opiate antagonist naloxone. After the plasma radioactivity was corrected for metabolites, the brain data were analyzed using a three-compartment model and nonlinear least-squares curve fitting. Linear differential equations were used to describe the high SA (low receptor occupancy) kinetics. The k3/k4 ratio varied from 1.0 +/- 0.2 (occipital cortex) to 8.6 +/- 1.6 (thalamus). Nonlinear differential equations were used to describe the low SA (high receptor occupancy) kinetics and the curve fits provided the konf2 product. The measured free fraction of (11C)diprenorphine in plasma (f1) was 0.30 +/- 0.03, the average K1/k2 ratio from the two naloxone studies was 1.1 +/- 0.2, and the calculated free fraction of (11C)diprenorphine in the brain (f2) was 0.3. Using the paired SA studies, the estimated kinetic parameters, and f2, separate estimates of Bmax and Kd were obtained. Bmax varied from 2.3 +/- 0.5 (occipital cortex) to 20.6 +/- 7.3 (cingulate cortex) nM. The average Kd (eight brain regions) was 0.85 +/- 0.17 nM.

  4. Pharmacokinetic modeling of P-glycoprotein function at the rat and human blood–brain barriers studied with (R)-[11C]verapamil positron emission tomography

    PubMed Central

    2012-01-01

    Background This study investigated the influence of P-glycoprotein (P-gp) inhibitor tariquidar on the pharmacokinetics of P-gp substrate radiotracer (R)-[11C]verapamil in plasma and brain of rats and humans by means of positron emission tomography (PET). Methods Data obtained from a preclinical and clinical study, in which paired (R)-[11C]verapamil PET scans were performed before, during, and after tariquidar administration, were analyzed using nonlinear mixed effects (NLME) modeling. Administration of tariquidar was included as a covariate on the influx and efflux parameters (Qin and Qout) in order to investigate if tariquidar increased influx or decreased outflux of radiotracer across the blood–brain barrier (BBB). Additionally, the influence of pilocarpine-induced status epilepticus (SE) was tested on all model parameters, and the brain-to-plasma partition coefficient (VT-NLME) was calculated. Results Our model indicated that tariquidar enhances brain uptake of (R)-[11C]verapamil by decreasing Qout. The reduction in Qout in rats during and immediately after tariquidar administration (sevenfold) was more pronounced than in the second PET scan acquired 2 h after tariquidar administration (fivefold). The effect of tariquidar on Qout in humans was apparent during and immediately after tariquidar administration (twofold reduction in Qout) but was negligible in the second PET scan. SE was found to influence the pharmacological volume of distribution of the central brain compartment Vbr1. Tariquidar treatment lead to an increase in VT-NLME, and pilocarpine-induced SE lead to increased (R)-[11C]verapamil distribution to the peripheral brain compartment. Conclusions Using NLME modeling, we were able to provide mechanistic insight into the effects of tariquidar and SE on (R)-[11C]verapamil transport across the BBB in control and 48 h post SE rats as well as in humans. PMID:23072492

  5. Tariquidar-induced P-glycoprotein inhibition at the rat blood-brain barrier studied with (R)-11C-verapamil and PET

    PubMed Central

    Bankstahl, Jens P.; Kuntner, Claudia; Abrahim, Aiman; Karch, Rudolf; Stanek, Johann; Wanek, Thomas; Wadsak, Wolfgang; Kletter, Kurt; Müller, Markus; Löscher, Wolfgang; Langer, Oliver

    2013-01-01

    The multidrug efflux transporter P-glycoprotein (P-gp) is expressed in high concentrations at the blood-brain barrier (BBB) and believed to be implicated in resistance to central nervous system drugs. We used small-animal positron emission tomography (PET) and (R)-11C-verapamil together with tariquidar, a new-generation P-gp modulator, to study the functional activity of P-gp at the BBB of rats. To enable a comparison with human PET data we performed kinetic modeling to estimate the rate constants of radiotracer transport across the rat BBB. Methods A group of 7 Wistar Unilever rats underwent paired (R)-11C-verapamil PET scans at an interval of 3 h, one baseline scan and one scan after i.v. injection of tariquidar (15 mg/kg, n=5) or vehicle (n=2). Results Following tariquidar administration, the distribution volume DV of (R)-11C-verapamil was 12-fold higher as compared to baseline (3.68±0.81 versus 0.30±0.08; p=0.0007, paired t-test), whereas the DVs were essentially the same when only vehicle was administered. The increase in DV could mainly be attributed to an increased influx rate constant K1 of (R)-11C-verapamil into the brain, which was about 8-fold higher after tariquidar. A dose-response assessment with tariquidar provided an estimated half-maximum effect dose (ED50) of 8.4±9.5 mg/kg. Conclusion Our data demonstrate that (R)-11C-verapamil PET combined with tariquidar administration is a promising approach to measure P-gp function at the BBB. PMID:18632828

  6. Description of interview data regarding Pittsburgh and confluence toxic chemical accidents

    SciTech Connect

    Rogers, G.O.; Shumpert, B.L.; Sorensen, J.H.

    1990-11-01

    Evacuation is the protective action most often recommended in response to chemical releases in the United States. The appropriateness of a decision to evacuate depends on whether the affected areas can be cleared of residents before it is contaminated by the chemical release. In determining whether an evacuation can be completed in time, emergency officials must consider both technical and behavioral aspects. The technical components can be readily conceived and quantified. In contrast, the behavioral components are much more abstract and more difficult to estimate. This report summarizes the univariate analysis of responses to surveys conducted in two communities where evacuation was recommended following train derailments involving hazardous chemicals. The surveys were designed to identify the actions taken by residents upon receiving the emergency warning; determine when people received the warning, decided to take action, and implemented the action; and ascertain factors that might explain the nature and timing of their actions. The surveys were conducted in the Bloomfield section of Pittsburgh, Pennsylvania, and in the town of Confluence, Pennsylvania. The study confirms that compliance with an emergency warning to evacuate varies and that potentially dangerous delays can be expected. Significant differences were noted, however, in the rate and speed of compliance in the two communities. The surveys provide information on several factors that may be useful in determining the reasons for differences in the responses from the two communities as well as differences among individual respondents. Such factors include the time of day when the accident occurred, where the respondent was at the time, whether the family was together, previous disaster experience, pet ownership, the content of the warning message, and demographic characteristics. 4 refs., 4 figs., 18 tabs.

  7. Validity of the Pittsburgh Sleep Quality Index in Indian University Students

    PubMed Central

    Manzar, Md. Dilshad; Moiz, Jamal A.; Zannat, Wassilatul; Spence, David W.; Pandi-Perumal, Seithikurippu R.; Hussain, M. Ejaz

    2015-01-01

    Objectives Despite the demonstrated utility of the Pittsburgh Sleep Quality Index (PSQI) in various demographic groups, it has never been validated in a sample of Indian subjects. To extend and confirm the PSQI’s applicability for South Asian subjects, this preliminary study aimed to assess its psychometric and diagnostic validity in a sample of university students. Methods Forty-seven male students were recruited from Jamia Millia Islamia, a public central university in New Delhi, India. The mean age of the students was 23.4±3.9 years, and they had a mean body mass index (BMI) of 23.3±3.3kg/m2. The PSQI was administered to all subjects and overnight polysomnographic testing was carried out as a concurrent validation measure. Results Cronbach’s alpha for the questionnaire was found to be 0.736. Internal homogeneity was high, with the majority of correlations between questionnaire component scores and the summed global score being significant (p<0.010). Criterion validity-correlations between the PSQI global score and polysomnography (PSG) measures were low. However, the questionnaire component scores and the related polysomnographic measures did show some significant relationships. The optimal cut-off scores for distinguishing students with/without sleep problems was >6 and was generated using receiver operating characteristic curve analysis. The area under the curve, sensitivity, specificity, positive and negative likelihood ratios at the cut-off score were 0.838 (p<0.0001), 75.0%, 88.9%, 6.75, and 0.280, respectively. Conclusion The study found evidence that the PSQI had internal consistency, internal homogeneity, and diagnostic characteristics that compared well with PSG among a sample of young adult male students in India. This supports the applicability and certain aspects of the validity of the PSQI in the population. PMID:26171126

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

    SciTech Connect

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

    1987-10-01

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

  9. Is There an Additional Value of {sup 11}C-Choline PET-CT to T2-weighted MRI Images in the Localization of Intraprostatic Tumor Nodules?

    SciTech Connect

    Van den Bergh, Laura; Koole, Michel; Isebaert, Sofie; Joniau, Steven; Deroose, Christophe M.; Oyen, Raymond; Lerut, Evelyne; Budiharto, Tom; Mottaghy, Felix; Bormans, Guy; Van Poppel, Hendrik; Haustermans, Karin

    2012-08-01

    Purpose: To investigate the additional value of {sup 11}C-choline positron emission tomography (PET)-computed tomography (CT) to T2-weighted (T2w) magnetic resonance imaging (MRI) for localization of intraprostatic tumor nodules. Methods and Materials: Forty-nine prostate cancer patients underwent T2w MRI and {sup 11}C-choline PET-CT before radical prostatectomy and extended lymphadenectomy. Tumor regions were outlined on the whole-mount histopathology sections and on the T2w MR images. Tumor localization was recorded in the basal, middle, and apical part of the prostate by means of an octant grid. To analyze {sup 11}C-choline PET-CT images, the same grid was used to calculate the standardized uptake values (SUV) per octant, after rigid registration with the T2w MR images for anatomic reference. Results: In total, 1,176 octants were analyzed. Sensitivity, specificity, and accuracy of T2w MRI were 33.5%, 94.6%, and 70.2%, respectively. For {sup 11}C-choline PET-CT, the mean SUV{sub max} of malignant octants was significantly higher than the mean SUV{sub max} of benign octants (3.69 {+-} 1.29 vs. 3.06 {+-} 0.97, p < 0.0001) which was also true for mean SUV{sub mean} values (2.39 {+-} 0.77 vs. 1.94 {+-} 0.61, p < 0.0001). A positive correlation was observed between SUV{sub mean} and absolute tumor volume (Spearman r = 0.3003, p = 0.0362). No correlation was found between SUVs and prostate-specific antigen, T-stage or Gleason score. The highest accuracy (61.1%) was obtained with a SUV{sub max} cutoff of 2.70, resulting in a sensitivity of 77.4% and a specificity of 44.9%. When both modalities were combined (PET-CT or MRI positive), sensitivity levels increased as a function of SUV{sub max} but at the cost of specificity. When only considering suspect octants on {sup 11}C-choline PET-CT (SUV{sub max} {>=} 2.70) and T2w MRI, 84.7% of these segments were in agreement with the gold standard, compared with 80.5% for T2w MRI alone. Conclusions: The additional value of {sup

  10. High Precision Determination of the β Decay Q(EC) Value of (11)C and Implications on the Tests of the Standard Model.

    PubMed

    Gulyuz, K; Bollen, G; Brodeur, M; Bryce, R A; Cooper, K; Eibach, M; Izzo, C; Kwan, E; Manukyan, K; Morrissey, D J; Naviliat-Cuncic, O; Redshaw, M; Ringle, R; Sandler, R; Schwarz, S; Sumithrarachchi, C S; Valverde, A A; Villari, A C C

    2016-01-01

    We report the determination of the Q(EC) value of the mirror transition of (11)C by measuring the atomic masses of (11)C and (11)B using Penning trap mass spectrometry. More than an order of magnitude improvement in precision is achieved as compared to the 2012 Atomic Mass Evaluation (Ame2012) [Chin. Phys. C 36, 1603 (2012)]. This leads to a factor of 3 improvement in the calculated Ft value. Using the new value, Q(EC)=1981.690(61)  keV, the uncertainty on Ft is no longer dominated by the uncertainty on the Q(EC) value. Based on this measurement, we provide an updated estimate of the Gamow-Teller to Fermi mixing ratio and standard model values of the correlation coefficients. PMID:26799013

  11. High Precision Determination of the β Decay QEC Value of 11C and Implications on the Tests of the Standard Model

    NASA Astrophysics Data System (ADS)

    Gulyuz, K.; Bollen, G.; Brodeur, M.; Bryce, R. A.; Cooper, K.; Eibach, M.; Izzo, C.; Kwan, E.; Manukyan, K.; Morrissey, D. J.; Naviliat-Cuncic, O.; Redshaw, M.; Ringle, R.; Sandler, R.; Schwarz, S.; Sumithrarachchi, C. S.; Valverde, A. A.; Villari, A. C. C.

    2016-01-01

    We report the determination of the QEC value of the mirror transition of 11C by measuring the atomic masses of 11C and 11B using Penning trap mass spectrometry. More than an order of magnitude improvement in precision is achieved as compared to the 2012 Atomic Mass Evaluation (Ame2012) [Chin. Phys. C 36, 1603 (2012)]. This leads to a factor of 3 improvement in the calculated F t value. Using the new value, QEC=1981.690 (61 ) keV , the uncertainty on F t is no longer dominated by the uncertainty on the QEC value. Based on this measurement, we provide an updated estimate of the Gamow-Teller to Fermi mixing ratio and standard model values of the correlation coefficients.

  12. [(11)C]Raclopride binding in the striatum of minimally restrained and free-walking awake mice in a positron emission tomography study.

    PubMed

    Takuwa, Hiroyuki; Maeda, Jun; Ikoma, Yoko; Tokunaga, Masaki; Wakizaka, Hidekatsu; Uchida, Shouko; Kanno, Iwao; Taniguchi, Junko; Ito, Hiroshi; Higuchi, Makoto

    2015-12-01

    Anesthesia and restraint stress have profound impacts on brain functions, including neural activity and cerebrovascular function, possibly influencing functional and neurochemical positron emission tomography (PET) imaging data. For circumventing this effect, we developed an experimental system enabling PET imaging of free-walking awake mice with minimal restraints by fixing the head to a holder. The applicability of this system was investigated by performing PET imaging of D2 dopamine receptors with [(11)C]raclopride under the following three different conditions: (1) free-walking awake state; (2) 1.5% isoflurane anesthesia; and (3) whole-body restraint without anesthesia. [(11)C]raclopride binding potential (BP(ND)) values under isoflurane anesthesia and restrained awake state were significantly lower than under free-walking awake state (P < 0.01). Heart rates in restrained awake mice were significantly higher than those in free-walking awake mice (P < 0.01), suggesting that free-walking awake state minimized restraint stress during the PET scan. [(11)C] raclopride-PET with methamphetamine (METH) injection was also performed in awake and anesthetized mice. METH-induced reduction of [(11)C]raclopride BP(ND) in anesthetized mice showed a trend to be less than that in free-walking awake mice, implying that pharmacological modulation of dopaminergic transmissions could be sensitively captured by PET imaging of free-walking awake mice. We concluded that our system is of utility as an in vivo assaying platform for studies of brain functions and neurotransmission elements in small animals, such as those modeling neuropsychiatric disorders.

  13. Extrastriatal dopaminergic abnormalities of DA homeostasis in Parkinson’s patients with medication-induced pathological gambling: A [11C] FLB-457 and PET study

    PubMed Central

    Ray, Nicola J.; Miyasaki, Janis M.; Zurowski, Mateusz; Ko, Ji Hyun; Cho, Sang Soo; Pellecchia, Giovanna; Antonelli, Francesca; Houle, Sylvain; Lang, Anthony E.; Strafella, Antonio P.

    2012-01-01

    Impulse control disorders such as pathological gambling (PG) are a serious and common adverse effect of dopamine (DA) replacement medication in Parkinson’s disease (PD). Patients with PG have increased impulsivity and abnormalities in striatal DA, in common with behavioural and substance addictions in the non-PD population. To date, no studies have investigated the role of extrastriatal dopaminergic abnormalities in PD patients with PG. We used the PET radiotracer, [11C] FLB-457, with high-affinity for extrastriatal DA D2/3 receptors. 14 PD patients on DA agonists were imaged while they performed a gambling task involving real monetary reward and a control task. Trait impulsivity was measured with the Barratt Impulsivity Scale (BIS). Seven of the patients had a history of PG that developed subsequent to DA agonist medication. Change in [11C] FLB-457 binding potential (BP) during gambling was reduced in PD with PG patients in the midbrain, where D2/D3 receptors are dominated by autoreceptors. The degree of change in [11C] FLB-457 binding in this region correlated with impulsivity. In the cortex, [11C] FLB-457 BP was significantly greater in the anterior cingulate cortex (ACC) in PD patients with PG during the control task, and binding in this region was also correlated with impulsivity. Our findings provide the first evidence that PD patients with PG have dysfunctional activation of DA autoreceptors in the midbrain and low DA tone in the ACC. Thus, altered striatal and cortical DA homeostasis may incur vulnerability for the development of PG in PD, linked with the impulsive personality trait. PMID:22766031

  14. Detection of Local, Regional, and Distant Recurrence in Patients With PSA Relapse After External-Beam Radiotherapy Using {sup 11}C-Choline Positron Emission Tomography

    SciTech Connect

    Breeuwsma, Anthonius J.; Pruim, Jan; Bergh, Alphons C.M. van den; Leliveld, Anna M.; Nijman, Rien J.M.; Dierckx, Rudi A.J.O.; Jong, Igle J. de

    2010-05-01

    Purpose: An elevated serum prostate-specific antigen (PSA) level cannot distinguish between local-regional recurrences and the presence of distant metastases after treatment with curative intent for prostate cancer. With the advent of salvage treatment such as cryotherapy, it has become important to localize the site of recurrence (local or distant). In this study, the potential of {sup 11}C-choline positron emission tomography (PET) to identify site of recurrence was investigated in patients with rising PSA after external-beam radiotherapy (EBRT). Methods and Materials: Seventy patients with histologically proven prostate cancer treated with EBRT and showing biochemical recurrence as defined by American Society for Therapeutic Radiology and Oncology consensus statement and 10 patients without recurrence underwent a PET scan using 400 MBq {sup 11}C-choline intravenously. Biopsy-proven histology from the site of suspicion, findings with other imaging modalities, clinical follow-up and/or response to adjuvant therapy were used as comparative references. Results: None of the 10 patients without biochemical recurrence had a positive PET scan. Fifty-seven of 70 patients with biochemical recurrence (median PSA 9.1 ng/mL; mean PSA 12.3 ng/mL) showed an abnormal uptake pattern (sensitivity 81%). The site of recurrence was only local in 41 of 57 patients (mean PSA 11.1 ng/mL at scan), locoregionally and/or distant in 16 of 57 patients (mean PSA 17.7 ng/mL). Overall the positive predictive value and negative predictive value for {sup 11}C-choline PET scan were 1.0 and 0.44 respectively. Accuracy was 84%. Conclusions: {sup 11}C-choline PET scan is a sensitive technique to identify the site of recurrence in patients with PSA relapse after EBRT for prostate cancer.

  15. Effects of point spread function-based image reconstruction on neuroreceptor binding in positron emission tomography study with [(11)C]FLB 457.

    PubMed

    Thongpraparn, Thonnapong; Ikoma, Yoko; Shiraishi, Takahiro; Yamaya, Taiga; Ito, Hiroshi

    2016-01-01

    The ordered subset expectation maximization with a point spread function (OSEM-PSF) was developed to improve the spatial resolution of reconstructed positron emission tomography (PET) images and has been reported to improve the contrast of hot spots in PET studies for oncology. However, in neuroreceptor imaging, the regional radioactivity concentration changes dynamically during the scan, and the effects of the PSF may differ among various radioligands or quantification methods. In this study, we investigated the effects of the PSF on quantification in PET studies with [(11)C]FLB 457 of dopamine D2 receptors, using both phantom and human data acquired by the Siemens Biograph 16 imaging platform. In the phantom studies, we evaluated the hot contrast recovery coefficient (HCRC) for variously sized hot spheres and the linearity between the measured and true radioactivities in OSEM-PSF images. Next, in the human studies with [(11)C]FLB 457, radioactivity concentrations and binding potentials for the cerebral cortex and thalamus were compared between images reconstructed with and without PSF. In the phantom studies, the OSEM-PSF images showed a better HCRC compared to images without PSF, and they showed a good linear correlation with true radioactivity. In the human studies, the radioactivity concentration increased especially in small regions with high accumulation of [(11)C]FLB 457 when the PSF was included. However, little difference in the binding potentials was observed for the target regions between both types of reconstructed images. In conclusion, PSF-based reconstruction reduced the spill-over phenomena in small hot regions; however, it caused no increase in the binding potentials in the [(11)C]FLB 457 studies.

  16. The diffusion-weighted imaging and 11-C-methionine positron emission tomography depiction of an endodermal cyst at the cervico-medullary junction.

    PubMed

    Riva, Marco; Rodriguez Y Baena, Riccardo; Pessina, Federico; Egesta, Lopci; Fernandes, Bethania; Galli, Carlo; Rossi, Marco; Bello, Lorenzo

    2015-01-01

    A case of a 52-year-old male with left-sided neck pain, vertigo and gait instability is reported. A MRI scan revealed an intra-dural mass at the cervico-medullary junction, further characterised by diffusion-weighted imaging and 11-C-methionine positron emission tomography. Pathological diagnosis was endodermal cyst. The clinico-surgical relevance of the imaging findings is discussed.

  17. Incidental 11C-choline PET/CT brain uptake due to meningioma in a patient studied for prostate cancer: correlation with MRI and imaging fusion.

    PubMed

    Bertagna, Francesco; Bosio, Giovanni; Pinelli, Lorenzo; Treglia, Giorgio; Giubbini, Raffaele

    2013-11-01

    We report a case of a 75-year-old male patient treated with radiotherapy in 1999 for prostate cancer. Due to a rise in prostate-specific antigen, he underwent (11)C-choline PET/CT. The study was negative for secondary lesions but revealed an incidental pathologic focal brain uptake. A subsequent magnetic resonance examination confirmed the presence of a brain lesion typical for meningioma.

  18. [Regional distribution of the muscarinic cholinergic receptor in the human brain studied with 11C-benztropine and PET using an anatomical standardization technique].

    PubMed

    Ono, S; Kawashima, R; Ito, H; Koyama, M; Goto, R; Inoue, K; Sato, K; Fujiwara, T; Meguro, K; Yanai, K; Sasaki, H; Ido, T; Ito, M; Fukuda, H

    1996-07-01

    We measured regional distribution of the muscarinic cholinergic receptor in the normal human brain with 11C-benztropine (BZT) and positron emission tomography (PET) using an anatomical standardization technique. Seven normal volunteers who gave informed consents were involved in this study. Immediately after intravenous injection of 11C-BZT into the subjects, we started dynamic PET scanning and serial frequent arterial blood sampling. Analyses of plasma metabolites were also performed at selected time points and plasma time activity curves (TAC) of unmetabolized ligand were generated. From these PET and TAC data, we obtained Patlak plot slope calculation images. Using the HBA (human brain atlas) system, the Patlak plot slope calculation image of each subject was transformed into the shape of the standard brain. Mean and standard deviation (SD) calculation images were generated from those anatomically standardized images. On these mean and SD images, we placed regions of interest which were previously outlined on a MR image of the standard brain. From those data, we found the highest receptor distribution in the striatum and occipital cortex, as well as high distribution in the frontal, parietal, and temporal cortices, which were consistent with previous reports. These results suggested that anatomical standardization of PET receptor images with 11C-BZT will be useful for delineating the physiological or pathological alterations of the muscarinic cholinergic receptor in the human brain.

  19. First-principles study of superconductivity in the hole self-doped LiB1.1C0.9

    NASA Astrophysics Data System (ADS)

    Miao, Rende; Yang, Jun; Jiang, Min; Zhang, Qilin; Cai, Dan; Fan, Chunhui; Bai, Zhong; Liu, Cuicui; Wu, Fangping; Ma, Shuyun

    2013-04-01

    Electronic density of states of LiBC, electronic band structure, lattice dynamics, and superconducting properties for hypothetical LiB1.1C0.9 are obtained by first-principles calculations within the virtual-crystal approximation treatment. It is found that the top of the valence band of LiBC are mainly due to the C 2p states, with sizable contributions of B 2p states and very small contributions from Li states. We thus suggest that the slight hole doping of LiBC through partial substitution of B or C atoms may more easily metallize LiBC than that of the removal of Li atoms from LiBC. For example, the partial substitution of C by B atoms can produce an insulator-metal transition and develop superconductivity. To assess the thermodynamic stability of LiB1+xC1-x, the formation energy is calculated using the supercell method. For LiB1.1C0.9, the obtained formation energy is -9.4 eV, indicating that it is energetically favorable. The electron-phonon coupling constant λ for LiB1.1C0.9 is 0.75, and superconducting transition temperature TC is as high as 36 K (μ∗=0.1).

  20. Striatal and frontal cortex binding of 11-C-labelled clozapine visualized by positron emission tomography (PET) in drug-free schizophrenics and healthy volunteers.

    PubMed

    Lundberg, T; Lindström, L H; Hartvig, P; Eckernâs, S A; Ekblom, B; Lundqvist, H; Fasth, K J; Gullberg, P; Långström, B

    1989-01-01

    The binding of 11C-labelled clozapine in the brain was studied in three drug-free schizophrenic patients and in three healthy volunteers. High radioactivities were found in the striatum and in the frontal cortex. The rate constant k3, which is proportional to receptor association rate and the number of receptors, was lower in the frontal cortex compared to the striatum. No obvious difference between the two brain areas was seen for the dissociation rate constant from the receptors (k4). Two schizophrenic patients were reexamined after pretreatment with haloperidol, one after 6 weeks of treatment with a low oral dose, the other one after an IV injection 1 h before 11C-clozapine was given. After haloperidol pretreatment, the binding of 11C-clozapine in striatum and frontal cortex was reduced, more pronounced in the striatum, indicating competition for D-2 dopamine binding sites. Our finding indicates that clozapine has an affinity for a receptor population in the frontal cortex that is predominantly not of the dopamine-D2 type. This feature might be of importance for the unique clinical profile of the drug.

  1. In vivo (R)-[11C]PK11195 PET imaging of 18kDa translocator protein in recent onset psychosis

    PubMed Central

    van der Doef, Thalia F; de Witte, Lot D; Sutterland, Arjen L; Jobse, Ellen; Yaqub, Maqsood; Boellaard, Ronald; de Haan, Lieuwe; Eriksson, Jonas; Lammertsma, Adriaan A; Kahn, René S; van Berckel, Bart N M

    2016-01-01

    Evidence is accumulating that immune dysfunction is involved in the pathophysiology of schizophrenia. It has been hypothesized that microglia activation is present in patients with schizophrenia. Various in vivo and post-mortem studies have investigated this hypothesis, but as yet with inconclusive results. Microglia activation is associated with elevations in 18 kDa translocator protein (TSPO) levels, which can be measured with the positron emission tomography (PET) tracer (R)-[11C]PK11195. The purpose of the present study was to investigate microglia activation in psychosis in vivo at an early stage of the disease. (R)-[11C]PK11195 binding potential (BPND) was measured in 19 patients with recent onset psychosis and 17 age and gender-matched healthy controls. Total gray matter, as well as five gray matter regions of interest (frontal cortex, temporal cortex, parietal cortex, striatum, and thalamus) were defined a priori. PET data were analysed using a reference tissue approach and a supervised cluster analysis algorithm to identify the reference region. No significant difference in (R)-[11C]PK11195 BPND between patients and controls was found in total gray matter, nor one of the regions of interest. These findings suggest that microglia activation is not present in recent onset psychosis or that it is a subtle phenomenon that could not be detected using the design of the present study.

  2. In vivo (R)-[(11)C]PK11195 PET imaging of 18kDa translocator protein in recent onset psychosis.

    PubMed

    van der Doef, Thalia F; de Witte, Lot D; Sutterland, Arjen L; Jobse, Ellen; Yaqub, Maqsood; Boellaard, Ronald; de Haan, Lieuwe; Eriksson, Jonas; Lammertsma, Adriaan A; Kahn, René S; van Berckel, Bart N M

    2016-01-01

    Evidence is accumulating that immune dysfunction is involved in the pathophysiology of schizophrenia. It has been hypothesized that microglia activation is present in patients with schizophrenia. Various in vivo and post-mortem studies have investigated this hypothesis, but as yet with inconclusive results. Microglia activation is associated with elevations in 18 kDa translocator protein (TSPO) levels, which can be measured with the positron emission tomography (PET) tracer (R)-[(11)C]PK11195. The purpose of the present study was to investigate microglia activation in psychosis in vivo at an early stage of the disease. (R)-[(11)C]PK11195 binding potential (BPND) was measured in 19 patients with recent onset psychosis and 17 age and gender-matched healthy controls. Total gray matter, as well as five gray matter regions of interest (frontal cortex, temporal cortex, parietal cortex, striatum, and thalamus) were defined a priori. PET data were analysed using a reference tissue approach and a supervised cluster analysis algorithm to identify the reference region. No significant difference in (R)-[(11)C]PK11195 BPND between patients and controls was found in total gray matter, nor one of the regions of interest. These findings suggest that microglia activation is not present in recent onset psychosis or that it is a subtle phenomenon that could not be detected using the design of the present study. PMID:27602389

  3. Acute effect of the anti-addiction drug bupropion on extracellular dopamine concentrations in the human striatum: an [11C]raclopride PET study.

    PubMed

    Egerton, Alice; Shotbolt, John P; Stokes, Paul R A; Hirani, Ella; Ahmad, Rabia; Lappin, Julia M; Reeves, Suzanne J; Mehta, Mitul A; Howes, Oliver D; Grasby, Paul M

    2010-03-01

    Bupropion is an effective medication in treating addiction and is widely used as an aid to smoking cessation. Bupropion inhibits striatal dopamine reuptake via dopamine transporter blockade, but it is unknown whether this leads to increased extracellular dopamine levels at clinical doses in man. The effects of bupropion on extracellular dopamine levels in the striatum were investigated using [(11)C]raclopride positron emission tomography (PET) imaging in rats administered saline, 11 or 25 mg/kg bupropion i.p. and in healthy human volunteers administered either placebo or 150 mg bupropion (Zyban Sustained-Release). A cognitive task was used to stimulate dopamine release in the human study. In rats, bupropion significantly decreased [(11)C]raclopride specific binding in the striatum, consistent with increases in extracellular dopamine concentrations. In man, no significant decreases in striatal [(11)C]raclopride specific binding were observed. Levels of dopamine transporter occupancy in the rat at 11 and 25 mg/kg bupropion i.p. were higher than predicted to occur in man at the dose used. Thus, these data indicate that, at the low levels of dopamine transporter occupancy achieved in man at clinical doses, bupropion does not increase extracellular dopamine levels. These findings have important implications for understanding the mechanism of action underlying bupropions' therapeutic efficacy and for the development of novel treatments for addiction and depression. PMID:19969097

  4. Parameter evaluation and fully-automated radiosynthesis of [11C]harmine for imaging of MAO-A for clinical trials

    PubMed Central

    Philippe, C.; Zeilinger, M.; Mitterhauser, M.; Dumanic, M.; Lanzenberger, R.; Hacker, M.; Wadsak, W.

    2015-01-01

    The aim of the present study was the evaluation and automation of the radiosynthesis of [11C]harmine for clinical trials. The following parameters have been investigated: amount of base, precursor concentration, solvent, reaction temperature and time. The optimum reaction conditions were determined to be 2–3 mg/mL precursor activated with 1 eq. 5 M NaOH in DMSO, 80 °C reaction temperature and 2 min reaction time. Under these conditions 6.1±1 GBq (51.0±11% based on [11C]CH3I, corrected for decay) of [11C]harmine (n=72) were obtained. The specific activity was 101.32±28.2 GBq/µmol (at EOS). All quality control parameters were in accordance with the standards for parenteral human application. Due to its reliability and high yields, this fully-automated synthesis method can be used as routine set-up. PMID:25594603

  5. PET imaging of serotoninergic neurotransmission with [11C]DASB and [18F]altanserin after focal cerebral ischemia in rats

    PubMed Central

    Martín, Abraham; Szczupak, Boguslaw; Gómez-Vallejo, Vanessa; Plaza, Sandra; Padró, Daniel; Cano, Ainhoa; Llop, Jordi

    2013-01-01

    The use of selective serotonin reuptake inhibitors has shown functional improvement after stroke. Despite this, the role of serotoninergic neurotransmission after cerebral ischemia evolution and its involvement in functional recovery processes are still largely unknown. For this purpose, we performed in parallel in vivo magnetic resonance imaging and positron emission tomography (PET) with [11C]DASB and [18F]altanserin at 1, 3, 7, 14, 21, and 28 days after middle cerebral artery occlusion (MCAO) in rats. In the ischemic territory, PET with [11C]DASB and [18F]altanserin showed a dramatic decline in serotonin transporter (SERT) and 5-HT2A binding potential in the cortex and striatum after cerebral ischemia. Interestingly, a slight increase in [11C]DASB binding was observed from days 7 to 21 followed by the uppermost binding at day 28 in the ipsilateral midbrain. In contrast, no changes were observed in the contralateral hemisphere by using both radiotracers. Likewise, both functional and behavior testing showed major impaired outcome at day 1 after ischemia onset followed by a recovery of the sensorimotor function and dexterity from day 21 to day 28 after cerebral ischemia. Taken together, these results might evidence that SERT changes in the midbrain could have a key role in the functional recovery process after cerebral ischemia. PMID:23982048

  6. Test-retest reproducibility of [11C]-(+)-propyl-hexahydro-naphtho-oxazin positron emission tomography using the bolus plus constant infusion paradigm.

    PubMed

    Lee, Dianne E; Gallezot, Jean-Dominique; Zheng, Ming-Qiang; Lim, Keunpoong; Ding, Yu-Shin; Huang, Yiyun; Carson, Richard E; Morris, Evan D; Cosgrove, Kelly P

    2013-01-01

    We examined the reproducibility of using the constant infusion paradigm for equilibrium measurement of D2/3 receptors using [11C]-(+)-propyl-hexahydro-naphtho-oxazin (PHNO) positron emission tomography (PET). Six subjects were scanned with a bolus plus constant infusion (Kbol = 80 minutes) of [11C]-(+)-PHNO. Binding potential (BPND) was computed using the equilibrium approach and compared to a simplified reference tissue model (SRTM). The rate of change in the concentration-activity curve from 60 to 90 minutes was -5 ± 13%/h in the caudate, putamen, substantia nigra, thalamus, and cerebellum but was 15 ± 15%/h in the ventral striatum and pallidum. Test-retest variability was lower in striatal compared to extrastriatal regions (4 ± 8% vs -8 ± 22%, respectively) using the equilibrium approach, with comparable results with SRTM. The equilibrium ratio and SRTM yielded reliable BPND estimates (intraclass correlation coefficient = 0.88 and 0.82, respectively). These studies support the reproducibility of the bolus plus constant infusion paradigm with [11C]-(+)-PHNO PET. PMID:23415395

  7. [11C]-Labeled Metformin Distribution in the Liver and Small Intestine Using Dynamic Positron Emission Tomography in Mice Demonstrates Tissue-Specific Transporter Dependency.

    PubMed

    Jensen, Jonas B; Sundelin, Elias I; Jakobsen, Steen; Gormsen, Lars C; Munk, Ole L; Frøkiær, Jørgen; Jessen, Niels

    2016-06-01

    Metformin is the most commonly prescribed oral antidiabetic drug, with well-documented beneficial preventive effects on diabetic complications. Despite being in clinical use for almost 60 years, the underlying mechanisms for metformin action remain elusive. Organic cation transporters (OCT), including multidrug and toxin extrusion proteins (MATE), are essential for transport of metformin across membranes, but tissue-specific activity of these transporters in vivo is incompletely understood. Here, we use dynamic positron emission tomography with [(11)C]-labeled metformin ([(11)C]-metformin) in mice to investigate the role of OCT and MATE in a well-established target tissue, the liver, and a putative target of metformin, the small intestine. Ablation of OCT1 and OCT2 significantly reduced the distribution of metformin in the liver and small intestine. In contrast, inhibition of MATE1 with pyrimethamine caused accumulation of metformin in the liver but did not affect distribution in the small intestine. The demonstration of OCT-mediated transport into the small intestine provides evidence of direct effects of metformin in this tissue. OCT and MATE have important but separate roles in uptake and elimination of metformin in the liver, but this is not due to changes in biliary secretion. [(11)C]-Metformin holds great potential as a tool to determine the pharmacokinetic properties of metformin in clinical studies.

  8. In vivo (R)-[11C]PK11195 PET imaging of 18kDa translocator protein in recent onset psychosis

    PubMed Central

    van der Doef, Thalia F; de Witte, Lot D; Sutterland, Arjen L; Jobse, Ellen; Yaqub, Maqsood; Boellaard, Ronald; de Haan, Lieuwe; Eriksson, Jonas; Lammertsma, Adriaan A; Kahn, René S; van Berckel, Bart N M

    2016-01-01

    Evidence is accumulating that immune dysfunction is involved in the pathophysiology of schizophrenia. It has been hypothesized that microglia activation is present in patients with schizophrenia. Various in vivo and post-mortem studies have investigated this hypothesis, but as yet with inconclusive results. Microglia activation is associated with elevations in 18 kDa translocator protein (TSPO) levels, which can be measured with the positron emission tomography (PET) tracer (R)-[11C]PK11195. The purpose of the present study was to investigate microglia activation in psychosis in vivo at an early stage of the disease. (R)-[11C]PK11195 binding potential (BPND) was measured in 19 patients with recent onset psychosis and 17 age and gender-matched healthy controls. Total gray matter, as well as five gray matter regions of interest (frontal cortex, temporal cortex, parietal cortex, striatum, and thalamus) were defined a priori. PET data were analysed using a reference tissue approach and a supervised cluster analysis algorithm to identify the reference region. No significant difference in (R)-[11C]PK11195 BPND between patients and controls was found in total gray matter, nor one of the regions of interest. These findings suggest that microglia activation is not present in recent onset psychosis or that it is a subtle phenomenon that could not be detected using the design of the present study. PMID:27602389

  9. Combined 18F-FDG and 11C-Methionine PET/CT scans in a case of metastatic hepatocellular carcinoma

    PubMed Central

    D’souza, Maria M.; Sharma, Rajnish; Jaimini, Abhinav; Saw, Sanjiv Kumar; Singh, Dinesh; Mondal, Anupam

    2014-01-01

    A 37-year-old male who underwent a central hepatectomy of the liver for hepatocellular carcinoma (HCC) was referred for an 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) study to rule out tumor recurrence or metastases. The scan showed a recurrent hepatic mass at the operative site, along with low-grade uptake in bilateral pulmonary metastases, mediastinal and hilar lymph nodes, and few skeletal sites. A non-FDG avid intracranial extradural mass was visualized in the right frontal lobe. The 11C-methionine PET/CT scan performed subsequently revealed a larger area of involvement at the primary site, along with widespread metastases to the lungs, mediastinal, hilar, and abdominal lymph nodes, and multiple skeletal sites. Further, dural metastasis with high tracer uptake was noted in the frontal region. To the best of our knowledge, this is the first case documented in the literature, wherein 11C-methionine PET/CT played a significant role in delineating the widespread dissemination, including the extremely rare dural involvement in a case of HCC. This report highlights the potential value of 11C-methionine PET/CT in assessing the hepatic and extrahepatic tumor burden in cases of HCC, especially in clinically unexpected locations. PMID:25210286

  10. 5-HT modulation of dopamine release in basal ganglia in psilocybin-induced psychosis in man--a PET study with [11C]raclopride.

    PubMed

    Vollenweider, F X; Vontobel, P; Hell, D; Leenders, K L

    1999-05-01

    The modulating effects of serotonin on dopamine neurotransmission are not well understood, particularly in acute psychotic states. Positron emission tomography was used to examine the effect of psilocybin on the in vivo binding of [11C]raclopride to D2-dopamine receptors in the striatum in healthy volunteers after placebo and a psychotomimetic dose of psilocybin (n = 7). Psilocybin is a potent indoleamine hallucinogen and a mixed 5-HT2A and 5-HT1A receptor agonist. Psilocybin administration (0.25 mg/kg p.o.) produced changes in mood, disturbances in thinking, illusions, elementary and complex visual hallucinations and impaired ego-functioning. Psilocybin significantly decreased [11C]raclopride receptor binding potential (BP) bilaterally in the caudate nucleus (19%) and putamen (20%) consistent with an increase in endogenous dopamine. Changes in [11C]raclopride BP in the ventral striatum correlated with depersonalization associated with euphoria. Together with previous reports of 5-HT receptor involvement in striatal dopamine release, it is concluded that stimulation of both 5-HT2A and 5-HT1A receptors may be important for the modulation of striatal dopamine release in acute psychoses. The present results indirectly support the hypothesis of a serotonin-dopamine dysbalance in schizophrenia and suggest that psilocybin is a valuable tool in the analysis of serotonin-dopamine interactions in acute psychotic states.

  11. Biodistribution of the radionuclides 18F-FDG, 11C-methionine, 11C-PK11195, and 68Ga-citrate in domestic juvenile female pigs and morphological and molecular imaging of the tracers in hematogenously disseminated Staphylococcus aureus lesions

    PubMed Central

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

    2016-01-01

    Approximately 5-7% of acute-care patients suffer from bacteremia. Bacteremia may give rise to bacterial spread to different tissues. Conventional imaging procedures as X-ray, Computed Tomography (CT), Magnetic Resonance Imaging (MRI), and ultrasound are often first-line imaging methods for identification and localization of infection. These methods are, however, not always successful. Early identification and localization of infection is critical for the appropriate and timely selection of therapy. The aim of this study was thus; a head to head comparison of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) to PET with tracers that potentially could improve uncovering of infectious lesions in soft tissues. We chose 11C-methionine, 11C-PK11195, and 68Ga-citrate as tracers and besides presenting their bio-distribution we validated their diagnostic utility in pigs with experimental bacterial infection. Four juvenile 14-15 weeks old female domestic pigs were scanned seven days after intra-arterial inoculation in the right femoral artery with a porcine strain of S. aureus using a sequential scanning protocol with 18F-FDG, 11C-methionine, 11C-PK11195 and 68Ga-citrate. This was followed by necropsy of the pigs consisting of gross pathology, histopathology and microbial examination. The pigs primarily developed lesions in lungs and neck muscles. 18F-FDG had higher infection to background ratios and accumulated in most infectious foci caused by S. aureus, while 11C-methionine and particularly 11C-PK11195 and 68Ga-citrate accumulated to a lesser extent in infectious foci. 18F-FDG-uptake was seen in the areas of inflammatory cells and to a much lesser extent in reparative infiltration surrounding necrotic regions. PMID:27069765

  12. Indoor air sampling for fine particulate matter and black carbon in industrial communities in Pittsburgh.

    PubMed

    Tunno, Brett J; Naumoff Shields, Kyra; Cambal, Leah; Tripathy, Sheila; Holguin, Fernando; Lioy, Paul; Clougherty, Jane E

    2015-12-01

    Impacts of industrial emissions on outdoor air pollution in nearby communities are well-documented. Fewer studies, however, have explored impacts on indoor air quality in these communities. Because persons in northern climates spend a majority of their time indoors, understanding indoor exposures, and the role of outdoor air pollution in shaping such exposures, is a priority issue. Braddock and Clairton, Pennsylvania, industrial communities near Pittsburgh, are home to an active steel mill and coke works, respectively, and the population experiences elevated rates of childhood asthma. Twenty-one homes were selected for 1-week indoor sampling for fine particulate matter (PM2.5) and black carbon (BC) during summer 2011 and winter 2012. Multivariate linear regression models were used to examine contributions from both outdoor concentrations and indoor sources. In the models, an outdoor infiltration component explained 10 to 39% of variability in indoor air pollution for PM2.5, and 33 to 42% for BC. For both PM2.5 models and the summer BC model, smoking was a stronger predictor than outdoor pollution, as greater pollutant concentration increases were identified. For winter BC, the model was explained by outdoor pollution and an open windows modifier. In both seasons, indoor concentrations for both PM2.5 and BC were consistently higher than residence-specific outdoor concentration estimates. Mean indoor PM2.5 was higher, on average, during summer (25.8±22.7 μg/m3) than winter (18.9±13.2 μg/m3). Contrary to the study's hypothesis, outdoor concentrations accounted for only little to moderate variability (10 to 42%) in indoor concentrations; a much greater proportion of PM2.5 was explained by cigarette smoking. Outdoor infiltration was a stronger predictor for BC compared to PM2.5, especially in winter. Our results suggest that, even in industrial communities of high outdoor pollution concentrations, indoor activities--particularly cigarette smoking--may play a larger

  13. Indoor air sampling for fine particulate matter and black carbon in industrial communities in Pittsburgh.

    PubMed

    Tunno, Brett J; Naumoff Shields, Kyra; Cambal, Leah; Tripathy, Sheila; Holguin, Fernando; Lioy, Paul; Clougherty, Jane E

    2015-12-01

    Impacts of industrial emissions on outdoor air pollution in nearby communities are well-documented. Fewer studies, however, have explored impacts on indoor air quality in these communities. Because persons in northern climates spend a majority of their time indoors, understanding indoor exposures, and the role of outdoor air pollution in shaping such exposures, is a priority issue. Braddock and Clairton, Pennsylvania, industrial communities near Pittsburgh, are home to an active steel mill and coke works, respectively, and the population experiences elevated rates of childhood asthma. Twenty-one homes were selected for 1-week indoor sampling for fine particulate matter (PM2.5) and black carbon (BC) during summer 2011 and winter 2012. Multivariate linear regression models were used to examine contributions from both outdoor concentrations and indoor sources. In the models, an outdoor infiltration component explained 10 to 39% of variability in indoor air pollution for PM2.5, and 33 to 42% for BC. For both PM2.5 models and the summer BC model, smoking was a stronger predictor than outdoor pollution, as greater pollutant concentration increases were identified. For winter BC, the model was explained by outdoor pollution and an open windows modifier. In both seasons, indoor concentrations for both PM2.5 and BC were consistently higher than residence-specific outdoor concentration estimates. Mean indoor PM2.5 was higher, on average, during summer (25.8±22.7 μg/m3) than winter (18.9±13.2 μg/m3). Contrary to the study's hypothesis, outdoor concentrations accounted for only little to moderate variability (10 to 42%) in indoor concentrations; a much greater proportion of PM2.5 was explained by cigarette smoking. Outdoor infiltration was a stronger predictor for BC compared to PM2.5, especially in winter. Our results suggest that, even in industrial communities of high outdoor pollution concentrations, indoor activities--particularly cigarette smoking--may play a larger

  14. Synthesis and preliminary biological evaluation of S-11C-methyl-D-cysteine as a new amino acid PET tracer for cancer imaging.

    PubMed

    Huang, Tingting; Tang, Ganghua; Wang, Hongliang; Nie, Dahong; Tang, Xiaolan; Liang, Xiang; Hu, Kongzhen; Yi, Chang; Yao, Baoguo; Tang, Caihua

    2015-04-01

    S-(11)C-methyl-L-cysteine (LMCYS) is an attractive amino acid tracer for clinical tumor positron emission tomography (PET) imaging. D-isomers of some radiolabeled amino acids are potential PET tracers for tumor imaging. In this work, S-(11)C-methyl-D-cysteine (DMCYS), a D-amino acid isomer of S-(11)C-methyl-cysteine for tumor imaging was developed and evaluated. DMCYS was prepared by (11)C-methylation of the precursor D-cysteine, with an uncorrected radiochemical yield over 50 % from (11)CH3I within a total synthesis time from (11)CO2 about 12 min. In vitro competitive inhibition studies showed that DMCYS uptake was primarily transported through the Na(+)-independent system L, and also the Na(+)-dependent system B(0,+) and system ASC, with almost no system A. In vitro incorporation experiments indicated that almost no protein incorporation was found in Hepa 1-6 hepatoma cell lines. Biodistribution studies demonstrated higher uptake of DMCYS in pancreas and liver at 5 min post-injection, relatively lower uptake in brain and muscle, and faster radioactivity clearance from most tissues than those of L-isomer during the entire observation time. In the PET imaging of S180 fibrosarcoma-bearing mice and turpentine-induced inflammatory model mice, 2-(18)F-fluoro-2-deoxy-D-glucose (FDG) exhibited significantly high accumulation in both tumor and inflammatory lesion with low tumor-to-inflammation ratio of 1.40, and LMCYS showed low tumor-to-inflammation ratio of 1.64 at 60 min post-injection. By contrast, DMCYS showed moderate accumulation in tumor and very low uptake in inflammatory lesion, leading to relatively higher tumor-to-inflammation ratio of 2.25 than (11)C-methyl-L-methionine (MET) (1.85) at 60 min post-injection. Also, PET images of orthotopic transplanted glioma models demonstrated that low uptake of DMCYS in normal brain tissue and high uptake in brain glioma tissue were observed. The results suggest that DMCYS is a little better than the corresponding L

  15. Simplified Space Conditioning in Low-Load Homes: Results from Pittsburgh, Pennsylvania, New Construction Unoccupied Test House

    SciTech Connect

    Poerschke, A.; Stecher, D.

    2014-06-01

    Field testing was performed in a new construction unoccupied test house in Pittsburgh, Pennsylvania. Four air-based heating, ventilation, and air conditioning distribution systems--a typical airflow ducted system to the bedrooms, a low airflow ducted system to the bedrooms, a system with transfer fans to the bedrooms, and a system with no ductwork to the bedrooms--were evaluated during heating, cooling, and midseason conditions. The relative ability of each system was assessed with respect to relevant Air Conditioning Contractors of America and ASHRAE standards for house temperature uniformity and stability, respectively.

  16. Simplified Space Conditioning in Low-Load Homes: Results from Pittsburgh, Pennsylvania, New Construction Unoccupied Test House

    SciTech Connect

    Poerschke, Andrew; Stecher, Dave

    2014-06-01

    Field testing was performed in a new construction unoccupied test house in Pittsburgh, PA. Four air-based heating, ventilation, and air conditioning distribution systems—a typical airflow ducted system to the bedrooms, a low airflow ducted system to the bedrooms, a system with transfer fans to the bedrooms, and a system with no ductwork to the bedrooms—were evaluated during heating, cooling, and midseason conditions. The relative ability of each system was assessed with respect to relevant Air Conditioning Contractors of America and ASHRAE standards for house temperature uniformity and stability, respectively.

  17. N-(3,4-Dimethylisoxazol-5-yl)piperazine-4-[4-(2-fluoro-4-[(11)C]methylphenyl)thiazol-2-yl]-1-carboxamide: A promising positron emission tomography ligand for fatty acid amide hydrolase.

    PubMed

    Shimoda, Yoko; Fujinaga, Masayuki; Hatori, Akiko; Yui, Joji; Zhang, Yiding; Nengaki, Nobuki; Kurihara, Yusuke; Yamasaki, Tomoteru; Xie, Lin; Kumata, Katsushi; Ishii, Hideki; Zhang, Ming-Rong

    2016-02-15

    To visualize fatty acid amide hydrolase (FAAH) in brain in vivo, we developed a novel positron emission tomography (PET) ligand N-(3,4-dimethylisoxazol-5-yl)piperazine-4-[4-(2-fluoro-4-[(11)C]methylphenyl)thiazol-2-yl]-1-carboxamide ([(11)C]DFMC, [(11)C]1). DFMC (1) was shown to have high binding affinity (IC50: 6.1nM) for FAAH. [(11)C]1 was synthesized by C-(11)C coupling reaction of arylboronic ester 2 with [(11)C]methyl iodide in the presence of Pd catalyst. At the end of synthesis, [(11)C]1 was obtained with a radiochemical yield of 20±10% (based on [(11)C]CO2, decay-corrected, n=5) and specific activity of 48-166GBq/μmol. After the injection of [(11)C]1 in mice, high uptake of radioactivity (>2% ID/g) was distributed in the lung, liver, kidney, and brain, organs with high FAAH expression. PET images of rat brains for [(11)C]1 revealed high uptakes in the cerebellar nucleus (SUV=2.4) and frontal cortex (SUV=2.0), two known brain regions with high FAAH expression. Pretreatment with the FAAH-selective inhibitor URB597 reduced the brain uptake. Higher than 90% of the total radioactivity in the rat brain was irreversible at 30min after the radioligand injection. The present results indicate that [(11)C]1 is a promising PET ligand for imaging of FAAH in living brain. PMID:26740152

  18. Experimental particle physics at the University of Pittsburgh. Progress report, 1 November 1993--31 October 1994

    SciTech Connect

    Engels, E. Jr.; Shepard, P.F.; Thompson, J.A.

    1994-05-01

    Task A involves the study of kaon decays. The overall physics focus of the current work is rare and semi-rare decays of the {phi} and the short-lived kaon, with an emphasis on those aspects needed in preparation for the proposed {Phi}-factory measurements of CPT violation. Another aspect of the rare kaon decay work is E865 at BNL, a search for K{sup +} yields {pi}{sup +}{mu}{sup +}e{sup {minus}}, a lepton number violating process. Pittsburgh`s E865 responsibilities are the design and construction of the Cerenkov counters. The major goals of task B are as follows: (1) the analysis of the E706 (direct photon production) data taken during the 1987--1988 and 1990--1991 target runs at Fermilab and (2) the continuation of work within SVXII group of the CDF collaboration. The CDF program involves a dedicated effort towards the design of the silicon vertex detector upgrade, SVXII.

  19. Improvements in the life expectancy of type 1 diabetes: the Pittsburgh Epidemiology of Diabetes Complications study cohort.

    PubMed

    Miller, Rachel G; Secrest, Aaron M; Sharma, Ravi K; Songer, Thomas J; Orchard, Trevor J

    2012-11-01

    Survival in type 1 diabetes has improved, but the impact on life expectancy in the U.S. type 1 diabetes population is not well established. Our objective was to estimate the life expectancy of the Pittsburgh Epidemiology of Diabetes Complications (EDC) study cohort and quantify improvements by comparing two subcohorts based on year of diabetes diagnosis (1950-1964 [n = 390] vs. 1965-1980 [n = 543]). The EDC study is a prospective cohort study of 933 participants with childhood-onset (aged <17 years) type 1 diabetes diagnosed at Children's Hospital of Pittsburgh from 1950 to 1980. Mortality ascertainment was censored 31 December 2009. Abridged cohort life tables were constructed to calculate life expectancy. Death occurred in 237 (60.8%) of the 1950-1964 subcohort compared with 88 (16.2%) of the 1965-1980 subcohort. The life expectancy at birth for those diagnosed 1965-1980 was ~15 years greater than participants diagnosed 1950-1964 (68.8 [95% CI 64.7-72.8] vs. 53.4 [50.8-56.0] years, respectively) (P < 0.0001); this difference persisted regardless of sex or pubertal status at diagnosis. This improvement in life expectancy emphasizes the need for insurance companies to update analysis of the life expectancy of those with childhood-onset type 1 diabetes because weighting of insurance premiums is based on outdated estimates.

  20. Legionellaceae in the hospital water-supply. Epidemiological link with disease and evaluation of a method for control of nosocomial legionnaires' disease and Pittsburgh pneumonia.

    PubMed

    Best, M; Yu, V L; Stout, J; Goetz, A; Muder, R R; Taylor, F

    1983-08-01

    An epidemiological link was found between contamination of a hospital water-supply by Legionella pneumophila and by Pittsburgh pneumonia agent (PPA) and subsequent cases of nosocomial legionnaires' disease and Pittsburgh pneumonia. The extent of L pneumophila isolation from the water-supply paralleled the occurrence of disease. Whenever L pneumophila was isolated from more than 30% of ten selected water sites, nosocomial legionellosis occurred. The temperature of the hot water tanks was raised to 60-77 degrees C for 72 h, and water outlets were flushed for 30 min with hot water. A decline in numbers of L pneumophila and PPA in the water-supply was followed by a fall in the incidence of legionnaires' disease and Pittsburgh pneumonia. In addition, intermittent raising of the temperature in the hot water system decreased both the number of months in which disease occurred and the proportion of nosocomial pneumonias caused by these organisms. PMID:6135832

  1. Comparison of the Pharmacokinetics of Different Analogs of 11C-Labeled TZTP for Imaging Muscarinic M2 Receptors with PET

    PubMed Central

    Reid, Alicia E.; Ding, Yu-Shin; Eckelman, William C.; Logan, Jean; Alexoff, David; Shea, Colleen; Xu, Youwen; Fowler, Joanna S.

    2011-01-01

    Introduction The only radiotracer available for the selective imaging of muscarinic M2 receptors in vivo is 3-(3-{3-[18F]fluoropropyl)thio}-1,2,5-thiadiazol-4-yl)-1,2,5,6-tetrahydro-1-methylpyridine) ([18F]FP-TZTP). We have prepared and labeled FP-TZTP and two other TZTP derivatives with 11C at the methylpyridine moiety to explore the potential of using C-11 labeled FP-TZTP for PET imaging of M2 receptors and to compare the effect of small structural changes on tracer pharmacokinetics (PK) in brain and peripheral organs. Methods 11C radiolabeled [FP-TZTP, 3], 3-(3-propyl)-TZTP [P-TZTP, 6], 3,3,3-(3-(3-trifluoropropyl)-TZTP [F3P-TZTP, 10] were prepared and log D, plasma protein binding (PPB), affinity constants, time-activity curves (TACs), area under the curve (AUC) for arterial plasma, distribution volumes (DV) and pharmacological blockade in baboons were compared. Results Values for log D, PPB and affinity constants were similar for 3, 6 and 10. The fraction of parent radiotracer in the plasma was higher and the AUC lower for 10 than for 3 and 6. TACs for brain regions were similar for 3 and 6, which showed PK similar to the F-18 tracer, while 10 showed slower uptake and little clearance over 90 min. DV’s for 3 and 6 were similar to the F-18 tracer but higher for 10. Uptake of the three tracers was significantly reduced by coinjection of unlabeled 3 and 6. Conclusion Small structural variations on the TZTP structure greatly altered the PK in brain and behavior in blood with little change in the log D, PPB or affinity. The study suggests that 11C radiolabeled 3 will be a suitable alternative to [18F]FP-TZTP for translational studies in humans. PMID:18355684

  2. Microglial activity in people at ultra high risk of psychosis and in schizophrenia; an [11C]PBR28 PET brain imaging study

    PubMed Central

    Veronese, Mattia; Rizzo, Gaia; Bertoldo, Alessandra; Owen, David R; Bloomfield, Michael AP; Bonoldi, Ilaria; Kalk, Nicola; Turkheimer, Federico; McGuire, Philip

    2016-01-01

    Objective To determine whether microglial activity, measured using translocator-protein positron emission tomographic imaging (PET), is increased in unmedicated subjects presenting with sub-clinical symptoms indicating they are at ultra high risk of psychosis, and to determine if it is elevated in schizophrenia after controlling for a translocator specific genetic polymorphism. Method Here we use the second generation radioligand [11C]PBR28 and PET to image microglial activity in the brains of subjects at ultra high risk for psychosis. Subjects were recruited from early intervention centres. We also imaged a cohort of patients with schizophrenia and healthy controls for comparison, in total 56 subjects completed the study. At screening, subjects were genotyped to account for the rs6971 polymorphism in the gene encoding the 18Kd Translocator Protein. The main outcome measure was total grey matter [11C]PBR28 binding ratio, representing microglial activity. Results [11C]PBR28 binding ratio in grey matter was elevated in ultra high risk subjects, compared to matched controls, (p=0.004, F= 10.3, Cohen’s d >1.2), and was positively correlated with symptom severity (r= 0.730, p<0.01). Patients with schizophrenia also demonstrated elevated microglial activity with respect to matched controls (p<0.001, F= 20.8, Cohen’s d >1.7). Conclusion Microglial activity is elevated in schizophrenia and in subjects with sub-clinical symptoms who are at ultra high risk of psychosis, and is related to at risk symptom severity. This indicates that neuroinflammation is linked to the risk of psychosis and related disorders, and the expression of sub-clinical symptoms. Follow up of ultra high risk subjects will determine whether this is specific to the later development of schizophrenia or risk factors in general. PMID:26472628

  3. Intravenous ethanol increases dopamine release in the ventral striatum in humans: PET study using bolus-plus-infusion administration of [11C]raclopride

    PubMed Central

    Aalto, Sargo; Ingman, Kimmo; Alakurtti, Kati; Kaasinen, Valtteri; Virkkala, Jussi; Någren, Kjell; Rinne, Juha O; Scheinin, Harry

    2015-01-01

    Ethanol increases the interstitial dopamine (DA) concentration in the nucleus accumbens (NAcc) of experimental animals, but positron emission tomography (PET) studies using the single-bolus protocol of the [11C]-raclopride competition paradigm have yielded conflicting results in humans. To resolve disparate previous findings, we utilized the bolus-plus-infusion (B/I) method, allowing both baseline and intervention quantification of [11C]raclopride binding during a single 105-minute PET scan, to investigate possible ethanol-induced DA release in nine healthy male subjects. A 25-minute intravenous ethanol (7.6%) infusion, resulting in a 1.3 g/L mean blood ethanol concentration, was administered using masked timing during the PET scan. Automated region-of-interest analysis testing the difference between baseline (40–50 minutes) and intervention (60–85 minutes) revealed an average 12.6% decrease in [11C]raclopride binding in the ventral striatum (VST, P=0.003) including the NAcc. In addition, a shorter time interval from the start of ethanol infusion to the first subjective effect was associated with a greater binding potential decrease bilaterally in the VST (r=0.92, P=0.004), and the feeling of pleasure was associated with a decrease in binding potential values in both the caudate nucleus (r=−0.87, P=0.003) and putamen (r=−0.74; P=0.02). These results confirm that ethanol induces rapid DA release in the limbic striatum, which can be reliably estimated using the B/I method in one imaging session. PMID:25492110

  4. CD11c+ dendritic cells and B cells contribute to the tumoricidal activity of anti-DR5 antibody therapy in established tumors.

    PubMed

    Haynes, Nicole M; Hawkins, Edwin D; Li, Ming; McLaughlin, Nicole M; Hämmerling, Günter J; Schwendener, Reto; Winoto, Astar; Wensky, Allen; Yagita, Hideo; Takeda, Kazuyoshi; Kershaw, Michael H; Darcy, Phillip K; Smyth, Mark J

    2010-07-01

    The selective targeting of the tumor-associated death-inducing receptors DR4 and DR5 with agonistic mAbs has demonstrated preclinical and clinical antitumor activity. However, the cellular and molecular mechanisms contributing to this efficacy remain poorly understood. In this study, using the first described C57BL/6 (B6) TRAIL-sensitive experimental tumor models, we have characterized the innate and adaptive immune components involved in the primary rejection phase of an anti-mouse DR5 (mDR5) mAb, MD5-1 in established MC38 colon adenocarcinomas. FcR mediated cross-linking of MD5-1 significantly inhibited the growth of MC38 colon adenocarcinomas through the induction of TRAIL-R-dependent tumor cell apoptosis. The loss of host DR5, TRAIL, perforin, FasL, or TNF did not compromise anti-DR5 therapy in vivo. By contrast, anti-DR5 therapy was completely abrogated in mice deficient of B cells or CD11c(+) dendritic cells (DCs), providing the first direct evidence that these cells play a critical role. Importantly, the requirement for an intact B cell compartment for optimal anti-DR5 antitumor efficacy was also observed in established AT-3 mammary tumors. Interestingly, MD5-1-mediated apoptosis as measured by early TUNEL activity was completely lost in B cell-deficient microMT mice, but intact in mice deficient in CD11c(+) DCs. Overall, these data show that Ab-mediated targeting of DR5 triggers tumor cell apoptosis in established tumors in a B cell-dependent manner and that CD11c(+) DCs make a critical downstream contribution to anti-DR5 antitumor activity.

  5. Ictal lack of binding to brain parenchyma suggests integrity of the blood–brain barrier for 11C-dihydroergotamine during glyceryl trinitrate-induced migraine

    PubMed Central

    Schankin, Christoph J.; Maniyar, Farooq H.; Seo, Youngho; Kori, Shashidar; Eller, Michael; Chou, Denise E.; Blecha, Joseph; Murphy, Stephanie T.; Hawkins, Randall A.; Sprenger, Till; VanBrocklin, Henry F.

    2016-01-01

    See Dreier (doi: 10.1093/aww112) for a scientific commentary on this article. For many decades a breakdown of the blood–brain barrier has been postulated to occur in migraine. Hypothetically this would facilitate access of medications, such as dihydroergotamine or triptans, to the brain despite physical properties otherwise restricting their entry. We studied the permeability of the blood–brain barrier in six migraineurs and six control subjects at rest and during acute glyceryl trinitrate-induced migraine attacks using positron emission tomography with the novel radioligand 11C-dihydroergotamine, which is chemically identical to pharmacologically active dihydroergotamine. The influx rate constant Ki, average dynamic image and time activity curve were assessed using arterial blood sampling and served as measures for receptor binding and thus blood–brain barrier penetration. At rest, there was binding of 11C-dihydroergotamine in the choroid plexus, pituitary gland, and venous sinuses as expected from the pharmacology of dihydroergotamine. However, there was no binding to the brain parenchyma, including the hippocampus, the area with the highest density of the highest-affinity dihydroergotamine receptors, and the raphe nuclei, a postulated brainstem site of action during migraine, suggesting that dihydroergotamine is not able to cross the blood–brain barrier. This binding pattern was identical in migraineurs during glyceryl trinitrate-induced migraine attacks as well as in matched control subjects. We conclude that 11C-dihydroergotamine is unable to cross the blood–brain barrier interictally or ictally demonstrating that the blood–brain barrier remains tight for dihydroergotamine during acute glyceryl trinitrate-induced migraine attacks. PMID:27234268

  6. Dose-dependent, Saturable Occupancy of the Metabotropic Glutamate Subtype 5 Receptor by Fenobam as Measured with [11C]ABP688 PET Imaging

    PubMed Central

    KUWABARA, HIROTO; STANSFIELD, KIRSTIE; VALENTINE, HEATHER; ALEXANDER, MOHAB; KUMAR, ANIL; HILTON, JOHN; DANNALS, ROBERT F.; WONG, DEAN F.; GASPARINI, FABRIZIO

    2014-01-01

    Fenobam is a negative allosteric modulator of the metabotropic glutamate receptor subtype 5 (mGluR5) with inverse agonist activity and is expected to contribute to the treatment of neuropsychiatric disorders involving dysfunction of mGluR5 including Fragile × syndrome. This study examined whether [11C]ABP688, an antagonist PET radioligand, competes with fenobam for the same binding site in the non-human primate brain and would allow examination of occupancy-plasma concentration relationships in the evaluation of the drug for target disorders in the human brain. Four paired PET studies with [11C]ABP688 were performed in baboons at a baseline condition and after intravenous treatment with fenobam at different dose levels (0.3 - 1.33 mg/kg). Total distribution volume (VT) and binding potential (BPND) using the cerebellum as a reference region were obtained by the plasma reference graphical method. Then it was examined whether occupancy follows a dose-dependent, saturating pattern that was predicted by a modified first-order Hill equation in individual regions. Baseline regional VT and BPND values agreed with previously published data. Occupancy showed dose-dependent and saturating patterns in individual regions, reaching >90% occupancy at 1.33 mg/kg dose of fenobam in the majority of regions. To our knowledge, this is the first use of PET to characterize the mGluR5 therapeutic drug fenobam. This study demonstrates a proof of principle for determining the in vivo occupancy of fenobam in primates. The results indicate that [11C]ABP688 and PET may be useful for examination of occupancy of mGluR5 by fenobam, which should prove to be useful for designing future studies and treatment of human disease states. PMID:25098663

  7. Arabidopsis PEROXIN11c-e, FISSION1b, and DYNAMIN-RELATED PROTEIN3A Cooperate in Cell Cycle–Associated Replication of Peroxisomes[W

    PubMed Central

    Lingard, Matthew J.; Gidda, Satinder K.; Bingham, Scott; Rothstein, Steven J.; Mullen, Robert T.; Trelease, Richard N.

    2008-01-01

    Although participation of PEROXIN11 (PEX11), FISSION1 (FISl), and DYNAMIN-RELATED PROTEIN (DRP) has been well established during induced peroxisome proliferation in response to external stimuli, their roles in cell cycle–associated constitutive replication/duplication have not been fully explored. Herein, bimolecular fluorescence complementation experiments with Arabidopsis thaliana suspension cells revealed homooligomerization of all five PEX11 isoforms (PEX11a-e) and heterooligomerizations of all five PEX11 isoforms with FIS1b, but not FIS1a nor DRP3A. Intracellular protein targeting experiments demonstrated that FIS1b, but not FIS1a nor DRP3A, targeted to peroxisomes only when coexpressed with PEX11d or PEX11e. Simultaneous silencing of PEX11c-e or individual silencing of DRP3A, but not FIS1a nor FIS1b, resulted in ∼40% reductions in peroxisome number. During G2 in synchronized cell cultures, peroxisomes sequentially enlarged, elongated, and then doubled in number, which correlated with peaks in PEX11, FIS1, and DRP3A expression. Overall, these data support a model for the replication of preexisting peroxisomes wherein PEX11c, PEX11d, and PEX11e act cooperatively during G2 to promote peroxisome elongation and recruitment of FIS1b to the peroxisome membrane, where DRP3A stimulates fission of elongated peroxisomes into daughter peroxisomes, which are then distributed between daughter cells. PMID:18539750

  8. Arabidopsis PEROXIN11c-e, FISSION1b, and DYNAMIN-RELATED PROTEIN3A cooperate in cell cycle-associated replication of peroxisomes.

    PubMed

    Lingard, Matthew J; Gidda, Satinder K; Bingham, Scott; Rothstein, Steven J; Mullen, Robert T; Trelease, Richard N

    2008-06-01

    Although participation of PEROXIN11 (PEX11), FISSION1 (FISl), and DYNAMIN-RELATED PROTEIN (DRP) has been well established during induced peroxisome proliferation in response to external stimuli, their roles in cell cycle-associated constitutive replication/duplication have not been fully explored. Herein, bimolecular fluorescence complementation experiments with Arabidopsis thaliana suspension cells revealed homooligomerization of all five PEX11 isoforms (PEX11a-e) and heterooligomerizations of all five PEX11 isoforms with FIS1b, but not FIS1a nor DRP3A. Intracellular protein targeting experiments demonstrated that FIS1b, but not FIS1a nor DRP3A, targeted to peroxisomes only when coexpressed with PEX11d or PEX11e. Simultaneous silencing of PEX11c-e or individual silencing of DRP3A, but not FIS1a nor FIS1b, resulted in approximately 40% reductions in peroxisome number. During G2 in synchronized cell cultures, peroxisomes sequentially enlarged, elongated, and then doubled in number, which correlated with peaks in PEX11, FIS1, and DRP3A expression. Overall, these data support a model for the replication of preexisting peroxisomes wherein PEX11c, PEX11d, and PEX11e act cooperatively during G2 to promote peroxisome elongation and recruitment of FIS1b to the peroxisome membrane, where DRP3A stimulates fission of elongated peroxisomes into daughter peroxisomes, which are then distributed between daughter cells.

  9. A PRELIMINARY STUDY OF DOPAMINE D2/3 RECEPTOR AVAILABILITY AND SOCIAL STATUS IN HEALTHY AND COCAINE DEPENDENT HUMANS IMAGED WITH [11C](+)PHNO

    PubMed Central

    Matuskey, David; Gaiser, Edward C.; Gallezot, Jean-Dominique; Angarita, Gustavo A.; Pittman, Brian; Nabulsi, Nabeel; Ropchan, Jim; MaCleod, Paige; Cosgrove, Kelly P.; Ding, Yu-Shin; Potenza, Marc N.; Carson, Richard E.; Malison, Robert T.

    2015-01-01

    Background Previous work in healthy non-human primates and humans has shown that social status correlates positively with dopamine 2/3 receptor (D2/3 R) availability imaged with antagonist radioligands and positron emission tomography (PET). Further work in non-human primates suggests that this relationship is disrupted by chronic cocaine administration. This exploratory study examined the relationship between social status and D2/3R availability in healthy (HH) and cocaine dependent (CD) humans using the D3-preferring, agonist radioligand, [11C](+)PHNO. Methods Sixteen HH and sixteen CD individuals completed the Barratt Simplified Measure of Social Status (BSMSS) and underwent [11C](+)PHNO scanning to measure regional brain D2/3R binding potentials (BPND). Correlations between BPND and BSMSS scores were then assessed within each group. Results Within HH and CD groups, inverse associations between BSMSS score and BPND were observed in the substantia nigra/ventral tegmental area (SN/VTA) and the ventral striatum, and for the CD group alone, the amygdala. After adjusting for body mass index and age, negative correlations remained significant in the SN/VTA for HH and in the amygdala for CD subjects. Conclusion These preliminary data utilizing a dopamine agonist tracer demonstrate, for the first time, an inverse association between social status and D2/3R availability in the D3R rich extrastriatal regions of HH and CD humans. PMID:26164205

  10. [(11)C]-DASB microPET imaging in the aged rat: frontal and meso-thalamic increases in serotonin transporter binding.

    PubMed

    Hoekzema, Elseline; Rojas, Santiago; Herance, Raúl; Pareto, Deborah; Abad, Sergio; Jiménez, Xavier; Figueiras, Francisca P; Popota, Foteini; Ruiz, Alba; Flotats, Núria; Fernández, Francisco J; Rocha, Milagros; Rovira, Mariana; Víctor, Víctor M; Gispert, Juan D

    2011-12-01

    Whereas molecular imaging studies in the aging human brain have predominantly demonstrated reductions in serotonin transporter (5-HTT) availability, the majority of the rodent studies, using autoradiographic methods, report increases in neural 5-HTT levels with age. To our knowledge, however, no previous rodent studies have assessed this topic in vivo, and therefore it remains unclear whether this discrepancy arises from methodological or inter-species differences. We performed an [(11)C]-DASB microPET study to evaluate the effects of aging on 5-HTT availability in the rat brain. To generate binding potential estimates, quantitative tracer kinetic modeling was applied using the simplified reference tissue model. A global increase in whole-brain [(11)C]-DASB binding potential was observed in the aged rats in comparison to the control group. More specifically, regional analyses revealed a highly significant increase in 5-HTT binding in the medial frontal cortex, and more modest increments in the midbrain/thalamus. Our results suggest that the frontal cortex represents a site of robust age-related alterations in the rat serotonergic system, and stress the need for further research assessing this topic in the human frontal cortex. Moreover, these findings suggest that the reported discrepancies between rodent and human data may reflect a divergence in the aging processes affecting human and rat serotonergic terminals.

  11. Use of Electronic Journals by Library and Information Science Faculty Members in Performing Various Academic Tasks: A Field Study Performed at the School of Information Sciences at the University of Pittsburgh (Modified Version)

    ERIC Educational Resources Information Center

    Abouserie, Hossam Eldin Mohamed Refaat

    2006-01-01

    The purpose of this study was to explore and investigate the ways faculty at The School of Information Science at the University of Pittsburgh use electronic journals to obtain information to support their academic tasks, teaching, research and services. Library and Information Sciences faculty at the University of Pittsburgh were chosen as the…

  12. Time- and size-resolved chemical composition of submicron particles in Pittsburgh: Implications for aerosol sources and processes

    NASA Astrophysics Data System (ADS)

    Zhang, Qi; Canagaratna, Manjula R.; Jayne, John T.; Worsnop, Douglas R.; Jimenez, Jose-Luis

    2005-04-01

    An Aerodyne aerosol mass spectrometer (AMS) was deployed at the Pittsburgh Environmental Protection Agency Supersite from 7 to 22 September 2002 as part of the Pittsburgh Air Quality Study (PAQS). The main objectives of this deployment were to characterize the concentrations, size distributions, and temporal variations of nonrefractory (NR) chemical species in submicron particles (approximately PM1) and to further develop and evaluate the AMS. Reasonably good agreement was observed on particle concentrations, composition, and size distributions between the AMS data and measurements from collocated instruments (given the difference between the PM1 and PM2.5 size cuts), including TEOM, semicontinuous sulfate, 2-hour- and 24-hour-averaged organic carbon, SMPS, 4-hour-averaged ammonium, and micro-orifice uniform deposit impactor. Total NR-PM1 mass concentration in Pittsburgh accumulates over periods of several days punctuated with rapid cleaning due to rain or air mass changes. Sulfate and organics are the major NR-PM1 components while the concentrations of nitrate and chloride are generally low. Significant amounts of ammonium, which most of the time are consistent with sulfate present as ammonium sulfate, are also present in particles. However, there are periods when the aerosols are relatively acidic and more than 50% of sulfate is estimated to be in the form of ammonium bisulfate. No major enhancement of the organic concentration is observed during these acidic periods, which suggests that acid-catalyzed SOA formation was not an important process during this study. Size distributions of particulate sulfate, ammonium, organics, and nitrate vary on timescales of hours to days, showing unimodal, bimodal and even trimodal characteristics. The accumulation mode (peaking around 350-600 nm in vacuum aerodynamic diameter for the mass distributions) and the ultrafine mode (<100 nm) are observed most frequently. The accumulation mode is dominated by sulfate that appears to

  13. 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

  14. Design and implementation of a library-based information service in molecular biology and genetics at the University of Pittsburgh

    PubMed Central

    Chattopadhyay, Ansuman; Tannery, Nancy Hrinya; Silverman, Deborah A. L.; Bergen, Phillip; Epstein, Barbara A.

    2006-01-01

    Setting: In summer 2002, the Health Sciences Library System (HSLS) at the University of Pittsburgh initiated an information service in molecular biology and genetics to assist researchers with identifying and utilizing bioinformatics tools. Program Components: This novel information service comprises hands-on training workshops and consultation on the use of bioinformatics tools. The HSLS also provides an electronic portal and networked access to public and commercial molecular biology databases and software packages. Evaluation Mechanisms: Researcher feedback gathered during the first three years of workshops and individual consultation indicate that the information service is meeting user needs. Next Steps/Future Directions: The service's workshop offerings will expand to include emerging bioinformatics topics. A frequently asked questions database is also being developed to reuse advice on complex bioinformatics questions. PMID:16888665

  15. How Far Do You Go and How Much Do You Show: Pittsburgh Television News Media and the R. Budd Dwyer Suicide.

    ERIC Educational Resources Information Center

    Matviko, John

    Only one Pittsburgh television station (WPXI) chose to show the entire event when R. Budd Dwyer, Pennsylvania state treasurer, shot himself at a televised news conference. Within 12 hours, the focus of the story had shifted from Dwyer himself to the media's coverage. Was WPXI wrong to show the suicide? Were the other stations wrong to curtail the…

  16. Education for Highway Engineering and Highway Transport. Report of the Regional Conference Held at University of Pittsburgh, Friday, November 26, 1920. Bulletin, 1921, No. 47

    ERIC Educational Resources Information Center

    Johnson, Pyke; John, Walton C.

    1921-01-01

    This bulletin provides information on the proceedings of the regional conference on education for highway engineering and highway transport that was held at the University of Pittsburgh on November 26, 1920, under the direction of the highway and highway transport education committee. The purpose of this report is: (1) To stimulate greater…

  17. EVALUATION OF THE CMB AND PMF MODELS USING ORGANIC MOLECULAR MARKERS IN FINE PARTICULATE MATTER COLLECTED DURING THE PITTSBURGH AIR QUALITY STUDY

    EPA Science Inventory

    This research investigated different strategies for source apportionment of airborne fine particulate matter (PM2.5) collected as part of the Pittsburgh Air Quality Study. Two source receptor models were used, the EPA Chemical Mass Balance 8.2 (CMB) and EPA Positive Matrix Facto...

  18. Resonances in (11)C observed in the (4)He((7)Be, alpha)(7)Be and (4)He((7)Be, p)(10)B reactions

    SciTech Connect

    Freer, M.; Ashwood, N. I.; Curtis, N.; Malcolm, J.; Munoz-Britton, T.; Price, D.; Wheldon, C.; Achouri, N. L.; Demaret, P.; Bardayan, Daniel W; Pain, Steven D; Brown, S.; Catford, W.; Harlin, Christopher W; Thomas, J. S.; Wilson, G.; Chipps, K.; Milin, M.; Raabe, R.; Soic, N.

    2012-01-01

    Measurements of the {sup 4}He({sup 7}Be,{alpha}){sup 7}Be and {sup 4}He({sup 7}Be,p){sup 10}B reactions were performed using {sup 7}Be beam energies of 7.1 and 23 MeV and a helium-4 target, employing the thick target technique. Resonances were observed between E{sub x}({sup 11}C) = 8.6 to 13.8 MeV. An R-matrix analysis was performed to characterize the spins and partial widths. This analysis showed that the observed sequence of states was consistent with that found for {sup 7}Li + {alpha} resonant scattering populating resonances in {sup 11}B. A comparison of the proposed partial widths for decay with the Wigner limit indicates that several of the states are associated with cluster-like structures.

  19. Synthesis of (R)-(-)- and (S)-(+)-4-fluorodeprenyl and (R)-(-)- and (S)-(+)-(N- sup 11 C-methyl)-4-fluorodeprenyl and positron emission tomography studies in baboon brain

    SciTech Connect

    Plenevaux, A.; Dewey, S.L.; Fowler, J.S.; Guillaume, M.; Wolf, A.P. )

    1990-07-01

    (R)-(-)- and (S)-(+)-alpha-methyl-beta-4-(fluorophenyl)-N-methyl-N- propynylethylamine (R)-(-)- and (S)-(+)-4-fluorodeprenyl were synthesized via the reaction of 4-fluorobenzaldehyde with nitroethane followed by reduction with lithium aluminum hydride to produce racemic 4-fluoroamphetamine, which was resolved by recrystallization with L- or D-N-acetylleucine to yield (R)-(-)-4-fluoroamphetamine or (S)-(+)-4-fluoroamphetamine in greater than 96% enantiomeric excesses and in yields of 42 and 39%, respectively. Alkylation with propargyl bromide gave (R)-(-)- or (S)-(+)-4-fluoronordeprenyl which was reductively methylated (Borch conditions) to produce (R)-(-)- or (S)-(+)-4-fluorodeprenyl. Alkylation of (R)-(-)- or (S)-(+)-4-fluoronordeprenyl with carbon-11 labeled methyl iodide gave (R)-(-)- or (S)-(+)-(N-11C-methyl)-4-fluorodeprenyl in a radiochemical yield of 30-40%. Comparative PET studies of the two labeled enantiomers in baboons showed a significantly lower retention of radioactivity in the striatum for the (S)-(+) enantiomer relative to the (R)-(-) enantiomer.

  20. Synthesis of ({sup 11}C) RO 19 6327, a highly selective and reversible monoamine oxidase B inhibitor potentially useful for treatment of Parkinson`s disease

    SciTech Connect

    Ding, Y.S.; Rehder, K.; Vassello, M.

    1994-05-01

    The potential neuroprotective effect of monoamine oxidase B (MAO B) inhibitors has stimulated intense interest in characterizing their modes of action and in developing new MAO B inhibitor drugs with different properties for clinical investigation in Parkinson`s disease and other enurodegenerative diseases. One of these drugs is Ro 19 6327 (N-(2-aminoethyl)-5-chloro-2-pyridine carboxamide {center_dot}HCl). Ro 19 6327 differs from the suicide inhibitor L-deprenyl in that it is more specific, greater than twenty times as potent in inhibiting MAO B, has no amphetamine metabolites, and is reversible. The recovery of MAO B activity 36 hours after Ro19 6327 treatment discontinuation is relevant in clinical studies since treatment can be withdrawn and changed without the complication of long term effects, as is seen with L-deprenyl. We report here a new synthetic approach to the precursor for Ro 19 6327 suitable for subsequent C-11 labeling for PET studies. Homolytic amidation of 3-chloropyridine afforded 5-chlor-2-pyridinecarboxamide which upon treatment with formaldehyde yielded 5-chlor-N-(hydroxymethyl)-2-pyridinecarboxamide. Conversion to the corresponding acetate afforded a substrate for the displacement reaction with ({sup 11}C) cyanide. Finding a highly selective reducing reagent for the following reduction step was crucial due t;o the presence of four reducible functional groups within the molecule, namely chlorine, pyridine ring, amide, and nitrile. Sodium borohydride in the presence of aluminum chloride was by far the most effective reagent. The final product was then purified by HPLC. The pharmacokinetics, regional distribution and metabolism of ({sup 11}C)Ro 19 6317 are currently under investigation with PET.

  1. In Vivo Evaluation of Blood Based and Reference Tissue Based PET Quantifications of [11C]DASB in the Canine Brain

    PubMed Central

    Polis, Ingeborgh; Neyt, Sara; Kersemans, Ken; Dobbeleir, Andre; Saunders, Jimmy; Goethals, Ingeborg; Peremans, Kathelijne; De Vos, Filip

    2016-01-01

    This first-in-dog study evaluates the use of the PET-radioligand [11C]DASB to image the density and availability of the serotonin transporter (SERT) in the canine brain. Imaging the serotonergic system could improve diagnosis and therapy of multiple canine behavioural disorders. Furthermore, as many similarities are reported between several human neuropsychiatric conditions and naturally occurring canine behavioural disorders, making this tracer available for use in dogs also provide researchers an interesting non-primate animal model to investigate human disorders. Five adult beagles underwent a 90 minutes dynamic PET scan and arterial whole blood was sampled throughout the scan. For each ROI, the distribution volume (VT), obtained via the one- and two- tissue compartment model (1-TC, 2-TC) and the Logan Plot, was calculated and the goodness-of-fit was evaluated by the Akaike Information Criterion (AIC). For the preferred compartmental model BPND values were estimated and compared with those derived by four reference tissue models: 4-parameter RTM, SRTM2, MRTM2 and the Logan reference tissue model. The 2-TC model indicated in 61% of the ROIs a better fit compared to the 1-TC model. The Logan plot produced almost identical VT values and can be used as an alternative. Compared with the 2-TC model, all investigated reference tissue models showed high correlations but small underestimations of the BPND-parameter. The highest correlation was achieved with the Logan reference tissue model (Y = 0.9266 x + 0.0257; R2 = 0.9722). Therefore, this model can be put forward as a non-invasive standard model for future PET-experiments with [11C]DASB in dogs. PMID:26859850

  2. (R)-[11C]PK11195 brain uptake as a biomarker of inflammation and antiepileptic drug resistance: evaluation in a rat epilepsy model.

    PubMed

    Bogdanović, Renée Marie; Syvänen, Stina; Michler, Christina; Russmann, Vera; Eriksson, Jonas; Windhorst, Albert D; Lammertsma, Adriaan A; de Lange, Elisabeth C; Voskuyl, Rob A; Potschka, Heidrun

    2014-10-01

    Neuroinflammation has been suggested as a key determinant of the intrinsic severity of epilepsy. Glial cell activation and associated inflammatory signaling can influence seizure thresholds as well as the pharmacodynamics and pharmacokinetics of antiepileptic drugs. Based on these data, we hypothesized that molecular imaging of microglia activation might serve as a tool to predict drug refractoriness of epilepsy. Brain uptake of (R)-[11C]PK11195, a ligand of the translocator protein 18 kDa and molecular marker of microglia activation, was studied in a chronic model of temporal lobe epilepsy in rats with selection of phenobarbital responders and non-responders. In rats with drug-sensitive epilepsy, (R)-[11C]PK11195 brain uptake values were comparable to those in non-epileptic controls. Analysis in non-responders revealed enhanced brain uptake of up to 39% in different brain regions. The difference might be related to the fact that non-responders exhibited higher baseline seizure frequencies than responders indicating a more pronounced intrinsic disease severity. In hippocampal sections, ED1 immunostaining argued against a general difference in microglia activation between both groups. Our data suggest that TSPO PET imaging might serve as a biomarker for drug resistance in temporal lobe epilepsy. However, it needs to be considered that our findings indicate that the TSPO PET data might merely reflect seizure frequency. Future experimental and clinical studies should further evaluate the validity of TSPO PET data to predict the response to phenobarbital and other antiepileptic drugs in longitudinal studies with scanning before drug exposure and with a focus on the early phase following an epileptogenic brain insult.

  3. Risky Decision-Making and Ventral Striatal Dopamine Responses to Amphetamine: A Positron Emission Tomography [11C] Raclopride Study in Healthy Adults

    PubMed Central

    Oswald, Lynn M.; Wand, Gary S.; Wong, Dean F.; Brown, Clayton H.; Kuwabara, Hiroto; Brašić, James R.

    2015-01-01

    Recent functional magnetic resonance imaging (fMRI) studies have provided compelling evidence that corticolimbic brain regions are integrally involved in human decision-making. Although much less is known about molecular mechanisms, there is growing evidence that the mesolimbic dopamine (DA) neurotransmitter system may be an important neural substrate. Thus far, direct examination of DA signaling in human risk-taking has centered onl gambling disorder. Findings from several positron emission tomography (PET) studies suggest that dysfunctions in mesolimbic DA circuits may play an important role in gambling behavior. Nevertheless, interpretation of these findings is currently hampered by a need for better understanding of how individual differences in regional DA function influence normative decision-making in humans. To further our understanding of these processes, we used [11C]raclopride PET to examine associations between ventral striatal (VS) DA responses to amphetamine (AMPH) and risky decision-making in a sample of healthy young adults with no history of psychiatric disorder, Forty-five male and female subjects, ages 18–29 years, completed a computerized version of the IOWA Gambling Task. Participants then underwent two 90-minute PET studies with high specific activity [11C]raclopride. The first scan was preceded by intravenous saline; the second, by intravenous AMPH (0.3 mg/kg). Findings of primary analyses showed that less advantageous decision-making was associated with greater right VS DA release; the relationship did not differ as a function of gender. No associations were observed between risk-taking and left VS DA release or baseline D2/D3 receptor availability in either hemisphere. Overall, the results support notions that variability in striatal DA function may mediate inter-individual differences in risky decision-making in healthy adults, further suggesting that hypersensitive DA circuits may represent a risk pathway in this population. PMID

  4. Washout rate in rat brain irradiated by a 11C beam after acetazolamide loading using a small single-ring OpenPET prototype

    NASA Astrophysics Data System (ADS)

    Hirano, Yoshiyuki; Takuwa, Hiroyuki; Yoshida, Eiji; Nishikido, Fumihiko; Nakajima, Yasunori; Wakizaka, Hidekatsu; Yamaya, Taiga

    2016-03-01

    In dose verification techniques of particle therapies based on in-beam positron emission tomography (PET), the causes of washout of positron emitters by physiological effects should be clarified to correct washout for accurate verification. As well, the quantitative washout rate has a potential usefulness as a diagnostic index which should be explored. Therefore, we measured washout rates of rat brain after vasodilator acetazolamide loading to investigate the possible effects of blood flow on washout. Six rat brains were irradiated by a radioisotope 11C beam and time activity curves on the whole brains were obtained with a small single-ring OpenPET prototype. Then, washout rates were calculated with the Mizuno model, where two washout rates (k 2m and k 2s ) were assumed, and a two-compartment model including efflux from tissue to blood (k 2) and influx (k 3) and efflux (k 4) between the two tissue compartments. Before the irradiations, we used laser-Doppler flowmetry to confirm that acetazolamide increased cerebral blood flow (CBF) of a rat. We compared means of k 2m , k 2s and k 2, k 3 and k 4 without acetazolamide loading (Rest) and with acetazolamide loading (ACZ). For all k values, ACZ values were lower than Rest values. In other words, though CBF increased, washout rates were decreased. This may be attributed to the implanted 11C reacting to form 11CO2. Because acetazolamide increased the concentration of CO2 in brain, suppressed diffusion of 11CO2 and decomposition of 11CO2 into ions were prevented.

  5. In vivo markers of inflammatory response in recent-onset schizophrenia: a combined study using [(11)C]DPA-713 PET and analysis of CSF and plasma.

    PubMed

    Coughlin, J M; Wang, Y; Ambinder, E B; Ward, R E; Minn, I; Vranesic, M; Kim, P K; Ford, C N; Higgs, C; Hayes, L N; Schretlen, D J; Dannals, R F; Kassiou, M; Sawa, A; Pomper, M G

    2016-01-01

    Several lines of evidence suggest aberrant immune response in schizophrenia, including elevated levels of cytokines. These cytokines are thought to be produced by activated microglia, the innate immune cells of the central nervous system. However, increase in translocator protein 18 kDa (TSPO), a marker of activated glia, has not been found in patients with chronic schizophrenia using second-generation radiotracers and positron emission tomography (PET)-based neuroimaging. In this study we focused on patients with recent onset of schizophrenia (within 5 years of diagnosis). Quantified levels of TSPO in the cortical and subcortical brain regions using the PET-based radiotracer [(11)C]DPA-713 were compared between the patients and healthy controls. Markers of inflammation, including interleukin 6 (IL-6), were assessed in the plasma and cerebrospinal fluid (CSF) in these participants. We observed no significant change in the binding of [(11)C]DPA-713 to TSPO in 12 patients with recent onset of schizophrenia compared with 14 controls. Nevertheless, the patients with recent onset of schizophrenia showed a significant increase in IL-6 in both plasma (P<0.001) and CSF (P=0.02). The CSF levels of IL-6 were significantly correlated with the levels of IL-6 in plasma within the total study population (P<0.001) and in patients with recent onset of schizophrenia alone (P=0.03). Our results suggest that increased levels of IL-6 may occur in the absence of changed TSPO PET signal in the brains of medicated patients with recent onset of schizophrenia. Future development of PET-based radiotracers targeting alternative markers of glial activation and immune response may be needed to capture the inflammatory signature present in the brains of patients with early-stage disease. PMID:27070405

  6. Early Ovariectomy Results in Reduced Numbers of CD11c+/CD11b+ Spleen Cells and Impacts Disease Expression in Murine Lupus

    PubMed Central

    Cunningham, Melissa A.; Wirth, Jena R.; Scott, Jennifer L.; Eudaly, Jackie; Collins, Erin L.; Gilkeson, Gary S.

    2016-01-01

    Ninety percent of those diagnosed with systemic lupus erythematosus are female, with peak incidence between the ages of 15 and 45, when women are most hormonally active. Despite significant research effort, the mechanisms underlying this sex bias remain unclear. We previously showed that a functional knockout of estrogen receptor alpha (ERα) resulted in significantly reduced renal disease and increased survival in murine lupus. Dendritic cell (DC) development, which requires both estrogen and ERα, is impacted, as is activation status and cytokine production. Since both estrogen and testosterone levels have immunomodulating effects, we presently studied the phenotype of NZM2410 lupus-prone mice following post- and prepubertal ovariectomy (OVX) ± estradiol (E2) replacement to determine the impact of hormonal status on disease expression and DC development in these mice. We observed a trend toward survival benefit in addition to decreased proteinuria and improved renal histology in the early OVX, but not late OVX- or E2-repleted WT mice. Interestingly, there was also a significant difference in splenic DC subsets by flow cytometry. Spleens from NZM mice OVX’d early had a significant decrease in proinflammatory CD11c+CD11b+ DCs (vs. unmanipulated WTs, late OVX- and E2-repleted mice). These early OVX’d animals also had a significant increase in tolerogenic CD11c+CD8a+ DCs vs. WT. These data join a growing body of evidence that supports a role for hormone modulation of DCs that likely impacts the penetrance and severity of autoimmune diseases, such as lupus. PMID:26913030

  7. Risky decision-making and ventral striatal dopamine responses to amphetamine: a positron emission tomography [(11)C]raclopride study in healthy adults.

    PubMed

    Oswald, Lynn M; Wand, Gary S; Wong, Dean F; Brown, Clayton H; Kuwabara, Hiroto; Brašić, James R

    2015-06-01

    Recent functional magnetic resonance imaging (fMRI) studies have provided compelling evidence that corticolimbic brain regions are integrally involved in human decision-making. Although much less is known about molecular mechanisms, there is growing evidence that the mesolimbic dopamine (DA) neurotransmitter system may be an important neural substrate. Thus far, direct examination of DA signaling in human risk-taking has centered on gambling disorder. Findings from several positron emission tomography (PET) studies suggest that dysfunctions in mesolimbic DA circuits may play an important role in gambling behavior. Nevertheless, interpretation of these findings is currently hampered by a need for better understanding of how individual differences in regional DA function influence normative decision-making in humans. To further our understanding of these processes, we used [(11)C]raclopride PET to examine associations between ventral striatal (VS) DA responses to amphetamine (AMPH) and risky decision-making in a sample of healthy young adults with no history of psychiatric disorder, Forty-five male and female subjects, ages 18-29 years, completed a computerized version of the Iowa Gambling Task. Participants then underwent two 90-minute PET studies with high specific activity [(11)C]raclopride. The first scan was preceded by intravenous saline; the second, by intravenous AMPH (0.3mg/kg). Findings of primary analyses showed that less advantageous decision-making was associated with greater right VS DA release; the relationship did not differ as a function of gender. No associations were observed between risk-taking and left VS DA release or baseline D2/D3 receptor availability in either hemisphere. Overall, the results support notions that variability in striatal DA function may mediate inter-individual differences in risky decision-making in healthy adults, further suggesting that hypersensitive DA circuits may represent a risk pathway in this population. PMID

  8. In vivo markers of inflammatory response in recent-onset schizophrenia: a combined study using [11C]DPA-713 PET and analysis of CSF and plasma

    PubMed Central

    Coughlin, J M; Wang, Y; Ambinder, E B; Ward, R E; Minn, I; Vranesic, M; Kim, P K; Ford, C N; Higgs, C; Hayes, L N; Schretlen, D J; Dannals, R F; Kassiou, M; Sawa, A; Pomper, M G

    2016-01-01

    Several lines of evidence suggest aberrant immune response in schizophrenia, including elevated levels of cytokines. These cytokines are thought to be produced by activated microglia, the innate immune cells of the central nervous system. However, increase in translocator protein 18 kDa (TSPO), a marker of activated glia, has not been found in patients with chronic schizophrenia using second-generation radiotracers and positron emission tomography (PET)-based neuroimaging. In this study we focused on patients with recent onset of schizophrenia (within 5 years of diagnosis). Quantified levels of TSPO in the cortical and subcortical brain regions using the PET-based radiotracer [11C]DPA-713 were compared between the patients and healthy controls. Markers of inflammation, including interleukin 6 (IL-6), were assessed in the plasma and cerebrospinal fluid (CSF) in these participants. We observed no significant change in the binding of [11C]DPA-713 to TSPO in 12 patients with recent onset of schizophrenia compared with 14 controls. Nevertheless, the patients with recent onset of schizophrenia showed a significant increase in IL-6 in both plasma (P<0.001) and CSF (P=0.02). The CSF levels of IL-6 were significantly correlated with the levels of IL-6 in plasma within the total study population (P<0.001) and in patients with recent onset of schizophrenia alone (P=0.03). Our results suggest that increased levels of IL-6 may occur in the absence of changed TSPO PET signal in the brains of medicated patients with recent onset of schizophrenia. Future development of PET-based radiotracers targeting alternative markers of glial activation and immune response may be needed to capture the inflammatory signature present in the brains of patients with early-stage disease. PMID:27070405

  9. Expression of CD11c+HLA-DR+dendritic cells and related cytokines in the follicular fluid might be related to pathogenesis of ovarian hyperstimulation syndrome

    PubMed Central

    Shi, Sen-Lin; Peng, Zhao-Feng; Yao, Gui-Dong; Jin, Hai-Xia; Song, Wen-Yan; Yang, Hong-Yi; Xue, Ru-Yue; Sun, Ying-Pu

    2015-01-01

    Objective: To explore the expressions of CD11c+HLA-DR+dentritic cells in the follicular fluid of patients with OHSS and their significances. Subjects: 100 individuals. Treatment: embryos were observed. The distribution of dentritic cells in follicular fluid and the levels of IL-10, IL-12, IL-18 and IL-23 in follicular fluid were detected. Methods: There were ovarian hyperstimulation syndrome (OHSS) group and control group in this study. The OHSS group consisted of 50 patients with OHSS and the control group consisted of 50 patients who underwent in vitro fertilization-embryo transfer (IVF-ET) only due to male factors. The statuses of embryos were compared between the two groups. The distribution of dentritic cells in follicular fluid was determined with flow cytometry, and the levels of IL-10, IL-12, IL-18 and IL-23 in follicular fluid were detected with enzyme-linked immunosorbent assay (ELISA) in all patients. Results: The two-pronuclear (2PN) fertility rate, high-quality embryo rate and available embryo rate were all significantly lower in OHSS group than in control group (all P<0.05). The number of CD11c+HLA-DR+dentritic cells (P<0.05) and the levels of IL-10, IL-12, IL-18 and IL-23 were all significantly higher in OHSS group than in control group (all P<0.01). Conclusion: The follicular fluid of the patients with OHSS is in an inflammatory status, the inflammatory status may be involved in OHSS and the microenvironment of follicular fluid may affects oocyte quality and embryo development. PMID:26823856

  10. Effect of chronic antipsychotic treatment on striatal phosphodiesterase 10A levels: a [11C]MP-10 PET rodent imaging study with ex vivo confirmation

    PubMed Central

    Natesan, S; Ashworth, S; Nielsen, J; Tang, S-P; Salinas, C; Kealey, S; Lauridsen, J B; Stensbøl, T B; Gunn, R N; Rabiner, E A; Kapur, S

    2014-01-01

    A number of phosphodiesterase 10A (PDE10) inhibitors are about to undergo clinical evaluation for their efficacy in treating schizophrenia. As phosphodiesterases are in the same signalling pathway as dopamine D2 receptors, it is possible that prior antipsychotic treatment could influence these enzyme systems in patients. Chronic, in contrast to acute, antipsychotic treatment has been reported to increase brain PDE10A levels in rodents. The aim of this study was to confirm these findings in a manner that can be translated to human imaging studies to understand its consequences. Positron emission tomography (PET) scanning was used to evaluate PDE10A enzyme availability, after chronic haloperidol administration, using a specific PDE10A ligand ([11C]MP-10). The binding of [11C]MP-10 in the striatum and the cerebellum was measured in rodents and a simplified reference tissue model (SRTM) with cerebellum as the reference region was used to determine the binding potential (BPND). In rats treated chronically with haloperidol (2 mg kg−1 per day), there was no significant difference in PDE10A levels compared with the vehicle-treated group (BPND±s.d.: 3.57±0.64 versus 2.86±0.71). Following PET scans, ex vivo analysis of striatal brain tissue for PDE10A mRNA (Pde10a) and PDE10A enzyme activity showed no significant difference. Similarly, the PDE10A protein content determined by western blot analysis was similar between the two groups, contrary to an earlier finding. The results of the study indicate that prior exposure to antipsychotic medication in rodents does not alter PDE10A levels. PMID:24690597

  11. Essential requirement of toll-like receptor 4 expression on CD11c+ cells for locoregional immunotherapy of malignant ascites using a streptococcal preparation OK-432.

    PubMed

    Hironaka, Katsuji; Yamaguchi, Yoshiyuki; Okita, Riki; Okawaki, Makoto; Nagamine, Ichiro

    2006-01-01

    Toll-like receptors (TLRs) are important molecules that stimulate the innate immunity in order to eradicate microbial pathogens, after which the adaptive immunity emerges. The involvement of TLRs in the action mechanism of OK-432, a bacterial preparation, was investigated in the locoregional treatment of malignant ascites from gastric cancer. The expression of TLRs in ascites cells was analyzed using reverse-transcription polymerase chain reaction specific for TLRs and by flow cytometry using anti-TLR2, -TLR4, -CD4, -CD8, and -CD11c antibodies. These measurements were compared with the locoregional response of OK-432 immunotherapy for malignant ascites, as well as TNF-alpha producing potential, which was measured by ELISA, of ascites cells stimulated in vitro with OK-432. It was observed that OK-432 immunotherapy for malignant ascites showed 8 positive (67%) and 4 negative responses with the tolerable adverse effects of fever elevation and abdominal pain. The TNF-alpha production of ascites cells by in vitro OK-432 stimulation was significantly higher in responder patients than in non-responders. The clinical responses were correlated with the expression of the TLR4 gene of ascites cells. The TNF-alpha-producing potential of ascites cells by in vitro OK-432 stimulation was dependent on the existence of a CD11c + TLR-4+ cell population in ascites cells. OK-432 was highly stimulatory for TNF-alpha production of ascites cells compared with other biological response modifiers of PSK and LEM. These results suggest that TLR-4 expression on ascites cells of a macrophage lineage is essential for ascites cells to produce TNF-alpha in relation to OK-432 stimulation and for subsequent positive clinical responses in locoregional immunotherapy using OK-432 for malignant ascites from gastric cancer.

  12. Noninvasive quantification of the differential portal and arterial contribution to the liver blood supply from PET measurements using the 11C-acetate kinetic model.

    PubMed

    Chen, Sirong; Feng, Dagan

    2004-09-01

    Our recent research has demonstrated that 11C-acetate could be a complementary tracer to 18F-fluorodeoxyglucose (FDG) in positron emission tomography (PET) imaging of hepatocellular carcinoma (HCC). In our previous modeling study, a three-compartment four-parameter model with a fixed contribution ratio of the liver's two blood supplies was proposed to characterize the kinetic behavior of 11C-acetate in liver. However, in real pathology, both tumor and nontumor liver tissue can be heterogeneous in the distribution and proportion of the two blood supplies. To further improve the accuracy of quantitative analysis, the actual proportion of the hepatic artery and portal vein (PV) in different regions of interest (ROIs) was investigated in this study. An extra parameter av was included in the model input function to describe the contribution of PV to the liver. Ten ROIs extracted from six patients were used to test the models with fixed/nonfixed weighted dual-input function. The weighted nonlinear least squares algorithm was used to estimate all of the parameters. Evaluation of the adequacy of the two models was conducted and the computer simulation was performed to test the estimation accuracy of the new model. The forward clearance K was also estimated by the linear Patlak method. The results show that the model with parameter av in the input function was more suitable for mapping the tracer time activity curves. Moreover, the estimated av value fits the practical physiological and pathological conditions well and could be a potential candidate to provide useful additional diagnostic information for the early detection of hepatic metastases.

  13. In Vivo Evaluation of Blood Based and Reference Tissue Based PET Quantifications of [11C]DASB in the Canine Brain.

    PubMed

    Van Laeken, Nick; Taylor, Olivia; Polis, Ingeborgh; Neyt, Sara; Kersemans, Ken; Dobbeleir, Andre; Saunders, Jimmy; Goethals, Ingeborg; Peremans, Kathelijne; De Vos, Filip

    2016-01-01

    This first-in-dog study evaluates the use of the PET-radioligand [11C]DASB to image the density and availability of the serotonin transporter (SERT) in the canine brain. Imaging the serotonergic system could improve diagnosis and therapy of multiple canine behavioural disorders. Furthermore, as many similarities are reported between several human neuropsychiatric conditions and naturally occurring canine behavioural disorders, making this tracer available for use in dogs also provide researchers an interesting non-primate animal model to investigate human disorders. Five adult beagles underwent a 90 minutes dynamic PET scan and arterial whole blood was sampled throughout the scan. For each ROI, the distribution volume (VT), obtained via the one- and two- tissue compartment model (1-TC, 2-TC) and the Logan Plot, was calculated and the goodness-of-fit was evaluated by the Akaike Information Criterion (AIC). For the preferred compartmental model BPND values were estimated and compared with those derived by four reference tissue models: 4-parameter RTM, SRTM2, MRTM2 and the Logan reference tissue model. The 2-TC model indicated in 61% of the ROIs a better fit compared to the 1-TC model. The Logan plot produced almost identical VT values and can be used as an alternative. Compared with the 2-TC model, all investigated reference tissue models showed high correlations but small underestimations of the BPND-parameter. The highest correlation was achieved with the Logan reference tissue model (Y = 0.9266 x + 0.0257; R2 = 0.9722). Therefore, this model can be put forward as a non-invasive standard model for future PET-experiments with [11C]DASB in dogs. PMID:26859850

  14. Imaging the impact of cyclosporin A and dipyridamole on P-glycoprotein (ABCB1) function at the blood-brain barrier: A [(11)C]-N-desmethyl-loperamide PET study in nonhuman primates.

    PubMed

    Damont, Annelaure; Goutal, Sébastien; Auvity, Sylvain; Valette, Héric; Kuhnast, Bertrand; Saba, Wadad; Tournier, Nicolas

    2016-08-25

    Cyclosporin A (CsA) and dipyridamole (DPy) are potent inhibitors of the P-glycoprotein (P-gp; ABCB1) in vitro. Their efficacy at inhibiting P-gp at the blood-brain barrier (BBB) is difficult to predict. Efficient and readily available (i.e. marketed) P-gp inhibitors are needed as probes to investigate the role of P-gp at the human BBB. In this study, the P-gp inhibition potency at the BBB of therapeutic doses of CsA or DPy was evaluated in baboons using Positron Emission Tomography (PET) imaging with [(11)C]-N-desmethyl-loperamide ([(11)C]dLop), a radiolabeled P-gp substrate. The preparation of dLop as authentic standard and [(11)C]dLop as radiotracer were revisited so as to improve their production yields. [(11)C]dLop PET imaging was performed in the absence (n=3, baseline condition) and the presence of CsA (15mg/kg/h i.v., n=3). Three animals were injected with i.v. DPy at either 0.56 or 0.96 or 2mg/kg (n=1), corresponding to the usual, maximal and twice the maximal dose in patients, respectively, administered immediately before PET. [(11)C]dLop brain kinetics as well as [(11)C]dLop kinetics and radiometabolites in arterial plasma were measured to calculate [(11)C]dLop area-under the time-activity curve from 10 to 30min in the brain (AUCbrain) and in plasma (AUCplasma). [(11)C]dLop brain uptake was described by AUCR=AUCbrain/AUCplasma. CsA as well as DPy did not measurably influence [(11)C]dLop plasma kinetics and metabolism. Baseline AUCR (0.85±0.29) was significantly enhanced in the presence of CsA (AUCR=10.8±3.6). Injection of pharmacologic dose of DPy did not enhance [(11)C]dLop brain distribution with AUCR being 1.2, 0.9 and 1.1 after administration of 0.56, 0.96 and 2mg/kg DPy doses, respectively. We used [(11)C]dLop PET imaging in baboons, a relevant in vivo model of P-gp function at the BBB, to show the P-gp inhibition potency of therapeutic dose CsA. Despite in vitro P-gp inhibition potency, usual doses DPy are not likely to inhibit P-gp function at

  15. Polybenzimidazole compounds

    DOEpatents

    Klaehn, John R.; Peterson, Eric S.; Wertsching, Alan K.; Orme, Christopher J.; Luther, Thomas A.; Jones, Michael G.

    2010-08-10

    A PBI compound that includes imidazole nitrogens, at least a portion of which are substituted with an organic-inorganic hybrid moiety. At least 85% of the imidazole nitrogens may be substituted. The organic-inorganic hybrid moiety may be an organosilane moiety, for example, (R)Me.sub.2SiCH.sub.2--, where R is selected from among methyl, phenyl, vinyl, and allyl. The PBI compound may exhibit similar thermal properties in comparison to the unsubstituted PBI. The PBI compound may exhibit a solubility in an organic solvent greater than the solubility of the unsubstituted PBI. The PBI compound may be included in separatory media. A substituted PBI synthesis method may include providing a parent PBI in a less than 5 wt % solvent solution. Substituting may occur at about room temperature and/or at about atmospheric pressure. Substituting may use at least five equivalents in relation to the imidazole nitrogens to be substituted or, preferably, about fifteen equivalents.

  16. Polybenzimidazole compounds

    DOEpatents

    Klaehn, John R.; Peterson, Eric S.; Orme, Christopher J.; Jones, Michael G.; Wertsching, Alan K.; Luther, Thomas A.; Trowbridge, Tammy L.

    2011-11-22

    A PBI compound includes imidazole nitrogens at least a portion of which are substituted with a moiety containing a carbonyl group, the substituted imidazole nitrogens being bonded to carbon of the carbonyl group. At least 85% of the nitrogens may be substituted. The carbonyl-containing moiety may include RCO--, where R is alkoxy or haloalkyl. The PBI compound may exhibit a first temperature marking an onset of weight loss corresponding to reversion of the substituted PBI that is less than a second temperature marking an onset of decomposition of an otherwise identical PBI compound without the substituted moiety. The PBI compound may be included in separatory media. A substituted PBI synthesis method may include providing a parent PBI in a less than 5 wt % solvent solution. Substituting may use more than 5 equivalents in relation to the imidazole nitrogens to be substituted.

  17. Rostrocaudal gradients of dopamine D2/3 receptor binding in striatal subregions measured with [(11)C]raclopride and high-resolution positron emission tomography.

    PubMed

    Alakurtti, Kati; Johansson, Jarkko J; Tuokkola, Terhi; Någren, Kjell; Rinne, Juha O

    2013-11-15

    The human striatum has structural and functional subdivisions, both dorsoventrally and rostrocaudally. To date, the gradients of dopamine D2/3 receptor binding in the human striatum have not been measured with positron emission tomography (PET). Seven healthy male subjects aged 24.5 ± 3.5 years were scanned with brain-dedicated high-resolution research tomography (HRRT, Siemens Medical Solutions, Knoxville, TN, USA) and [(11)C]raclopride. Coronally defined regions of interest (ROIs) of the caudate nucleus, putamen and ventral striatum (VST) were sampled plane-by-plane, 1.5mm apart, on spatially normalized binding potential (BPND) images. Regional [(11)C]raclopride BPND values were calculated using the simplified reference tissue model (SRTM) from a total of 25 coronal planes. An increasing rostrocaudal gradient of the D2/3 receptor binding was detected in the putamen, which is consistent with the known distribution of D2/3 dopamine receptors. In the caudate nucleus, there was an initial increase in the BPND values in the most anterior planes, suggesting that the highest D2/3 receptor binding occurred in the head; however, there was an overall descending gradient. A declining trend was also observed in the VST. The novelty of this study lies in the presentation, for the first time, of the D2/3 receptor binding gradients in each striatal subregion in the brains of living healthy humans. The high spatial resolution provided by HRRT enables frequent sampling of BPND along the longitudinal extent of striatum; this method is superior to the sectioning used in previous post mortem studies. Regarding the functional organization of the striatum, our findings can inform future investigations of normal neurophysiology as well as efforts to differentiate neuropsychiatric disorders affecting the brain dopamine (DA) system. Furthermore, the average distribution of D2/3 receptor binding revealed in this study could serve as a basis for a database that includes distributions of

  18. Effect of {sup 11}C-Methionine-Positron Emission Tomography on Gross Tumor Volume Delineation in Stereotactic Radiotherapy of Skull Base Meningiomas

    SciTech Connect

    Astner, Sabrina T. Dobrei-Ciuchendea, Mihaela; Essler, Markus; Bundschuh, Ralf A.; Sai, Heitetsu; Schwaiger, Markus; Molls, Michael; Weber, Wolfgang A.; Grosu, Anca-Ligia

    2008-11-15

    Purpose: To evaluate the effect of trimodal image fusion using computed tomography (CT), magnetic resonance imaging (MRI) and {sup 11}C-methionine positron emission tomography (MET-PET) for gross tumor volume delineation in fractionated stereotactic radiotherapy of skull base meningiomas. Patients and Methods: In 32 patients with skull base meningiomas, the gross tumor volume (GTV) was outlined on CT scans fused to contrast-enhanced MRI (GTV-MRI/CT). A second GTV, encompassing the MET-PET positive region only (GTV-PET), was generated. The additional information obtained by MET-PET concerning the GTV delineation was evaluated using the PET/CT/MRI co-registered images. The sizes of the overlapping regions of GTV-MRI/CT and GTV-PET were calculated and the amounts of additional volumes added by the complementing modality determined. Results: The addition of MET-PET was beneficial for GTV delineation in all but 3 patients. MET-PET detected small tumor portions with a mean volume of 1.6 {+-} 1.7 cm{sup 3} that were not identified by CT or MRI. The mean percentage of enlargement of the GTV using MET-PET as an additional imaging method was 9.4% {+-} 10.7%. Conclusions: Our data have demonstrated that integration of MET-PET in radiotherapy planning of skull base meningiomas can influence the GTV, possibly resulting in an increase, as well as in a decrease.

  19. Time-course of serotonin transporter occupancy by single dose of three SSRIs in human brain: A positron emission tomography study with [(11)C]DASB.

    PubMed

    Arakawa, Ryosuke; Tateno, Amane; Kim, WooChan; Sakayori, Takeshi; Ogawa, Kohei; Okubo, Yoshiro

    2016-05-30

    Sixteen healthy volunteers were enrolled and divided into four groups according to the single administration of 10mg or 20mg escitalopram, 50mg sertraline, or 20mg paroxetine. Four positron emission tomography scans with [(11)C]DASB were performed on each subject, the first prior to taking the drug, followed by the others at 4, 24, and 48h after. Serotonin transporter occupancies of the drugs at each time point were calculated. All drugs showed maximum occupancy at 4h after dosing and then decreasing occupancies with time. Escitalopram and sertraline showed high occupancies of 69.1-77.9% at 4h, remaining at 52.8-57.8% after 48h. On the other hand, paroxetine showed relatively low occupancy of 44.6%, then decreasing to 10.3% at 48h. Escitalopram (both 10mg and 20mg) and sertraline (50mg) showed high and sustained occupancy. Paroxetine (20mg) showed relatively low and rapidly decreasing occupancy, possibly due to the low plasma concentration by single dosing schedule. Applying the reported concentration of multiple dosing, 20mg paroxetine will induce over 80% occupancy. The present study suggested that these drugs and doses would be sufficient for the treatment of depression. PMID:27082864

  20. Dizocilpine and reduced body temperature do not prevent methamphetamine-induced neurotoxicity in the vervet monkey: [11C]WIN 35,428 - positron emission tomography studies.

    PubMed

    Melega, W P; Lacan, G; Harvey, D C; Huang, S C; Phelps, M E

    1998-12-11

    [11C]WIN 35,428 (WIN), a cocaine analog that binds to the dopamine transporter (DAT), and positron emission tomography (PET) were used to evaluate the potential neuroprotective effects of dizocilpine (MK-801) on methamphetamine (MeAmp) induced neurotoxicity in the striatal dopamine system of the vervet monkey. MK-801 (1 mg/kg, i.m.) was administered 30 min prior to a neurotoxic MeAmp dosage for this species (2 x 2 mg/kg, 4 h apart); control subjects received MeAmp. MK-801 treated subjects were anesthetized by the drug for 6-8 h; throughout that period, a 2-3 degrees C decrease in body temperature was measured. At 1-2 weeks post-MeAmp, decreases of approximately 75% in striatal WIN binding were observed for both MK-801/MeAmp and MeAmp subjects. Thus, in this non-human primate species, the combination of MK-801 pretreatment and reduced body temperature did not provide protection from the MeAmp-induced loss of DAT. Further, the absence of an elevated body temperature during the acute MeAmp exposure period indicated that hyperthermia, per se, was not a necessary concomitant of the MeAmp neurotoxicity profile as has been previously demonstrated in rodents. These results provide evidence that different regulatory factors maintain the integrity of the rodent and primate striatal dopamine systems.

  1. Unique Distribution of Aromatase in the Human Brain: In Vivo Studies With PET and [N-Methyl-11C]Vorozole

    SciTech Connect

    Biegon, A.; Biegon, A.; Kim, S.W.; Alexoff, D.; Millard, J.; Carter, P.; Hubbard, B.; King, P.; Logan, J.; Muench, L.; Pareto, D.; Schlyer, D.; Shea, C.; Telang, F.; Wang, G.-J.; Xu, Y.; Fowler, J.

    2010-10-01

    Aromatase catalyzes the last step in estrogen biosynthesis. Brain aromatase is involved in diverse neurophysiological and behavioral functions including sexual behavior, aggression, cognition, and neuroprotection. Using positron emission tomography (PET) with the radiolabeled aromatase inhibitor [N-methyl-{sup 11}C]vorozole, we characterized the tracer distribution and kinetics in the living human brain. Six young, healthy subjects, three men and three women, were administered the radiotracer alone on two separate occasions. Women were scanned in distinct phases of the menstrual cycle. Specificity was confirmed by pretreatment with a pharmacological (2.5 mg) dose of the aromatase inhibitor letrozole. PET data were acquired over a 90-min period and regions of interest placed over selected brain regions. Brain and plasma time activity curves, corrected for metabolites, were used to derive kinetic parameters. Distribution volume (V{sub T}) values in both men and women followed the following rank order: thalamus > amygdala = preoptic area > medulla (inferior olive) > accumbens, pons, occipital and temporal cortex, putamen, cerebellum, and white matter. Pretreatment with letrozole reduced VT in all regions, though the size of the reduction was region-dependent, ranging from {approx}70% blocking in thalamus andpreoptic area to {approx}10% in cerebellum. The high levels of aromatase in thalamus and medulla (inferior olive) appear to be unique to humans. These studies set the stage for the noninvasive assessment of aromatase involvement in various physiological and pathological processes affecting the human brain.

  2. Downregulation of MicroRNA-107 in intestinal CD11c+ myeloid cells in response to microbiota and proinflammatory cytokines increases IL-23p19 expression

    PubMed Central

    Xue, Xiaochang; Cao, Anthony T.; Cao, Xiaocang; Yao, Suxia; Carlson, Eric D.; Soong, Lynn; Liu, Chang-Gong; Liu, Xiuping; Liu, Zhanju; Duck, L. Wayne; Elson, Charles O.; Cong, Yingzi

    2014-01-01

    Summary Commensal flora plays an important role in the development of the mucosal immune system and in maintaining intestinal homeostasis. However, the mechanisms involved in regulation of host-microbiota interaction are still not completely understood. In this study, we examined how microbiota and intestinal inflammatory conditions regulate host microRNA expression and observed lower microRNA-107 (miR-107) expression in the inflamed intestines of colitic mice, compared with that in normal control mice. miR-107 was predominantly reduced in epithelial cells and CD11c+ myeloid cells including dendritic cells and macrophages in the inflamed intestines. We demonstrate that IL-6, IFN-γ and TNF-α downregulated, whereas TGF-β promoted, miR-107 expression. In addition, miR-107 expression was higher in the intestines of germ-free mice than in mice housed under specific pathogen-free conditions, and the presence of microbiota downregulated miR-107 expression in DCs and macrophages in a MyD88- and NF-κB-dependent manner. We determined that the ectopic expression of miR-107 specifically repressed the expression of IL-23p19, a key molecule in innate immune responses to commensal bacteria. We concluded that regulation of miR-107 by intestinal microbiota and pro-inflammatory cytokine serve as an important pathway for maintaining intestinal homeostasis. PMID:24293139

  3. Striatal and extrastriatal dopamine transporter levels relate to cognition in Lewy body diseases: an 11C altropane positron emission tomography study

    PubMed Central

    2014-01-01

    Introduction The biological basis of cognitive impairment in parkinsonian diseases is believed to be multifactorial. We investigated the contribution of dopamine deficiency to cognition in Parkinson disease (PD) and dementia with Lewy bodies (DLB) with dopamine transporter (DAT) imaging. Methods We acquired 11C altropane PET, magnetic resonance imaging and cognitive testing in 19 nondemented subjects with PD, 10 DLB and 17 healthy control subjects (HCS). We analyzed DAT concentration in putamen, caudate, anterior cingulate (AC), orbitofrontal and prefrontal regions, using the Standardized Uptake Volume Ratio with partial volume correction, and we related DAT concentration and global cortical thickness to neuropsychological performance. Results DAT concentration in putamen and in caudate were similar in PD and DLB groups and significantly lower than in HCS. Reduced caudate DAT concentration was associated with worse Clinical Dementia Rating Scale–sum of boxes (CDR-SB) scores and visuospatial skills in DLB but not in PD or HCS groups. Adjusting for putamen DAT concentration, as a measure of severity of motor disease, caudate DAT concentration was lower in DLB than in PD. Higher AC DAT concentration was associated with lower putamen DAT concentration in DLB and with higher putamen DAT concentration in PD. Higher AC DAT concentration in DLB correlated with greater impairment in semantic memory and language. Conclusions Caudate and AC dopamine dysfunction contribute in opposing directions to cognitive impairment in DLB. PMID:25429309

  4. Immunoscintigraphy of prostatic cancer: preliminary results with sup 111 In-labeled monoclonal antibody 7E11-C5. 3 (CYT-356)

    SciTech Connect

    Wynant, G.E.; Murphy, G.P.; Horoszewicz, J.S.; Neal, C.E.; Collier, B.D.; Mitchell, E.; Purnell, G.; Tyson, I.; Heal, A.; Abdel-Nabi, H. )

    1991-01-01

    A phase 1 study was conducted with the investigational immunoscintigraphic agent, {sup 111}In-CYT-356, a radiolabeled, site-specific immunoconjugate of monoclonal antibody 7E11-C5.3, in 40 patients with prostatic carcinoma and known distant metastases. Each patient received a single intravenous infusion of CYT-356 (dose range, 0.1-5 mg) radiolabeled with approximately 5 mCi of {sup 111}In. None of the patients experienced adverse reactions. One patient who received a 5-mg dose developed antibodies to the CYT-356 immunoconjugate. {sup 111}In-CYT-356 immunoscintigraphy detected bony metastases in 21 of 38 patients (55%), including 12 of 14 (86%) receiving concomitant hormonal therapy, and soft tissue lesions in four of six patients (67%). Antibody imaging detected occult lesions in the bony pelvis and lumbar spine, which were confirmed by follow-up imaging tests, in one patient. Higher CYT-356 doses may clear the blood pool more slowly. These results suggest that {sup 111}In-CYT-356 can be safely administered to patients with prostatic carcinoma and that further clinical investigation of this agent is warranted.

  5. Age and sex effects on 5-HT4 receptors in the human brain: a [11C]SB207145 PET study

    PubMed Central

    Madsen, Karine; Haahr, Mette T; Marner, Lisbeth; Keller, Sune H; Baaré, William F; Svarer, Claus; Hasselbalch, Steen G; Knudsen, Gitte M

    2011-01-01

    Experimental studies indicate that the 5-HT4 receptor activation influence cognitive function, affective symptoms, and the development of Alzheimer's disease (AD). The prevalence of AD increases with aging, and women have a higher predisposition to both AD and affective disorders than men. This study aimed to investigate sex and age effects on 5-HT4 receptor-binding potentials in striatum, the limbic system, and neocortex. Positron-emission tomographic scans were conducted using the radioligand [11C]SB207145 in a cohort of 30 healthy subjects (mean age 44 years; range 20 to 86 years; 14 men and 16 women). The output parameter, BPND, was modeled using the simplified reference tissue model, and partial volume correction was performed with the Muller–Gartner method. A decline with age of 1% per decade was found only in striatum. Women had a 13% lower 5-HT4 receptor binding in the limbic system. The lower limbic 5-HT4 receptor binding in women supports a role for 5-HT4 receptors in the sex-specific differences in emotional control and might contribute to the higher prevalence of affective diseases and AD in women. The relatively stable 5-HT4 receptor binding with aging contrasts others in subtypes of receptors, which generally decrease with aging. PMID:21364600

  6. High dose CD11c-driven IL15 is sufficient to drive NK cell maturation and anti-tumor activity in a trans-presentation independent manner

    PubMed Central

    Polansky, Julia K.; Bahri, Rajia; Divivier, Mylene; Duitman, Erwin H.; Vock, Christina; Goyeneche-Patino, Diego A.; Orinska, Zane; Bulfone-Paus, Silvia

    2016-01-01

    The common gamma (γc)-chain cytokine interleukin 15 (IL15) is a multifunctional immune-modulator which impacts the generation, maturation and activity of many cell types of the innate, as well as the adaptive immune system, including natural killer (NK) and CD8+ T cells. Using a new series of transgenic mice, we analyzed the in vivo potential of IL15 as an immune-regulator when available at different concentrations or delivery modes, i.e. soluble monomer or complexed to its specific receptor α (Rα)-chain. We have identified distinct effects on selected IL15-responsive populations. While CD8+ T cells required complexed forms of IL15/IL15Rα for full functionality, mature NK populations were rescued in an IL15/IL15Rα-deficient environment by high levels of CD11c-restricted IL15. These IL15-conditions were sufficient to limit tumor formation in a lung metastasis model indicating that the NK cell populations were fully functional. These data underline the potential of “free” IL15 in the absence of Rα-complex as a powerful and specific immuno-modulator, which may be beneficial where selective immune-activation is desired. PMID:26822794

  7. Characterization and use of new monoclonal antibodies to CD11c, CD14, and CD163 to analyze the phenotypic complexity of ruminant monocyte subsets.

    PubMed

    Elnaggar, Mahmoud M; Abdellrazeq, Gaber S; Mack, Victoria; Fry, Lindsay M; Davis, William C; Park, Kun Taek

    2016-10-01

    The sequencing of the bovine genome and development of mass spectrometry, in conjunction with flow cytometry (FC), have afforded an opportunity to complete the characterization of the specificity of monoclonal antibodies (mAbs), only partially characterized during previous international workshops focused on antibody development for livestock (1991, Leukocyte Antigens in Cattle, Sheep, and Goats; 1993, Leukocyte Antigens of Cattle and Sheep; 1996, Third Workshop on Ruminant Leukocyte Antigens). The objective of this study was to complete the characterization of twelve mAbs incompletely characterized during the workshops that reacted with molecules predominantly expressed on bovine monocytes and use them to provide further information on the phenotypic complexity of monocyte subsets in ruminants. Analysis revealed that the mAbs could be grouped into three clusters that recognize three different molecules: CD11c, CD14, and CD163. Following characterization, comparison of the patterns of expression of CD14 and CD163 with expression of CD16, CD172a, and CD209 revealed the mononuclear cell population is comprised of multiple subsets with differential expression of these molecules. Further analysis revealed the epitopes recognized by mAbs to CD14 and CD163 are conserved on orthologues in sheep and goats. In contrast to CD14 that is also expressed on sheep and goat granulocytes, CD163 is a definitive marker for their monocytes. PMID:27496743

  8. Cortical Dopamine Transmission as Measured with the [11C]FLB 457 – Amphetamine PET Imaging Paradigm Is Not Influenced by COMT Genotype

    PubMed Central

    Narendran, Rajesh; Tumuluru, Divya; May, Maureen A.; Chowdari, Kodavali V.; Himes, Michael L.; Fasenmyer, Kelli; Frankle, W. Gordon; Nimgaonkar, Vishwajit L.

    2016-01-01

    Basic investigations link a Val158Met polymorphism (rs4680) in the catechol-O-methyltransferase (COMT) gene to not only its enzymatic activity, but also to its dopaminergic tone in the prefrontal cortex. Previous PET studies have documented the relationship between COMT Val158Met polymorphism and D1 and D2/3 receptor binding potential (BP), and interpreted them in terms of dopaminergic tone. The use of baseline dopamine D1 and D2/3 receptor binding potential (BPND) as a proxy for dopaminergic tone is problematic because they reflect both endogenous dopamine levels (a change in radiotracer's apparent affinity) and receptor density. In this analysis of 31 healthy controls genotyped for the Val158Met polymorphism (Val/Val, Val/Met, and Met/Met), we used amphetamine-induced displacement of [11C]FLB 457 as a direct measure of dopamine release. Our analysis failed to show a relationship between COMT genotype status and prefrontal cortical dopamine release. COMT genotype was also not predictive of baseline dopamine D2/3 receptor BPND. PMID:27322568

  9. Increased neurokinin-1 receptor availability in the amygdala in social anxiety disorder: a positron emission tomography study with [11C]GR205171

    PubMed Central

    Frick, A; Ahs, F; Linnman, C; Jonasson, M; Appel, L; Lubberink, M; Långström, B; Fredrikson, M; Furmark, T

    2015-01-01

    The neurokinin-1 (NK1) receptor is abundantly expressed in the fear circuitry of the brain, including the amygdala, where it modulates stress and anxiety. Despite its proposed involvement in psychopathology, only a few studies of NK1 receptor availability in human subjects with anxiety disorders exist. Here, we compared NK1 receptor availability in patients with social anxiety disorder (SAD; n=17) and healthy controls (n=17) using positron emission tomography and the radiotracer [11C]GR205171. The Patlak Graphical plot using a cerebellar reference region was used to model the influx parameter, Ki measuring NK1 receptor availability. Voxel-wise statistical parametric mapping analyses revealed increased NK1 receptor availability specifically in the right amygdala in SAD patients relative to controls. Thus, we demonstrate that exaggerated social anxiety is related to enhanced NK1 receptor availability in the amygdala. This finding supports the contribution of NK1 receptors not only in animal models of stress and anxiety but also in humans with anxiety disorders. PMID:26151925

  10. Selective alterations of brain dopamine D(2) receptor binding in cirrhotic patients: results of a (11)C-N-methylspiperone PET study.

    PubMed

    Watanabe, Yuki; Kato, Akinobu; Sawara, Kei; Butterworth, Roger F; Sasaki, Toshiaki; Terasaki, Kazunori; Sera, Koichiro; Suzuki, Kazuyuki

    2008-09-01

    Alterations of the brain dopamine system have been implicated in the neurological complications of chronic liver failure. The present study was aimed at the measurement of dopamine D(2) binding sites in cirrhotic patients by positron emission tomography (PET) using (11)C-N-methylspiperone as ligand. The regions of interest (ROI) were designated on a three-dimensional stereotaxic ROI template (3DSRT). The pixel values of twelve ROIs corrected by the pixel value of the cerebellum after 80 min static scanning were used to quantitate changes in binding. D(2) binding sites were significantly decreased in the hippocampus and thalamus of cirrhotic patients and were positively correlated with serum bilirubin levels and Child-Pugh scores and were negatively correlated with prothrombin times (thalamus). Loss of D(2) sites was greater in thalamus and hippocampus of alcoholic cirrhotics compared to non-alcoholics. Statistically significant correlations were also observed between D(2) binding sites in hippocampus, thalamus and lenticular nuclei and history of overt encephalopathy. These findings suggest that D(2) receptor binding in some regions of brain in cirrhotic patients is influenced by factors such as the severity of liver damage and history of alcohol dependency or overt encephalopathy. Alterations of D(2) receptor sites indicative of dopaminergic synaptic dysfunction could play an important role in the pathogenesis of the cognitive and motor disturbances associated with chronic liver failure. PMID:18686022

  11. Unique distribution of aromatase in the human brain: in vivo studies with PET and [N-methyl-11C]vorozole.

    PubMed

    Biegon, Anat; Kim, Sung Won; Alexoff, David L; Jayne, Millard; Carter, Pauline; Hubbard, Barbara; King, Payton; Logan, Jean; Muench, Lisa; Pareto, Deborah; Schlyer, David; Shea, Colleen; Telang, Frank; Wang, Gene-Jack; Xu, Youwen; Fowler, Joanna S

    2010-11-01

    Aromatase catalyzes the last step in estrogen biosynthesis. Brain aromatase is involved in diverse neurophysiological and behavioral functions including sexual behavior, aggression, cognition, and neuroprotection. Using positron emission tomography (PET) with the radiolabeled aromatase inhibitor [N-methyl-(11)C]vorozole, we characterized the tracer distribution and kinetics in the living human brain. Six young, healthy subjects, three men and three women, were administered the radiotracer alone on two separate occasions. Women were scanned in distinct phases of the menstrual cycle. Specificity was confirmed by pretreatment with a pharmacological (2.5 mg) dose of the aromatase inhibitor letrozole. PET data were acquired over a 90-min period and regions of interest placed over selected brain regions. Brain and plasma time activity curves, corrected for metabolites, were used to derive kinetic parameters. Distribution volume (V(T)) values in both men and women followed the following rank order: thalamus > amygdala = preoptic area > medulla (inferior olive) > accumbens, pons, occipital and temporal cortex, putamen, cerebellum, and white matter. Pretreatment with letrozole reduced V(T) in all regions, though the size of the reduction was region-dependent, ranging from ∼70% blocking in thalamus andpreoptic area to ∼10% in cerebellum. The high levels of aromatase in thalamus and medulla (inferior olive) appear to be unique to humans. These studies set the stage for the noninvasive assessment of aromatase involvement in various physiological and pathological processes affecting the human brain.

  12. Unique distribution of aromatase in the human brain: in vivo studies with PET and [N-methyl-11C]vorozole

    PubMed Central

    Biegon, Anat; Kim, Sung Won; Alexoff, David L.; Jayne, Millard; Carter, Pauline; Hubbard, Barbara; King, Payton; Logan, Jean; Muench, Lisa; Pareto, Deborah; Schlyer, David; Shea, Colleen; Telang, Frank; Wang, Gene-Jack; Xu, Youwen; Fowler, Joanna S.

    2010-01-01

    Aromatase catalyzes the last step in estrogen biosynthesis. Brain aromatase is involved in diverse neurophysiological and behavioral functions including sexual behavior, aggression, cognition and neuroprotection. Using positron emission tomography (PET) with the radiolabeled aromatase inhibitor [N-methyl-11C]vorozole, we characterized the tracer distribution and kinetics in the living human brain. Six young, healthy subjects, 3 men and 3 women, were administered the radiotracer alone on two separate occasions. Women were scanned in distinct phases of the menstrual cycle. Specificity was confirmed by pretreatment with a pharmacological (2.5mg) dose of the aromatase inhibitor letrozole. PET data were acquired over a 90 min period and regions of interest placed over selected brain regions. Brain and plasma time activity curves, corrected for metabolites, were used to derive kinetic parameters. Distribution volume (VT) values in both men and women followed the rank order: thalamus>amygdala=preoptic area>medulla(inferior olive) > accumbens, pons, occipital and temporal cortex, putamen, cerebellum and white matter. Pretreatment with letrozole reduced VT in all regions, though the size of the reduction was region dependent; ranging from ~70% blocking in thalamus and preoptic area to ~10% in cerebellum. The high levels of aromatase in thalamus and medulla (inferior olive) appear to be unique to humans. These studies set the stage for the non-invasive assessment of aromatase involvement in various physiological and pathological processes affecting the human brain. PMID:20842717

  13. Does insomnia in prison improve with time? Prospective study among remanded prisoners using the Pittsburgh Sleep Quality Index.

    PubMed

    Elger, Bernice S

    2003-10-01

    Insomnia is a frequent health problem in prison, but little is known about its severity and duration. The objective was to find out whether subjective sleep quality improves during time and which factors influence improvement. Fifty-two randomly chosen prisoners complaining of insomnia at the Geneva remand prison were interviewed (T1) and followed up ten days (T2) and two months (T3) later. They received hypnotics habitually prescribed by prison physicians (benzodiazepines, chloralhydrate, zolpidem). After ten days 40 patients were still in prison and agreed to participate and after two months 16 prisoners could be re-evaluated. Total Pittsburgh Sleep Quality Index (PSQI) scores at T1 were 12.3 +/- 4.7. At T2 and T3, PSQI scores improved significantly, whereas General Health Questionnaire (GHQ) scores and conditions of imprisonment were similar. Only 12.5% of patients at T2, and 6.25% at T3, were 'good sleepers' (PSQI scores =/< 5). Cocaine users and prisoners with a healthy lifestyle reported the greatest improvement of PSQI scores. Our study shows that significant improvement of PSQI scores takes place in the first one to two weeks. However, in spite of regular drug treatment during the following weeks, PSQI scores persisted at a clinically significant level two months later. Drug treatment in prison only partially improves insomnia. PMID:14655964