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Sample records for imaging neuroleptic receptors

  1. Imaging dopamine-2 receptors in cebus apella at PET with F-18 fluoropropylspiperone and F-18 fluorinated benzamide neuroleptic

    International Nuclear Information System (INIS)

    Mukherjee, J.; Yasillo, N.J.; Luh, K.E.; Diamond, M.; Levy, D.; Chen, C.T.; Cooper, M.

    1990-01-01

    Tardive dyskinesia (TD), an intractable disorder believed to involve dysfunction of dopamine D-2 receptors, often occurs with neuroleptic treatment in neuropsychiatric illness. This paper investigates the role of these receptors using a unique primate model of TD with newly developed (F-18) fluorinated radioligands. Two radioligands, (F-18)FPMB (one of a new class of fluorinated benzamide neuroleptics) have been used to image these receptors in a normal Cebus apella. Either (F-18)FPSP or (F-18)FPMB was administered intravenously to a normal Cebus, which was scanned for 2 hours in a PETT VI tomograph

  2. Receptor imaging of schizophrenic patients under treatment with typical and atypical neuroleptics

    International Nuclear Information System (INIS)

    Dresel, S.; Tatsch, K.; Meisenzahl, E.; Scherer, J.

    2002-01-01

    Schizophrenic psychosis is typically treated by typical and atypical neuroleptics. Both groups of drugs differ with regard to induction of extrapyramidal side effects. The occupancy of postsynaptic dopaminergic D2 receptors is considered to be an essential aspect of their antipsychotic properties. The dopamine D2 receptor status can be assessed by means of [I-123]IBZM SPECT. Studies on the typical neuroleptic haloperidol revealed an exponential dose response relationship measured by IBZM. Extrapyramidal side effects were presented by all patients below a threshold of the specific binding of IBZM below 0.4 (with one exception, norm value: >0.95). Also under treatment with the atypical neuroleptic clozapine an exponential dose response relationship was found. However, none of these patients showed extrapyramidal side effects. Recently introduced, new atypical neuroleptics such as risperidone and olanzapine again presented with an exponential relationship between daily dose and IBZM binding. The curves of the latter were in between the curves of haloperidol and clozapine. Extrapyramidal side effects were documented in a less number of patients treated with risperidone as compared to haloperidol, for olanzapine only one patient revealed these findings in our own patient group. The pharmacological profile of atypical neuroleptics shows - in addition to their binding to dopamine receptors - also high affinities to the receptors of other neurotransmitter systems, particularly the serotonergic system. Therefore, the lower incidence of extrapyramidal side effects seen by atypical in comparison to typical neuroleptics is at least in part most likely due to a complex interaction on a variety of neurotransmitter systems. (orig.) [de

  3. Receptor imaging of schizophrenic patients under treatment with typical and atypical neuroleptics; Nuklearmedizinische Rezeptordiagnostik bei schizophrenen Patienten unter Therapie mit typischen und atypischen Neuroleptika

    Energy Technology Data Exchange (ETDEWEB)

    Dresel, S.; Tatsch, K. [Klinik und Poliklinik fuer Nuklearmedizin der Ludwig-Maximilians-Univ. Muenchen (Germany); Meisenzahl, E. [Psychiatrische Klinik der Ludwig-Maximilians-Univ. Muenchen (Germany); Scherer, J. [Bezirkskrankenhaus Haar (Germany)

    2002-09-01

    Schizophrenic psychosis is typically treated by typical and atypical neuroleptics. Both groups of drugs differ with regard to induction of extrapyramidal side effects. The occupancy of postsynaptic dopaminergic D2 receptors is considered to be an essential aspect of their antipsychotic properties. The dopamine D2 receptor status can be assessed by means of [I-123]IBZM SPECT. Studies on the typical neuroleptic haloperidol revealed an exponential dose response relationship measured by IBZM. Extrapyramidal side effects were presented by all patients below a threshold of the specific binding of IBZM below 0.4 (with one exception, norm value: >0.95). Also under treatment with the atypical neuroleptic clozapine an exponential dose response relationship was found. However, none of these patients showed extrapyramidal side effects. Recently introduced, new atypical neuroleptics such as risperidone and olanzapine again presented with an exponential relationship between daily dose and IBZM binding. The curves of the latter were in between the curves of haloperidol and clozapine. Extrapyramidal side effects were documented in a less number of patients treated with risperidone as compared to haloperidol, for olanzapine only one patient revealed these findings in our own patient group. The pharmacological profile of atypical neuroleptics shows - in addition to their binding to dopamine receptors - also high affinities to the receptors of other neurotransmitter systems, particularly the serotonergic system. Therefore, the lower incidence of extrapyramidal side effects seen by atypical in comparison to typical neuroleptics is at least in part most likely due to a complex interaction on a variety of neurotransmitter systems. (orig.) [German] Die pharmakologische Therapie von Erkrankungen aus dem schizophrenen Formenkreis erfolgt durch typische und atypische Neuroleptika. Beide Gruppen unterscheiden sich klinsich im Wesentlichen durch die Eigenschaft, extrapyramidal

  4. Use of 76Br-bromospiperone for the analysis of dopamine receptors in neuroleptic treated patients

    International Nuclear Information System (INIS)

    Maziere, B.; Cambon, H.; Baron, J.C.; Loc'h, C.

    1987-06-01

    The determination of the optimal prescription dosage of neuroleptic medications is of great importance to optimize the therapeutic response and to minimize the occurrence of tardive dyskinesia and other side-effects. PET, a non-invasive methodology which provides in-vivo the actual binding (occupation) of brain dopamine receptors, can be used as an in-vivo radioreceptor assay to indirectly estimate the neuroleptic tissue levels. In this study, 76Br-BSP was used in conjunction with PET to provide a semi-quantitative estimate of the neuroleptic (D2) binding sites occupancy rate during and following oral treatment by neuroleptics. On neuroleptic treatment, the fraction of unoccupied sites showed a striking dose-dependence ranging from .94 to .27 for lowest and highest doses. The CPZ equivalent daily oral doses occupying 50 and 100% of the neuroleptic sites were found to be respectively about 6 and 60 μmol/kg. The results establish that washout of neuroleptics from striatal binding sites is a rapid process that strongly suggest that the long-lasting remissions of psychotic patients following neuroleptic withdrawal are not due to persistent dopamine receptor occupation

  5. Role of dopamine receptor and muscarinic acetylcholine receptor blockade in the antiapomorphine action of neuroleptics

    Energy Technology Data Exchange (ETDEWEB)

    Zharkovskii, A.M.; Langel, Yu.L.; Chereshka, K.S.; Zharkovskaya, T.A.

    1987-08-01

    The authors analyze the role of dopamine and muscarinic acetylcholine receptor blocking components in the antistereotypic action of neuroleptics with different chemical structure. To determine dopamine-blocking activity in vitro, binding of /sup 3/H-spiperone with membranes of the rat striatum was measured. To study the blocking action of the substances on muscarinic acetylcholine receptors, binding of /sup 3/H-quinuclidinyl benzylate with brain membranes was chosen.

  6. Sulpiride and the role of dopaminergic receptor blockade in the antipsychotic activity of neuroleptics

    Energy Technology Data Exchange (ETDEWEB)

    Memo, M; Battaini, F; Spano, P F; Trabucchi, M [University of Brescia, (Italy). Dept. of Pharmacology

    1981-01-01

    It is now generally recognized that dopamine receptors excist in the CNS as different subtypes: D/sub 1/ receptors, associated with adenylyl cyclase activity, and D/sub 2/ receptor, uncoupled to a cyclic AMP generating system. In order to understand the role of D/sub 1/ and D/sub 2/ receptors in the antipsychotic action of neuroleptics, we have performed subchronic treatment with haloperidol, a drug which acts on D/sub 1/ receptors, and sulpiride, a selective antagonist to D/sub 2/ receptors. Long-term treatment with haloperidol does not induce significant supersensitivity of the D/sub 2/ receptors. In fact under these conditions /sup 3/H-(-)-sulpiride binding, which is a marker of D/sub 2/ receptor function, does not increase in rat striatum, while the long-term administration of sulpiride, itself produces supersensitivity of D/sub 2/ receptors. Moreover, sulpiride does not induce supersensitivity of the D/sub 1/ receptors, characterized by /sup 3/H-spiroperidol binding. These data suggest that both types of dopamine receptors may be involved in the clinical antipsychotic effects of neuroleptics. Unilateral leison of the nigrostriatal dopaminergic pathway produces an increase of striatal dopaminergic receptors, measured either by /sup 3/H-spiroperidol and /sup 3/H-(-)-sulpiride binding. These findings suggest that D/sub 1/ and D/sub 2/ receptors are present in postsynaptic membranes while it is still not known whether they exist in the same cellular elements.

  7. Sulpiride and the role of dopaminergic receptor blockade in the antipsychotic activity of neuroleptics

    International Nuclear Information System (INIS)

    Memo, M.; Battaini, F.; Spano, P.F.; Trabucchi, M.

    1981-01-01

    It is now generally recognized that dopamine receptors excist in the CNS as different subtypes: D 1 receptors, associated with adenylyl cyclase activity, and D 2 receptor, uncoupled to a cyclic APM generating system. In order to understand the role of D 1 and D 2 receptors in the antipsychotic action of neuroleptics, we have performed subchronic treatment with haloperidol, a drug which acts on D 1 receptors, and sulpiride, a selective antagonist to D 2 receptors. Long-term treatment with haloperidol does not induce significant supersensitivity of the D 2 receptors. In fact under these conditions 3 H-(-)-sulpiride binding, which is a marker of D 2 receptor function, does not increase in rat striatum, while the long-term administration of sulpiride, itself produces supersensitivity of D 2 receptors. Moreover, sulpiride does not induce supersensitivity of the D 1 receptors, characterized by 3 H-spiroperidol binding. These data suggest that both types of dopamine receptors may be involved in the clinical antipsychotic effects of neuroleptics. Unilateral leison of the nigrostriatal dopaminergic pathway produces an increase of striatal dopaminergic receptors, measured either by 3 H-spiroperidol and 3 H-(-)-sulpiride binding. These findings suggest that D 1 and D 2 receptors are present in postsynaptic membranes while it is still not known whether they exist in the same cellular elements. (author)

  8. Kinetic modeling of receptor-ligand binding applied to positron emission tomographic studies with neuroleptic tracers

    Energy Technology Data Exchange (ETDEWEB)

    Logan, J; Wolf, A P; Shiue, C Y; Fowler, J S

    1987-01-01

    Positron emission tomography (PET) with labeled neuroleptics has made possible the study of neurotransmitter-receptor systems in vivo. In this study we investigate the kinetics of the 3,4-dihydroxyphenylethylamine (dopamine) receptor-ligand binding using PET data from a series of experiments in the baboon with the /sup 18/F-labeled drugs spiperone, haloperidol, and benperidol. Models used to describe these systems are based on first-order kinetics which applies at high specific activity (low receptor occupancy). The parameters governing the uptake and loss of drug from the brain were found by fitting PET data from regions with little or no receptor concentration (cerebellum) and from experiments in which specific binding was blocked by pretreatment with the drug (+)-butaclamol. Receptor constants were determined by fitting data from receptor-containing structures. Correcting the arterial plasma activities (the model driving function) for the presence of drug metabolites was found to be important in the modeling of these systems.

  9. Assessment of dopamine receptor blockade by neuroleptic drugs in the living human brain

    International Nuclear Information System (INIS)

    Wong, D.F.; Wagner, H.N. Jr.; Coyle, J.

    1985-01-01

    Positron emission tomography (PET) makes it possible to attempt to relate directly the antipsychotic effect of neuroleptic drugs and their blocking effect on dopamine receptors (D2) in vivo. The authors have examined the ability of haloperidol (HAL) and molindone (MOL) to block the binding of C-11 n-methylspiperone (NMSP) in 6 normal subjects. A dose of 0.05 mg/kg of HAL resulted in a 68% drop in the slope of the caudate/cerebellum (Ca/Cb) vs. time. This slope is related to the rate of specific binding of NMSP to the receptor. A dose response was seen with both drugs. With increasing doses of HAL from .05 to 0.082 mg/kg, CA/Cb vs. time slope fell from .235 to .156/min. (N=4), progressively. Similarly with increasing doses of MOL of .16-.44 mg/kg slopes decreased from .0335 to .0155/min. (N=4). Similar degrees of post injection Ca/Cb ratio were produced with quantities of MOL and HAL administered in the oral dose ratio of doses 3-5:1 times greater than HAL. This is also the dose ratio at which we found similar dopamine receptor blockade by PET in vivo. A question that arises is why the in vitro affinity of HAL for D2 is 30 times greater than that of MOL in the human brain. The results raise the possibility that MOL metabolites are not only active in blocking D2 but indeed may possibly be more potent than MOL itself. It also helps confirm the site of action of MOL and its in vivo metabolites

  10. D2 dopamine receptors in neuroleptic-naive schizophrenic patients. A positron emission tomography study with [11C]raclopride

    International Nuclear Information System (INIS)

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

    1990-01-01

    Several groups have reported increased densities of D2 dopamine receptors in the basal ganglia of schizophrenic brains postmortem. The significance of this finding has been questioned, since an upregulation of receptor number may be a neuronal response to neuroleptic drug treatment. We have used positron emission tomography and [ 11 C]raclopride to examine central D2 dopamine receptor binding in 20 healthy subjects and 18 newly admitted, young, neuroleptic-naive patients with schizophrenia. An in vivo saturation procedure was applied for quantitative determination of D2 dopamine receptor density (Bmax) and affinity (Kd). When the two groups were compared, no significant difference in Bmax or Kd values was found in the putamen or the caudate nucleus. The hypothesis of generally elevated central D2 dopamine receptor densities in schizophrenia was thus not supported by the present findings. In the patients but not in the healthy controls, significantly higher densities were found in the left than in the right putamen but not in the caudate nucleus

  11. Autoradiographic analysis of regional alterations in brain receptors following chronic administration and withdrawal of typical and atypical neuroleptics in rats

    International Nuclear Information System (INIS)

    See, R.E.; Ellison, G.; Toga, A.W.

    1990-01-01

    Rats were administered haloperidol, clozapine, raclopride, or no drug for 28 days or 8 months. Following a 3 week withdrawal period, in vitro autoradiography was utilized to examine receptor binding for dopamine D2([ 3 H]spiperone and [ 3 H]raclopride), dopamine D1([ 3 H]SCH23390), GABA A ([ 3 H]muscimol), benzodiazepine ([ 3 H]RO15-1788), and muscarinic ACh receptors ([ 3 H]QNB). [ 3 H]spiperone was elevated in striatal subregions only in haloperidol-treated rats, with the largest increases seen in the 8 month duration animals. Striatal [ 3 H]raclopride binding was increased after both short- and long-term treatment in both haloperidol and raclopride, but not clozapine-treated animals. Clozapine-treated rats showed significant increases in [ 3 H]SCH23390 in the nucleus accumbens after 28-day administration; otherwise no changes were seen for this ligand in any other groups. Increases in [ 3 H]muscimol binding in the substantia nigra reticulata were seen in haloperidol-treated rats after 8 month treatment. Binding of [ 3 H]QNB and [ 3 H]RO15-1788 were not significantly different from control for any of the drug-treated groups. These data suggest that persisting alterations in receptor binding are primarily seen in dopamine D2 and GABA receptors after withdrawal from chronic administration of haloperidol but not the atypical neuroleptics, clozapine and raclopride. (Authors)

  12. Autoradiographic analysis of regional alterations in brain receptors following chronic administration and withdrawal of typical and atypical neuroleptics in rats

    Energy Technology Data Exchange (ETDEWEB)

    See, R E; Ellison, G; Toga, A W [California Univ., Los Angeles, CA (USA). School of Medicine

    1990-01-01

    Rats were administered haloperidol, clozapine, raclopride, or no drug for 28 days or 8 months. Following a 3 week withdrawal period, in vitro autoradiography was utilized to examine receptor binding for dopamine D2(({sup 3}H)spiperone and ({sup 3}H)raclopride), dopamine D1(({sup 3}H)SCH23390), GABA{sub A}(({sup 3}H)muscimol), benzodiazepine (({sup 3}H)RO15-1788), and muscarinic ACh receptors (({sup 3}H)QNB). ({sup 3}H)spiperone was elevated in striatal subregions only in haloperidol-treated rats, with the largest increases seen in the 8 month duration animals. Striatal ({sup 3}H)raclopride binding was increased after both short- and long-term treatment in both haloperidol and raclopride, but not clozapine-treated animals. Clozapine-treated rats showed significant increases in ({sup 3}H)SCH23390 in the nucleus accumbens after 28-day administration; otherwise no changes were seen for this ligand in any other groups. Increases in ({sup 3}H)muscimol binding in the substantia nigra reticulata were seen in haloperidol-treated rats after 8 month treatment. Binding of ({sup 3}H)QNB and ({sup 3}H)RO15-1788 were not significantly different from control for any of the drug-treated groups. These data suggest that persisting alterations in receptor binding are primarily seen in dopamine D2 and GABA receptors after withdrawal from chronic administration of haloperidol but not the atypical neuroleptics, clozapine and raclopride. (Authors).

  13. Why are doctors still prescribing neuroleptics?

    Science.gov (United States)

    Charlton, B G

    2006-06-01

    There are two main pharmacological methods of suppressing undesired behaviour: sedation or neuroleptics. Traditionally, the invention of neuroleptics has been hailed as one of the major clinical breakthroughs of the twentieth century, since they calmed agitation without (necessarily) causing sedation. The specifically neuroleptic form of behavioural control is achieved by making patients psychologically Parkinsonian, which entails emotional blunting and consequent demotivation. Furthermore, chronic neuroleptic usage creates dependence, so that in the long term, neuroleptics are doing most patients more harm than good. The introduction of 'atypical' neuroleptics (neuroleptically-weak but strongly sedative neuroleptics) has made only a difference in degree, and at the cost of a wide range of potentially fatal metabolic and other side-effects. For half a century, the creation of millions of Parkinsonian patients may have been misinterpreted as a 'cure' for schizophrenia. Such a wholesale re-interpretation of neuroleptic therapy represents an unprecedented disaster for the self-image and public reputation of both psychiatry and the whole medical profession. Nonetheless, except as a last resort, neuroleptics should swiftly be replaced by gentler and safer sedatives.

  14. Neuroleptic Malignant Syndrome

    Science.gov (United States)

    ... such as neuroleptic malignant syndrome. Much of this research focuses on finding ways to prevent and treat the disorder. Show More Show Less Search Disorders SEARCH SEARCH Definition Treatment Prognosis Clinical Trials Organizations Publications Definition Neuroleptic malignant syndrome is ...

  15. Synthesis and evaluation of three iodinated haloperidol derivatives as potential dopamine receptor imaging agents

    International Nuclear Information System (INIS)

    Hunter, D.H.; Strickland, L.A.; Zabel, P.L.

    1990-01-01

    Haloperidol, a neuroleptic which shows D-2 receptor affinity and selectivity, has been labelled primarily with positron emitting isotopes. The authors have synthesized three iodinated analogues of Haloperidol to investigate the possibility of an iodine-123 labelled agent for SPECT imaging. These compounds were obtained from the substitution of halogenated butyrophenones by halogenated arylpiperidols. In vitro and in vivo experiments will be discussed

  16. Cortical and subcortical 5-HT2A receptor binding in neuroleptic-naive first-episode schizophrenic patients

    DEFF Research Database (Denmark)

    Erritzoe, David; Rasmussen, Hans; Kristiansen, Klaus Nyegaard

    2008-01-01

    MRIs and PET images. The cerebellum was used as a reference region. The binding potential of specific tracer binding (BP(p)) was used as the outcome measure. No significant difference was seen in cortical receptor distribution between patients and controls. An increase in 5-HT(2A) receptor binding...

  17. GABA receptor imaging

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jong Doo [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2007-04-15

    GABA is primary an inhibitory neurotransmitter that is localized in inhibitory interneurons. GABA is released from presynaptic terminals and functions by binding to GABA receptors. There are two types of GABA receptors, GABA{sub A}-receptor that allows chloride to pass through a ligand gated ion channel and GABA{sub B}-receptor that uses G-proteins for signaling. The GABA{sub A}-receptor has a GABA binding site as well as a benzodiazepine binding sites, which modulate GABA{sub A}-receptor function. Benzodiazepine GABAA receptor imaging can be accomplished by radiolabeling derivates that activates benzodiazepine binding sites. There has been much research on flumazenil (FMZ) labeled with {sup 11}C-FMZ, a benzodiazepine derivate that is a selective, reversible antagonist to GABAA receptors. Recently, {sup 18}F-fluoroflumazenil (FFMZ) has been developed to overcome {sup 11}C's short half-life. {sup 18}F-FFMZ shows high selective affinity and good pharmacodynamics, and is a promising PET agent with better central benzodiazepine receptor imaging capabilities. In an epileptic focus, because the GABA/benzodiazepine receptor amount is decreased, using '1{sup 1}C-FMZ PET instead of {sup 18}F-FDG, PET, restrict the foci better and may also help find lesions better than high resolution MR. GABA{sub A} receptors are widely distributed in the cerebral cortex, and can be used as an viable neuronal marker. Therefore it can be used as a neuronal cell viability marker in cerebral ischemia. Also, GABA-receptors decrease in areas where neuronal plasticity develops, therefore, GABA imaging can be used to evaluate plasticity. Besides these usages, GABA receptors are related with psychological diseases, especially depression and schizophrenia as well as cerebral palsy, a motor-related disorder, so further in-depth studies are needed for these areas.

  18. GABA receptor imaging

    International Nuclear Information System (INIS)

    Lee, Jong Doo

    2007-01-01

    GABA is primary an inhibitory neurotransmitter that is localized in inhibitory interneurons. GABA is released from presynaptic terminals and functions by binding to GABA receptors. There are two types of GABA receptors, GABA A -receptor that allows chloride to pass through a ligand gated ion channel and GABA B -receptor that uses G-proteins for signaling. The GABA A -receptor has a GABA binding site as well as a benzodiazepine binding sites, which modulate GABA A -receptor function. Benzodiazepine GABAA receptor imaging can be accomplished by radiolabeling derivates that activates benzodiazepine binding sites. There has been much research on flumazenil (FMZ) labeled with 11 C-FMZ, a benzodiazepine derivate that is a selective, reversible antagonist to GABAA receptors. Recently, 18 F-fluoroflumazenil (FFMZ) has been developed to overcome 11 C's short half-life. 18 F-FFMZ shows high selective affinity and good pharmacodynamics, and is a promising PET agent with better central benzodiazepine receptor imaging capabilities. In an epileptic focus, because the GABA/benzodiazepine receptor amount is decreased, using '1 1 C-FMZ PET instead of 18 F-FDG, PET, restrict the foci better and may also help find lesions better than high resolution MR. GABA A receptors are widely distributed in the cerebral cortex, and can be used as an viable neuronal marker. Therefore it can be used as a neuronal cell viability marker in cerebral ischemia. Also, GABA-receptors decrease in areas where neuronal plasticity develops, therefore, GABA imaging can be used to evaluate plasticity. Besides these usages, GABA receptors are related with psychological diseases, especially depression and schizophrenia as well as cerebral palsy, a motor-related disorder, so further in-depth studies are needed for these areas

  19. Neurotransmitter receptor imaging

    International Nuclear Information System (INIS)

    Cordes, M.; Hierholzer, J.; Nikolai-Beyer, K.

    1993-01-01

    The importance of neuroreceptor imaging in vivo using single photon emission tomography (SPECT) and positron emission tomography (PET) has increased enormously. The principal neurotransmitters, such as dopamine, GABA/benzodiazepine, acetylcholine, and serotonin, are presented with reference to anatomical, biochemical, and physiological features. The main radioligands for SPECT and PET are introduced, and methodological characteristics of both PET and SPECT presented. Finally, the results of neurotransmitter receptor imaging obtained so far will be discussed. (orig.) [de

  20. Ritanserin as add-on medication to neuroleptic therapy for patients with chronic or subchronic schizophrenia

    NARCIS (Netherlands)

    Den Boer, JA; Vahlne, JO; Post, P; Heck, AH; Daubenton, F; Olbrich, R

    The effect of ritanserin, a potent 5HT(2A/2C) receptor antagonist, used as an add-on medication to neuroleptic treatmentin patients with schizophrenia, was compared with that of placebo, in an international, double-blind, parallel-group study. Previously established neuroleptic therapy was

  1. Quantitative analysis of receptor imaging

    International Nuclear Information System (INIS)

    Fu Zhanli; Wang Rongfu

    2004-01-01

    Model-based methods for quantitative analysis of receptor imaging, including kinetic, graphical and equilibrium methods, are introduced in detail. Some technical problem facing quantitative analysis of receptor imaging, such as the correction for in vivo metabolism of the tracer and the radioactivity contribution from blood volume within ROI, and the estimation of the nondisplaceable ligand concentration, is also reviewed briefly

  2. Negative symptoms in nondeficit syndrome respond to neuroleptic treatment with changes in plasma homovanillic acid concentrations.

    OpenAIRE

    Suzuki, E; Kanba, S; Koshikawa, H; Nibuya, M; Yagi, G; Asai, M

    1996-01-01

    Deficit syndrome (DS) in schizophrenia is characterized by serious, chronic, and primary negative symptoms. We investigated differences in response to neuroleptic treatment between 8 DS patients and 6 nondeficit syndrome (NDS) patients who had the selective dopamine-D2 receptor blocker bromperidol added to their neuroleptic regimens. First, 9 mg/d was administered for 4 weeks, followed by 18 mg/d for another 4 weeks. Plasma homovanillic acid (pHVA) and plasma bromperidol concentrations were m...

  3. Risk factors in neuroleptic malignant syndrome.

    Science.gov (United States)

    Gupta, Vinay; Magon, Rakesh; Mishra, B P; Sidhu, G B S; Mahajan, Ranjiv

    2003-01-01

    Neuroleptic malignant syndrome (NMS) is an uncommon but potentially serious idiosyncratic response to neuroleptic antipsychotics. It usually affects young males, but the risk has been seen to increase with certain factors including the administration practices of antipsychotic neuroleptics in these individuals. Even though no predictors for NMS are yet known, this article highlights the findings on certain risk factors as seen from a series of fifteen patients who developed NMS. Cautious use of neuroleptics in those at risk, early recognition and institution of immediate management is important.

  4. Acute psychosis followed by fever: Malignant neuroleptic syndrome or viral encephalitis?

    Directory of Open Access Journals (Sweden)

    Stojanović Zvezdana

    2014-01-01

    Full Text Available Introduction. Neuroleptic malignant syndrome is rare, but potentially fatal idiosyncratic reaction to antipsychotic medications. It is sometimes difficult to diagnose some clinical cases as neuroleptic malignant syndrome and differentiate it from the acute viral encephalitis. Case report. We reported a patient diagnosed with acute psychotic reaction which appeared for the first time. The treatment started with typical antipsychotic, which led to febrility. The clinical presentation of the patient was characterised by the signs and symptoms that might have indicated the neuroleptic malignant syndrome as well as central nervous system viral disease. In order to make a detailed diagnosis additional procedures were performed: electroencephalogram, magnetic resonance imaging of the head, lumbar puncture and a serological test of the cerebrospinal fluid. Considering that after the tests viral encephalitis was ruled out and the diagnosis of neuroleptic malignant syndrome made, antipsychotic therapy was immediately stopped. The patient was initially treated with symptomatic therapy and after that with atypical antipsychotic and electroconvulsive therapy, which led to complete recovery. Conclusion. We present the difficulties of early diagnosis at the first episode of acute psychotic disorder associated with acute febrile condition. Concerning the differential diagnosis it is necessary to consider both neuroleptic malignant syndrome and viral encephalitis, i.e. it is necessary to make the neuroradiological diagnosis and conduct cerebrospinal fluid analysis and blood test. In neuroleptic malignant syndrome treatment a combined use of electroconvulsive therapy and low doses of atypical antipsychotic are confirmed to be successful.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1980-09-01

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

  6. Quantitative structure-activity relationships of salicylamide neuroleptic agents.

    Science.gov (United States)

    Gupta, S P; Saha, R N; Singh, P

    1990-05-01

    The in vitro antidopamine activity of substituted N-[(1-alkyl-2-pyrrolidinyl)methyl]-6-methoxysalicylamides was found to be well correlated with the hydrophobic and electronic nature of substituents at the 3-position, and with the steric nature of groups replacing the hydrogen atom of the salicyl hydroxy group. In contrast, only the hydrophobic and steric characteristics were found to be important in the in vivo activity of these neuroleptics. This difference suggests that different mechanisms are probably involved in their in vitro and in vivo actions, and that the relevant receptors are slightly different in structure. The in vitro results suggest that electron donation by the 3-substituent strengthens the formation of a hydrogen bond between the carbonyl group of the amide moiety and a hydrogen of the receptor.

  7. [Case with difficulty in differentiating between transient neuroleptic malignant syndrome and catatonia after neuroleptic analgesia].

    Science.gov (United States)

    Yanagawa, Youichi; Miyazaki, Masaki

    2010-02-01

    An 18-year-old woman was treated with neuroleptic analgesia using fentanyl, morphine, droperidol and haloperidol for general anesthesia and pain control for her knee operation. Postoperatively, she showed emotional unstableness, following dyspnea, tachycardia, fever, hyperhydrosis, muscle rigidity and myoclonus like involuntary movement. She received infusion of 140 mg dantrolene in total under suspicion of having neuroleptic malignant syndrome, but her symptoms improved slightly. After being transferred to our hospital, she exhibited immobility, mutism, rigidity, and catalepsy, and she was suspected of having lethal catatonia. Infusion of diazepam 10 mg resulted in dramatical improvement of her symptoms. Differential diagnosis between neuroleptic malignant syndrome and catatonia is difficult; however, a first line therapy is differential diagnosis. Thus, physician should consider catatonia when treating neuroleptic malignant like syndrome.

  8. Neuroleptic malignant syndrome (a case report.

    Directory of Open Access Journals (Sweden)

    Patkar A

    1991-07-01

    Full Text Available An adult schizophrenic patient developed neuroleptic malignant syndrome following treatment with parenteral haloperidol. An early recognition of the syndrome, immediate discontinuation of the offending agent and prompt treatment with bromocriptine and lorazepam produced a good recovery. The various features of the case are discussed in view of the potential lethality of the syndrome.

  9. Acute cardiac failure in neuroleptic malignant syndrome.

    LENUS (Irish Health Repository)

    Sparrow, Patrick

    2012-02-03

    We present a case of rapid onset acute cardiac failure developing as part of neuroleptic malignant syndrome in a 35-year-old woman following treatment with thioridazine and lithium. Post mortem histology of cardiac and skeletal muscle showed similar changes of focal cellular necrosis and vacuolation suggesting a common disease process.

  10. Delirium followed by neuroleptic malignant syndrome in ...

    African Journals Online (AJOL)

    Delirium and neuroleptic malignant syndrome (NMS) are two uncommon syndromes that are often unrecognized or misdiagnosed by the primary physicians as functional psychiatric disorders. The infrequency and the heterogeneity of clinical manifestation, progression and outcome with which those diagnoses are ...

  11. Contribution of the central histaminergic transmission in the cataleptic and neuroleptic effects of haloperidol.

    Science.gov (United States)

    Jain, Nishant S; Tandi, Lakshyapati; Verma, Lokesh

    2015-12-01

    The antipsychotic properties of haloperidol are primarily attributed to its ability to block dopamine D2 receptors. Histaminergic transmission modulates some of the behavioral effects of haloperidol. Hence, the present study investigated the contribution of central histaminergic transmission in the cataleptic and neuroleptic effect of haloperidol respectively, using bar test and conditioned avoidance response (CAR) in a two-way shuttle box. The studies revealed that haloperidol (0.50 or 1 mg/kg, i.p.) exhibited cataleptic behavior and inhibited conditioned avoidance response (CAR) in the doses 0.25 or 0.50 mg in rats. The rats, pretreated centrally (i.c.v.) with histamine precursor, L-histidine (1, 2.5 μg) or histamine neuronal inducer (H3 receptor antagonist), thioperamide (20, 50 μg/rat), showed an enhanced cataleptic effect with sub-maximal dose of haloperidol (0.5 mg/kg, i.p.). Similarly, the neuroleptic effect of haloperidol (0.25 mg/kg, i.p.) in CAR was also potentiated in the rats pretreated with L-histidine (2.5 μg) or thioperamide (50 μg/rat). Further, the cataleptic effect of haloperidol (1 mg/kg, i.p.) was attenuated in rats pretreated with the H1 receptor antagonist, chlorpheniramine (60, 80 μg/rat, i.c.v.) or H2 receptor antagonist, ranitidine (60 μg/rat, i.c.v.). However, the neuroleptic effect of haloperidol (0.5 mg/kg, i.p.) was completely reversed by pretreatment with ranitidine (60 μg/rat, i.c.v.), and partially attenuated by chlorpheniramine (80 μg/rat, i.c.v.). These findings suggest the possible involvement of histaminergic transmission in the cataleptic and neuroleptic effects of haloperidol probably via H1 or H2 receptor stimulation. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Low dosage of aripiprazole induced neuroleptic malignant syndrome after interaction with other neuroleptic drugs

    Directory of Open Access Journals (Sweden)

    Albino Petrone

    2013-09-01

    Full Text Available Aripiprazole is a 2nd generation antipsychotic medication, atypical neuroleptic used for treatment of schizophrenia improving symptoms such as hallucinations, delusions, and disorganized thinking. A potentially fatal symptom complex sometimes referred to as neuroleptic malignant syndrome (NMS has been reported in association with administration of antipsychotic drugs, including aripiprazole. Rare cases of NMS occurred during aripiprazole treatment in the worldwide clinical database. The disease is characterized by a distinctive clinical syndrome of mental status change, rigidity, fever, and dysautonomia. We report on a 63-year old woman with depression syndrome who developed neuroleptic malignant syndrome after twelve days of aripripazole 5 mg per day. Our case is added to the small number already described and suggests the need for caution when aripripazole is added to increase the effect of other antipsychotics.

  13. PET imaging for receptor occupancy: meditations on calculation and simplification.

    Science.gov (United States)

    Zhang, Yumin; Fox, Gerard B

    2012-03-01

    This invited mini-review briefly summarizes procedures and challenges of measuring receptor occupancy with positron emission tomography. Instead of describing the detailed analytic procedures of in vivo ligand-receptor imaging, the authors provide a pragmatic approach, along with personal perspectives, for conducting positron emission tomography imaging for receptor occupancy, and systematically elucidate the mathematics of receptor occupancy calculations in practical ways that can be understood with elementary algebra. The authors also share insights regarding positron emission tomography imaging for receptor occupancy to facilitate applications for the development of drugs targeting receptors in the central nervous system.

  14. PET imaging of human cardiac opioid receptors

    Energy Technology Data Exchange (ETDEWEB)

    Villemagne, Patricia S.R.; Dannals, Robert F. [Department of Radiology, The Johns Hopkins University School of Medicine, 605 N Caroline St., Baltimore, Maryland (United States); Department of Environmental Health Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Ravert, Hayden T. [Department of Radiology, The Johns Hopkins University School of Medicine, 605 N Caroline St., Baltimore, Maryland (United States); Frost, James J. [Department of Radiology, The Johns Hopkins University School of Medicine, 605 N Caroline St., Baltimore, Maryland (United States); Department of Environmental Health Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States)

    2002-10-01

    The presence of opioid peptides and receptors and their role in the regulation of cardiovascular function has been previously demonstrated in the mammalian heart. The aim of this study was to image {mu} and {delta} opioid receptors in the human heart using positron emission tomography (PET). Five subjects (three females, two males, 65{+-}8 years old) underwent PET scanning of the chest with [{sup 11}C]carfentanil ([{sup 11}C]CFN) and [{sup 11}C]-N-methyl-naltrindole ([{sup 11}C]MeNTI) and the images were analyzed for evidence of opioid receptor binding in the heart. Either [{sup 11}C]CFN or [{sup 11}C]MeNTI (20 mCi) was injected i.v. with subsequent dynamic acquisitions over 90 min. For the blocking studies, either 0.2 mg/kg or 1 mg/kg of naloxone was injected i.v. 5 min prior to the injection of [{sup 11}C]CFN and [{sup 11}C]MeNTI, respectively. Regions of interest were placed over the left ventricle, left ventricular chamber, lung and skeletal muscle. Graphical analysis demonstrated average baseline myocardial binding potentials (BP) of 4.37{+-}0.91 with [{sup 11}C]CFN and 3.86{+-}0.60 with [{sup 11}C]MeNTI. Administration of 0.2 mg/kg naloxone prior to [{sup 11}C]CFN produced a 25% reduction in BP in one subject in comparison with baseline values, and a 19% decrease in myocardial distribution volume (DV). Administration of 1 mg/kg of naloxone before [{sup 11}C]MeNTI in another subject produced a 14% decrease in BP and a 21% decrease in the myocardial DV. These results demonstrate the ability to image these receptors in vivo by PET. PET imaging of cardiac opioid receptors may help to better understand their role in cardiovascular pathophysiology and the effect of abuse of opioids and drugs on heart function. (orig.)

  15. Negative symptoms in nondeficit syndrome respond to neuroleptic treatment with changes in plasma homovanillic acid concentrations.

    Science.gov (United States)

    Suzuki, E; Kanba, S; Koshikawa, H; Nibuya, M; Yagi, G; Asai, M

    1996-05-01

    Deficit syndrome (DS) in schizophrenia is characterized by serious, chronic, and primary negative symptoms. We investigated differences in response to neuroleptic treatment between 8 DS patients and 6 nondeficit syndrome (NDS) patients who had the selective dopamine-D2 receptor blocker bromperidol added to their neuroleptic regimens. First, 9 mg/d was administered for 4 weeks, followed by 18 mg/d for another 4 weeks. Plasma homovanillic acid (pHVA) and plasma bromperidol concentrations were measured, and psychiatric symptoms were scored. In the NDS patients, both positive and negative symptoms improved. However, only the positive symptom scores changed in the DS patients. On day 4, pHVA concentrations of the NDS patients alone were significantly elevated. Plasma bromperidol concentrations did not differ between the groups. These results suggest that bromperidol exerts different effects on negative symptoms and pHVA concentrations between NDS and DS patients, effects that are unrelated to plasma bromperidol concentrations.

  16. Imaging opiate receptors with positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Frost, J.J.; Dannals, R.F.; Ravert, H.T.; Wilson, A.A.; Wong, D.F.; Links, J.M.; Burns, H.D.; Kuhar, M.J.; Snyder, S.H.; Wagner, H.N. Jr.

    1984-01-01

    Opiate receptors exist in the mammalian brain and are thought to meditate the diverse pharmacological actions of the opiates, such as analgesia, euphoria, and sedation. The 4-carbomethoxyl derivatives of fentanyl, such as lofentanil and R31833 (4-carbomethoxyfentanyl) bind to the opiate receptor with high affinity. C-11 R31833 was synthesized by reacting C-11 methyl iodide with the appropriate carboxylate. Male ICR mice were injected intravenously with C-11 R31833 (5..mu..g/kg), killed 30 minutes later, and the brains rapidly dissected. The thalami, striata, and cerebral cortex are rich in opiate receptors, but the cerebellum contains a very low concentration of opiate receptors. The thalamus/cerebellum and striatum/cerebellum activity ratios, calculated per mg of wet tissue, were 4.1 and 5.2 respectively. Coinjection of 5mg/kg naloxone reduced the ratios to 1.1, which indicates that the preferential localization of C-11 R31833 in the thalami and striata is due to binding to opiate is due to binding to opiate receptors. A 22 kg anesthetized male baboon was imaged using the NeuroECAT after injection of 18.9 mCi of C-11 R13833 (0.50 ..mu..g/kg, specific activity 616 Ci/mmole at time of injection). From 15-70 minutes after injection preferential accumulation of activity could be seen in the thalami, caudate nuclei, and cerebral cortex and, conversely, low activity was demonstrated in the cerebellum. At one hour postinjection the maximum measured caudate/cerebellum activity ratio per pixel was 2.9. For the NeuroECAT the recovery coefficient for the baboon caudate is ca. 0.2-0.3, and therefore the actual caudate/cerebellum ratio is ca. 10-15.

  17. Imaging opiate receptors with positron emission tomography

    International Nuclear Information System (INIS)

    Frost, J.J.; Dannals, R.F.; Ravert, H.T.

    1984-01-01

    Opiate receptors exist in the mammalian brain and are thought to meditate the diverse pharmacological actions of the opiates, such as analgesia, euphoria, and sedation. The 4-carbomethoxyl derivatives of fentanyl, such as lofentanil and R31833 (4-carbomethoxyfentanyl) bind to the opiate receptor with high affinity. C-11 R31833 was synthesized by reacting C-11 methyl iodide with the appropriate carboxylate. Male ICR mice were injected intravenously with C-11 R31833 (5μg/kg), killed 30 minutes later, and the brains rapidly dissected. The thalami, striata, and cerebral cortex are rich in opiate receptors, but the cerebellum contains a very low concentration of opiate receptors. The thalamus/cerebellum and striatum/cerebellum activity ratios, calculated per mg of wet tissue, were 4.1 and 5.2 respectively. Coinjection of 5mg/kg naloxone reduced the ratios to 1.1, which indicates that the preferential localization of C-11 R31833 in the thalami and striata is due to binding to opiate is due to binding to opiate receptors. A 22 kg anesthetized male baboon was imaged using the NeuroECAT after injection of 18.9 mCi of C-11 R13833 (0.50 μg/kg, specific activity 616 Ci/mmole at time of injection). From 15-70 minutes after injection preferential accumulation of activity could be seen in the thalami, caudate nuclei, and cerebral cortex and, conversely, low activity was demonstrated in the cerebellum. At one hour postinjection the maximum measured caudate/cerebellum activity ratio per pixel was 2.9. For the NeuroECAT the recovery coefficient for the baboon caudate is ca. 0.2-0.3, and therefore the actual caudate/cerebellum ratio is ca. 10-15

  18. Olanzapine-Induced Neuroleptic Malignant Syndrome

    Directory of Open Access Journals (Sweden)

    Seyedhamze Hosseini

    2017-05-01

    Full Text Available Neuroleptic malignant syndrome (NMS is a rare but life-threatening idiosyncratic side effect resulting from neuroleptic drugs. NMS mainly occurs in patients treated with high-potency typical antipsychotics, but rarely caused by atypical antipsychotics. Although NMS is less common with atypical antipsychotic, but it seems that its incidence is rising due to increased administration of such drugs. We present the case of a 27-year-old man with a history of paranoid schizophrenia that showed signs consistent with NMS that occurred after treatment with olanzapine. The patient was adherent to treatment. He had decreased level of consciousness, muscle rigidity, diaphoresis, fever, drooling, urinary incontinence, and high blood pressure. This patient illustrates that NMS can occur due to treatment with atypical antipsychotic drugs like olanzapine, particularly in the presence of risk factors. This phenomenon is often unrecognized, underdiagnosed, or not treated properly. Physicians should be aware that NMS with extrapyramidal syndrome could occur with olanzapine at steady state doses without recent dosage adjustments or titration. It is essential that adequate and safe dose of medication is chosen and the patient is monitored by the signs and symptoms of this lethal syndrome.

  19. Somatostatin receptor imaging in intracranial tumours

    International Nuclear Information System (INIS)

    Schmidt, M.; Scheidhauer, K.; Voth, E.; Schicha, H.; Luyken, C.; Hildebrandt, G.; Klug, N.

    1998-01-01

    The somatostatin analogue [ 111 In-DTPA-d-Phe 1 ]-octreotide ( 111 In-octreotide) allows scintigraphic visualization of somatostatin receptor-expressing tissue. While it is well known that a large variety of tissues express somatostatin receptors and 111 In-octreotide scintigraphy has a clearly defined role in various neuroendocrine diseases, the clinical value of 111 In-octreotide scintigraphy in brain tumours is still under clinical investigation. In 124 patients with 141 brain lesions (63 meningiomas, 24 pituitary adenomas, 10 gliomas WHO class I and II, 12 gliomas WHO class III and IV, 11 neurinomas and 2 neurofibromas, 7 metastases and 12 other varieties: three non-Hodgkin B-cell lymphomas, two epidermoids, one abscess, one angioleiomyoma, one chordoma, one haemangiopericytoma, one osteosarcoma, one plasmacytoma and one pseudocyst), 111 In-octreotide scintigraphy was performed 4-6 and 24 h after i.v. injection of 110-220 MBq 111 In-octreotide. Planar images of the head in four views with a 128 x 128 matrix and single-photon emission tomographic images (64 x 64 matrix) were acquired, and lesions were graded according to qualitative tracer uptake. Fifty-nine of the 63 meningiomas showed moderate to intense tracer uptake. Nine of 24 pituitary adenomas were visible; the remaining 15 did not show any tracer uptake. None of the class I and II gliomas with an intact blood-brain barrier were detected whereas 11/12 class III and IV gliomas showed 111 In-octreotide uptake. None of the neurinomas or neurofibromas were positive. Five of seven metastases were classified as positive, as were the osteosarcoma, two of three non-Hodgkin B-cell lymphomas, one abscess, one angioleiomyoma, one chordoma and one haemangiopericytoma. The other varieties (one non-Hodgkin B-cell lymphoma, two epidermoids, one plasmacytoma and one pseudocyst) did not show 111 In-octreotide uptake. The results demonstrate that a large variety of intracranial lesions express somatostatin receptors and

  20. Somatostatin receptor imaging in intracranial tumours

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, M.; Scheidhauer, K.; Voth, E.; Schicha, H. [Department of Nuclear Medicine, University of Koeln (Germany); Luyken, C.; Hildebrandt, G.; Klug, N. [Department of Neurosurgery, University of Kolen (Germany)

    1998-07-01

    The somatostatin analogue [{sup 111}In-DTPA-d-Phe{sup 1}]-octreotide ({sup 111}In-octreotide) allows scintigraphic visualization of somatostatin receptor-expressing tissue. While it is well known that a large variety of tissues express somatostatin receptors and {sup 111}In-octreotide scintigraphy has a clearly defined role in various neuroendocrine diseases, the clinical value of {sup 111}In-octreotide scintigraphy in brain tumours is still under clinical investigation. In 124 patients with 141 brain lesions (63 meningiomas, 24 pituitary adenomas, 10 gliomas WHO class I and II, 12 gliomas WHO class III and IV, 11 neurinomas and 2 neurofibromas, 7 metastases and 12 other varieties: three non-Hodgkin B-cell lymphomas, two epidermoids, one abscess, one angioleiomyoma, one chordoma, one haemangiopericytoma, one osteosarcoma, one plasmacytoma and one pseudocyst), {sup 111}In-octreotide scintigraphy was performed 4-6 and 24 h after i.v. injection of 110-220 MBq {sup 111}In-octreotide. Planar images of the head in four views with a 128 x 128 matrix and single-photon emission tomographic images (64 x 64 matrix) were acquired, and lesions were graded according to qualitative tracer uptake. Fifty-nine of the 63 meningiomas showed moderate to intense tracer uptake. Nine of 24 pituitary adenomas were visible; the remaining 15 did not show any tracer uptake. None of the class I and II gliomas with an intact blood-brain barrier were detected whereas 11/12 class III and IV gliomas showed {sup 111}In-octreotide uptake. None of the neurinomas or neurofibromas were positive. Five of seven metastases were classified as positive, as were the osteosarcoma, two of three non-Hodgkin B-cell lymphomas, one abscess, one angioleiomyoma, one chordoma and one haemangiopericytoma. The other varieties (one non-Hodgkin B-cell lymphoma, two epidermoids, one plasmacytoma and one pseudocyst) did not show {sup 111}In-octreotide uptake. The results demonstrate that a large variety of intracranial

  1. Experimental research for tumor VIP receptor imaging

    International Nuclear Information System (INIS)

    Li Qianwei; Tan Tianzhi

    1998-01-01

    To study the possibility of radioactive labelled vasoactive intestinal peptide (VIP) for tumor VIP receptor imaging. 125 I-VIP was prepared by chloramine-T method, and purified by Sephadex G-50 column chromatography. The bioactivity and stability of 125 I-VIP were measured by silica 60 F 254 TLC and competition test to SGC7901 cell in vitro. The biodistribution of 125 I-VIP was studied in the nude mice bearing tumor. The results showed that labelled rate of 125 I was 73.8%, the specific activity was 18.2 PBq/mol, the radiochemical purity (RCP) was over 98% and remained 96.3% after 48 days stored at -80 degree C. The specific binding of 125 I-VIP to the SGC7901 cell was inhibited by VIP in dose dependence in the competition experiment. The radioactivity of tumor was higher than that of muscles in all phases (P<0.05-0.01), the peak activity of tumor occurred at 30 min (3.58 +- 0.48ID%/g) and the peak ratio of T/N occurred at 60 min after the injection. The activity of lungs was obviously higher than that of blood, the intestine was always in low level. Most of the activity in the body was mainly eliminated from kidney. The present study demonstrated that the radioactive labelled VIP is a promising agent for tumor VIP receptor scintigraphy

  2. Real-Time G-Protein-Coupled Receptor Imaging to Understand and Quantify Receptor Dynamics

    Directory of Open Access Journals (Sweden)

    María S. Aymerich

    2011-01-01

    Full Text Available Understanding the trafficking of G-protein-coupled receptors (GPCRs and their regulation by agonists and antagonists is fundamental to develop more effective drugs. Optical methods using fluorescent-tagged receptors and spinning disk confocal microscopy are useful tools to investigate membrane receptor dynamics in living cells. The aim of this study was to develop a method to characterize receptor dynamics using this system which offers the advantage of very fast image acquisition with minimal cell perturbation. However, in short-term assays photobleaching was still a problem. Thus, we developed a procedure to perform a photobleaching-corrected image analysis. A study of short-term dynamics of the long isoform of the dopamine type 2 receptor revealed an agonist-induced increase in the mobile fraction of receptors with a rate of movement of 0.08 μm/s For long-term assays, the ratio between the relative fluorescence intensity at the cell surface versus that in the intracellular compartment indicated that receptor internalization only occurred in cells co-expressing G protein-coupled receptor kinase 2. These results indicate that the lateral movement of receptors and receptor internalization are not directly coupled. Thus, we believe that live imaging of GPCRs using spinning disk confocal image analysis constitutes a powerful tool to study of receptor dynamics.

  3. Neuroleptic malignant syndrome revisited in the perspective of pakistan

    International Nuclear Information System (INIS)

    Shakoor, A.

    2012-01-01

    Objective: Neuroleptic malignant syndrome (NMS) is a life threatening adverse reaction of antipsychotic drugs, especially of dopamine receptor antagonists (DRA's). In addition to clinical and pharmacological risk factors, legal and ethical risk factors may be contributory towards the incidence, diagnosis and prognosis of NMS in Pakistan. Study Design: Experimental case study. Place and Duration of Study: The department of psychiatry and behavioral sciences of Bahawal Victoria Hospital affiliated with Quaid-e-Azam Medical College, from July 2011 to October 2012. Subjects and Methods: All the patients with probable NMS, received consecutively at the inpatient department of psychiatry, were included and investigated to rule out any other medical condition mimicking the syndrome. The patients were treated till complete recovery from the syndrome. The psychiatric diagnoses were confirmed, during their hospital stay, according to ICD10 Diagnostic Criteria for Research, the residual symptoms were recorded and tabulated along with other important characteristics of the patients. Results: Reckless use of DRA's in the form of intramuscular depot injections or high initial oral doses, along with certain other previously perceived clinical risk factors, increased the chance of developing NMS. Female gender and younger age along with early detection and prudent management proved to be good pro-gnostic factors for NMS in our study. The diverse categories of the first hand attending health providers e.g. doctors, quacks and faith healers of our psychiatric patients frequently used antipsychotics. This scenario points towards the lapses in determination of pathways to care, legality and ethics governing the mental health care in Pakistan. Conclusion: Standard protocol must be followed to start antipsychotics in psychotic patients, especially while planning to use depot DRA's. The manic patients are even more sensitive to develop extrapyramidal side effects and neuroleptic

  4. Imaging of receptors in clinical neurosciences

    NARCIS (Netherlands)

    Korf, J

    This article deals with the question why should one determine receptors in the brain with positron and single photon emission tomography (PET and SPECT, respectively). Radiopharmaceuticals for a wide variety of receptors are available now. Receptors studies with PET and SPECT have thus far focused

  5. Side effects in preventive maintenance therapy with neuroleptics with special emphasis on tardive dyskinesia.

    Science.gov (United States)

    Logothetis, J; Paraschos, A; Frangos, E

    1981-01-01

    Neuroleptics induce hypersensitivity reactions, and toxic, systemic and extrapyramidal manifestations. The latter mainly include acute dystonic reactions, other early dyskinesias, akathisia, parkinsonism and TD. These drugs have been implicated for DA antagonism exerted by an adenylate cyclase inhibition. Prolonged blockade of DA receptors is considered as the motivation for a counterbalancing mechanism inducing the DA supersensitivity from which TD results. Recent reports suggest cholinergic and GABA ergic insufficiency as secondary participants. The increasing frequency of TD calls for prevention by modifying treatment practices and searching for effective measures to combat the symptoms.

  6. Dynamics of Corticosteroid Receptors: Lessons from Live Cell Imaging

    International Nuclear Information System (INIS)

    Nishi, Mayumi

    2011-01-01

    Adrenal corticosteroids (cortisol in humans or corticosterone in rodents) exert numerous effects on the central nervous system that regulates the stress response, mood, learning and memory, and various neuroendocrine functions. Corticosterone (CORT) actions in the brain are mediated via two receptor systems: the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR). It has been shown that GR and MR are highly colocalized in the hippocampus. These receptors are mainly distributed in the cytoplasm without hormones and translocated into the nucleus after treatment with hormones to act as transcriptional factors. Thus the subcellular dynamics of both receptors are one of the most important issues. Given the differential action of MR and GR in the central nervous system, it is of great consequence to clarify how these receptors are trafficked between cytoplasm and nucleus and their interactions are regulated by hormones and/or other molecules to exert their transcriptional activity. In this review, we focus on the nucleocytoplasmic and subnuclear trafficking of GR and MR in neural cells and non-neural cells analyzed by using molecular imaging techniques with green fluorescent protein (GFP) including fluorescence recovery after photobleaching (FRAP) and fluorescence resonance energy transfer (FRET), and discuss various factors affecting the dynamics of these receptors. Furthermore, we discuss the future directions of in vivo molecular imaging of corticosteroid receptors at the whole brain level

  7. Fluorinated benzamide neuroleptics--III. Development of (S)-N-[(1-allyl-2-pyrrolidinyl)methyl]-5-(3-[{sup 18}F]fluoropropyl)-2,3- dimethoxybenzamide as an improved dopamine D-2 receptor tracer

    Energy Technology Data Exchange (ETDEWEB)

    Mukherjee, Jogeshwar; Zhiying, Yang; Das, Malay K; Brown, Terry

    1995-04-01

    We have prepared five new analogs (n-propyl, iso-propyl, allyl, n-butyl, and iso-butyl) of the dopamine D-2 receptor antagonist, FPMB which result from modifications of the ethyl group at the pyrrolidine nitrogen in FPMB. As expected, all new derivatives showed higher apparent lipophilicity (log k{sub w}), with iso-butyl being the most lipophilic (log k{sub w} = 2.52), followed by the allyl derivative (log k{sub w} = 2.43). The allyl group showed the largest increase in affinity (from 0.26 nM for the ethyl substituent to 0.03 nM for the allyl substituent, almost 10-fold), followed by the n-propyl substituent which showed approximately five-fold better affinity than did the ethyl substituent. Radiosynthesis of S-N-[(1-allyl-2-pyrrolidinyl)methyl]-5-(3-[{sup 18}F]fluoropropyl)-2,3-dimethoxybenzamide ([{sup 18}F]fallypride) was carried out by nucleophilic substitution reaction of (S)-N-[(1-allyl-2-pyrrolidinyl)methyl]-5-(3-tosyloxypropyl)-2,3- dimethoxybenzamide with no carrier added {sup 18}F{sup -}. [{sup 18}F]Fallypride was obtained in approximately 20-40% yields (EOS/EOB, decay corrected) in specific activities of 900-1700 Ci/mmol after reverse phase HPLC purification in 60 min from EOB. High striatal uptake (upto 2.5% injected dose/g) of [{sup 18}F]fallypride in rats was observed with striatal/cerebellar ratios of 17, 42, 63 and 122 at 30, 60, 90 and 120 min post-injection, respectively. PET experiments with [{sup 18}F]fallypride in a cebus monkey showed a brain uptake of 0.10% injected dose/cc. In rhesus monkeys [{sup 18}F]fallypride showed rapid specific uptake in the striata (0.04-0.06% injected dose/cc) with striata/cerebellum ratios of approx. 3.0 at 14 min, 5.0 at 35 min and 8 at 70 min post-injection. Specifically bound [{sup 18}F]fallypride was displaced with haloperidol (1 mg/kg) with a half-life of 18 min in the rhesus monkey.

  8. [Identification and evaluation of the neuroleptic activity of phenotropil].

    Science.gov (United States)

    Akhapkina, V I; Akhapkin, R V

    2013-01-01

    The neuroleptic (antipsychotic) activity of phenotropil was studied in an experimental animal model. Phenotropil had a marked neuroleptic activity in models of positive (apomorphine-induced verticalization test) and negative (5-HTP-induced hyperkinesis test) symptoms of psychoses as well as in the m-cholinergic pathway hyperactivation (arecoline-induced tremor test). The compound markedly antagonized haloperidol catalepsy. Used in a single dose or as a course treatment, phenotropil did not provoke aggression nor intensify it. In contrast to typical and atypical antipsychotics, phenotropil had no sedative action and other adverse effects. It exhibited a positive effect on exploratory behavior and motor activity, had anxiolytic and antidepressant action.

  9. Atypical Neuroleptic Malignant Syndrome Associated with Use of Clozapine

    Directory of Open Access Journals (Sweden)

    Quevedo-Florez Leonardo

    2017-01-01

    Full Text Available The Neuroleptic Malignant Syndrome (NMS is a medical emergency of infrequent presentation in the emergency department, which is associated with the use of psychiatric drugs, such as typical and atypical antipsychotics. Our case addresses a 55-year-old patient diagnosed with undifferentiated schizophrenia for 10 years, who had been receiving clozapine and clonazepam as part of their treatment. This patient presents the symptoms of Neuroleptic Malignant Syndrome without fever, which improves with treatment especially with the withdrawal of clozapine. In the absence of fever and clinical improvement, the patient is considered to have an atypical presentation of this disease.

  10. Development of radiodiagnostics for image diagnosis of intracerebral dopamine receptor

    International Nuclear Information System (INIS)

    Fujita, Motoi; Kitamura, Hideaki; Nakajima, Takashi

    1999-01-01

    By measuring Vd value as an index to catch a functional change of nonspecific amine receptor at pathological regeneration region, Table Look Up method was thought to be useful for evaluation on functions of cerebellum and brainstem in Machado-Joseph disease. As it could simply calculate r-CBF and Vd values only adding SPWCT image to single time artery blood collection, it was thought to be useful for evaluation of Machado-Joseph disease. In last fiscal years, some animal experiments and clinical SPECT were conducted and evaluated to conduct research and development of a receptor imaging chemicals for clinics using radioactive reagent. In 1997 fiscal year, some examination of quantitative image analysis method on Vd value considering to reflex change of neural degeneration and receptor by using SPECT was conducted. (G.K.)

  11. A rare case of neuroleptic malignant syndrome presenting with serious hyperthermia treated with a non-invasive cooling device: a case report

    Directory of Open Access Journals (Sweden)

    Storm Christian

    2009-02-01

    Full Text Available Abstract Introduction A rare side effect of antipsychotic medication is neuroleptic malignant syndrome, mainly characterized by hyperthermia, altered mental state, haemodynamic dysregulation, elevated serum creatine kinase and rigor. There may be multi-organ dysfunction including renal and hepatic failure as well as serious rhabdomyolysis, acute respiratory distress syndrome and disseminated intravascular coagulation. The prevalence of neuroleptic malignant syndrome is between 0.02% and 2.44% for patients taking neuroleptics and it is not necessary to fulfil all cardinal features characterizing the syndrome to be diagnosed with neuroleptic malignant syndrome. Because of other different life-threatening diseases matching the various clinical findings, the correct diagnosis can sometimes be hard to make. A special problem of intensive care treatment is the management of severe hyperthermia. Lowering of body temperature, however, may be a major clinical problem because hyperthermia in neuroleptic malignant syndrome is typically unresponsive to antipyretic agents while manual cooling proves difficult due to peripheral vasoconstriction. Case presentation A 22-year-old Caucasian man was admitted unconscious with a body temperature of 42°C, elevated serum creatine phosphokinase, tachycardia and hypotonic blood pressure. In addition to intensive care standard therapy for coma and shock, a non-invasive cooling device (Arctic Sun 2000®, Medivance Inc., USA, originally designed to induce mild therapeutic hypothermia in patients after cardiopulmonary resuscitation, was used to lower body temperature. After successful treatment it became possible to obtain information from the patient about his recent ambulant treatment with Olanzapin (Zyprexa® for schizophrenia. Conclusion Numerous case reports have been published about patients who developed neuroleptic malignant syndrome due to Olanzapin (Zyprexa® medication. Frequently hyperthermia has been observed

  12. Neuroleptic-induced deficit syndrome in bipolar disorder with psychosis

    Directory of Open Access Journals (Sweden)

    Ueda S

    2016-02-01

    Full Text Available Satoshi Ueda,1 Takeshi Sakayori,1 Ataru Omori,2 Hajime Fukuta,3 Takashi Kobayashi,3 Kousuke Ishizaka,1 Tomoyuki Saijo,4 Yoshiro Okubo1 1Department of Neuropsychiatry, Nippon Medical School, Tokyo, Japan; 2Tamachuo Hospital, Tokyo, Japan; 3Kurumegaoka Hospital, Tokyo, Japan; 4Saijo Clinic, Tokyo, Japan Abstract: Neuroleptics can induce not only physical adverse effects but also mental effects that produce deficit status in thought, affect, cognition, and behavior. This condition is known as neuroleptic-induced deficit syndrome (NIDS, which includes apathy, lack of initiative, anhedonia, indifference, blunted affect, and reduced insight into disease. Although this old concept now appears almost forgotten, neuroleptics, whether typical or atypical, can make depression or bipolar disorder resemble other more refractory conditions, readily leading to mistaken diagnosis and inappropriate treatment. The authors describe three cases of NIDS superimposed on depressive phase in bipolar disorder with psychosis, where the attending psychiatrist’s failure to recognize NIDS prevented patients from receiving effective treatment and achieving remission. All cases achieved remission after reduction of neuroleptics and intensive therapy, including electroconvulsive therapy, for bipolar depression. The concept of NIDS was originally introduced for schizophrenia, and it has rarely been highlighted in other diseases. In recent years, however, atypical antipsychotics are being more often administered to patients with bipolar disorder. Psychiatrists, therefore, should also remember and exercise caution regarding NIDS in the pharmacotherapy of bipolar disorder with and without psychosis. The authors believe that the concept of NIDS needs to be reappraised in current psychiatry. Keywords: neuroleptic-induced deficit syndrome (NIDS, bipolar disorder, psychosis, atypical antipsychotics, electroconvulsive therapy

  13. PET imaging of adenosine A2A receptors

    NARCIS (Netherlands)

    Zhou, Xiaoyun

    2017-01-01

    This thesis describes the development and evaluation of [11C]preladenant as a novel radioligand for in vivo imaging of adenosine A2A receptors in the brain with positron-emission tomography (PET). The 11C-labeled drug [11C]preladenant was produced with high radiochemical yield and specific activity.

  14. Development of radiodiagnostics for image diagnosis of intracerebral dopamine receptor

    Energy Technology Data Exchange (ETDEWEB)

    Fujita, Motoi; Kitamura, Hideaki; Nakajima, Takashi [Saigata, National Hospital, Niigata (Japan)

    1998-02-01

    Single photon emission tomography (SPECT) able to evaluate the local blood flow in the brain is a safety and effective system for clinical diagnosis and pathological evaluation of incurable neulopsychotic diseases. Development of receptor imaging agents for SPECT, which has not been approved are progressing now. Using gerbits as an animal model for cerebrovascular diseases, an investigation was made on {sup 125}I-Iomazenil (Ro16-0154), an antagonist of benzodiazepin receptor in CNS as well as dopamine receptor ligands. {sup 125}I-Iomazenil was found to markedly accumulate in the regions; cerebral cortex (especially, layer VI and V), amygdala, thalamus, hypothalamus, nigra, cerebellar cortex, etc., where benzodiazepin is specifically localized. The accumulation was inhibited by preadministered flumazenil, indicating that {sup 125}I-Iomazenil can bind to the benzodiazepin receptor in CNS. The present study demonstrated that the late images of {sup 123}I-Iomazenil-SPECT are useful for detecting a lesion in the crebral cortex and cerabellar one, but it was unable to image out a lesion in the dentate-red nuclei due to DRPLA or Joseph disease. Therefore, {sup 123}I-Iomazenil was thought to be a valuable radiomedicine for imaging out and pathological evaluation. (M.N.)

  15. Dental image receptors - the changing scenario

    International Nuclear Information System (INIS)

    Fazik, K.A.

    2013-01-01

    Dental radiology has made rapid changes in the recent years. There is overall improvement in quality of the images and reduction in imaging time. But the most important milestone that has been achieved is the reduction in the radiation dose to the patient. There has been a constant effort to reduce the patient dose during dental radiography by several methods. A key challenge is to develop films that require lesser exposure to the radiation. A constant change has been witnessed in the properties of the dental X-ray film to make it more sensitive to X-ray which literally means to achieve a reasonably good image with a minimum possible exposure. A lot of scientific papers in the past decades have highlighted on the importance of film speed and radiation dosage. Western countries have consistently upgraded their dental radiographic films over the years. This has led to high speed films being used in general practice. We have been more slow to react to these changes and have not consistently upgraded to these films. The current paper highlights the importance of film speed in reducing the radiation dosage to the patient in dental radiology. (author)

  16. Prevalence of neuroleptic-induced movement disorders in chronic schizophrenia inpatients.

    Science.gov (United States)

    Janno, Sven; Holi, Matti; Tuisku, Katinka; Wahlbeck, Kristian

    2004-01-01

    Since most of the world's schizophrenia patients are treated with conventional antipsychotics, the authors evaluated various methods for establishing the prevalence of neuroleptic-induced movement disorders in these patients. DSM-IV criteria and established score thresholds on a movement disorder rating scale were used to identify cases of neuroleptic-induced movement disorder in a representative Estonian patient sample of 99 chronic institutionalized schizophrenia patients, 18-65 years old, treated with conventional neuroleptics (79.8%) or clozapine (20.2%). Neuroleptic-induced movement disorders according to DSM-IV criteria were found in 61.6% of the group: 31.3% had neuroleptic-induced akathisia, 23.2% had neuroleptic-induced parkinsonism, and 32.3% had neuroleptic-induced tardive dyskinesia. Prevalence rates for akathisia and tardive dyskinesia were similar when either DSM-IV criteria or rating scale scores were used, but the prevalence rate for parkinsonism was much lower per DSM-IV criteria than according to rating scale score. Nearly two-thirds of chronic schizophrenia patients suffered from a neuroleptic-induced movement disorder. Globally, extrapyramidal adverse effects still impose a huge burden on the majority of neuroleptic-treated individuals with schizophrenia. The discrepancy between the standard identification methods for neuroleptic-induced movement disorder indicate the need for further research.

  17. Imaging GABAc Receptors with Ligand-Conjugated Quantum Dots

    Directory of Open Access Journals (Sweden)

    Ian D. Tomlinson

    2007-01-01

    Full Text Available We report a methodology for labeling the GABAc receptor on the surface membrane of intact cells. This work builds upon our earlier work with serotonin-conjugated quantum dots and our studies with PEGylated quantum dots to reduce nonspecific binding. In the current approach, a PEGylated derivative of muscimol was synthesized and attached via an amide linkage to quantum dots coated in an amphiphilic polymer derivative of a modified polyacrylamide. These conjugates were used to image GABAC receptors heterologously expressed in Xenopus laevis oocytes.

  18. Comparison of three /sup 18/F-labeled butyrophenone neuroleptic drugs in the baboon using positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Arnett, C D; Shiue, C Y; Wolf, A P; Fowler, J S; Logan, J; Watanabe, M

    1985-03-01

    The butyrophenone neuroleptics spiroperidol, benperidol, and haloperidol were radiolabeled with fluorine-/sup 18/ and studied in baboon brain using positron emission transaxial tomography (PETT). Pretreatment of the baboon with a high pharmacological dose of (+)-butaclamol reduced the specifically bound component of radioactivity distribution in the striatum to approximately the radioactivity distribution found in the cerebellum. Comparative studies of brain distribution kinetics over a 4-h period indicated that either (/sup 18/F)spiroperidol or (/sup 18/F)benperidol may be suitable for specific labeling of neuroleptic receptors. In an 8-h study with (/sup 18/F)spiroperidol, striatal radioactivity did not decline, suggesting that spiroperidol either has a very slow dissociation rate or that it binds irreversibly to these receptors in vivo. (/sup 18/F)Haloperidol may not be suitable for in vivo PETT studies, because of a relatively high component of nonspecific distribution and a faster dissociation from the receptor. Analysis of /sup 18/F in plasma after injection of (/sup 18/F)spiroperidol indicated rapid metabolism to polar and acidic metabolites, with only 40% of the total radioactivity being present as unchanged drug after 30 min. Analysis of the metabolic stability of the radioactively labeled compound in rat striatum indicated that greater than 95% of (/sup 18/F)spiroperidol remains unchanged after 4 h.

  19. Catatonia versus neuroleptic malignant syndrome: the diagnostic dilemma and treatment.

    Science.gov (United States)

    Sahoo, Manoj Kumar; Agarwal, Sanjay; Biswas, Harshita

    2014-01-01

    Catatonia is a syndrome, comprised of symptoms such as motor immobility, excessive motor activity, extreme negativism, and stereotyped movements. Neuroleptic is able to induce catatonia like symptoms, that is, the neuroleptic malignant syndrome (NMS). In NMS, patients typically show symptoms such as an altered mental state, muscle rigidity, tremor, tachycardia, hyperpyrexia, leukocytosis, and elevated serum creatine phosphorous kinase. Several researchers have reported studies on catatonia and the association between catatonia and NMS, but none were from this part of the eastern India. In our case, we observed overlapping symptoms of catatonia and NMS; we wish to present a case of this diagnostic dilemma in a patient with catatonia, where a detailed history, investigation, and symptom management added as a great contribution to the patient's rapid improvement.

  20. Catatonia versus neuroleptic malignant syndrome: the diagnostic dilemma and treatment

    Directory of Open Access Journals (Sweden)

    Manoj Kumar Sahoo

    2014-01-01

    Full Text Available Catatonia is a syndrome, comprised of symptoms such as motor immobility, excessive motor activity, extreme negativism, and stereotyped movements. Neuroleptic is able to induce catatonia like symptoms, that is, the neuroleptic malignant syndrome (NMS. In NMS, patients typically show symptoms such as an altered mental state, muscle rigidity, tremor, tachycardia, hyperpyrexia, leukocytosis, and elevated serum creatine phosphorous kinase. Several researchers have reported studies on catatonia and the association between catatonia and NMS, but none were from this part of the eastern India. In our case, we observed overlapping symptoms of catatonia and NMS; we wish to present a case of this diagnostic dilemma in a patient with catatonia, where a detailed history, investigation, and symptom management added as a great contribution to the patient′s rapid improvement.

  1. Measuring neuroleptic-induced akathisia by three-channel actometry.

    Science.gov (United States)

    Tuisku, K; Lauerma, H; Holi, M; Markkula, J; Rimon, R

    1999-11-30

    Three-channel actometry was used to study neuroleptic-induced akathisia (NIA), a common and often serious disorder in association of traditional neuroleptic therapy. The aim was to explore the diagnostic possibilities of actometry in NIA and to examine in detail the motor phenomenology of the disorder in detail. The actometers were attached to the ankles and waists of ten patients, suffering from NIA, and to ten matched healthy controls. Five of the patients were changed to olanzapine treatment, and these patients were re-examined during the no-NIA condition. NIA was associated with manyfold movement activity during controlled rest (sitting) but not with increased daily overall motor activity. Movement frequencies in NIA seemed to be pathognomonic. Actometry is promising for investigation and clinical assessment of NIA. Olanzapine proved to be an adequate treatment choice for NIA patients.

  2. Plasma homovanillic acid levels and therapeutic outcome in schizophrenics: comparisons of neuroleptic-naive first-episode patients and patients with disease exacerbation due to neuroleptic discontinuance.

    Science.gov (United States)

    Akiyama, K; Tsuchida, K; Kanzaki, A; Ujike, H; Hamamura, T; Kondo, K; Mutoh, S; Miyanagi, K; Kuroda, S; Otsuki, S

    1995-11-15

    Plasma homovanillic acid (pHVA) levels were measured and the Brief Psychiatric Rating Scale (BPRS) scores were evaluated in 26 schizophrenic patients who had either never been medicated (neuroleptic-naive, first-episode subjects) or whose condition had become exacerbated following neuroleptic discontinuance (exacerbated subjects). All the subjects received medication with a fixed dose of a neuroleptic (haloperidol or fluphenazine, both 9 mg/day) for the first week and variable doses for the subsequent 4 weeks. In the neuroleptic-naive subjects, pHVA levels increased significantly 1 week after starting the protocol; this increase correlated significantly with clinical improvement of the BPRS positive symptom scores at week 5. In the neuroleptic-naive subjects, pHVA levels had declined to the baseline level by week 5. In the exacerbated subjects, there were no significant correlations between pHVA level changes at week 1 and later improvements of the BPRS positive symptom scores. These results suggest that the rise in pHVA levels occurring within 1 week after starting a fixed neuroleptic dose may predict a favorable clinical response in neuroleptic-naive schizophrenic patients.

  3. Evaluation of radioiodinated vesamicol analogs for sigma receptor imaging in tumor and radionuclide receptor therapy.

    Science.gov (United States)

    Ogawa, Kazuma; Shiba, Kazuhiro; Akhter, Nasima; Yoshimoto, Mitsuyoshi; Washiyama, Kohshin; Kinuya, Seigo; Kawai, Keiichi; Mori, Hirofumi

    2009-11-01

    It has been reported that sigma receptors are highly expressed in a variety of human tumors. In this study, we selected (+)-2-[4-(4-iodophenyl)piperidino] cyclohexanol [(+)-pIV] as a sigma receptor ligand and evaluated the potential of radioiodinated (+)-pIV for tumor imaging and therapy. (+)-[(125/131)I]pIV was prepared by an iododestannylation reaction under no-carrier-added conditions with radiochemical purity over 99% after HPLC purification. Biodistribution experiments were performed by the intravenous injection of (+)-[(125)I]pIV into mice bearing human prostate tumors (DU-145). Blocking studies were performed by intravenous injection of (+)-[(125)I]pIV mixed with an excess amount of unlabeled sigma ligand into DU-145 tumor-bearing mice. For therapeutic study, (+)-[(131)I]pIV was injected at a dose of 7.4 MBq followed by measurement of the tumor size. In biodistribution experiments, (+)-[(125)I]pIV showed high uptake and long residence in the tumor. High tumor to blood and muscle ratios were achieved because the radioactivity levels of blood and muscle were low. However, the accumulations of radioactivity in non-target tissues, such as liver and kidney, were high. The radioactivity in the non-target tissues slowly decreased over time. Co-injection of (+)-[(125)I]pIV with an excess amount of unlabeled sigma ligand resulted in a significant decrease in the tumor/blood ratio, indicating sigma receptor-mediated tumor uptake. In therapeutic study, tumor growth in mice treated with (+)-[(131)I]pIV was significantly inhibited compared to that of an untreated group. These results indicate that radioiodinated (+)-pIV has a high potential for sigma receptor imaging in tumor and radionuclide receptor therapy.

  4. Progress of study on the dopamine D4 receptor imaging agent

    International Nuclear Information System (INIS)

    Tian Haibin; Zhang Lan; Zhang Chunfu; Li Junling; Yin Duanzhi

    2001-01-01

    Dopamine receptors were originally classified into five receptors subtypes, the dopamine D 4 receptor was included. Schizophrenic pathophysiology may be associated with expression and function of the dopamine D 4 receptor; it is of great importance to study the imaging agent of dopamine D 4 receptor. The study on radioactivity distribution and metabolize of radioligand remains hampered by the lack radioligand for the D 4 receptor which can be labeled using suitable nuclei. This paper reviews the progress of study on the dopamine D 4 receptor imaging agent, with particular emphasis vary nuclei, for example 11 C, 18 F, 123 I, labeled D 4 receptor ligands, antagonists and analogs as PET or SPECT imaging agents. Authors estimated affinity and selectivity of radioligands for the dopamine D 4 receptor in laboratory animal tests

  5. Nicotinic α4β2 receptor imaging agents

    International Nuclear Information System (INIS)

    Pichika, Rama; Easwaramoorthy, Balasubramaniam; Collins, Daphne; Christian, Bradley T.; Shi, Bingzhi; Narayanan, Tanjore K.; Potkin, Steven G.; Mukherjee, Jogeshwar

    2006-01-01

    The α4β2 nicotinic acetylcholine receptor (nAChR) has been implicated in various neurodegenerative diseases. Optimal positron emission tomography (PET) imaging agents are therefore highly desired for this receptor. We report here the development and initial evaluation of 2-fluoro-3-[2-((S)-3-pyrrolinyl)methoxy]pyridine (nifene). In vitro binding affinity of nifene in rat brain homogenate using 3 H-cytisine exhibited a K i =0.50 nM for the α4β2 sites. The radiosynthesis of 2- 18 F-fluoro-3-[2-((S)-3-pyrrolinyl)methoxy]pyridine ( 18 F-nifene) was accomplished in 2.5 h with an overall radiochemical yield of 40-50%, decay corrected. The specific activity was estimated to be approx. 37-185 GBq/μmol. In vitro autoradiography in rat brain slices indicated selective binding of 18 F-nifene to anteroventral thalamic (AVT) nucleus, thalamus, subiculum, striata, cortex and other regions consistent with α4β2 receptor distribution. Rat cerebellum showed some binding, whereas regions in the hippocampus had the lowest binding. The highest ratio of >13 between AVT and cerebellum was measured for 18 F-nifene in rat brain slices. The specific binding was reduced (>95%) by 300 μM nicotine in these brain regions. Positron emission tomography imaging study of 18 F-nifene (130 MBq) in anesthetized rhesus monkey was carried out using an ECAT EXACT HR+ scanner. PET study showed selective maximal uptake in the regions of the anterior medial thalamus, ventro-lateral thalamus, lateral geniculate, cingulate gyrus, temporal cortex including the subiculum. The cerebellum in the monkeys showed lower binding than the other regions. Thalamus-to-cerebellum ratio peaked at 30-35 min postinjection to a value of 2.2 and subsequently reduced. The faster binding profile of 18 F-nifene indicates promise as a PET imaging agent and thus needs further evaluation

  6. Neuroleptic Malignant Syndrome: A Case Aimed at Raising Clinical Awareness

    Directory of Open Access Journals (Sweden)

    Jad Al Danaf

    2015-01-01

    Full Text Available A 60-year-old man with a history of bipolar disorder on risperidone, bupropion, and escitalopram was admitted for community acquired streptococcal pneumonia. Four days later, he developed persistent hyperthermia, dysautonomia, rigidity, hyporeflexia, and marked elevation of serum creatine phosphokinase. He was diagnosed with neuroleptic malignant syndrome (NMS and improved with dantrolene, bromocriptine, and supportive therapy. This case emphasizes the importance of considering a broad differential diagnosis for fever in the ICU, carefully reviewing the medication list for all patients, and considering NMS in patients with fever and rigidity.

  7. Correlates of rapid neuroleptic response in male patients with schizophrenia.

    Science.gov (United States)

    Petrie, E C; Faustman, W O; Moses, J A; Lombrozo, L; Csernansky, J G

    1990-08-01

    Correlates of neuroleptic response latency were assessed in 16 male schizophrenic inpatients during 4 weeks of fixed dose (20 mg/day) haloperidol treatment. Rapid responders showed a mean 40% reduction in Brief Psychiatric Rating Scale (BPRS) positive symptom scores by day 10 of treatment. Rapid responders had significantly lower plasma homovanillic acid (pHVA) concentrations compared to non-rapid responders during week 4 of haloperidol treatment. However, rapid versus non-rapid responders did not differ with respect to demographics, baseline positive or negative BPRS symptom scores, performance on tests of neuropsychological function, or mean plasma haloperidol concentrations.

  8. Increments in plasma homovanillic acid concentrations after neuroleptic discontinuation are associated with worsening of schizophrenic symptoms.

    Science.gov (United States)

    Khan, R S; Amin, F; Powchik, P; Knott, P; Goldstein, M; Apter, S; Kerman, B; Jaff, S; Davidson, M

    1990-01-01

    1. Thirty-two male schizophrenic patients participated in this study. 2. Plasma concentrations of the dopamine metabolite, homovanillic acid (pHVA) were assessed once on neuroleptic medication and twice a week for a maximum of six weeks after its discontinuation. 3. Psychiatric symptomatology was assessed once on neuroleptic medication and once a week for a maximum of six weeks after its discontinuation, using the brief psychiatric rating scale (BPRS). 4. pHVA and total BPRS score increased significantly after discontinuation of neuroleptic as compared to baseline. 5. The magnitude of pHVA and BPRS increments after discontinuation of neuroleptic correlated significantly. 6. Results of this study suggest that worsening of schizophrenic symptoms after discontinuation of neuroleptic treatment is associated with increased pHVA concentrations.

  9. Nicotinic {alpha}4{beta}2 receptor imaging agents

    Energy Technology Data Exchange (ETDEWEB)

    Pichika, Rama [Brain Imaging Center, Department of Psychiatry and Human Behavior, University of California, Irvine, CA 92697-3960 (United States); Easwaramoorthy, Balasubramaniam [Brain Imaging Center, Department of Psychiatry and Human Behavior, University of California, Irvine, CA 92697-3960 (United States); Collins, Daphne [Brain Imaging Center, Department of Psychiatry and Human Behavior, University of California, Irvine, CA 92697-3960 (United States); Christian, Bradley T. [Department of Nuclear Medicine, Kettering Medical Center, Dayton, OH 45429 (United States); Shi, Bingzhi [Department of Nuclear Medicine, Kettering Medical Center, Dayton, OH 45429 (United States); Narayanan, Tanjore K. [Department of Nuclear Medicine, Kettering Medical Center, Dayton, OH 45429 (United States); Potkin, Steven G. [Brain Imaging Center, Department of Psychiatry and Human Behavior, University of California, Irvine, CA 92697-3960 (United States); Mukherjee, Jogeshwar [Brain Imaging Center, Department of Psychiatry and Human Behavior, University of California, Irvine, CA 92697-3960 (United States)]. E-mail: j.mukherjee@uci.edu

    2006-04-15

    The {alpha}4{beta}2 nicotinic acetylcholine receptor (nAChR) has been implicated in various neurodegenerative diseases. Optimal positron emission tomography (PET) imaging agents are therefore highly desired for this receptor. We report here the development and initial evaluation of 2-fluoro-3-[2-((S)-3-pyrrolinyl)methoxy]pyridine (nifene). In vitro binding affinity of nifene in rat brain homogenate using {sup 3}H-cytisine exhibited a K {sub i}=0.50 nM for the {alpha}4{beta}2 sites. The radiosynthesis of 2-{sup 18}F-fluoro-3-[2-((S)-3-pyrrolinyl)methoxy]pyridine ({sup 18}F-nifene) was accomplished in 2.5 h with an overall radiochemical yield of 40-50%, decay corrected. The specific activity was estimated to be approx. 37-185 GBq/{mu}mol. In vitro autoradiography in rat brain slices indicated selective binding of {sup 18}F-nifene to anteroventral thalamic (AVT) nucleus, thalamus, subiculum, striata, cortex and other regions consistent with {alpha}4{beta}2 receptor distribution. Rat cerebellum showed some binding, whereas regions in the hippocampus had the lowest binding. The highest ratio of >13 between AVT and cerebellum was measured for {sup 18}F-nifene in rat brain slices. The specific binding was reduced (>95%) by 300 {mu}M nicotine in these brain regions. Positron emission tomography imaging study of {sup 18}F-nifene (130 MBq) in anesthetized rhesus monkey was carried out using an ECAT EXACT HR+ scanner. PET study showed selective maximal uptake in the regions of the anterior medial thalamus, ventro-lateral thalamus, lateral geniculate, cingulate gyrus, temporal cortex including the subiculum. The cerebellum in the monkeys showed lower binding than the other regions. Thalamus-to-cerebellum ratio peaked at 30-35 min postinjection to a value of 2.2 and subsequently reduced. The faster binding profile of {sup 18}F-nifene indicates promise as a PET imaging agent and thus needs further evaluation.

  10. Electrochemical behaviour of some neuroleptics: Haloperidol and its derivatives.

    Science.gov (United States)

    Vire, J C; Fischer, M; Patriarche, G J; Christian, G D

    1981-05-01

    The electrochemical characteristics of Haloperidol and related compounds, representative neuroleptics of the butyrophenone family, have been investigated as a function of pH and concentration by direct-current, alternating-current and differential-pulse polarography and cyclic voltammetry at a hanging mercury drop electrode. A single cathodic wave representing an irreversible two-electron reduction is obtained, and its half-wave potential differs from that characteristic of aromatic ketone reduction. Adsorption processes disturb the wave behaviour and an adsorption prewave is observed at high concentrations. Quantitative measurements were successful in the concentration range 1 x 10(-4)-1 x 10(-6)M (0.4 mg/l.), the lower concentration representing the detection limit by differential-pulse polarography.

  11. Anaesthesia For ECT In Neuroleptic Malignant Syndrome - What Is Ideal?

    Directory of Open Access Journals (Sweden)

    Priyaneka Baskaran

    2017-09-01

    Full Text Available We report a case involving a 46 year old male with schizophrenia who presented with fever, inability to speak, sialorrhoea, limb stiffness, profuse sweating, tremors and rigidity of bilateral upper and lower limbs following an increase in dosage of his antipsychotics.  A provisional diagnosis of neuroleptic malignant syndrome (NMS was made based on the Levensen criteria. His anti psychotics were promptly discontinued and he was transferred to ICU for critical care support. We utilised lorazepam and prescribed bromocriptine and his NMS symptoms improved. However, in view of residual catatonic symptoms, decision was made to commence ECT. A combination of rocuronium sugammadex was used successfully in all his ECT procedures and found to be an excellent alternative to succinycholine in this patient.

  12. Optimization studies concerning the direct nucleophilic fluorination of butyrophenone neuroleptics

    Energy Technology Data Exchange (ETDEWEB)

    Katsifis, A; Hamacher, K; Schnitter, J; Stoecklin, G [Forschungszentrum Juelich GmbH (Germany). Inst. fuer Chemie 1 - Nuklearchemie

    1993-07-01

    Based on the direct nucleophilic aromatic substitution described previously for [[sup 18]F]N-methylspiperone the butyrophenone neuroleptics benperidol, droperidol, fluanisone and haloperidol were labelled with fluorine-18. The n.c.a. aromatic nucleophilic NO[sub 2] [yields] [sup 18]F substitution takes place in the presence of the moderately basic cryptate system consisting of Kryptofix 2.2.2., potassium oxalate and potassium carbonate. The one step labeling reaction was performed in different solvents and is equally successful in dimethylsulfoxide, dimethylformamide or dimethylacetamide yielding 25-35% (EOS) within a reaction time of 5-30 min in the range of 140-160[sup o]C at analytical activity levels. (author).

  13. Detection and management of the neuroleptic malignant syndrome.

    Science.gov (United States)

    Bond, W S

    1984-01-01

    Two patients who developed the neuroleptic malignant syndrome (NMS) are described, and pertinent literature is reviewed. A 30-year-old man developed NMS, apparently as a result of haloperidol treatment of chronic undifferentiated schizophrenia. Treatment with cooling blankets, acetaminophen, dantrolene sodium, and bromocriptine mesylate decreased abnormal vital signs, but catatonia continued. After 30 treatments with electroconvulsive therapy over a one-month period, the patient's catatonia was resolved, and he was discharged on no medication with the schizophrenia in remission. The second patient was a 22-year-old woman who developed NMS after five weeks of therapy with haloperidol and thiothixene for an acute episode of abnormal behavior. She did not respond to therapy with cooling blankets, acetaminophen, antibiotics, and amobarbital sodium. Dantrolene sodium therapy produced no improvement except for some relief of muscular rigidity. Electroconvulsive therapy (22 treatments over one month) successfully decreased the patient's elevated liver enzymes and leukocyte count, but periodic temperature elevations and catatonia continued. Prompt diagnosis and treatment of NMS are essential, as the mortality rate is 20%. Acute lethal catatonia and malignant hyperthermia are considered in differential diagnosis. Both central and peripheral pathophysiologic mechanisms are probably involved in NMS, and most cases are seen in patients with psychiatric illness. Onset of NMS does not seem related to duration of neuroleptic therapy and, in susceptible persons, additional factors may be required to trigger onset of NMS. Symptoms, including diffuse muscular rigidity, akinesia, and fever, develop within 24-72 hours. Neurologic symptoms may develop or worsen, and leukocytosis and elevated levels of liver enzymes occur. Death can result from respiratory or cardiovascular failure, and rhabdomyolysis can lead to acute renal failure.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. [Selective attention and schizophrenia before the administration of neuroleptics].

    Science.gov (United States)

    Lussier, I; Stip, E

    1999-01-01

    In recent years, the presence of attention deficits has been recognized as a key feature of schizophrenia. Past studies reveal that selective attention, or the ability to select relevant information while ignoring simultaneously irrelevant information, is disturbed in schizophrenic patients. According to Treisman feature-integration theory of selective attention, visual search for conjunctive targets (e.g., shape and color) requires controlled processes, that necessitate attention and operate in a serial manner. Reaction times (RTs) are therefore function of the number of stimuli in the display. When subjects are asked to detect the presence or absence of a target in an array of a variable number of stimuli, different performance patterns are expected for positive (present target) and negative trials (absent target). For positive trials, a self-terminating search is triggered, that is, the search is ended when the target is encountered. For negative trials, an exhaustive search strategy is displayed, where each stimulus is examined before the search can end; the RT slope pattern is thus double that of the positive trials. To assess the integrity of these processes, thirteen drug naive schizophrenic patients were compared to twenty normal control subjects. Neuroleptic naive patients were chosen as subjects to avoid the potential influence of medication and chronicity-related factors on performance. The subjects had to specify as fast as possible the presence or absence of the target in an array of a variable number of stimuli presented in a circular display, and comprising or not the target. Results showed that the patients can use self-terminating search strategies as well as normal control subjects. However, their ability to trigger exhaustive search strategies is impaired. Not only were patients slower than controls, but their pattern of RT results was different. These results argue in favor of an early impairment in selective attention capacities in

  15. Neuroleptic Malignant Syndrome After the Use of Venlafaxine in a Patient with Generalized Anxiety Disorder

    Directory of Open Access Journals (Sweden)

    Tsung-Chien Lu

    2006-01-01

    Full Text Available Neuroleptic malignant syndrome (NMS is a potentially lethal adverse reaction to neuroleptics, which is characterized by hyperthermia, extrapyramidal symptoms, altered consciousness and autonomic dysfunction. Although NMS is most commonly induced by the high-potency neuroleptics, its development has also been associated with the use of non-neuroleptic agents that block central dopamine pathways. A 68-year-old man with generalized anxiety disorder and depressive symptoms presented at the emergency department (ED with high fever, tremor, muscle rigidity, rhabdomyolysis and altered mental status. NMS was considered to have been caused by the recent addition and subsequent dose increase in his treatment regimen of venlafaxine, a serotonin norepinephrine reuptake inhibitor. He was successfully treated with bromocriptine, lorazepam, and fluid hydration in the ED and intensive care unit.

  16. Malignant neuroleptic syndrome following deep brain stimulation surgery: a case report

    OpenAIRE

    Themistocleous, Marios S; Boviatsis, Efstathios J; Stavrinou, Lampis C; Stathis, Pantelis; Sakas, Damianos E

    2011-01-01

    Abstract Background The neuroleptic malignant syndrome is an uncommon but dangerous complication characterized by hyperthermia, autonomic dysfunction, altered mental state, hemodynamic dysregulation, elevated serum creatine kinase, and rigor. It is most often caused by an adverse reaction to anti-psychotic drugs or abrupt discontinuation of neuroleptic or anti-parkinsonian agents. To the best of our knowledge, it has never been reported following the common practice of discontinuation of anti...

  17. Cure or curse? Ambivalent attitudes towards neuroleptic medication in schizophrenia and non-schizophrenia patients

    OpenAIRE

    Dieter Naber; Peter Tonn; Azra Deljkovic; Anne Karow; Maarten J.V. Peters; Steffen Moritz

    2009-01-01

    Neuroleptic non-compliance remains a serious challenge for the treatment of psychosis. Non-compliance is predominantly attributed to side effects, lack of illness insight, reduced well-being or poor therapeutic alliance. However, other still neglected factors may also play a role. Further, little is known about whether psychiatric patients without psychosis who are increasingly prescribed neuroleptics differ in terms of medication compliance or about reasons for non-compliance by psychosis pa...

  18. Imaging of a glioma using peripheral benzodiazepine receptor ligands

    Energy Technology Data Exchange (ETDEWEB)

    Starosta-Rubinstein, S.; Ciliax, B.J.; Penney, J.B.; McKeever, P.; Young, A.B.

    1987-02-01

    Two types of benzodiazepine receptors have been demonstrated in mammalian tissues, one which is localized on neuronal elements in brain and the other, on glial cells and in peripheral tissues such as kidney. In vivo administration of /sup 3/H-labeled PK 11195 (1-(2-chlorophenyl-N-methyl-N-(1-methylpropyl)-3-isoquinoline carboxamide) or (/sup 3/H)flunitrazepam with 5 mg of clonazepam per kg to rats with intracranial C6 gliomas resulted in high levels of tritiated-drug binding to the tumor as shown by quantitative autoradiography. Pharmacological studies indicated that the bound drugs labeled the peripheral benzodiazepine binding site. Binding to the peripheral benzodiazepine site was confirmed primarily to malignant cells with little binding to adjacent normal brain tissue or to necrotic tissue. Tumor cell binding was completely inhibited by preadministration of the peripheral benzodiazepine blocking agent PK 11195 at 5 mg/kg. The centrally selective benzodiazepine ligand clonazepam had no effect on PK 11195 binding to the tumor cells. When binding to other tumor cell lines grown in nude mice and nude athymic rats was evaluated, little or no peripheral benzodiazepine binding was detected on human pheochromocytoma (RN1) and neuroblastoma (SK-N-MC, SK-N-SH) tumor cells, respectively. However, high densities of peripheral benzodiazepine binding sites were observed on tumors derived from a human glioma cell line (ATCC HTB 14, U-87 MG). The presence of high concentrations of specific peripheral benzodiazepine receptors on glial tumors suggests that human primary central nervous system tumors could be imaged and diagnosed using peripheral benzodiazepine ligands labeled with positron- or gamma-emitting isotopes.

  19. Differential Expression of Chemokine Receptors and their Roles in Cancer Imaging

    Energy Technology Data Exchange (ETDEWEB)

    Nimmagadda, Sridhar, E-mail: snimmag1@jhmi.edu [Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD (United States)

    2012-05-30

    Chemokine/chemokine receptor interactions play diverse roles in cell migration and homeostasis. Emerging evidence suggests that cancer cells co-opt chemokine networks for survival, proliferation, immune evasion, and metastasis. Most of the chemokine receptors are reported to be involved in tumor progression. Given their extensive implication in cancer progression, several chemokine receptor/ligand axes are considered as potential therapeutic targets. This review provides a survey of chemokine receptor expression in cancer and evaluates the potential of chemokine receptor imaging as a tool for molecular characterization of cancer.

  20. Differential Expression of Chemokine Receptors and their Roles in Cancer Imaging

    International Nuclear Information System (INIS)

    Nimmagadda, Sridhar

    2012-01-01

    Chemokine/chemokine receptor interactions play diverse roles in cell migration and homeostasis. Emerging evidence suggests that cancer cells co-opt chemokine networks for survival, proliferation, immune evasion, and metastasis. Most of the chemokine receptors are reported to be involved in tumor progression. Given their extensive implication in cancer progression, several chemokine receptor/ligand axes are considered as potential therapeutic targets. This review provides a survey of chemokine receptor expression in cancer and evaluates the potential of chemokine receptor imaging as a tool for molecular characterization of cancer.

  1. The development of epidermal growth factor receptor molecular imaging in cancer

    International Nuclear Information System (INIS)

    Zhou Xiaoliang; Wang Hao; Shi Peiji; Liu Jianfeng; Meng Aimin

    2013-01-01

    In vivo epidermal growth factor receptor (EGFR) targeted therapy has great potential for cancer diagnosis and the evaluation of curative effects. Enhancement of EGFR-targeted therapy needs a reliable quantitative molecular imaging method which could enable monitoring of receptor drug binding and receptor occupancy in vivo, and identification of the mutation in EGFR. PET or SPECT is the most advanced molecular imaging technology of non-invasively selecting responders, predicting therapeutic outcome and monitoring EGFR-targeted treatment. This review analyzed the present situation and research progress of molecular imaging agents. (authors)

  2. Immunohistochemical evidence for the involvement of gonadotropin releasing hormone in neuroleptic and cataleptic effects of haloperidol in mice.

    Science.gov (United States)

    Fegade, Harshal A; Umathe, Sudhir N

    2016-04-01

    Blockade of dopamine D2 receptor by haloperidol is attributed for neuroleptic and cataleptic effects; and also for the release of gonadotropin releasing hormone (GnRH) from the hypothalamus. GnRH agonist is reported to exhibit similar behavioural effects as that of haloperidol, and pre-treatment with GnRH antagonist is shown to attenuate the effects of haloperidol, suggesting a possibility that GnRH might mediate the effects of haloperidol. To substantiate such possibility, the influence of haloperidol on GnRH immunoreactivity (GnRH-ir) in the brain was studied in vehicle/antide pre-treated mice by peroxidase-antiperoxidase method. Initially, an earlier reported antide-haloperidol interaction in rat was confirmed in mice, wherein haloperidol (250μg/kg, i.p.) exhibited suppression of conditioned avoidance response (CAR) on two-way shuttle box, and induced catalepsy in bar test; and pre-treatment with antide (50μg/kg, s.c., GnRH antagonist) attenuated both effects of haloperidol. Immunohistochemical study was carried out to identify GnRH-ir in the brain, isolated 1h after haloperidol treatment to mice pre-treated with vehicle/antide. The morphometric analysis of microphotographs of brain sections revealed that haloperidol treatment increased integrated density units of GnRH-ir in various regions of the limbic system. Considering basal GnRH-ir in vehicle treated group as 100%, the increase in GnRH-ir after haloperidol treatment was by 100.98% in the medial septum; 54.26% in the bed nucleus of the stria terminalis; 1152.85% in the anteroventral periventricular nucleus; 120.79% in the preoptic area-organum vasculosum of the lamina terminalis and 138.82% in the arcuate nucleus. Antide did not influence basal and haloperidol induced increase in GnRH-ir in any of the regions. As significant increase in GnRH-ir after haloperidol treatment was observed in such regions of the brain which are reported to directly or indirectly communicate with the hippocampus and basal

  3. Does elevating image receptor increase breast receptor footprint and improve pressure balance?

    International Nuclear Information System (INIS)

    Smith, H.; Szczepura, K.; Mercer, C.; Maxwell, A.; Hogg, P.

    2015-01-01

    There is no consensus in the literature regarding the image receptor (IR) position for the cradio-caudal projection in mammography. Some literature indicates the IR should be positioned to the infra mammary fold (IMF); other literature suggests the IR be raised 2 cm relative to the IMF. Using 16 female volunteers (32 breasts) and a pressure sensitive mat we investigated breast footprint and pressure balance with IR at IMF and IR 2 cm above the IMF. Breast area on IR and paddle and interface pressure between IR/breast and paddle/breast were recorded. A uniformity index (UI) gave a measure of pressure balance between IR/breast and paddle/breast. IR breast footprint increases significantly by 13.81 cm 2 (p < 0.02) when IR is raised by 2 cm. UI reduces from 0.4 to 0.00 (p = 0.04) when positioned at IMF +2 cm demonstrating an improved pressure balance. Practitioners should consider raising the IR by 2 cm relative to the IMF in clinical practice. Further work is suggested to investigate the effects of practitioner variability and breast asymmetry. - Highlights: • Experimental study. • 16 female volunteers/32 breasts. • Compares two methods of conducting the cranio-caudal project. • Provides sufficient evidence to indicate which method is likely to be superior. • Has value to clinical mammography.

  4. Positron emission tomography imaging studies of dopamine receptors in primate models of addiction

    OpenAIRE

    Nader, Michael A; Czoty, Paul W; Gould, Robert W; Riddick, Natallia V

    2008-01-01

    Animal models have provided valuable information related to trait and state variables associated with vulnerability to drug addiction. Our brain imaging studies in monkeys have implicated D2 receptors in cocaine addiction. For example, an inverse relationship between D2 receptor availability and rates of cocaine self-administration has been documented. Moreover, environmental variables, such as those associated with formation of the social hierarchy, can impact receptor availability and sensi...

  5. Predictors of response to neuroleptic treatment in schizophrenia.

    Science.gov (United States)

    Stern, R G; Kahn, R S; Davidson, M

    1993-06-01

    Baseline symptom severity, early reduction in symptom severity, initial subjective response to neuroleptic treatment, the degree of brain atrophy, and early changes in pHVA levels appear to predict treatment outcome in schizophrenic patients. Computerized EEG results, neuropsychological and neurophysiologic tests, and baseline pHVA concentrations require further examination. Only a limited proportion of variance in treatment response, however, could be explained by either of the nine predictors alone or combined. Therefore, further research is necessary to discover yet unidentified determinants of treatment response. Future studies should test the validity and reliability of these five promising predictors in large groups of male and female patients, employ high standards for assessment reliability of clinical parameters, and use absolute rating scores on psychopathology as well as functional scales for the definition of good and poor treatment response. Furthermore, the statistical approach for data analysis should take in consideration the need for appropriate corrections when multiple correlations are performed and should test the extent to which these predictors are interdependent.

  6. Serotonin type-1A receptor imaging in depression

    International Nuclear Information System (INIS)

    Drevets, Wayne C.; Frank, Ellen; Price, Julie C.; Kupfer, David J.; Greer, Phil J.; Mathis, Chester

    2000-01-01

    Regional 5-hydroxytryptamine 1A (5-HT 1A ) receptor binding potential (BP) of depressed subjects with primary, recurrent, familial mood disorders was compared to that of healthy controls by using positron emission tomography and [carbonyl- 11 C]WAY-100635 {[ 11 C]N-(2-(4-(2-methoxyphenyl)-1-piperazin-1-yl)ethyl)-N-(2-pyridyl) cyclohexanecarboxamide}. The mean 5-HT 1A receptor BP was reduced 42% in the midbrain raphe and 25-33% in limbic and neocortical areas in the mesiotemporal, occipital, and parietal cortex. The magnitude of these abnormalities was most prominent in bipolar depressives and unipolar depressives who had bipolar relatives. These abnormal reductions in 5-HT 1A receptor BP are consistent with in vivo evidence that 5-HT 1A receptor sensitivity is reduced in major depressive disorder and postmortem data showing a widespread deficit of 5-HT 1A receptor expression in primary mood disorders

  7. Somatostatin receptor-mediated imaging and therapy: basic science, current knowledge, limitations and future perspectives

    Energy Technology Data Exchange (ETDEWEB)

    Breeman, W.A.P.; Jong, M. de; Kwekkeboom, D.J.; Valkema, R.; Bakker, W.H.; Kooij, P.P.M. [Dept. of Nuclear Medicine, Erasmus Medical Centre Rotterdam (Netherlands); Visser, T.J. [Dept. of Internal Medicine, Erasmus Medical Centre Rotterdam (Netherlands); Krenning, E.P. [Dept. of Nuclear Medicine, Erasmus Medical Centre Rotterdam (Netherlands); Dept. of Internal Medicine, Erasmus Medical Centre Rotterdam (Netherlands)

    2001-09-01

    In vivo somatostatin receptor-mediated scintigraphy has proven to be a valuable method for the visualisation of neuroendocrine tumours and their metastases. A new application is the use of radiolabelled analogues for somatostatin receptor-mediated therapy. This paper presents a review on the basic science, historical background and current knowledge of somatostatin receptor subtypes and their expression in neuroendocrine tumours. New somatostatin analogues, new chelators, ''new'' radionuclides and combinations thereof are also discussed. Due attention is given to limitations and future perspectives of somatostatin receptor-mediated imaging and therapy. (orig.)

  8. Somatostatin receptor-mediated imaging and therapy: basic science, current knowledge, limitations and future perspectives

    International Nuclear Information System (INIS)

    Breeman, W.A.P.; Jong, M. de; Kwekkeboom, D.J.; Valkema, R.; Bakker, W.H.; Kooij, P.P.M.; Visser, T.J.; Krenning, E.P.

    2001-01-01

    In vivo somatostatin receptor-mediated scintigraphy has proven to be a valuable method for the visualisation of neuroendocrine tumours and their metastases. A new application is the use of radiolabelled analogues for somatostatin receptor-mediated therapy. This paper presents a review on the basic science, historical background and current knowledge of somatostatin receptor subtypes and their expression in neuroendocrine tumours. New somatostatin analogues, new chelators, ''new'' radionuclides and combinations thereof are also discussed. Due attention is given to limitations and future perspectives of somatostatin receptor-mediated imaging and therapy. (orig.)

  9. Increased brain dopamine and dopamine receptors in schizophrenia

    International Nuclear Information System (INIS)

    Mackay, A.V.; Iversen, L.L.; Rossor, M.; Spokes, E.; Bird, E.; Arregui, A.; Creese, I.; Synder, S.H.

    1982-01-01

    In postmortem samples of caudate nucleus and nucleus accumbens from 48 schizophrenic patients, there were significant increases in both the maximum number of binding sites (Bmax) and the apparent dissociation constant (KD) for tritiated spiperone. The increase in apparent KD probably reflects the presence of residual neuroleptic drugs, but changes in Bmax for tritiated spiperone reflect genuine changes in receptor numbers. The increases in receptors were seen only in patients in whom neuroleptic medication had been maintained until the time of death, indicating that they may be entirely iatrogenic. Dopamine measurements for a larger series of schizophrenic and control cases (n greater than 60) show significantly increased concentrations in both the nucleus accumbens and caudate nucleus. The changes in dopamine were not obviously related to neuroleptic medication and, unlike the receptor changes, were most severe in younger patients

  10. Positron Emission Tomography (PET) Imaging of Opioid Receptors

    NARCIS (Netherlands)

    van Waarde, Aren; Absalom, Anthony; Visser, Anniek; Dierckx, Rudi; Dierckx, Rudi AJO; Otte, Andreas; De Vries, Erik FJ; Van Waarde, Aren; Luiten, Paul GM

    2014-01-01

    The opioid system consists of opioid receptors (which mediate the actions of opium), their endogenous ligands (the enkephalins, endorphins, endomorphins, dynorphin, and nociceptin), and the proteins involved in opioid production, transport, and degradation. PET tracers for the various opioid

  11. Neuroleptic malignant syndrome following catatonia: Vigilance is the price of antipsychotic prescription

    Directory of Open Access Journals (Sweden)

    Thomas J Reilly

    2017-03-01

    Full Text Available Objectives: To describe a case of neuroleptic malignant syndrome following antipsychotic treatment of catatonia, highlighting the potentially serious complications of this rare adverse drug reaction. Methods: We present a case report of a patient who developed this syndrome with various sequelae. Results: The patient developed neuroleptic after being treated with lorazepam and olanzapine for catatonia. He subsequently developed the complications of rhabdomyolysis, acute kidney injury, pulmonary embolism, urinary retention and ileus. He received high-dose lorazepam, anticoagulation and intravenous fluids. Antipsychotic medication in the form of haloperidol was reinstated with no adverse effect, and he went on to make a full recovery. Conclusions: This case illustrates the potential life-threatening complications of neuroleptic malignant syndrome and the need for a low index of clinical suspicion. It also highlights the lack of evidence for treatment of catatonia, including the use of antipsychotics.

  12. Rocuronium-sugammadex for electroconvulsive therapy management in neuroleptic malignant syndrome: A case report.

    Science.gov (United States)

    Casas Reza, P; Gestal Vázquez, M; Outeiro Rosato, Á; López Álvarez, S; Diéguez García, P

    2017-02-01

    Neuroleptics are a group of drugs widely used in the treatment of psychotic symptoms. Among their adverse effects is the ability to trigger a neuroleptic malignant syndrome (NMS). The diagnosis of NMS is determined by exclusion, and its initial therapeutic management should be the withdrawal of neuroleptics, the administration of benzodiazepines, and electroconvulsive therapy (ECT). ECT is an effective treatment in these patients, and in those cases with a poor response to treatment with antipsychotic drugs. A review is presented on the treatment options and anaesthetic implications of ECT used to handle a patient diagnosed with paranoid schizophrenia in the context of NMS. Copyright © 2016 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  13. Cure or curse? Ambivalent attitudes towards neuroleptic medication in schizophrenia and non-schizophrenia patients.

    Science.gov (United States)

    Moritz, Steffen; Peters, Maarten J V; Karow, Anne; Deljkovic, Azra; Tonn, Peter; Naber, Dieter

    2009-10-30

    Neuroleptic non-compliance remains a serious challenge for the treatment of psychosis. Non-compliance is predominantly attributed to side effects, lack of illness insight, reduced well-being or poor therapeutic alliance. However, other still neglected factors may also play a role. Further, little is known about whether psychiatric patients without psychosis who are increasingly prescribed neuroleptics differ in terms of medication compliance or about reasons for non-compliance by psychosis patients. As direct questioning is notoriously prone to social desirability biases, we conducted an anonymous survey. After a strict selection process blind to results, 95 psychiatric patients were retained for the final analyses (69 participants with a presumed diagnosis of schizophrenia psychosis, 26 without psychosis). Self-reported neuroleptic non-compliance was more prevalent in psychosis patients than non-psychosis patients. Apart from side effects and illness insight, main reasons for non-compliance in both groups were forgetfulness, distrust in therapist, and no subjective need for treatment. Other notable reasons were stigma and advice of relatives/acquaintances against neuroleptic medication. Gain from illness was a reason for non-compliance in 11-18% of the psychosis patients. Only 9% of all patients reported no side effects and full compliance and at the same time acknowledged that neuroleptics worked well for them. While pills were preferred over depot injections by the majority of patients, depot was judged as an alternative by a substantial subgroup. Although many patients acknowledge the need and benefits of neuroleptic medication, non-compliance was the norm rather than the exception in our samples.

  14. Cure or curse? Ambivalent attitudes towards neuroleptic medication in schizophrenia and non-schizophrenia patients

    Directory of Open Access Journals (Sweden)

    Dieter Naber

    2009-10-01

    Full Text Available Neuroleptic non-compliance remains a serious challenge for the treatment of psychosis. Non-compliance is predominantly attributed to side effects, lack of illness insight, reduced well-being or poor therapeutic alliance. However, other still neglected factors may also play a role. Further, little is known about whether psychiatric patients without psychosis who are increasingly prescribed neuroleptics differ in terms of medication compliance or about reasons for non-compliance by psychosis patients. As direct questioning is notoriously prone to social desirability biases, we conducted an anonymous survey. After a strict selection process blind to results, 95 psychiatric patients were retained for the final analyses (69 participants with a presumed diagnosis of schizophrenia psychosis, 26 without psychosis. Self-reported neuroleptic non-compliance was more prevalent in psychosis patients than non-psychosis patients. Apart from side effects and illness insight, main reasons for non-compliance in both groups were forgetfulness, distrust in therapist, and no subjective need for treatment. Other notable reasons were stigma and advice of relatives/acquaintances against neuroleptic medication. Gain from illness was a reason for non-compliance in 11-18% of the psychosis patients. Only 9% of all patients reported no side effects and full compliance and at the same time acknowledged that neuroleptics worked well for them. While pills were preferred over depot injections by the majority of patients, depot was judged as an alternative by a substantial subgroup. Although many patients acknowledge the need and benefits of neuroleptic medication, non-compliance was the norm rather than the exception in our samples.

  15. Neuroleptic Malignant Syndrome Caused by a Combination of Carbamazepine and Amitriptyline

    Directory of Open Access Journals (Sweden)

    A. Bruce Janati

    2012-01-01

    Full Text Available A 32-year-old female, with a history of secondarily-generalized convulsive epilepsy, mental retardation, and a psychiatric illness, developed neuroleptic malignant syndrome while receiving carbamazepine and amitriptyline concurrently. We hypothesize that the addition of amitriptyline to carbamazepine caused a decrease in the serum level of carbamazepine, resulting in NMS. We conclude that combination therapy with carbamazepine and amitriptyline should be avoided in patients who are predisposed to NMS. The purpose of this paper is to warn physicians against combination therapy with carbamazepine and tricyclic antidepressants which may be conducive to neuroleptic malignant syndrome in susceptible patients.

  16. Neuroleptic malignant syndrome and subsequent clozapine-withdrawal effects in a patient with refractory schizophrenia

    Directory of Open Access Journals (Sweden)

    Cheng MF

    2016-03-01

    Full Text Available Minfeng Cheng,* Huaying Gu,* Liangrong Zheng, Houliang Wang, Zhiyong Zhong, Shenglin Wen Department of Psychiatry, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Here, we report a female patient developing neuroleptic malignant syndrome following the use of a combination of clozapine and haloperidol. Subsequently, the patient presented withdrawal effects after an abrupt discontinuation of clozapine. Psychiatrists not aware of possible clozapine-withdrawal effects may misdiagnose as a part of the primary mental illness or as the initial symptoms worsening, if unrecognized. Keywords: clozapine, neuroleptic malignant syndrome, withdrawal effect, schizophrenia

  17. Serotonin type-1A receptor imaging in depression

    Energy Technology Data Exchange (ETDEWEB)

    Drevets, Wayne C. E-mail: drevets@pet.upmc.edu; Frank, Ellen; Price, Julie C.; Kupfer, David J.; Greer, Phil J.; Mathis, Chester

    2000-07-01

    Regional 5-hydroxytryptamine{sub 1A} (5-HT{sub 1A}) receptor binding potential (BP) of depressed subjects with primary, recurrent, familial mood disorders was compared to that of healthy controls by using positron emission tomography and [carbonyl-{sup 11}C]WAY-100635 {l_brace}[{sup 11}C]N-(2-(4-(2-methoxyphenyl)-1-piperazin-1-yl)ethyl)-N-(2-pyridyl) cyclohexanecarboxamide{r_brace}. The mean 5-HT{sub 1A} receptor BP was reduced 42% in the midbrain raphe and 25-33% in limbic and neocortical areas in the mesiotemporal, occipital, and parietal cortex. The magnitude of these abnormalities was most prominent in bipolar depressives and unipolar depressives who had bipolar relatives. These abnormal reductions in 5-HT{sub 1A} receptor BP are consistent with in vivo evidence that 5-HT{sub 1A} receptor sensitivity is reduced in major depressive disorder and postmortem data showing a widespread deficit of 5-HT{sub 1A} receptor expression in primary mood disorders.

  18. Evaluation of potential PET imaging probes for the orexin 2 receptors

    International Nuclear Information System (INIS)

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

    2013-01-01

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

  19. Synthesis of the possible receptor Ligand [125I]-spiperone for D2-dopamine receptor and in-vivo biodistribution

    International Nuclear Information System (INIS)

    Amin, A.M.; Shoukry, M.; Abd EL-Bary, A.

    2009-01-01

    The spiperone is a selective D2-dopamine receptor antagonist radioiodination of spiperone is of interest for dopamine (DA) receptor studies both in vivo and in vitro. The labeling of spiperone with iodine-125 was extremely done in a neutral ph 7, using chloramine-T as oxidizing agent via heating the reaction mixture at 70 C (degree) for 10 - 15 minutes producing radiochemical yield of 97 %. In vivo biodistribution studies showed that the initial brain uptake correlated fairly well with the brain uptake index and that the kinetics of the radioactivity specifically bound to the striatum were strongly influenced by the dopamine receptor binding affinity of the compound. The brain uptake of 125 I-Spiperone was high and equal to 3.5, 3.25,2.75 and 1.7 % per gram tissue at 5, 30, 60 and 120 minutes post injection, respectively. 125 I-Spiperone binds with high affinity to dopamine receptors in vivo. Specific binding is about 65% of the total binding as is displaced stereo-specifically by clozapine. 125 I-spiperone may prove to be a useful ligand in studies examining D2-dopamine receptors. Furthermore iodinated spiperone may be useful in radioreceptor assays of neuroleptic drug levels and, in a 123 I-labeled form, for imaging of dopamine receptors, in vivo, using single photon tomography.

  20. Quantitative Impact of Plasma Clearance and Down-regulation on GLP-1 Receptor Molecular Imaging.

    Science.gov (United States)

    Zhang, Liang; Thurber, Greg M

    2016-02-01

    Quantitative molecular imaging of beta cell mass (BCM) would enable early detection and treatment monitoring of type 1 diabetes. The glucagon-like peptide-1 (GLP-1) receptor is an attractive target due to its beta cell specificity and cell surface location. We quantitatively investigated the impact of plasma clearance and receptor internalization on targeting efficiency in healthy B6 mice. Four exenatide-based probes were synthesized that varied in molecular weight, binding affinity, and plasma clearance. The GLP-1 receptor internalization rate and in vivo receptor expression were quantified. Receptor internalization (54,000 receptors/cell in vivo) decreased significantly within minutes, reducing the benefit of a slower-clearing agent. The multimers and albumin binding probes had higher kidney and liver uptake, respectively. Slow plasma clearance is beneficial for GLP-1 receptor peptide therapeutics. However, for exendin-based imaging of islets, down-regulation of the GLP-1 receptor and non-specific background uptake result in a higher target-to-background ratio for fast-clearing agents.

  1. Receptor studies in biological psychiatry

    International Nuclear Information System (INIS)

    Fujiwara, Yutaka

    1992-01-01

    Recent advances in the pharmacological treatment of endogenous psychosis have led to the development of biological studies in psychiatry. Studies on neurotransmitter receptors were reviewed in order to apply positron-emission tomograph (PET) for biological psychiatry. The dopamine (DA) hypothesis for schizophrenia was advanced on the basis of the observed effects of neuroleptics and methamphetamine, and DA(D 2 ) receptor supersensitivity measured by PET and receptor binding in the schizophrenic brain. The clinical potencies of neuroleptics for schizophrenia were correlated with their abilities to inhibit the D 2 receptor, and not other receptors. The σ receptor was expected to be a site of antipsychotic action. However, the potency of drugs action on it was not correlated with clinical efficacy. Haloperidol binds with high affinity to the σ receptor, which may mediate acute dystonia, an extrapyramidal side effect of neuroleptics. Behavioral and neurochemical changes induced by methamphetamine treatment were studied as an animal model of schizophrenia, and both a decrease of D 2 receptor density and an increase of DA release were detected. The monoamine hypothesis for manic-depressive psychosis was advanced on the basis of the effect of reserpine, monoamine oxidase inhibitor and antidepressants. 3 H-clonidine binding sites were increased in platelet membranes of depressive patients, 3 H-imipramine binding sites were decreased. The GABA A receptor is the target site for the action of anxiolytics and antiepileptics such as benzodiazepines and barbiturates. Recent developments in molecular biology techniques have revealed the structure of receptor proteins, which are classified into two receptor families, the G-protein coupled type (D 2 ) and the ion-channel type (GABA A ). (J.P.N.)

  2. Hydrotherapy as a possible neuroleptic and sedative treatment.

    Science.gov (United States)

    Shevchuk, Nikolai A

    2008-01-01

    Psychotic symptoms such as delusions and hallucinations can have a devastating effect on a patient's social functioning. Since psychosis is rarely congenital, it is possible that lifestyle factors play a role in its etiology. This paper offers a hypothesis that some of these factors could be: (a) A lifestyle lacking evolutionarily conserved stressors such as frequent exposure to heat and/or cold, resulting in a lack of "thermal exercise" which could lead to malfunctioning of the brain. (b) Partial retention and absorption of toxic waste in the colon, as described in more detail below. (c) Genetic makeup that makes a person vulnerable to the above conditions. To test the hypothesis, three types of hydrotherapy are proposed (to be tested separately) as a putative neuroleptic treatment: head-out hot showers, adapted cold showers (twice daily each), and colon hydrotherapy (every 3-12 weeks, which also includes a dietary change according to Harvard's Healthy Eating Pyramid). The following is supporting evidence: Dopaminergic transmission in the mesolimbic pathway is involved in central processing of pain and negative stimuli (e.g. stress-induced analgesia) in addition to its role in the pathophysiology of psychosis. It is also known that if a neural pathway can perform two different functions, then the execution of one function will often suppress the other (e.g. gate control theory of pain). Thus, a pain-based therapy, such as a moderately hot shower, could have a "crowding out" effect on pathological processes within the mesolimbic system. In addition, hyperthermia is known to induce fatigue and depress activity of the frontal cortex (the sedative effect). As described previously, an adapted cold shower could work as a mild electroshock applied to the sensory cortex and, therefore, it might have an antipsychotic effect similar to that of electroconvulsive therapy. Additionally, a cold shower is a vivid example of stress-induced analgesia and would also be expected to

  3. Clinical value of somatostatin receptor imaging in patients with suspected head and neck paragangliomas

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, Matthias; Dietlein, Markus; Weber, Kerstin; Moka, Detlef; Schicha, Harald [Klinik und Poliklinik fuer Nuklearmedizin, Universitaet zu Koeln, Joseph-Stelzmann-Strasse 9, 50924 Koeln (Germany); Fischer, Eva; Michel, Olaf; Stennert, Eberhard [Klinik und Poliklinik fuer Hals-, Nasen- und Ohrenheilkunde, Universitaet zu Koeln, Koeln (Germany)

    2002-12-01

    Paragangliomas or glomus tumours of the head and neck region are rare somatostatin receptor-expressing neuroendocrine tumours. Precise preoperative diagnosis is of special importance in order to adequately weigh the potential benefit of the operation against the inherent risks of the procedure. In this study, the clinical value of somatostatin receptor imaging was assessed in 19 patients who underwent somatostatin receptor scintigraphy because of known or suspected paraganglioma of the head and neck region. The results were compared with the results of computed tomography and/or magnetic resonance imaging, histology and clinical follow-up. [{sup 111}In-DTPA-D-Phe{sup 1}]-octreotide scintigraphy was performed 4-6 and 24 h after i.v. injection of 140-220 MBq {sup 111}In-octreotide. Whole-body and planar images as well as single-photon emission tomography images were acquired and lesions were graded according to qualitative tracer uptake. Somatostatin receptor imaging was positive in nine patients, identifying paragangliomas for the first time in three patients and recurrent disease in six patients. In one patient, a second, previously unknown paraganglioma site was identified. Negative results were obtained in ten patients. These patients included one suffering from chronic hyperplastic otitis externa, one with granuloma tissue and an organised haematoma, one with an acoustic neuroma, one with an asymmetric internal carotid artery, two with ectasia of the bulbus venae jugularis and one with a jugular vein thrombosis. In two patients with a strong family history of paraganglioma, individual involvement could be excluded. In only one patient did somatostatin receptor imaging and magnetic resonance imaging yield false negative results in respect of recurrent paraganglioma tissue. It is concluded that somatostatin receptor scintigraphy provides important information in patients with suspected paragangliomas of the head and neck region and has a strong impact on further

  4. Malignant neuroleptic syndrome following deep brain stimulation surgery: a case report

    Directory of Open Access Journals (Sweden)

    Stavrinou Lampis C

    2011-06-01

    Full Text Available Abstract Background The neuroleptic malignant syndrome is an uncommon but dangerous complication characterized by hyperthermia, autonomic dysfunction, altered mental state, hemodynamic dysregulation, elevated serum creatine kinase, and rigor. It is most often caused by an adverse reaction to anti-psychotic drugs or abrupt discontinuation of neuroleptic or anti-parkinsonian agents. To the best of our knowledge, it has never been reported following the common practice of discontinuation of anti-parkinsonian drugs during the pre-operative preparation for deep brain stimulation surgery for Parkinson's disease. Case presentation We present the first case of neuroleptic malignant syndrome associated with discontinuation of anti-parkinsonian medication prior to deep brain stimulation surgery in a 54-year-old Caucasian man. Conclusion The characteristic neuroleptic malignant syndrome symptoms can be attributed to other, more common causes associated with deep brain stimulation treatment for Parkinson's disease, thus requiring a high index of clinical suspicion to timely establish the correct diagnosis. As more centers become eligible to perform deep brain stimulation, neurologists and neurosurgeons alike should be aware of this potentially fatal complication. Timely activation of the deep brain stimulation system may be important in accelerating the patient's recovery.

  5. Malignant neuroleptic syndrome following deep brain stimulation surgery: a case report.

    Science.gov (United States)

    Themistocleous, Marios S; Boviatsis, Efstathios J; Stavrinou, Lampis C; Stathis, Pantelis; Sakas, Damianos E

    2011-06-29

    The neuroleptic malignant syndrome is an uncommon but dangerous complication characterized by hyperthermia, autonomic dysfunction, altered mental state, hemodynamic dysregulation, elevated serum creatine kinase, and rigor. It is most often caused by an adverse reaction to anti-psychotic drugs or abrupt discontinuation of neuroleptic or anti-parkinsonian agents. To the best of our knowledge, it has never been reported following the common practice of discontinuation of anti-parkinsonian drugs during the pre-operative preparation for deep brain stimulation surgery for Parkinson's disease. We present the first case of neuroleptic malignant syndrome associated with discontinuation of anti-parkinsonian medication prior to deep brain stimulation surgery in a 54-year-old Caucasian man. The characteristic neuroleptic malignant syndrome symptoms can be attributed to other, more common causes associated with deep brain stimulation treatment for Parkinson's disease, thus requiring a high index of clinical suspicion to timely establish the correct diagnosis. As more centers become eligible to perform deep brain stimulation, neurologists and neurosurgeons alike should be aware of this potentially fatal complication. Timely activation of the deep brain stimulation system may be important in accelerating the patient's recovery.

  6. Neuroleptic malignant syndrome during zuclopenthixol therapy in X-linked cerebral adrenoleukodystrophy.

    NARCIS (Netherlands)

    Rubio Gozalbo, M.E.; Waardenburg, D.A. van; Forget, P.P.; Spaapen, L.J.; Verrips, A.; Vroomen, P.C.

    2001-01-01

    An 8 year-old boy with X-ALD under treatment with simvastatin developed a severe adverse reaction when the dose of his other medication, zuclopenthixol was increased. Both drugs were withdrawn after a diagnosis of neuroleptic malignant syndrome was made.

  7. Afebrile Neuroleptic Malignant Syndrome associated with Fluphenazine decanoate: A case report

    Directory of Open Access Journals (Sweden)

    Marzieh Assareh

    2010-06-01

    Full Text Available "nNeuroleptic Malignant Syndrome (NMS is unusual but could be a lethal reaction associated with neuroleptic drugs. It occurs in almost 0.07-2.2% of patients under treatment with neuroleptics. There are some medical treatments that may also be helpful for its treatment, including dopamine agonists, muscle relaxants, and electroconvulsive therapy (ECT. We present this case to alert the clinicians to the potential for inducing afebrile NMS. Our case is a 41-year-old man with a history of schizophrenia showing signs and symptoms in accordance with NMS, 2 weeks after receiving one dose of 12.5 mg fluphenazine decanoate, abruptly following the 3rdsession of ECT. The patient presented with decreased level of consciousness, muscular rigidity, waxy flexibility, mutism ,generalized tremor, sever diaphoresis and tachycardia which progressed during the previous 24 h. Laboratory data indicated primarily leukocytosis, an increasing level of creatinine phosphokinase and hypokalemia during the next 72h. In patients receiving antipsychotics, any feature of NMS should carefully be evaluated whether it is usual or unusual particularly in patients receiving long acting neuroleptics.

  8. [Case of neuroleptic malignant syndrome following open heart surgery for thoracic aortic aneurysm with parkinson's disease].

    Science.gov (United States)

    Shinoda, Maiko; Sakamoto, Mik; Shindo, Yuki; Ando, Yumi; Tateda, Takeshi

    2013-12-01

    An 80-year-old woman with Parkinson's disease was scheduled for open heart surgery to repair thoracic aortic aneurysm. Parkinson's symptoms were normally treated using oral levodopa (200 mg), selegiline-hydrochloride (5 mg), bromocriptine-mesilate (2 mg), and amantadine-hydrochloride (200 mg) daily. On the day before surgery, levodopa 50mg was infused intravenously. Another 25 mg of levodopa was infused immediately after surgery. Twenty hours later, the patient developed tremors, heyperventilation, but no obvious muscle rigidity. Two days after surgery, the patient exhibited high fever, hydropoiesis, elevated creatine kinase, and a rise in blood leukocytes. She was diagnosed with neuroleptic malignant syndrome. She was intubated, and received dantrolene sodium. Symptoms of neuroleptic malignant syndrome disappeared on the fourth postoperative day. The stress of open heart surgery, specifically extracorporeal circulation and concomitant dilution of levodopa, triggered neuroleptic malignant syndrome in this patient. Parkinson's patients require higher doses of levodopa prior to surgery to compensate and prevent neuroleptic malignant syndrome after surgery.

  9. Sex differences in plasma homovanillic acid levels in schizophrenia and normal controls: relation to neuroleptic resistance.

    Science.gov (United States)

    Sumiyoshi, T; Hasegawa, M; Jayathilake, K; Meltzer, H Y

    1997-03-01

    Plasma homovanillic acid (pHVA) levels were compared in a large number of neuroleptic-resistant and -responsive schizophrenic patients (male/female = 161/46) and normal controls (67/27), and correlated with various measures of psychopathology. Psychopathology was evaluated with the brief psychiatric rating scale, the Schedule for Affective Disorders and Schizophrenia-Change version (SADS-C) and SADS-C Global Assessment Scale, the Scale for Assessment of Negative Symptoms, the Scale for Assessment of Positive Symptoms (SAPS), and the Quality of Life Scale. No significant differences in pHVA levels between neuroleptic-resistant (n = 104) or -responsive (n = 103) schizophrenic patients, and normal controls, were found; however, there was a main effect for sex, due to higher pHVA levels in women than men. There were no diagnosis x gender or age effects on pHVA levels. No significant correlations were observed between psychopathology ratings and baseline pHVA levels, except with the Hallucinations subscale of SAPS in neuroleptic-responsive patients. Neither duration of neuroleptic washout nor plasma prolactin levels correlated with pHVA levels. Further studies on the origin and significance of the gender difference in pHVA are indicated.

  10. Short-term cognitive improvement in schizophrenics treated with typical and atypical neuroleptics.

    Science.gov (United States)

    Rollnik, Jens D; Borsutzky, Marthias; Huber, Thomas J; Mogk, Hannu; Seifert, Jürgen; Emrich, Hinderk M; Schneider, Udo

    2002-01-01

    Atypical neuroleptics seem to be more beneficial than typical ones with respect to long-term neuropsychological functioning. Thus, most studies focus on the long-term effects of neuroleptics. We were interested in whether atypical neuroleptic treatment is also superior to typical drugs over relatively short periods of time. We studied 20 schizophrenic patients [10 males, mean age 35.5 years, mean Brief Psychiatric Rating Scale (BPRS) score at entry 58.9] admitted to our hospital with acute psychotic exacerbation. Nine of them were treated with typical and 11 with atypical neuroleptics. In addition, 14 healthy drug-free subjects (6 males, mean age 31.2 years) were enrolled in the study and compared to the patients. As neuropsychological tools, a divided attention test, the Vienna reaction time test, the Benton visual retention test, digit span and a Multiple Choice Word Fluency Test (MWT-B) were used during the first week after admission, within the third week and before discharge (approximately 3 months). Patients scored significantly worse than healthy controls on nearly all tests (except Vienna reaction time). Clinical ratings [BPRS and Positive and Negative Symptom Scale for Schizophrenia (PANSS)] improved markedly (p divided attention task (r = 0.705, p = 0.034). Neuropsychological functioning (explicit memory, p divided attention, p < 0.05) moderately improved for both groups under treatment but without a significant difference between atypical and typical antipsychotic drugs. Over short periods of time (3 months), neuropsychological disturbances in schizophrenia seem to be moderately responsive to both typical and atypical neuroleptics. Copyright 2002 S. Karger AG, Basel

  11. Organic anion and cation transport in vitro by dog choroid plexus: Effects of neuroleptics and tricyclic antidepressants

    Energy Technology Data Exchange (ETDEWEB)

    Barany, E H [Uppsala Univ. (Sweden)

    1979-01-01

    Dog lateral choroid plexus accumulates the cation /sup 14/C-emepronium and the divalent anion /sup 125/I-iodipamide in vitro. At 10 ..mu..M, high potency neuroleptics with a substituted piperazine side chain and also haloperidol depress only the uptake of the cation and even stimulate the uptake of the anion. In contrast, at 1-10..mu..M, the accumulation of both test substances is inhibited by neuroleptics and tricyclic antidepresssants with an aliphatic side chain. Such unspecific effects on seemingly unrelated transport systems at concentrations reached clinically in the CSF might explain some side actions of low potency neuroleptics and antidepressants.

  12. Development of 99mTc agents for imaging central neural system receptors

    International Nuclear Information System (INIS)

    2004-01-01

    Radiopharmaceuticals that bind to central neural system (CNS) receptors in vivo are potentially useful for understanding the pathophysiology of anumber of neurological and psychiatric disorders, their diagnosis and treatment. Carbon-11 labelled compounds and positron emission tomography(PET) imaging have played a vital role in establishing the usefulness of imaging the dopaminergic, cholinergic, serotonergic and benzodiazapine receptors, and relating the receptor density to disease status. Since the use of 11C agents is constrained due to their 20 min half-life, various radiohalogenated analogues based on the structure of 11C compounds have been successfully developed, providing comparable information. Iodine- 123 is the most widely employed of these radioisotopes; it has a longer, 13 h, half-life. Through the use of 123I, there has been a steady growth in CNS receptor imaging studies employing single photon emission computerized tomography (SPECT). SPECT, as compared with PET, has slightly inferior image resolution but has the advantage of being readily available worldwide. However, the 123I radiopharmaceutical is expensive and the distribution system outside of the major markets is not well developed for its supply on a routine basis. The ideal radioisotope for SPECT imaging is 99mTc, due to its low cost per dose, availability through commercially available generator systems and physical decay characteristics. Over 80% of all diagnostic nuclear medicine imaging studies worldwide are conducted using this radioisotope. Development of 99mTc radiopharmaceuticals for imaging CNS receptors is therefore of considerable importance. On the basis of the recommendations of a consultants meeting, the International Atomic Energy Agency (IAEA) initiated in 1996 a Co-ordinated Research Project (CRP) on Development of Agents for Imaging CNS Receptors based on 99mTc. At that time there were no 99mTc CNS receptor imaging radiopharmaceuticals available even though work on

  13. Imaging dopamine and opiate receptors in the human brain in health and disease

    International Nuclear Information System (INIS)

    Wagner, H.N. Jr.; Dannals, R.F.; Frost, J.J.

    1986-01-01

    Chemical activity accompanies mental activity, but only recently has it been possible to begin to examine its nature. In 1983 the first imaging of a neuroreceptor in the human brain was accomplished with carbon-11 methyl spipeone, a ligand that binds preferentially to dopamine-2 receptors, 80% of which are located in the caudate nucleus and putamen. Quantitative imaging of serotonin-2, opiate, benzodiazapine and muscarinic cholinergic receptors has subsequently been accomplished. In studies of normal men and women, it has been found that dopamine and serotonin receptor activity decreases dramatically with age, such a decrease being more pronounced in men than in women and greater in the case of dopamine receptors than serotonin-2 receptors. Preliminary studies in patients with neuropsychiatric disorders suggests that dopamine-2 receptor activity is diminished in the caudate nucleus of patients with Huntington's disease. Positron tomography permits quantitative assay of picomolar quantities of neuroreceptors within the living human brain. Studies of patients with Parkinson's disease, Alzheimer's disease, depression, anxiety, schizophrenia, acute and chronic pain states and drug addiction are now in progress

  14. Somatostatin-receptor imaging in the localization of endocrine tumors

    International Nuclear Information System (INIS)

    Lamberts, S.W.; Bakker, W.H.; Reubi, J.C.; Krenning, E.P.

    1990-01-01

    A number of different tumors have receptors for somatostatin. We evaluated the efficacy of scanning with 123 I-labeled Tyr3-octreotide, a somatostatin analogue, for tumor localization in 42 patients with carcinoid tumors, pancreatic endocrine tumors, or paragangliomas. We then evaluated the response to octreotide therapy in some of these patients. Primary tumors or metastases, often previously unrecognized, were visualized in 12 of 13 patients with carcinoid tumors and in 7 of 9 patients with pancreatic endocrine tumors. The endocrine symptoms of these patients responded well to therapy with octreotide. Among 20 patients with paragangliomas, 8 of whom had more than one tumor, 10 temporal (tympanic or jugular), 9 carotid, and 10 vagal tumors could be visualized. One small tympanic tumor and one small carotid tumor were not seen on the scan. The 123 I-labeled Tyr3-octreotide scanning technique is a rapid and safe procedure for the visualization of some tumors with somatostatin receptors. A positive scan may predict the ability of octreotide therapy to control symptoms of hormonal hypersecretion

  15. Synthesis of opioid receptor imaging agent 7α-o-IA-DPN

    International Nuclear Information System (INIS)

    Wang Rongfu

    1997-01-01

    A new opioid receptor imaging agent is designed and synthesized. 7α-o-iodoallyl diprenorphine (7α-o-IA-DPN) was obtained in one step by radioiododestannylation, which involved in the selection of DPN as an opioid antagonist, the regioselective protection of the DPN phenol tertiary-OH using acetylation and the introduction of vinylstannane as prosthetic group into the tertiary alcohol group position in the 7α-side chain. The iodinated DPN derivation was possessed of high radiolabeled yield (>90%) with 80 TBq/mmol specific radioactivity and more than 95% radiochemical purity. In vitro opioid receptor binding analysis showed very high affinity (Ki = 0.4 nmol/L). This new radioiodinated opioid ligand is suitable for SPECT study of opioid receptor imaging

  16. Pet imaging of human pituitary 5-HT2 receptors with F-18 setoperone

    Energy Technology Data Exchange (ETDEWEB)

    Fischman, A.J.; Bonab, A.A.; Babich, J.W. [Massachusetts General Hospital, Boston, MA (United States)] [and others

    1995-05-01

    Serotonin (5-HT) receptors play an important role in the regulation of pituitary function. In particular, 5HT agonists stimulate ACTH, {beta}-endorphin, prolactin and growth hormone secretion but inhibit TSH release. 5-HT binding sites have been identified by autoradiographic studies of rat and human pituitary. In the present investigation, we used PET with F-18 setoperone to image 5-HT2 receptors in normal humans. Setoperone, a piperidine derivative with potent 5-HT2 receptor blocking properties was labelled with F-18 by nucleophilic substitution on the nitro derivative. After HPLC purification, specific activity was between 10,000 and 15,000 mCi/{mu} mole and radiochemical purity was >98%. Six healthy male volunteers were injected with 5-7 mCi of F-18. Setoperone and serial PET images and arterial blood samples were collected over 2 hrs. Specific binding to 5-HT2 receptors in the frontal cortex (FC), striatum (ST) and pituitary (P) was quantitated using the cerebellum (C) as reference. The tracer showed clear retention in FC, ST and P (known to contain a high density of 5-HT2 receptors) relative to C (known to be devoid of 5-HT2 receptors). In all subjects, FC/C, ST/C and P/C ratios increased during the first hr. and remained stable thereafter. For FC and ST, the ratios reached similar values; 3.92{plus_minus}0.73 and 3.53{plus_minus}0.32. For pituitary, a significantly higher ratio, was measured at all times; 6.53{plus_minus}1.82 (p<0.01). These results indicate that F-18 setoperone is an effective PET radiopharmaceutical for imaging 5-HT2 receptors in the human pituitary. Future applications of this agent could provide important new insights into neuroendocrine function.

  17. Molecular imaging of neuroendocrine tumors using 68Ga-labeled peptides (Somatostatin receptor PET/CT)

    International Nuclear Information System (INIS)

    Baum, R.P.; Prasad, V.; Hoersch, D.

    2009-01-01

    Receptor PET/CT using 68 Ga-labeled somatostatin analogues (DOTA-NOC, DOTA-TOC or DOTA-TATE) enables the highly sensitive molecular imaging of neuroendocrine tumors (NETs) based on the expression of somatostatin receptors and even the detection of receptor subtypes. Our experience after more than 3000 studies shows that receptor PET/CT has a significantly higher tumor detection rate than conventional scintigraphy (even in SPECT/CT technique), and that tumor lesions can be very accurately localized. By calculating standardized uptake values (SUV) - which are reproducible and investigator-independent - patients can be selected for peptide receptor radiotherapy and also the course after therapy can be controlled. Receptor-PET/CT is the most sensitive imaging modality for the detection of unknown primary tumors (CUP syndrome), which is especially true for the detection of neuroendocrine tumors of the pancreas and small bowel; whole-body staging (''one stop shop'') as well as restaging and selection of patients for peptide receptor radiotherapy can be performed using a patient-friendly procedure (examination finished within one hour) exposing the patient to less radiation than whole-body CT scanning. The 68 Ge/ 68 Ga generator has proved very reliable over the years - even in a hospital environment. The effective costs for 68 Ga labeled somatostatin analogues might be less than for scintigraphic agents, provided a certain number of studies per year are performed. The development of new tumor-specific peptides as well as of other DOTA- or NOTA-coupled radiopharmaceuticals opens a new avenue into the future: finally, the 68 Ga generator could play a similar important role for PET/CT as did the 99m Tc-Generator for conventional gamma camera imaging over the last decades. (orig.)

  18. Development of radiotracers for imaging NR2B subtype NMDA receptors with positron emission tomography

    International Nuclear Information System (INIS)

    Labas, R.

    2007-01-01

    The aim of this thesis was to develop new radioactive tracers for imaging NR2B subtype NMDA receptors with positron emission tomography. Several compounds including 4-(4-fluoro-benzyl)piperidine and presenting interesting in vivo biological properties were the object of a labelling with a positrons emitter atom ( 11 C or 18 F)

  19. The analytical of radiochemical purity of tumor receptor imaging agent 99Tcm-octreotide

    International Nuclear Information System (INIS)

    Wang Xufu; Zuo Shuyao; Shao Wenbo; Wang Guoming; Sun Jianwen; Zhang Qin

    2003-01-01

    The radiochemical purity of tumor receptor imaging agent 99 Tc m -octreotide is measured by High Pressure Liquid Chromatography (HPLC) and two systems of chromatography combining method of silver stain. The results show that the radiochemical purity of 98 Tc m -octreotide measured by both methods are effective and correct. It can separate 99 Tc m -octreotide from other radioactive compositions correctly and effectively

  20. PET tracers for somatostatin receptor imaging of neuroendocrine tumors

    DEFF Research Database (Denmark)

    Johnbeck, Camilla Bardram; Knigge, Ulrich; Kjær, Andreas

    2014-01-01

    Neuroendocrine tumors have shown rising incidence mainly due to higher clinical awareness and better diagnostic tools over the last 30 years. Functional imaging of neuroendocrine tumors with PET tracers is an evolving field that is continuously refining the affinity of new tracers in the search...... these PET tracers further....

  1. Advances of 11C-flumazenil receptor imaging in ischemic penumbra

    International Nuclear Information System (INIS)

    Zhang Jun

    2004-01-01

    The ischemic penumbra is the target of therapy for ischemic stroke patients, so it is extremely important to investigate an imaging technique that may identify accurately the viability of cerebral tissues early. The neuroreceptor imaging with positron emission tomography has achieved some successes in this study field, in particular, the 11 C-flumazenil receptor imaging, which can not only differentiate between the neurons of functional impairment and those of morphological destruction, and then distinguish the ischemic penumbra from the irreversible damage tissues, but predict the malignant course of cerebral infarction. Consequently, these will help to select the patients benefiting from the intervention therapy and plan effectively the therapeutic strategies. (authors)

  2. In Vivo Imaging of Retinoic Acid Receptor Activity using a Sodium/Iodide Symporter and Luciferase Dual Imaging Reporter Gene

    Directory of Open Access Journals (Sweden)

    Min Kyung So

    2004-07-01

    Full Text Available Retinoic acids are natural derivatives of vitamin A, and play important roles in modulating tumor cell growth by regulating differentiation, thus suggesting the potential use of these derivatives in cancer therapy and prevention. To visualize the intranuclear responses of functional retinoic acid receptors, we have developed a dual-imaging reporter gene system based on the use of sodium/iodide symporter (NIS and luciferase in cancer cell lines. NIS and luciferase genes were linked with an internal ribosome entry site, and placed under the control of an artificial cis-acting retinoic acid responsive element (pRARE/NL. After retinoic acid treatment, I-125 uptake by pRARE/NL transfected cells was found to have increased by up to about five times that of nontreated cells. The bioluminescence intensity of pRARE/NL transfected cells showed dose-dependency. In vivo luciferase images showed higher intensity in retinoic acid treated SK-RARE/NL tumors, and scintigraphic images of SK-RARE/NL tumors showed increased Tc-99m uptake after retinoic acid treatment. The NIS/luciferase imaging reporter system was sufficiently sensitive to allow the visualization of intranuclear retinoic acid receptor activity. This cis-enhancer imaging reporter system may be useful in vitro and in vivo for the evaluation of retinoic acid responses in such areas as cellular differentiation and chemoprevention.

  3. Neuroleptics as therapeutic compounds stabilizing neuromuscular transmission in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Patten, Shunmoogum A; Aggad, Dina; Martinez, Jose; Tremblay, Elsa; Petrillo, Janet; Armstrong, Gary Ab; La Fontaine, Alexandre; Maios, Claudia; Liao, Meijiang; Ciura, Sorana; Wen, Xiao-Yan; Rafuse, Victor; Ichida, Justin; Zinman, Lorne; Julien, Jean-Pierre; Kabashi, Edor; Robitaille, Richard; Korngut, Lawrence; Parker, J Alexander; Drapeau, Pierre

    2017-11-16

    Amyotrophic lateral sclerosis (ALS) is a rapidly progressing, fatal disorder with no effective treatment. We used simple genetic models of ALS to screen phenotypically for potential therapeutic compounds. We screened libraries of compounds in C. elegans, validated hits in zebrafish, and tested the most potent molecule in mice and in a small clinical trial. We identified a class of neuroleptics that restored motility in C. elegans and in zebrafish, and the most potent was pimozide, which blocked T-type Ca2+ channels in these simple models and stabilized neuromuscular transmission in zebrafish and enhanced it in mice. Finally, a short randomized controlled trial of sporadic ALS subjects demonstrated stabilization of motility and evidence of target engagement at the neuromuscular junction. Simple genetic models are, thus, useful in identifying promising compounds for the treatment of ALS, such as neuroleptics, which may stabilize neuromuscular transmission and prolong survival in this disease.

  4. Neuroleptic Malignant Syndrome in a Patient with Tongue Cancer: A Report of a Rare Case

    Directory of Open Access Journals (Sweden)

    Osamu Baba

    2013-01-01

    Full Text Available Background. Neuroleptic malignant syndrome (NMS is a rare but life-threatening complication of neuroleptic drugs, which are used widely in head and neck cancer (HANC patients who develop delirium. Methods and Results. Postoperative delirium in a 39-year-old man with tongue cancer was treated with haloperidol and chlorpromazine. Three days after the first administration of antipsychotics, the patient exhibited elevated body temperature, autonomic and extrapyramidal symptoms, and impaired consciousness. A definitive diagnosis was made using the research diagnostic criteria for NMS in the DSM-IV, and the antipsychotics were immediately discontinued. The patient was given dantrolene and bromocriptine to treat the NMS. The patient’s hyperthermia, elevated creatinin kinase (CK, and muscle rigidity improved gradually, with all symptoms of NMS resolving completely by 13 days after the diagnosis. Conclusions. HANC surgeons must be alert for early signs of NMS and use antipsychotics conservatively to avoid NMS and its potentially fatal outcome.

  5. Neuroleptic malignant syndrome: a case responding to electroconvulsive therapy plus bupropion

    Directory of Open Access Journals (Sweden)

    Quintí Foguet-Boreu

    2018-01-01

    Full Text Available Neuroleptic malignant syndrome (NMS is a severe motor syndrome occurring as a consequence of neuroleptic treatment. We present a case of a 67-year-old Caucasian woman with a history of a major depressive disorder with psychotic features. During her third hospital admission, symptoms of autonomic instability, hyperpyrexia, severe extrapyramidal side effects, and delirium appeared, suggesting NMS due to concomitant treatment with risperidone and quetiapine, among other drugs. Despite several consecutive pharmacological treatments (lorazepam, bromocriptine and amantadine and prompt initiation of electroconvulsive therapy (ECT, clinical improvement was observed only after combining bupropion with ECT. The symptoms that had motivated the admission gradually remitted and the patient was discharged home. Bupropion increases dopaminergic activity in both the nucleus accumbens and the prefrontal cortex. Therefore, from a physiopathological standpoint, bupropion has a potential role in treating NMS. However, there is scarce evidence supporting this approach and therefore future cases should be carefully considered.

  6. Imaging of sigma receptors in tumors by PET with [C-11]SA4503

    International Nuclear Information System (INIS)

    Kawamura, K.; Kobayashi, T.; Oda, K.; Ishiwata, K.; Kubota, K.

    2002-01-01

    Aim: Sigma receptors are implicated in some diseases in the central nervous system (CNS), such as schizophrenia, depression, dementia and ischemia, and are also expressed in a variety of human tumors, such as melanoma, carcinoma of the breast, lung and prostate, and the brain tumor. Therefore, several radioligands have been proposed for imaging of sigma receptors by positron emission tomography (PET) and by single photon emission computed tomography. Recently, we have applied [C-11]labeled 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine ([C-11]SA4503) to mapping sigma1 receptors in the brain of monkeys and human. In the present study, we evaluated the potential of the [C-11]SA4503 PET for imaging of sigma receptors using the AH109A bearing rats, and the VX-2 carcinoma bearing rabbits. Materials and Methods: [C-11]SA4503 was injected i.v. into AH109A bearing rats, and the tissue distribution was measured by tissue dissection. To determine the receptor-specific uptake, cold SA4503 or haloperidol was co-injected into the other group of rats. The PET scanning were performed in the rats in the baseline condition and after pretreatment with haloperidol. In the VX-2 carcinoma bearing rabbits, PET scanning was also performed in the baseline and blockade conditions. The sigma receptors in the AH109A and VX-2 were measured in vitro by the standard membrane binding assays. Results: The sigma receptors were found in AH109A and VX-2. The density was much higher in VX-2 than in AH109A. In the tissue dissection study, the AH109A uptake of [C-11]SA4503 increased for 60 min after injection. By the co-injection of SA4503 or haloperidol, the AH109A uptake was enhanced. The PET study also confirmed that the radioactivity level in the AH109A was enhanced by the pretreatment with haloperidol. On the other hand, In the VX-2 carcinoma bearing rabbits, the radioactivity level of in VX-2 remained constant after initial uptake in the baseline PET measurement, but the VX-2 uptake was

  7. Application of 5-hydroxytryptamine receptor imaging for study of neuropsychiatric disorders and brain functions

    International Nuclear Information System (INIS)

    Qiu Chun; Guan Yihui

    2011-01-01

    In the central nervous system, the widely distributed 5-hydroxytryptamine (5-HT)receptors are involved in regulating a large number of psychological and physiological functions, including mood, sleep, endocrine and autonomic nervous system. Abnormal 5-HT transmission has been implicated in a variety of neuropsychiatric disorders, such as pain, depression and epilepsy. With the development of radioligands, non-invasive nuclear imaging technique with exquisite sensitivity and specificity has been applied for delineation of neurotransmitter function in vivo. It does great benefit for researches of these diseases and development of drugs. This review provided an overview of 5-HT receptors radioligands and recent findings. (authors)

  8. Actometry and Barnes Akathisia Rating Scale in neuroleptic-induced akathisia.

    Science.gov (United States)

    Janno, Sven; Holi, Matti M; Tuisku, Katinka; Wahlbeck, Kristian

    2005-01-01

    We evaluated Barnes Akathisia Rating Scale (BARS) and standardized lower limb actometry in quantifying neuroleptic-induced akathisia (NIA) in 99 schizophrenia patients. Both instruments discriminated well between NIA and non-NIA patients and they correlated weakly but significantly. BARS was superior to actometry in screening DSM-IV diagnosed NIA patients. The results of this methodological study provide BARS with objective validation through movement measuring, that it has been suggested to need.

  9. Neuroleptic malignant syndrome and subsequent clozapine-withdrawal effects in a patient with refractory schizophrenia

    OpenAIRE

    Cheng, Minfeng; Gu, Huaying; Zheng, Liangrong; Wang, Houliang; Zhong, Zhiyong; Wen, Shenglin

    2016-01-01

    Minfeng Cheng,* Huaying Gu,* Liangrong Zheng, Houliang Wang, Zhiyong Zhong, Shenglin Wen Department of Psychiatry, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Here, we report a female patient developing neuroleptic malignant syndrome following the use of a combination of clozapine and haloperidol. Subsequently, the patient presented withdrawal effects after an abrupt ...

  10. A Rare Case of Myxedema Coma with Neuroleptic Malignant Syndrome (NMS)

    OpenAIRE

    Dixit, Siddharth; Dutta, Manoj Kumar; Namdeo, Mayank

    2015-01-01

    Myxedema coma or hypothyroid crisis is an endocrine emergency and needs ICU management. Neuroleptic malignant syndrome (NMS) is another medical emergency which needs high degree of clinical suspicion else mortality can be high. There is a paradox in co existence of myxedema coma and NMS. While one is hypometabolic state another is hypermetabolic state and both can be precipitated by antipsychotics use. Hypothermia and flaccidity commonly expected in myxedema coma may mask fever and rigidity o...

  11. Neuroleptic-induced movement disorders in a naturalistic schizophrenia population: diagnostic value of actometric movement patterns

    Directory of Open Access Journals (Sweden)

    Tuisku Katinka

    2008-04-01

    Full Text Available Abstract Background Neuroleptic-induced movement disorders (NIMDs have overlapping co-morbidity. Earlier studies have described typical clinical movement patterns for individual NIMDs. This study aimed to identify specific movement patterns for each individual NIMD using actometry. Methods A naturalistic population of 99 schizophrenia inpatients using conventional antipsychotics and clozapine was evaluated. Subjects with NIMDs were categorized using the criteria for NIMD found in the Diagnostic and Statistical Manual for Mental Disorders – Fourth Edition (DSM-IV. Two blinded raters evaluated the actometric-controlled rest activity data for activity periods, rhythmical activity, frequencies, and highest acceleration peaks. A simple subjective question was formulated to test patient-based evaluation of NIMD. Results The patterns of neuroleptic-induced akathisia (NIA and pseudoakathisia (PsA were identifiable in actometry with excellent inter-rater reliability. The answers to the subjective question about troubles with movements distinguished NIA patients from other patients rather well. Also actometry had rather good screening performances in distinguishing akathisia from other NIMD. Actometry was not able to reliably detect patterns of neuroleptic-induced parkinsonism and tardive dyskinesia. Conclusion The present study showed that pooled NIA and PsA patients had a different pattern in lower limb descriptive actometry than other patients in a non-selected sample. Careful questioning of patients is a useful method of diagnosing NIA in a clinical setting.

  12. Neuroleptic-induced movement disorders in a naturalistic schizophrenia population: diagnostic value of actometric movement patterns.

    Science.gov (United States)

    Janno, Sven; Holi, Matti M; Tuisku, Katinka; Wahlbeck, Kristian

    2008-04-18

    Neuroleptic-induced movement disorders (NIMDs) have overlapping co-morbidity. Earlier studies have described typical clinical movement patterns for individual NIMDs. This study aimed to identify specific movement patterns for each individual NIMD using actometry. A naturalistic population of 99 schizophrenia inpatients using conventional antipsychotics and clozapine was evaluated. Subjects with NIMDs were categorized using the criteria for NIMD found in the Diagnostic and Statistical Manual for Mental Disorders - Fourth Edition (DSM-IV).Two blinded raters evaluated the actometric-controlled rest activity data for activity periods, rhythmical activity, frequencies, and highest acceleration peaks. A simple subjective question was formulated to test patient-based evaluation of NIMD. The patterns of neuroleptic-induced akathisia (NIA) and pseudoakathisia (PsA) were identifiable in actometry with excellent inter-rater reliability. The answers to the subjective question about troubles with movements distinguished NIA patients from other patients rather well. Also actometry had rather good screening performances in distinguishing akathisia from other NIMD. Actometry was not able to reliably detect patterns of neuroleptic-induced parkinsonism and tardive dyskinesia. The present study showed that pooled NIA and PsA patients had a different pattern in lower limb descriptive actometry than other patients in a non-selected sample. Careful questioning of patients is a useful method of diagnosing NIA in a clinical setting.

  13. A case of neuroleptic malignant syndrome induced by risperidone in a schizophrenic woman.

    Science.gov (United States)

    Gallelli, Luca; Spagnuolo, Vincenzo; Palleria, Caterina; De Sarro, Giovambattista; Ferraro, Maria

    2009-05-01

    We report a case of neuroleptic malignant syndrome in a woman who assumed risperidone for schizoaffective disorders. A 45-year-old woman affected by schizoaffective disorders was admitted to Infectious Disease unit of Crotone Hospital because of a diagnosis of a fever of unknown origin. Clinical evaluation documented confusion and dysphoria, whereas chemical blood evaluation revealed acidosis and liver dysfunction. After few days she was transferred to the Operative Unit of Internal Medicine of San Giovanni in Fiore Hospital because of an increase in liver transaminases. Clinical evaluation showed the persistence of fever (38.8 degrees Celsius), with an increase in CPK, and liver enzymes. Pharmacological evaluation indicated a probable relationship between risperidone and NMS and led to a diagnosis of neuroleptic malignant syndrome associated with risperidone in a woman with schizophrenia. About seven days later, we recorded a complete resolution of her psychiatric symptoms. We postulate a possible interaction between risperidone and neuroleptic malignant syndrome and we suggest to use risperidone with caution in both young and middle aged people.

  14. Multivariate cluster analysis of dynamic iodine-123 iodobenzamide SPET dopamine D2receptor images in schizophrenia

    International Nuclear Information System (INIS)

    Acton, P.D.; Pilowsky, L.S.; Costa, D.C.; Ell, P.J.

    1997-01-01

    This paper describes the application of a multivariate statistical technique to investigate striatal dopamine D 2 receptor concentrations measured by iodine-123 iodobenzamide ( 123 I-IBZM) single-photon emission tomography (SPET). This technique enables the automatic segmentation of dynamic nuclear medicine images based on the underlying time-activity curves present in the data. Once the time-activity curves have been extracted, each pixel can be mapped back on to the underlying distribution, considerably reducing image noise. Cluster analysis has been verified using computer simulations and phantom studies. The technique has been applied to SPET images of dopamine D 2 receptors in a total of 20 healthy and 20 schizophrenic volunteers (22 male, 18 female), using the ligand 123 I-IBZM. Following automatic image segmentation, the concentration of striatal dopamine D 2 receptors shows a significant left-sided asymmetry in male schizophrenics compared with male controls. The mean left-minus-right laterality index for controls is -1.52 (95% CI -3.72-0.66) and for patients 4.04 (95% CI 1.07-7.01). Analysis of variance shows a case-by-sex-by-side interaction, with F=10.01, P=0.005. We can now demonstrate that the previously observed male sex-specific D 2 receptor asymmetry in schizophrenia, which had failed to attain statistical significance, is valid. Cluster analysis of dynamic nuclear medicine studies provides a powerful tool for automatic segmentation and noise reduction of the images, removing much of the subjectivity inherent in region-of-interest analysis. The observed striatal D 2 asymmetry could reflect long hypothesized disruptions in dopamine-rich cortico-striatal-limbic circuits in schizophrenic males. (orig.). With 4 figs., 2 tabs

  15. Benchmarking the performance of fixed-image receptor digital radiographic systems part 1: a novel method for image quality analysis.

    Science.gov (United States)

    Lee, Kam L; Ireland, Timothy A; Bernardo, Michael

    2016-06-01

    This is the first part of a two-part study in benchmarking the performance of fixed digital radiographic general X-ray systems. This paper concentrates on reporting findings related to quantitative analysis techniques used to establish comparative image quality metrics. A systematic technical comparison of the evaluated systems is presented in part two of this study. A novel quantitative image quality analysis method is presented with technical considerations addressed for peer review. The novel method was applied to seven general radiographic systems with four different makes of radiographic image receptor (12 image receptors in total). For the System Modulation Transfer Function (sMTF), the use of grid was found to reduce veiling glare and decrease roll-off. The major contributor in sMTF degradation was found to be focal spot blurring. For the System Normalised Noise Power Spectrum (sNNPS), it was found that all systems examined had similar sNNPS responses. A mathematical model is presented to explain how the use of stationary grid may cause a difference between horizontal and vertical sNNPS responses.

  16. Quantitative Analysis of HER2 Receptor Expression In Vivo by Near-Infrared Optical Imaging

    Directory of Open Access Journals (Sweden)

    Victor Chernomordik

    2010-07-01

    Full Text Available Human epidermal growth factor receptor 2 (HER2 overexpression in breast cancers is associated with poor prognosis and resistance to therapy. Current techniques for estimating this important characteristic use ex vivo assays that require tissue biopsies. We suggest a novel noninvasive method to characterize HER2 expression in vivo, using optical imaging, based on HER2-specific probes (albumin-binding domain–fused-(ZHER2:3422-Cys Affibody molecules [Affibody AB, Solna, Sweden], labeled with Alexa Fluor 750 [Molecular Probes, Invitrogen, Carlsbad, CA] that could be used concomitantly with HER2-targeted therapy. Subcutaneous tumor xenografts, expressing different levels of HER2, were imaged with a near-infrared fluorescence small-animal imaging system at several times postinjection of the probe. The compartmental ligand-receptor model was used to calculate HER2 expression from imaging data. Correlation between HER2 amplification/overexpression in tumor cells and parameters, directly estimated from the sequence of optical images, was observed (eg, experimental data for BT474 xenografts indicate that initial slope, characterizing the temporal dependence of the fluorescence intensity detected in the tumor, linearly depends on the HER2 expression, as measured ex vivo by an enzyme-linked immunosorbent assay for the same tumor. The results obtained from tumors expressing different levels of HER2 substantiate a similar relationship between the initial slope and HER2 amplification/overexpression. This work shows that optical imaging, combined with mathematical modeling, allows noninvasive monitoring of HER2 expression in vivo.

  17. Registration of dynamic dopamine D2receptor images using principal component analysis

    International Nuclear Information System (INIS)

    Acton, P.D.; Ell, P.J.; Pilowsky, L.S.; Brammer, M.J.; Suckling, J.

    1997-01-01

    This paper describes a novel technique for registering a dynamic sequence of single-photon emission tomography (SPET) dopamine D 2 receptor images, using principal component analysis (PCA). Conventional methods for registering images, such as count difference and correlation coefficient algorithms, fail to take into account the dynamic nature of the data, resulting in large systematic errors when registering time-varying images. However, by using principal component analysis to extract the temporal structure of the image sequence, misregistration can be quantified by examining the distribution of eigenvalues. The registration procedures were tested using a computer-generated dynamic phantom derived from a high-resolution magnetic resonance image of a realistic brain phantom. Each method was also applied to clinical SPET images of dopamine D 2 receptors, using the ligands iodine-123 iodobenzamide and iodine-123 epidepride, to investigate the influence of misregistration on kinetic modelling parameters and the binding potential. The PCA technique gave highly significant (P 123 I-epidepride scans. The PCA method produced data of much greater quality for subsequent kinetic modelling, with an improvement of nearly 50% in the χ 2 of the fit to the compartmental model, and provided superior quality registration of particularly difficult dynamic sequences. (orig.)

  18. The clinical impact of a combined gamma camera/CT imaging system on somatostatin receptor imaging of neuroendocrine tumours

    International Nuclear Information System (INIS)

    Hillel, P.G.; Beek, E.J.R. van; Taylor, C.; Lorenz, E.; Bax, N.D.S.; Prakash, V.; Tindale, W.B.

    2006-01-01

    AIM: With a combined gamma camera/CT imaging system, CT images are obtained which are inherently registered to the emission images and can be used for the attenuation correction of SPECT and for mapping the functional information from these nuclear medicine tomograms onto anatomy. The aim of this study was to evaluate the clinical impact of SPECT/CT using such a system for somatostatin receptor imaging (SRI) of neuroendocrine tumours. MATERIALS AND METHODS: SPECT/CT imaging with 111 In-Pentetreotide was performed on 29 consecutive patients, the majority of whom had carcinoid disease. All SPECT images were first reported in isolation and then re-reported with the addition of the CT images for functional anatomical mapping (FAM). RESULTS: Fifteen of the 29 SPECT images were reported as abnormal, and in 11 of these abnormal images (73%) FAM was found to either establish a previously unknown location (7/11) or change the location (4/11) of at least one lesion. The revised location could be independently confirmed in 64% of these cases. Confirmation of location was not possible in the other patients due to either a lack of other relevant investigations, or the fact that lesions seen in the SPECT images were not apparent in the other investigations. FAM affected patient management in 64% of the cases where the additional anatomical information caused a change in the reported location of lesions. CONCLUSION: These results imply that FAM can improve the reporting accuracy for SPECT SRI with significant impact on patient management

  19. Cellular imaging and folate receptor targeting delivery of gum kondagogu capped gold nanoparticles in cancer cells.

    Science.gov (United States)

    Kumar, Sathish Sundar Dhilip; Mahesh, Ayyavu; Antoniraj, M Gover; Rathore, Hanumant Singh; Houreld, N N; Kandasamy, Ruckmani

    2018-04-01

    In this study, the green synthesis of gum kondagogu capped gold nanoparticles (GK-GNPs) was prepared using a naturally available polysaccharide. The anionic gum capped GK-GNPs enabled the successful coupling of folic acid (FA) and fluorescein isothiocyanate (FITC) to produce a fluorescently labelled GNP (F2-GNP). F2-GNPs were further characterized using different physicochemical methods Cellular viability, cellular imaging, and targeted delivery of F2-GNPs were further evaluated in both folate receptor positive (MCF-7) and folate receptor negative (A549) cancer cells. Physicochemical characterization revealed a nanoparticle with a small size (37 nm), smooth surface (surface charge of -23.7 mV), crystallinity of gold nanoparticles and existence of gum kondagogu in the F2-GNPs. Cellular uptake of F2-GNPs indicated a greater affinity towards folate receptor positive cells. This study shows that the F2-GNPs is as an effective nanocarrier for targeted drug delivery and cellular imaging via folate receptors. Copyright © 2017. Published by Elsevier B.V.

  20. Automated synthesis of the estrogen receptors imaging agent 18F-FES

    International Nuclear Information System (INIS)

    Guo Shen; Chen Guobao; Dai Hongfeng; Lin Meifu; Chen Wenxin

    2011-01-01

    Objective: 18 F-16α-17β-fluoroestradiol ( 18 F-FES), an estrogen receptors imaging agent, is synthesized with Tracerlab FX FN system. Methods: 18 F-FES is obtained by two steps reactions, including the nucleophilic displacement reaction of no-carrier-added 18 F-fluoride with 3-O-methoxymethyl-16, 17-O-sulfuryl-16-epiesteriol, then the intermediate is evaporated and hydrolyzed with HCI and finally gives 18 F-FES. Results: The synthesis of 18 F-FES can be completed in about 80 min.The radiochemical yield and radio-chemical purity are about 10% and 95% respectively. Conclusion: The procedure of synthesis is simple and automatical. 18 F-FES has an extremely low toxicity, which suggests that 18 F-FES may be a safe, a nd effective estrogen receptors imaging agent. (authors)

  1. Ligand-Induced Dynamics of Neurotrophin Receptors Investigated by Single-Molecule Imaging Approaches

    Science.gov (United States)

    Marchetti, Laura; Luin, Stefano; Bonsignore, Fulvio; de Nadai, Teresa; Beltram, Fabio; Cattaneo, Antonino

    2015-01-01

    Neurotrophins are secreted proteins that regulate neuronal development and survival, as well as maintenance and plasticity of the adult nervous system. The biological activity of neurotrophins stems from their binding to two membrane receptor types, the tropomyosin receptor kinase and the p75 neurotrophin receptors (NRs). The intracellular signalling cascades thereby activated have been extensively investigated. Nevertheless, a comprehensive description of the ligand-induced nanoscale details of NRs dynamics and interactions spanning from the initial lateral movements triggered at the plasma membrane to the internalization and transport processes is still missing. Recent advances in high spatio-temporal resolution imaging techniques have yielded new insight on the dynamics of NRs upon ligand binding. Here we discuss requirements, potential and practical implementation of these novel approaches for the study of neurotrophin trafficking and signalling, in the framework of current knowledge available also for other ligand-receptor systems. We shall especially highlight the correlation between the receptor dynamics activated by different neurotrophins and the respective signalling outcome, as recently revealed by single-molecule tracking of NRs in living neuronal cells. PMID:25603178

  2. Imaging of Prostate Cancer Using Urokinase-Type Plasminogen Activator Receptor PET

    DEFF Research Database (Denmark)

    Skovgaard, Dorthe; Persson, Morten; Kjaer, Andreas

    2017-01-01

    Urokinase-type plasminogen activator receptor (uPAR) overexpression is an important biomarker for aggressiveness in cancer including prostate cancer (PC) and provides independent clinical information in addition to prostate-specific antigen and Gleason score. This article focuses on uPAR PET...... as a new diagnostic and prognostic imaging biomarker in PC. Many preclinical uPAR-targeted PET imaging studies using AE105 in cancer models have been undertaken with promising results. A major breakthrough was obtained with the recent human translation of uPAR PET in using 64Cu- and 68Ga-labelled versions...

  3. Improved localization of cellular membrane receptors using combined fluorescence microscopy and simultaneous topography and recognition imaging

    International Nuclear Information System (INIS)

    Duman, M; Pfleger, M; Chtcheglova, L A; Neundlinger, I; Bozna, B L; Ebner, A; Schuetz, G J; Hinterdorfer, P; Zhu, R; Mayer, B; Rankl, C; Moertelmaier, M; Kada, G; Kienberger, F; Salio, M; Shepherd, D; Polzella, P; Cerundolo, V; Dieudonne, M

    2010-01-01

    The combination of fluorescence microscopy and atomic force microscopy has a great potential in single-molecule-detection applications, overcoming many of the limitations coming from each individual technique. Here we present a new platform of combined fluorescence and simultaneous topography and recognition imaging (TREC) for improved localization of cellular receptors. Green fluorescent protein (GFP) labeled human sodium-glucose cotransporter (hSGLT1) expressed Chinese Hamster Ovary (CHO) cells and endothelial cells (MyEnd) from mouse myocardium stained with phalloidin-rhodamine were used as cell systems to study AFM topography and fluorescence microscopy on the same surface area. Topographical AFM images revealed membrane features such as lamellipodia, cytoskeleton fibers, F-actin filaments and small globular structures with heights ranging from 20 to 30 nm. Combined fluorescence and TREC imaging was applied to detect density, distribution and localization of YFP-labeled CD1d molecules on α-galactosylceramide (αGalCer)-loaded THP1 cells. While the expression level, distribution and localization of CD1d molecules on THP1 cells were detected with fluorescence microscopy, the nanoscale distribution of binding sites was investigated with molecular recognition imaging by using a chemically modified AFM tip. Using TREC on the inverted light microscope, the recognition sites of cell receptors were detected in recognition images with domain sizes ranging from ∼ 25 to ∼ 160 nm, with the smaller domains corresponding to a single CD1d molecule.

  4. Improved localization of cellular membrane receptors using combined fluorescence microscopy and simultaneous topography and recognition imaging

    Energy Technology Data Exchange (ETDEWEB)

    Duman, M; Pfleger, M; Chtcheglova, L A; Neundlinger, I; Bozna, B L; Ebner, A; Schuetz, G J; Hinterdorfer, P [Institute for Biophysics, University of Linz, Altenbergerstrasse 69, A-4040 Linz (Austria); Zhu, R; Mayer, B [Christian Doppler Laboratory for Nanoscopic Methods in Biophysics, Institute for Biophysics, University of Linz, Altenbergerstrasse 69, A-4040 Linz (Austria); Rankl, C; Moertelmaier, M; Kada, G; Kienberger, F [Agilent Technologies Austria GmbH, Aubrunnerweg 11, A-4040 Linz (Austria); Salio, M; Shepherd, D; Polzella, P; Cerundolo, V [Cancer Research UK Tumor Immunology Group, Weatherall Institute of Molecular Medicine, Nuffield Department of Medicine, University of Oxford, Oxford OX3 9DS (United Kingdom); Dieudonne, M, E-mail: ferry_kienberger@agilent.com [Agilent Technologies Belgium, Wingepark 51, Rotselaar, AN B-3110 (Belgium)

    2010-03-19

    The combination of fluorescence microscopy and atomic force microscopy has a great potential in single-molecule-detection applications, overcoming many of the limitations coming from each individual technique. Here we present a new platform of combined fluorescence and simultaneous topography and recognition imaging (TREC) for improved localization of cellular receptors. Green fluorescent protein (GFP) labeled human sodium-glucose cotransporter (hSGLT1) expressed Chinese Hamster Ovary (CHO) cells and endothelial cells (MyEnd) from mouse myocardium stained with phalloidin-rhodamine were used as cell systems to study AFM topography and fluorescence microscopy on the same surface area. Topographical AFM images revealed membrane features such as lamellipodia, cytoskeleton fibers, F-actin filaments and small globular structures with heights ranging from 20 to 30 nm. Combined fluorescence and TREC imaging was applied to detect density, distribution and localization of YFP-labeled CD1d molecules on {alpha}-galactosylceramide ({alpha}GalCer)-loaded THP1 cells. While the expression level, distribution and localization of CD1d molecules on THP1 cells were detected with fluorescence microscopy, the nanoscale distribution of binding sites was investigated with molecular recognition imaging by using a chemically modified AFM tip. Using TREC on the inverted light microscope, the recognition sites of cell receptors were detected in recognition images with domain sizes ranging from {approx} 25 to {approx} 160 nm, with the smaller domains corresponding to a single CD1d molecule.

  5. Intravascular optical imaging of high-risk plaques in vivo by targeting macrophage mannose receptors

    Science.gov (United States)

    Kim, Ji Bak; Park, Kyeongsoon; Ryu, Jiheun; Lee, Jae Joong; Lee, Min Woo; Cho, Han Saem; Nam, Hyeong Soo; Park, Ok Kyu; Song, Joon Woo; Kim, Tae Shik; Oh, Dong Joo; Gweon, Daegab; Oh, Wang-Yuhl; Yoo, Hongki; Kim, Jin Won

    2016-03-01

    Macrophages mediate atheroma expansion and disruption, and denote high-risk arterial plaques. Therefore, they are substantially gaining importance as a diagnostic imaging target for the detection of rupture-prone plaques. Here, we developed an injectable near-infrared fluorescence (NIRF) probe by chemically conjugating thiolated glycol chitosan with cholesteryl chloroformate, NIRF dye (cyanine 5.5 or 7), and maleimide-polyethylene glycol-mannose as mannose receptor binding ligands to specifically target a subset of macrophages abundant in high-risk plaques. This probe showed high affinity to mannose receptors, low toxicity, and allowed the direct visualization of plaque macrophages in murine carotid atheroma. After the scale-up of the MMR-NIRF probe, the administration of the probe facilitated in vivo intravascular imaging of plaque inflammation in coronary-sized vessels of atheromatous rabbits using a custom-built dual-modal optical coherence tomography (OCT)-NIRF catheter-based imaging system. This novel imaging approach represents a potential imaging strategy enabling the identification of high-risk plaques in vivo and holds promise for future clinical implications.

  6. Registration of dynamic dopamine D{sub 2}receptor images using principal component analysis

    Energy Technology Data Exchange (ETDEWEB)

    Acton, P.D.; Ell, P.J. [Institute of Nuclear Medicine, University College London Medical School, London (United Kingdom); Pilowsky, L.S.; Brammer, M.J. [Institute of Psychiatry, De Crespigny Park, London (United Kingdom); Suckling, J. [Clinical Age Research Unit, Kings College School of Medicine and Dentistry, London (United Kingdom)

    1997-11-01

    This paper describes a novel technique for registering a dynamic sequence of single-photon emission tomography (SPET) dopamine D{sub 2}receptor images, using principal component analysis (PCA). Conventional methods for registering images, such as count difference and correlation coefficient algorithms, fail to take into account the dynamic nature of the data, resulting in large systematic errors when registering time-varying images. However, by using principal component analysis to extract the temporal structure of the image sequence, misregistration can be quantified by examining the distribution of eigenvalues. The registration procedures were tested using a computer-generated dynamic phantom derived from a high-resolution magnetic resonance image of a realistic brain phantom. Each method was also applied to clinical SPET images of dopamine D {sub 2}receptors, using the ligands iodine-123 iodobenzamide and iodine-123 epidepride, to investigate the influence of misregistration on kinetic modelling parameters and the binding potential. The PCA technique gave highly significant (P <0.001) improvements in image registration, leading to alignment errors in x and y of about 25% of the alternative methods, with reductions in autocorrelations over time. It could also be applied to align image sequences which the other methods failed completely to register, particularly {sup 123}I-epidepride scans. The PCA method produced data of much greater quality for subsequent kinetic modelling, with an improvement of nearly 50% in the {chi}{sup 2}of the fit to the compartmental model, and provided superior quality registration of particularly difficult dynamic sequences. (orig.) With 4 figs., 2 tabs., 26 refs.

  7. Radiosynthesis and pharmacokinetics of high specific activity /sup 75,77/Br-bromperidol, a potent butyrophenone neuroleptic

    International Nuclear Information System (INIS)

    Moerlein, S.M.; Stocklin, G.

    1984-01-01

    Bromperidol, 4-[4-(4-bromophenyl)-4-hydroxypiperidino]-4'- fluorobutyrophenone, is a potent neuroleptic which has found clinical use in the treatment of schizophrenia. Of the major dopaminergic receptor-binding ligands, bromperidol has the greatest specificity for binding to cerebral dopamine receptors (K/sub i/ = 3.7 nM) relative to competitive cerebral serotonin (K/sub i/ = 26 nM), α-adrenergic (K/sub i/ = 100 nM) or histamine (K/sub i/ = 700 nM) receptors. The authors have therefore prepared bromperidol labelled with no-carrier-added (n.c.a.) /sup 75/Br (t/sub 1/2/ = 1.6 hr β/sup +/) or /sup 77/Br (t/sub 1/2/ = 52 hr EC) for evaluation as a radiopharmaceutical for mapping cerebral dopamine receptor areas with PECT technology, as well as for non-invasive pharmacodynamic studies in man with conventional nuclear medicine equipment. 4-[4-(4-trimethylstannylphenyl)-4-hydroxypiperidino]-4'- fluorobutyrophenone, TMSn-P, was synthesized in 40% chemical yield by reaction of trimethylstannyl sodium with bromperidol. TMSn-P was purified by preparative HPLC and characterized by /sup 1/H-NMR and GC-MS. TMSn-P was radiobrominated in methanol using n.c.a. /sup 75/Br/sup -/ or /sup 77/Br/sup -/ and dichloramine-T as oxidizing agent. Product /sup 75,77/Br-bromperidol was separated from impurities, including chlorinated side-product halo-peridol, using HPLC (RP-18; MeOH/H/sub 2/O/Et/sub 3/N = 70/30/0.3). For a reaction time of 5 minutes, and an overall radiopharmaceutical production time of 30 minutes, /sup 75,77/Br-bromperidol was obtained in physiological saline solution with 40% radiochemical yield and a specific activity > 10,000 Ci/mmole. The pharmacokinetics in rodents and PECT studies in primates using /sup 75,77/Br-bromperidol are compared with that of previously-reported /sup 75,77/Br-brombenperidol

  8. Morphological Imaging in the Localization of Neuroendocrine Gastroenteropancreatic Tumors Found by Somatostatin Receptor Scintigraphy

    International Nuclear Information System (INIS)

    Saga, T.; Doi, R.; Endo, K.; Shimatsu, A.; Koizumi, K.; Ichikawa, T.; Yamamoto, K.; Noguchi, S.; Ishibashi, M.; Machinami, R.; Nakamura, K.; Sakahara, H.

    2005-01-01

    Purpose: To evaluate the necessity of morphological images (MI) in reading somatostatin receptor scintigraphy (SRS) in patients with suspected neuroendocrine gastroenteropancreatic (GEP) tumors. Material and Methods: A Japanese multicenter clinical trial of SRS was conducted in 40 patients with suspected GEP tumors. Three experienced radiologists interpreted the images in three separate sessions in a blinded manner (1: SRS images alone, 2: MI alone, 3: SRS and MI analyzed simultaneously), and the reading results of each session were compared. In addition, the diagnostic abilities of SRS, MI and SRS alone and simultaneous SRS and MI readings were compared for patients where final diagnosis was obtained. Results: SRS detected more suspected lesions (positive or inconclusive uptake) than morphological images did (51 vs 27 lesions), but included many physiological uptakes detected as positive or inconclusive uptakes. Combined reading of SRS and morphological images helped to correctly recognize these physiological uptakes, and also helped in determining the anatomical localization of the abnormal uptakes. Combined reading of SRS and morphological images gave the highest diagnostic impact. Conclusion: The sensitivity of SRS with regard to GEP is high. However the specificity is very low. Morphologic imaging is necessary for the exclusion of physiological uptake and correct anatomic location of an abnormal tracer uptake. The combined reading of SRS and morphologic imaging studies gives the highest diagnostic impact

  9. Development of gamma emitting receptor-binding radiotracers for imaging the brain and pancreas. Progress report, February 1983-September 1984

    International Nuclear Information System (INIS)

    Reba, R.C.

    1984-01-01

    The possibility of measuring the change in receptor concentration as a function of disease by external imaging was investigated. The structure-binding-relationship which provides optimal localization of radiolabelled antagonist of the muscarinic acetylcholine receptors in the brain was studied. These relationships were also studied with respect to localization in the pancreas

  10. Advances in technetium chemistry towards 99mTc receptor imaging agents

    International Nuclear Information System (INIS)

    Johannsen, B.; Spies, H.

    1997-01-01

    The development of the chemistry of technetium and its non-radioactive surrogate rhenium has been prompted by the trends and needs of nuclear medicine, which predominantly uses 99m Tc radiopharmaceuticals for a broad range of diagnostics. Technetium-99m is the ideal radioisotope for tomographic single-photon emission tomography (SPECT) imaging due to its nuclear properties (6.2 h, E γ 140 keV) and ready availability through generator systems. Transition metals offer many opportunities for designing molecules by modifying the environment around the core, allowing certain biological properties to be imposed upon the molecule. Whereas research in the past was mainly concerned with biological properties that allow relatively unspecific functional imaging, as in brain or myocardium perfusion studies, nuclear medicine is now requiring more and more biochemical information on low capacity, high specificity targets. Many research groups have become involved in the search for new technetium-based compounds, called the third generation of 99m Tc radiopharmaceuticals, that employ the principles of modern pharmacology to achieve biochemical specificity. There has been considerable interest in imaging CNS and other receptors with 99m Tc receptor-binding ligands. Such a 99m Tc CNS receptor-imaging agent is currently not yet in use because of the significant hurdles to be overcome in attaining this ambitious goal. However, some Tc and Re complexes of remarkable affinity in vitro, and the first high-affinity 99m Tc probes able to label the dopamine transporter in the brain by SPECT imaging prove the feasibility of this approach. (Author)

  11. Study on folate receptor PET imaging agent 18F-flurophenethyl folate

    International Nuclear Information System (INIS)

    Guo Congying; Zhu Jianhua; Qian Jun; Yang Yang; Shen Haixing; Zhang Zhengwei

    2009-01-01

    This work is aimed at synthesizing an 18 F-labelled folate derivative that can be used as folate-receptor induced tumor PET imaging agent. Under the optimal reaction and testing specification formulated during the cold-labeling experiments, 18 F labeling of folic acid was achieved in three steps of 18 F pre-labeling,bromination and esterification. The receptor binding property of the newly-synthesized folate radio-derivative was studied through β-lactoglobulin binding test. Tumor-bearing nude mice injected with the new compound were used to study whether the derivative can accumulate within tumor issue. Preliminary studies in vitro and in vivo showed that this new PET agent still possessed receptor binding qualities of folic acid. 18 F-flurophenethyl folate remained good affinity and specificity with β-lactoglobulin. Accumulation of activities in tumor tissues was found in tumor-bearing nude mice. A new folate receptor ligand: 18 F-flurophenethyl folate was synthesized,with high yield and good stability. Since the pre-labeling method was used, the fluorine labeling was not directly imposed upon folic acid.In this way, the structure destruction, which happens in high temperature reaction of folic acid, can be avoided. The synthesized folate derivative remained the binding structural quality of folic acid and could bind with the folate-binding protein: β-lactoglobulin. Through the folate receptors located on tumor tissues, 18 F-flurophenethyl folate accumulated in the tumor tissue, exhibiting its potential as a tumor PET imaging agent. (authors)

  12. GLP-1 receptor antagonist as a potential probe for pancreatic β-cell imaging

    International Nuclear Information System (INIS)

    Mukai, Eri; Toyoda, Kentaro; Kimura, Hiroyuki; Kawashima, Hidekazu; Fujimoto, Hiroyuki; Ueda, Masashi; Temma, Takashi; Hirao, Konomu; Nagakawa, Kenji; Saji, Hideo; Inagaki, Nobuya

    2009-01-01

    We examined exendin(9-39), an antagonist of glucagon-like peptide-1 (GLP-1) receptor (GLP-1R), as a potential probe for imaging of pancreatic β-cells. To evaluate in vitro receptor specificity, binding assay was performed using dispersed mouse islet cells. Binding assay showed competitive inhibition of [ 125 I]BH-exendin(9-39) binding by non-radioactive exendin(9-39). To assess in vivo selectivity, the biodistribution was evaluated by intravenous administration of [ 125 I]BH-exendin(9-39) to mice. Radioactivity of harvested pancreas reached highest levels at 60 and 120 min among organs examined except lung. Pre-administration of excess non-radioactive exendin(9-39) remarkably and specifically blocked the radioactivity of pancreas. After [ 125 I]BH-exendin(9-39) injection into transgenic mice with pancreatic β-cells expressing GFP, fluorescent and radioactive signals of sections of pancreas were evaluated with an image analyzer. Imaging analysis showed that the fluorescent GFP signals and the radioactive signals were correspondingly located. Thus, the GLP-1R antagonist exendin(9-39) may serve as a useful probe for pancreatic β-cell imaging.

  13. An inquiry into the semiquantitative parameters of striatal dopamine receptor imaging

    International Nuclear Information System (INIS)

    Cao Guoxiang; Tan Tianzhi; Kuang Anren; Liang Zhenglu

    1998-01-01

    Purpose: To inquire into the optimal striatal reference region for nonspecific IBZM uptake in brain dopamine receptor imaging. Methods: Using in vivo data from rats, the authors compared the results of 125 I-iodobenzamide ( 125 I-IBZM) striatal specific binding that were respectively obtained taking cerebellum and frontal cortex as striatal reference region of nonspecific uptake of ligand. Results: Radioiodination labelled IBZM bound stereoselectively and reversibly to striatal D2 receptors. Frontal cortex and cerebellum showed rapid uptake and rapid washout of ligand. When cerebellar uptake was used as a reference of nonspecific uptake in striatum, IBZM saturation could not be demonstrated. But when the frontal cortex was used as reference region, saturation could be demonstrated with B max = 44 pmol/g striatum tissue. The percentage of haloperidol replacement and the percentage of uptake difference between striatum and other brain regions which were derived from competitive inhibition experiments with a large does of spiperone or haloperidol, suggested that the cerebellar uptake underestimated nonspecific uptake in the striatum while frontal cortex was an appropriate reference region for nonspecific uptake of ligand in striatum. Conclusions: For the calculation of specific IBZM binding and other semiquantitative parameters of striatal dopamine D2 receptor imaging, frontal cortex would be the nonspecific reference region of choice

  14. The development of fluoroandrogens and fluoroprogestins as potential imaging agents for receptor-positive prostate and breast tumors

    International Nuclear Information System (INIS)

    Brandes, S.J.; Katzenellenbogen, J.A.

    1986-01-01

    The assay of progesterone receptor (PR) concentration in breast tumors and androgen receptor (AR) concentration in prostate tumors enables hormone responsive neoplasms to be distinguished from those that are non-responsive. In principle, a positron-emitting progestin or androgen with suitably high affinity and selectivity for PR and AR, respectively, and an adequately high specific activity might provide a means for imaging receptor-positive tumors and quantifying their receptor content in vivo. The use of fluorine-18 as a radiolabel, coupled with the use of positron emission transaxial tomography, appears to be a most favorable approach in the development of receptor binding radiopharmaceuticals for in vivo imaging. Therefore, we have begun a systematic investigation of the development of fluorine-substituted androgens and progestins that might be prepared in F-18 labeled form as probes for AR and PR. (author)

  15. Synthesis and 131I labelling of epidepride as a dopamine D2 receptor imaging agent

    International Nuclear Information System (INIS)

    Yang Min; Hu Mingyang; Pei Zhuguo; Wang Bocheng; Zhou Xingqin

    2001-01-01

    S-(-)-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-iodo-2, 3-dimethoxybenzamide (Epidepride) and its iodine labeling precursor S-(-)-N-[(1-Ethyl-2-pyrrolidinyl)methyl]-5-tributyltin-2, 3-dimethoxybenzamide are synthesized from 3-methoxy salicylic acid. The labeling precursor is labeled with 131 I by hydrogen peroxide method, and 131 I-epidepride is gained, its radiolabelling yield (RLY) and the radiochemical purity (RCP) are all over 95%. The RCP of 131 I-epidepride is over 90% under 4 degree C after 15 days. 131 I-epidepride has high affinity to dopamine D 2 receptor. The striatal uptake can be blocked completely by spiperone. The striatum and cerebellum uptake ratio can reach 237 at 320 min in rats. The results show that 131 I-epidepride may be used as a dopamine D 2 receptor imaging agent for SPECT

  16. Pavor nocturnus: a complication of single daily tricyclic or neuroleptic dosage.

    Science.gov (United States)

    Flemenbaum, A

    1976-05-01

    The author tested the hypothesis that a single bedtime dosage schedule of tricyclic or neuroleptic medication produces increased frequency of night terrors by administering a questionnaire to 30 medical patients who were not receiving such medications and 100 psychiatric patients on either multiple- or single-dosage schedules. Psychiatric patients on multiple-dosage schedules reported no more frightening dreams than the medical patients, whereas almost three-fourths of those receiving single bedtime doses had frightening dreams, a significant difference from the medical sample. This preliminary report is presented to call attention to the possible undesirable effects of a single dose schedule.

  17. Stimulation of (3H) spiroperidol binding after prolonged neuroleptic therapy by the cholecystokinin octapeptide analog cerulein

    International Nuclear Information System (INIS)

    Vasar, E.E.; Allikmets, L.K.; Maimets, O.O.; Nurk, A.M.

    1985-01-01

    Evidence has recently been obtained that cholecystokinin and its analog cerulein have marked antipsychotic action on patients with schizophrenia who are resistant to neuroleptics; this is the basis for interest in this study of the effect of cerulein, a high-affinity analog of the octapeptide cholecystokinin, on binding of tritium-spiroperidol in vivo. Considering the apormorphine-like action of cerulein, this biochemical analysis was undertaken in the form of a comparative study with N-propyl-norapomorphine, a high-affinity analogy of apomorphine

  18. Drug information update. Atypical antipsychotics and neuroleptic malignant syndrome: nuances and pragmatics of the association.

    Science.gov (United States)

    Sarkar, Siddharth; Gupta, Nitin

    2017-08-01

    Neuroleptic malignant syndrome (NMS) is a rare but potentially fatal adverse event associated with the use of antipsychotics. Although atypical antipsychotics were initially considered to carry no risk of NMS, reports have accumulated over time implicating them in NMS causation. Almost all atypical antipsychotics have been reported to be associated with NMS. The clinical profile of NMS caused by certain atypical antipsychotics such as clozapine has been reported to be considerably different from the NMS produced by typical antipsychotics, with diaphoresis encountered more commonly, and rigidity and tremor encountered less frequently. This article briefly discusses the evidence relating to the occurrence, presentation and management of NMS induced by atypical antipsychotics.

  19. Progressive Encephalomyelitis with Rigidity and Myoclonus in an Intellectually Disabled Patient Mimicking Neuroleptic Malignant Syndrome

    Directory of Open Access Journals (Sweden)

    Zheyu Xu

    2017-05-01

    Full Text Available We present a case of 32-year-old male with profound mental retardation and autism spectrum disorder who had presented with seizures, rigidity and elevated creatine kinase and was initially diagnosed as neuroleptic malignant syndrome (NMS. The patient subsequently had a complicated clinical course, developing refractory status epilepticus, which lead to the eventual diagnosis of progressive encephalomyelitis with rigidity and myoclonus (PERM. We discuss the clinical similarities and differences between NMS and PERM, and highlight the need to consider alternative diagnoses when the clinical picture of NMS is atypical, particularly in this patient group where the history and clinical examination may be challenging.

  20. Application of photoshop-based image analysis to quantification of hormone receptor expression in breast cancer.

    Science.gov (United States)

    Lehr, H A; Mankoff, D A; Corwin, D; Santeusanio, G; Gown, A M

    1997-11-01

    The benefit of quantifying estrogen receptor (ER) and progesterone receptor (PR) expression in breast cancer is well established. However, in routine breast cancer diagnosis, receptor expression is often quantified in arbitrary scores with high inter- and intraobserver variability. In this study we tested the validity of an image analysis system employing inexpensive, commercially available computer software on a personal computer. In a series of 28 invasive ductal breast cancers, immunohistochemical determinations of ER and PR were performed, along with biochemical analyses on fresh tumor homogenates, by the dextran-coated charcoal technique (DCC) and by enzyme immunoassay (EIA). From each immunohistochemical slide, three representative tumor fields (x20 objective) were captured and digitized with a Macintosh personal computer. Using the tools of Photoshop software, optical density plots of tumor cell nuclei were generated and, after background subtraction, were used as an index of immunostaining intensity. This immunostaining index showed a strong semilogarithmic correlation with biochemical receptor assessments of ER (DCC, r = 0.70, p < 0.001; EIA, r = 0.76, p < 0.001) and even better of PR (DCC, r = 0.86; p < 0.01; EIA, r = 0.80, p < 0.001). A strong linear correlation of ER and PR quantification was also seen between DCC and EIA techniques (ER, r = 0.62, p < 0.001; PR, r = 0.92, p < 0.001). This study demonstrates that a simple, inexpensive, commercially available software program can be accurately applied to the quantification of immunohistochemical hormone receptor studies.

  1. STRATEGIES FOR QUANTIFYING PET IMAGING DATA FROM TRACER STUDIES OF BRAIN RECEPTORS AND ENZYMES.

    Energy Technology Data Exchange (ETDEWEB)

    Logan, J.

    2001-04-02

    A description of some of the methods used in neuroreceptor imaging to distinguish changes in receptor availability has been presented in this chapter. It is necessary to look beyond regional uptake of the tracer since uptake generally is affected by factors other than the number of receptors for which the tracer has affinity. An exception is the infusion method producing an equilibrium state. The techniques vary in complexity some requiring arterial blood measurements of unmetabolized tracer and multiple time uptake data. Others require only a few plasma and uptake measurements and those based on a reference region require no plasma measurements. We have outlined some of the limitations of the different methods. Laruelle (1999) has pointed out that test/retest studies to which various methods can be applied are crucial in determining the optimal method for a particular study. The choice of method will also depend upon the application. In a clinical setting, methods not involving arterial blood sampling are generally preferred. In the future techniques for externally measuring arterial plasma radioactivity with only a few blood samples for metabolite correction will extend the modeling options of clinical PET. Also since parametric images can provide information beyond that of ROI analysis, improved techniques for generating such images will be important, particularly for ligands requiring more than a one-compartment model. Techniques such as the wavelet transform proposed by Turkheimer et al. (2000) may prove to be important in reducing noise and improving quantitation.

  2. Genetic Imaging of the Association of Oxytocin Receptor Gene (OXTR Polymorphisms with Positive Maternal Parenting

    Directory of Open Access Journals (Sweden)

    Kalina J. Michalska

    2014-02-01

    Full Text Available Background: Well-validated models of maternal behavior in small-brain mammals posit a central role of oxytocin in parenting, by reducing stress and enhancing the reward value of social interactions with offspring. In contrast, human studies are only beginning to gain insights into how oxytocin modulates maternal behavior and affiliation. Methods: To explore associations between oxytocin receptor genes and maternal parenting behavior in humans, we conducted a genetic imaging study of women selected to exhibit a wide range of observed parenting when their children were 4-6 years old. Results: In response to child stimuli during functional magnetic resonance imaging, hemodynamic responses in brain regions that mediate affect, reward, and social behavior were significantly correlated with observed positive parenting. Furthermore, single nucleotide polymorphisms (rs53576 and rs1042778 in the gene encoding the oxytocin receptor were significantly associated with both positive parenting and hemodynamic responses to child stimuli in orbitofrontal cortex, anterior cingulate cortex and hippocampus. Conclusions: These findings contribute to the emerging literature on the role of oxytocin in human social behavior and support the feasibility of tracing biological pathways from genes to neural regions to positive maternal parenting behaviors in humans using genetic imaging methods.

  3. Radioiodination of central nerves system dopamine D2 receptor imaging agent. IBZM preparation and preclinical study

    International Nuclear Information System (INIS)

    Lin Yansong; Lin Xiangtong; Hu Mingyang; Pan Shangren; Wang Bocheng

    1996-01-01

    To study preparation of central nerves system dopamine D2 imaging agent 131 I-IBZM and its preclinical investigation, peracetic acid was used as the oxidant for preparing radioiodinated 125 I-IBZM and 131 I-IBZM, D2 binding properties of IBZM were examined by in vitro binding saturation analysis, rat whole body and regional brain biodistribution, rat brain autoradiography and rabbit SPECT static imaging, etc. The results are: 1. The radiolabelling yields of 125 I-IBZM and 131 I-IBZM were 84.18% +- 3.06% and 78.50% +- 3.47%. The radiochemical purity were over 95% after being isolated by HPLC; and were over 90% after being isolated by organic extraction. 2. Scatchard plot of D2 receptor saturation binding analysis showed: K d = 0.53 +- 0.06 nmol/L, B max = 466.45 +- 45.88 fmol/mg protein. 3. The rat brain autoradiography and analysis showed that there was high 125 I-IBZM uptake in striatal area 2 hr after injection, the striatal/cerebellum ratio was 6.22 +- 0.48; the high 125 -IBZM uptake can be blocked by haloperidol--a special dopamine D2 receptor antagonist. 4. 131 I-IBZM rat biodistribution and rabbit SPECT planar imaging showed good initial brain uptake and retention, the initial uptake of rat brain was 1.893 +- 0.147% ID/g at 2 min and 1.044 +- 0.135% ID/g at 60 min. The results showed that the radioiodinated IBZM had high affinity, saturation and specificity to rat's and rabbit's central nerves system dopamine D2 receptors

  4. Radioiodination of central nerves system dopamine D2 receptor imaging agent. IBZM preparation and preclinical study

    Energy Technology Data Exchange (ETDEWEB)

    Yansong, Lin; Xiangtong, Lin; Mingyang, Hu; Shangren, Pan; Bocheng, Wang [Huashan Hospital of Shanghai Medical Univ., Shanghai (China)

    1996-11-01

    To study preparation of central nerves system dopamine D2 imaging agent {sup 131}I-IBZM and its preclinical investigation, peracetic acid was used as the oxidant for preparing radioiodinated {sup 125}I-IBZM and {sup 131}I-IBZM, D2 binding properties of IBZM were examined by in vitro binding saturation analysis, rat whole body and regional brain biodistribution, rat brain autoradiography and rabbit SPECT static imaging, etc. The results are: 1. The radiolabelling yields of {sup 125}I-IBZM and {sup 131}I-IBZM were 84.18% +- 3.06% and 78.50% +- 3.47%. The radiochemical purity were over 95% after being isolated by HPLC; and were over 90% after being isolated by organic extraction. 2. Scatchard plot of D2 receptor saturation binding analysis showed: K{sub d} = 0.53 +- 0.06 nmol/L, B{sub max} = 466.45 +- 45.88 fmol/mg protein. 3. The rat brain autoradiography and analysis showed that there was high {sup 125}I-IBZM uptake in striatal area 2 hr after injection, the striatal/cerebellum ratio was 6.22 +- 0.48; the high {sup 125}-IBZM uptake can be blocked by haloperidol--a special dopamine D2 receptor antagonist. 4. {sup 131}I-IBZM rat biodistribution and rabbit SPECT planar imaging showed good initial brain uptake and retention, the initial uptake of rat brain was 1.893 +- 0.147% ID/g at 2 min and 1.044 +- 0.135% ID/g at 60 min. The results showed that the radioiodinated IBZM had high affinity, saturation and specificity to rat`s and rabbit`s central nerves system dopamine D2 receptors.

  5. Molecular imaging of neutropilin-1 receptor using photoacoustic spectroscopy in breast tumors

    Science.gov (United States)

    Stantz, Keith M.; Cao, Minsong; Liu, Bo; Miller, Kathy D.; Guo, Lili

    2010-02-01

    Purpose: Our purpose is to develop and test a molecular probe that can detect the expression of neutropilin-1 receptor (NPR-1) in vivo using fluorescence imaging and photoacoustic spectroscopy. Introduction: NPR-1 is expressed on endothelial cells and some breast cancer cells, and binds to vascular endothelial growth factor VEGF165, a growth factor associated with pathological tumor angiogenesis. This receptor is coexpressed with VEGFR2 and shown to enhance the binding of VEGF165; therefore, it has the potential to be used as a marker of angiogenic activity and targeted for therapy. Material and Methods: A peptide specific to NPR-1 receptor was synthesized and conjugated to a NIR fluorochrome (IRDye800CW) and was intravenously injected into mice with breast tumors (MCF7VEGF). Probe kinetics was monitored in vivo via near infrared fluorescence (NIRF) within an optical imager for up to 72 hours within the tumor and compared to other organs (liver, muscle) for binding specificity. A multivariate fitting algorithm was used to spectrally deconvolve the IRDye800CW from endogenous hemoglobin signature (hemoglobin concentration and oxygen saturation). Results: Dynamics of the NIR fluorescence signal within the first hour after injection indicates specific binding compared to muscle, with an average tumor-to-muscle ration of 2.00 (+/- 0.27). Spectral analysis clearly indentified the presence of the NPR-1 probe. Based on calibration data, the average tumor concentration from both NIRF and PCT-S was measured to be ~200-300nM. Conclusion: These preliminary results show the capability of PCT to image an exogenous probe in vivo in addition to its hemoglobin state.

  6. Radiolabeled cetuximab: dose optimization for epidermal growth factor receptor imaging in a head-and-neck squamous cell carcinoma model

    NARCIS (Netherlands)

    Hoeben, B.A.W.; Molkenboer-Kuenen, J.D.M.; Oyen, W.J.G.; Peeters, W.J.M.; Kaanders, J.H.A.M.; Bussink, J.; Boerman, O.C.

    2011-01-01

    Noninvasive imaging of the epidermal growth factor receptor (EGFR) in head-and-neck squamous cell carcinoma could be of value to select patients for EGFR-targeted therapy. We assessed dose optimization of (111) Indium-DTPA-cetuximab ((111) In-cetuximab) for EGFR imaging in a head-and-neck squamous

  7. [18F]Fluoroethylflumazenil: a novel tracer for PET imaging of human benzodiazepine receptors

    International Nuclear Information System (INIS)

    Gruender, G.; Lange-Asschenfeldt, C.; Vernaleken, I.; Lueddens, H.; Siessmeier, T.; Buchholz, H.-G.; Bartenstein, P.; Stoeter, P.; Drzezga, A.; Roesch, F.

    2001-01-01

    5-(2'-[ 18 F]Fluoroethyl)flumazenil ([ 18 F]FEF) is a fluorine-18 labelled positron emission tomography (PET) tracer for central benzodiazepine receptors. Compared with the established [ 11 C]flumazenil, it has the advantage of the longer half-life of the fluorine-18 label. After optimisation of its synthesis and determination of its in vitro receptor affinities, we performed first PET studies in humans. PET studies in seven healthy human volunteers were performed on a Siemens ECAT EXACT whole-body scanner after injection of 100-280 MBq [ 18 F]FEF. In two subjects, a second PET scan was conducted after pretreatment with unlabelled flumazenil (1 mg or 2.5 mg i.v., 3 min before tracer injection). A third subject was studied both with [ 18 F]FEF and with [ 11 C]flumazenil. Brain radioactivity was measured for 60-90 min p.i. and analysed with a region of interest-oriented approach and on a voxelwise basis with spectral analysis. Plasma radioactivity was determined from arterial blood samples and metabolites were determined by high-performance liquid chromatography. In human brain, maximum radioactivity accumulation was observed 4±2 min p.i., with a fast clearance kinetics resulting in 50% and 20% of maximal activities at about 10 and 30 min, respectively. [ 18 F]FEF uptake followed the known central benzodiazepine receptor distribution in the human brain (occipital cortex >temporal cortex >cerebellum >thalamus >pons). Pretreatment with unlabelled flumazenil resulted in reduced tracer uptake in all brain areas except for receptor-free reference regions like the pons. Parametric images of distribution volume and binding potential generated on a voxelwise basis revealed two- to three-fold lower in vivo receptor binding of [ 18 F]FEF compared with [ 11 C]flumazenil, while relative uptake of [ 18 F]FEF was higher in the cerebellum, most likely owing to its relatively higher affinity for benzodiazepine receptors containing the α6 subunit. Metabolism of [ 18 F]FEF was very

  8. Brain dopaminergic systems : imaging with positron tomography

    Energy Technology Data Exchange (ETDEWEB)

    Baron, J C [University of Caen/INSERM U, Caen (France). CYCERON; Comar, D [E.E.C. Concerted Action on P.E.T. Investigations of Cellular Regeneration and Degeneration, Orsay (France) CEA, 91 - Orsay (France). Service Hospitalier Frederic Joliot; Farde, L [Karolinska Sjukhuset, Stockholm (Sweden); Martinot, J L; Mazoyer, B [CEA, 91 - Orsay (France). Service Hospitalier Frederic Joliot Paris-

    1991-01-01

    Imaging of the dopaminergic system in the human brain with the in vivo use of Positron Emission Tomography emerged in the late 1980s as a tool of major importance in clinical neurosciences and pharmacology. The last few years have witnessed rapid development of new radiotracers specific to receptors, reuptake sites and enzymes of the dopamine system; the application of these radiotracers has led to major break-troughs in the pathophysiology and therapy of movement disorders and schizophrenic-like psychoses. This book is the first to collect, in a single volume, state-of-the-art contributions to the various aspects of this research. Its contents address methodological issues related to the design, labelling, quantitative imaging and compartmental modeli-sation of radioligands of the post-synaptic, pre-synaptic and enzyme sites of the dopamine system and to their use in clinical research in the fields of Parkinson's disease as well as other movement disorders, psychoses and neuroleptic receptor occupancy. The chapters were written by leading European scientists in the field of PET, gathered together in Caen (France, November 1990) under the aegis of the EEC Concerted Action on PET Investigations of Cellular Regeneration and Degeneration. This book provides a current and comprehensive overview on PET studies of the brain dopamine system which should aid and interest neurologists , psychiatrists, pharmacologists and medical imaging scientists. (author). refs.; figs.; tabs.

  9. Radiolabeled pertuzumab for imaging of human epidermal growth factor receptor 2 expression in ovarian cancer

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Dawei [Shenzhen University, Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Shenzhen (China); University of Wisconsin - Madison, Department of Radiology, Madison, WI (United States); Im, Hyung-Jun [University of Wisconsin - Madison, Department of Radiology, Madison, WI (United States); Seoul National University, Graduate School of Convergence Science and Technology, Seoul (Korea, Republic of); Sun, Haiyan; Cho, Steve Y. [University of Wisconsin - Madison, Department of Radiology, Madison, WI (United States); Valdovinos, Hector F.; England, Christopher G.; Ehlerding, Emily B.; Nickles, Robert J. [University of Wisconsin - Madison, Department of Medical Physics, Madison, WI (United States); Lee, Dong Soo [Seoul National University, Graduate School of Convergence Science and Technology, Seoul (Korea, Republic of); Huang, Peng [Shenzhen University, Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Shenzhen (China); Cai, Weibo [University of Wisconsin - Madison, Department of Radiology, Madison, WI (United States); University of Wisconsin - Madison, Department of Medical Physics, Madison, WI (United States); University of Wisconsin Carbone Cancer Center, Madison, WI (United States)

    2017-08-15

    Human epidermal growth factor receptor 2 (HER2) is over-expressed in over 30% of ovarian cancer cases, playing an essential role in tumorigenesis and metastasis. Non-invasive imaging of HER2 is of great interest for physicians as a mean to better detect and monitor the progression of ovarian cancer. In this study, HER2 was assessed as a biomarker for ovarian cancer imaging using {sup 64}Cu-labeled pertuzumab for immunoPET imaging. HER2 expression and binding were examined in three ovarian cancer cell lines (SKOV3, OVCAR3, Caov3) using in vitro techniques, including western blot and saturation binding assays. PET imaging and biodistribution studies in subcutaneous models of ovarian cancer were performed for non-invasive in vivo evaluation of HER2 expression. Additionally, orthotopic models were employed to further validate the imaging capability of {sup 64}Cu-NOTA-pertuzumab. HER2 expression was highest in SKOV3 cells, while OVCAR3 and Caov3 displayed lower HER2 expression. {sup 64}Cu-NOTA-pertuzumab showed high specificity for HER2 (K{sub a} = 3.1 ± 0.6 nM) in SKOV3. In subcutaneous tumors, PET imaging revealed tumor uptake of 41.8 ± 3.8, 10.5 ± 3.9, and 12.1 ± 2.3%ID/g at 48 h post-injection for SKOV3, OVCAR3, and Caov3, respectively (n = 3). In orthotopic models, PET imaging with {sup 64}Cu-NOTA-pertuzumab allowed for rapid and clear delineation of both primary and small peritoneal metastases in HER2-expressing ovarian cancer. {sup 64}Cu-NOTA-pertuzumab is an effective PET tracer for the non-invasive imaging of HER2 expression in vivo, rendering it a potential tracer for treatment monitoring and improved patient stratification. (orig.)

  10. Characterization of the Distance Relationship Between Localized Serotonin Receptors and Glia Cells on Fluorescence Microscopy Images of Brain Tissue.

    Science.gov (United States)

    Jacak, Jaroslaw; Schaller, Susanne; Borgmann, Daniela; Winkler, Stephan M

    2015-08-01

    We here present two new methods for the characterization of fluorescent localization microscopy images obtained from immunostained brain tissue sections. Direct stochastic optical reconstruction microscopy images of 5-HT1A serotonin receptors and glial fibrillary acidic proteins in healthy cryopreserved brain tissues are analyzed. In detail, we here present two image processing methods for characterizing differences in receptor distribution on glial cells and their distribution on neural cells: One variant relies on skeleton extraction and adaptive thresholding, the other on k-means based discrete layer segmentation. Experimental results show that both methods can be applied for distinguishing classes of images with respect to serotonin receptor distribution. Quantification of nanoscopic changes in relative protein expression on particular cell types can be used to analyze degeneration in tissues caused by diseases or medical treatment.

  11. Optical Molecular Imaging of Epidermal Growth Factor Receptor Expression to Improve Detection of Oral Neoplasia

    Directory of Open Access Journals (Sweden)

    Nitin Nitin

    2009-06-01

    Full Text Available Background: The development of noninvasive molecular imaging approaches has the potential to improve management of cancer. Methods: In this study, we demonstrate the potential of noninvasive topical delivery of an epidermal growth factor-Alexa 647 (EGF-Alexa 647 conjugate to image changes in epidermal growth factor receptor expression associated with oral neoplasia. We report a series of preclinical analyses to evaluate the optical contrast achieved after topical delivery of EGF-Alexa 647 in a variety of model systems, including cells, three-dimensional tissue cultures, and intact human tissue specimens using wide-field and high-resolution fluorescence imaging. Data were collected from 17 different oral cancer patients: eight pairs of normal and abnormal biopsies and nine resected tumors were examined. Results: The EGF-dye conjugate can be uniformly delivered throughout the oral epithelium with a penetration depth exceeding 500 µm and incubation time of less than 30 minutes. After EGF-Alexa 647 incubation, the presence of oral neoplasia is associated with a 1.5- to 6.9-fold increase in fluorescence contrast compared with grossly normal mucosa from the same patient with both wide-field and high-resolution fluorescence imaging. Conclusions: Results illustrate the potential of EGF-targeted fluorescent agents for in vivo molecular imaging, a technique that may aid in the diagnosis and characterization of oral neoplasia and allow real-time detection of tumor margins.

  12. Granulocytopenia associated with neuroleptic therapy in a patient with benign familial leukopenia.

    Science.gov (United States)

    Reznik, Ilya; Loewenthal, Ron; Kotler, Moshe; Apter, Inna; Mester, Roberto; Weizman, Abraham

    2003-01-01

    Benign familial leukopenia (BFL) has been reported in several ethnic groups, including Ethiopians of Jewish origin. To date, there are no reported cases of patients with BFL developing granulocytopenia following administration of neuroleptics. We report a case of a young Ethiopian Jew suffering from schizophrenia, who exhibited premorbid benign reduced white blood cells (WBC) count and developed leukopenia and neutropenia following exposure to typical (zuclopentixol, perphenazine, haloperidol) antipsychotics and the atypical antipsychotic risperidone. The diagnosis of BFL was established and tissue typing of the patient was determined. To the best of our knowledge, this is the first report of leukopenia with neutropenia in an ethnically susceptible (due to BFL) schizophrenia patient following exposure to typical and atypical antipsychotics. HLA typing of this patient was distinct from that reported in patients susceptible to clozapine-induced agranulocytosis. Further extensive investigations including HLA typing in a larger cohort of schizophrenic patients is needed in order to define the association between HLA haplotypes and neuroleptic-induced hematological reactions and to identify the potentially vulnerable individuals.

  13. Evaluation of an image receptor for computed radiography system in mammography

    International Nuclear Information System (INIS)

    Dantas, Marcelino V.A.; Rosado, Paulo H.G.; Santana, Priscila C.; Alvarenga, Frederico L.; Nogueira, Maria S.

    2009-01-01

    In this work, the performance of an image receptor for computed radiography system, Kodak CR850, was assessed through tests, recommended by the European protocol, with a specific image plate for mammography where were analyzed the Contrast-to-noise ratio (CNR) and uniformity and linearity of detector. The CNRs were 14.1, 11.7, 10.3, 8.4, 7.1 and 5.9 for 2, 3, 4, 5, 6 and 7 cm polymethylmethacrylate (PMMA) thickness, respectively. The linearity between detector response and dose, obtained a correlation coefficient (R 2 ) greater than 0.99, and the maximum variation found in the detector uniformity calculation was 3.94 in the lower right corner. (author)

  14. PET imaging of urokinase-type plasminogen activator receptor (uPAR) in prostate cancer

    DEFF Research Database (Denmark)

    Skovgaard, Dorthe; Persson, Morten; Kjaer, Andreas

    2016-01-01

    Overexpression of urokinase-type plasminogen activator receptors (uPAR) represents an important biomarker for aggressiveness in most common malignant diseases, including prostate cancer (PC). Accordingly, uPAR expression either assessed directly in malignant PC tissue or assessed directly in plasma...... and prognostic imaging method. In this review, we will focus on the recent development of uPAR PET and the relevance within prostate cancer imaging. Novel antibody and small-molecule radiotracers-targeting uPAR, including a series of uPAR-targeting PET ligands, based on the high affinity peptide ligand AE105......, have been synthesized and tested in vitro and in vivo in preclinical murine xenograft models and, recently, in a first-ever clinical uPAR PET study in cancer patients, including patients with PC. In this phase I study, a high and specific uptake of the tracer 64Cu-DOTA-AE105 was found in both primary...

  15. In vivo (/sup 3/H)flunitrazepam binding: imaging of receptor regulation

    Energy Technology Data Exchange (ETDEWEB)

    Ciliax, B.J.; Penney, J.B. Jr.; Young, A.B.

    1986-08-01

    The use of (/sup 3/H)flunitrazepam as a ligand to measure alterations in benzodiazepine receptors in vivo in rats was investigated. Animals were injected with (/sup 3/H)flunitrazepam i.v., arterial samples of (/sup 3/H)flunitrazepam were obtained and, later, the animals were sacrificed to assay brain binding. (/sup 3/H)flunitrazepam enters the brain rapidly and binds to benzodiazepine receptors. About two-thirds of this binding is blocked by predosing the animals with 5 mg/kg of clonazepam. The amount of remaining (nonspecific) binding correlates very well (r = 0.88) with the amount of radioactivity found in plasma at the time of death. A series of rats were lesioned unilaterally with kainic acid in the caudate-putamen several months before the infusion of (/sup 3/H)flunitrazepam. In vivo autoradiography in lesioned rats showed that benzodiazepine binding in globus pallidus and substantia nigra on the side of the lesion was increased significantly as compared to the intact side. The observed changes in benzodiazepine binding were similar to those observed previously in lesioned rats using in vitro techniques. Thus, benzodiazepine receptor regulation can be imaged quantitatively using in vivo binding techniques.

  16. Development of a Ga-68 labeled triptorelin analog for GnRH receptor imaging

    Energy Technology Data Exchange (ETDEWEB)

    Zoghi, Masoumeh; Niazi, Ali [Islamic Azad Univ., Arak (Iran, Islamic Republic of). Dept. of Chemistry; Jalilian, Amir R.; Johari-daha, Fariba; Alirezapour, Behrouz [Nuclear Science and Technology Research Institute (NSTRI) (Iran, Islamic Republic of). Radiation Application Research School; Ramezanpour, Sorour [K.N. Toosi Univ. of Technology, Tehran (Iran, Islamic Republic of). Peptide Chemistry Research Center

    2016-08-01

    Optimized total synthesis, radiolabeling and quality control of [{sup 68}Ga]-DOTA-Hyd-TRP as an efficient and possible PET radiotracer for GnRH receptor imaging in various tumors is of great interest. DOTA-Hyd-TRP was synthesized using solid phase peptide synthesis followed by conjugation to DOTA using pSCN-Bn-DOTA. [{sup 68}Ga]-DOTA-Hyd-TRP was prepared using generator-based [{sup 68}Ga]GaCl{sub 3} and DOTA-Hyd-TRP under optimized conditions for time, temperature, ligand amount, gallium content and column cartridge purification followed by proper formulation. The biodistribution of the tracer in rats was studied using tissue counting up to 120 min. [{sup 68}Ga]-DOTA-Hyd-TRP was prepared at optimized conditions in 5-7 min at 95 C followed by separation using C{sub 18} cartridge (radiochemical purity ∼99 ± 0.88% ITLC, > 99% HPLC, specific activity: 300 ± 15 MBq/nM). The biodistribution of the tracer demonstrated high kidney uptake of the tracer in 10-20 min as well as significant testicular uptake consistent with reported GnRH receptor mappings. Block test studies by triptorelin pretreatment of the animals prior to tracer administration demonstrated significant specific uptake in receptor rich organs including testes and stomach.

  17. Nicotinic receptor imaging with F-18 A85380 PET in Alzheimer's disease and normal ageing

    International Nuclear Information System (INIS)

    Bottlaender, M.; Maziere, B.; Pappata, S.; Dolle, F.; Rowe, C.; Tochon-Danguy, H.; Reutens, D.; Chan, G.; Woodward, M.

    2002-01-01

    Full text: Central nicotinic acetylcholine receptors (nAChR) mediate excitatory neurotransmission and contribute to a variety of brain functions including learning and memory. Post mortem studies in patients with Alzheimer's disease have revealed losses of nAChR from the neocortex and hippocampal formation with ligand binding studies showing a reduction of over 50% compared to normal elderly brains in the temporal cortex and hippocampus (Sabbagh 1998). This is consistent with the loss of cholinergic neurones that has been well documented in this condition. Nicotinic AChR are predominantly located presynaptically on the cholinergic neurones. Consequently the ability to image and quantify these receptors may provide a measure of cholinergic loss and therefore a test for the early diagnosis of Alzheimer's disease and for monitoring therapy designed' to preserve cholinergic neurones. Aging is known to effect nAChR (Hellstrom-Lindahl 2000) so this variable must be quantified and incorporated into analysis of the scans. Nicotinic receptors also have important modulatory effects on glutamate, dopamine, serotonin and noradrenaline release and profound receptor loss has been documented in Parkinson's disease and Diffuse Lewy Body disease in addition to AD. Abnormalities in the alpha 7 subtype have been reported in schizophrenia. Imaging studies of nAChR have been hampered by the lack of a suitable tracer for in-vivo imaging. Nicotine itself labelled with carbon-11 for PET imaging has been used but has been shown to reflect regional cerebral blood flow not nAChR due to high nonspecific binding (Nyback et al, 1994). Potent nAChR ligands such as Epibatidine have been very useful for in-vitro studies but are too toxic for routine human use due to strong activation of nAChR including those in the sympathetic ganglia (A3B4 subtype). Recently, the Abbott Laboratories developed A85380 (3-[2(S)-2- azetidinylmethoxyl]pyridine) an azetidine derivative of the 3-pyridyl ethers that has

  18. Megavoltage cone-beam computed tomography using a high-efficiency image receptor

    International Nuclear Information System (INIS)

    Seppi, Ed J.; Munro, Peter; Johnsen, Stan W.; Shapiro, Ed G.; Tognina, Carlo; Jones, Dan; Pavkovich, John M.; Webb, Chris; Mollov, Ivan; Partain, Larry D.; Colbeth, Rick E.

    2003-01-01

    Purpose: To develop an image receptor capable of forming high-quality megavoltage CT images using modest radiation doses. Methods and Materials: A flat-panel imaging system consisting of a conventional flat-panel sensor attached to a thick CsI scintillator has been fabricated. The scintillator consists of individual CsI crystals 8 mm thick by 0.38 mm x 0.38-mm pitch. Five sides of each crystal are coated with a reflecting powder/epoxy mixture, and the sixth side is in contact with the flat-panel sensor. A timing interface coordinates acquisition by the imaging system and pulsing of the linear accelerator. With this interface, as little as one accelerator pulse (0.023 cGy at the isocenter) can be used to form projection images. Different CT phantoms irradiated by a 6-MV X-ray beam have been imaged to evaluate the performance of the imaging system. The phantoms have been mounted on a rotating stage and rotated while 360 projection images are acquired in 48 s. These projections have been reconstructed using the Feldkamp cone-beam CT reconstruction algorithm. Results and Discussion: Using an irradiation of 16 cGy (360 projections x 0.046 cGy/projection), the contrast resolution is ∼1% for large objects. High-contrast structures as small as 1.2 mm are clearly visible. The reconstructed CT values are linear (R 2 =0.98) for electron densities between 0.001 and 2.16 g/cm 3 , and the reconstruction time for a 512 x 512 x 512 data set is 6 min. Images of an anthropomorphic phantom show that soft-tissue structures such as the heart, lung, kidneys, and liver are visible in the reconstructed images (16 cGy, 5-mm-thick slices). Conclusions: The acquisition of megavoltage CT images with soft-tissue contrast is possible with irradiations as small as 16 cGy

  19. Identification and super-resolution imaging of ligand-activated receptor dimers in live cells

    Science.gov (United States)

    Winckler, Pascale; Lartigue, Lydia; Giannone, Gregory; de Giorgi, Francesca; Ichas, François; Sibarita, Jean-Baptiste; Lounis, Brahim; Cognet, Laurent

    2013-08-01

    Molecular interactions are key to many chemical and biological processes like protein function. In many signaling processes they occur in sub-cellular areas displaying nanoscale organizations and involving molecular assemblies. The nanometric dimensions and the dynamic nature of the interactions make their investigations complex in live cells. While super-resolution fluorescence microscopies offer live-cell molecular imaging with sub-wavelength resolutions, they lack specificity for distinguishing interacting molecule populations. Here we combine super-resolution microscopy and single-molecule Förster Resonance Energy Transfer (FRET) to identify dimers of receptors induced by ligand binding and provide super-resolved images of their membrane distribution in live cells. By developing a two-color universal-Point-Accumulation-In-the-Nanoscale-Topography (uPAINT) method, dimers of epidermal growth factor receptors (EGFR) activated by EGF are studied at ultra-high densities, revealing preferential cell-edge sub-localization. This methodology which is specifically devoted to the study of molecules in interaction, may find other applications in biological systems where understanding of molecular organization is crucial.

  20. Peptides and receptors in image-guided therapy: theranostics for neuroendocrine neoplasms.

    Science.gov (United States)

    Baum, Richard P; Kulkarni, Harshad R; Carreras, Cecilia

    2012-05-01

    Theranostics of neuroendocrine neoplasms (NENs) based on molecular imaging using receptor positron emission tomography/computed tomography (PET/CT) with (68)Ga-labeled somatostatin (SMS) analogs and molecular radiotherapy applying peptide receptor radionuclide therapy (PRRNT) with (90)Y- and/or (177)Lu-labeled peptides has paved the way to personalized medicine. SMS receptor PET/CT enables very accurate detection of NENs and their metastases with high diagnostic sensitivity and specificity and provides quantitative, reproducible data that can be used for selecting patients for PRRNT and evaluation of therapy response. Among other advantages are the fast imaging protocol (total study time, 60-90 minutes), low radiation burden (10-12 mSv), flexibility in daily use, and lower cost than octreotide scintigraphy. As we move toward personalized medicine, the diagnostic information obtained from PET/CT must be improved, that is, by fast routine quantification of lesions. PRRNT is highly effective for the treatment of NENs, even in very advanced cases, and lends a benefit in overall survival of several years. In addition, significant improvement in clinical symptoms and excellent palliation can be achieved. In patients with progressive NENs, fractionated, personalized PRRNT with lower doses of radioactivity given over a longer period (Bad Berka Concept) results in good therapeutic responses. By this concept, severe hematologic and/or renal toxicity can be reduced or completely avoided, and the quality of life can be improved. Sequential (DUO-PRRNT) and concurrent (TANDEM-PRRNT) administrations of radiopeptides are more effective in progressive NEN than using either radionuclide alone. PRRNT should only be performed at specialized centers, as NEN patients need highly individualized interdisciplinary treatment and long-term care. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Dopamine denervation does not alter in vivo 3H-spiperone binding in rat striatum: implications for external imaging of dopamine receptors in Parkinson's disease

    International Nuclear Information System (INIS)

    Bennett, J.P. Jr.; Wooten, G.F.

    1986-01-01

    Striatal particulate preparations, both from rats with lesion-induced striatal dopamine (DA) loss and from some striatal dopamine (DA) loss and from some patients with Parkinson's disease, exhibit increased 3 H-neuroleptic binding, which is interpreted to be the mechanism of denervation-induced behavioral supersensitivity to dopaminergic compounds. After intravenous 3 H-spiperone ( 3 H-SP) administration to rats with unilateral nigral lesions, we found no differences in accumulation of total or particulate-bound 3 H-SP in dopamine-denervated compared with intact striata. 3 H-SP in vivo binds to less than 10% of striatal sites labeled by 3 H-SP incubated with striatal particulate preparations in vitro. Quantitative autoradiography of 3 H-SP binding to striatal sections in vitro also failed to reveal any effects of dopamine denervation. 3 H-SP bound to striatal sites in vivo dissociates more slowly than that bound to striatal particulate preparations labeled in vitro. Striatal binding properties of 3 H-SP administered in vivo are quite different from the same kinetic binding parameters estimated in vitro using crude membrane preparations of striatum. In addition, striatal binding of in vivo-administered 3H-SP is not affected by prior lesion of the substantia nigra, which results in profound ipsilateral striatal dopamine depletion. Thus, behavioral supersensitivity to dopaminergic compounds may not be associated with altered striatal binding properties for dopamine receptor ligands in vivo

  2. Rocuronium and sugammadex: An alternative to succinylcholine for electro convulsive therapy in patients with suspected neuroleptic malignant syndrome.

    LENUS (Irish Health Repository)

    Ramamoorthy, Karthik G

    2012-01-31

    We report a case of presumptive neuroleptic malignant syndrome requiring muscle relaxation for electro-convulsive therapy. short acting muscle relaxation without the use of succinylcholine was achieved using rocvronivm reversed with the novel reversal agent sugammadex. We suggest that this combination is a safe and effective alternative to succinylcholine in such cases.

  3. Rocuronium and sugammadex: An alternative to succinylcholine for electro convulsive therapy in patients with suspected neuroleptic malignant syndrome

    Directory of Open Access Journals (Sweden)

    Karthik G Ramamoorthy

    2011-01-01

    Full Text Available We report a case of presumptive neuroleptic malignant syndrome requiring muscle relaxation for electro-convulsive therapy. short acting muscle relaxation without the use of succinylcholine was achieved using rocvronivm reversed with the novel reversal agent sugammadex. We suggest that this combination is a safe and effective alternative to succinylcholine in such cases.

  4. The effects of psychoactive drugs and neuroleptics on language in normal subjects and schizophrenic patients: a review.

    Science.gov (United States)

    Salomé, F; Boyer, P; Fayol, M

    2000-12-01

    The aim of this survey is to present an overview of research into psychopharmacology as regards the effects of different psychoactive drugs and neuroleptics (NL) on language in normal subjects and schizophrenic patients. Eighteen studies that have investigated the effects of different drugs (alcohol, amphetamines, secobarbital, L-dopa, psilocybin, ketamine, fenfluramine) and neuroleptics (conventional and atypical) on language are reviewed. There are no studies concerning the effects of neuroleptics on language in healthy subjects. The results of the effects of other molecules indicate that language production can be increased (alcohol, amphetamine, secobarbital), rendered more complex (d-amphetamine), more focused (L-dopa) or more unfocused (psilocybin) and clearly impaired (ketamine). For schizophrenic patients, most studies show that conventional neuroleptic treatments, at a therapeutic dosage and in acute or chronic mode, reduce language disorders at all levels (clinic, linguistic, psycholinguistic). In conjunction with other molecules, the classical NL, when administered at a moderate dosage and in chronic mode, modify language in schizophrenia, either by improving the verbal flow and reducing pauses and positive thought disorder (NL + amphetamine) or by inducing an impairment in the language measurements (NL + fenfluramine). Clinical, methodological and theoretical considerations of results are debated in the framework of schizophrenic language disorders.

  5. Neuroleptics and β-carbolines displace (3H)imipramine from its binding sites in human and rat tissues

    International Nuclear Information System (INIS)

    Rommelspacher, H.; Strauss, S.

    1985-01-01

    Most investigations dealing with the pharmacological characterization of ( 3 H)imipramine binding sites focus on tricyclic antidepressants (TCA). This approach seemed to be justified since imipramine belongs to that chemical group. Langer and coworkers, however, introduced a tetrahydro-β-carboline (THβC) as a possible endogenous ligand. Thus, the high affinity of imipramine towards the binding sites might not be due to its special chemical structure but due to its tricyclic nature. In the present paper the structure-activity-relationships of neuroleptics and β-carbolines were investigated and compared with that of tricyclic antidepressants. Among the tricyclic neuroleptics those with an electron attracting substituent (-Cl) exerted highest affinity. The effect was attenuated by a long, cyclic side chain. The affinity of tricyclic neuroleptics was only slightly weaker than that of 6-Meo-THβC the suggested endogenous ligand. The experiments with other THβCs supported the observation that an electron attracting substituent increases the affinity of a compound to the ( 3 H)imipramine binding sites. Comparison of the binding characteristics of ( 3 H)imipramine to membranes of human brain and thrombocytes as well as those of rat brain and thrombocytes revealed no differences among both species. Furthermore, the displacing potencies of neuroleptics were very similar with only slightly more activity in human tissue. As a methodological aspect the applicability of the 'Lowry' method to determine the protein concentration is discussed. (Author)

  6. Molecular Imaging of Hepatocellular Carcinoma Xenografts with Epidermal Growth Factor Receptor Targeted Affibody Probes

    Directory of Open Access Journals (Sweden)

    Ping Zhao

    2013-01-01

    Full Text Available Hepatocellular carcinoma (HCC is a highly aggressive and lethal cancer. It is typically asymptomatic at the early stage, with only 10%–20% of HCC patients being diagnosed early enough for appropriate surgical treatment. The delayed diagnosis of HCC is associated with limited treatment options and much lower survival rates. Therefore, the early and accurate detection of HCC is crucial to improve its currently dismal prognosis. The epidermal growth factor receptor (EGFR has been reported to be involved in HCC tumorigenesis and to represent an attractive target for HCC imaging and therapy. In this study, an affibody molecule, Ac-Cys-ZEGFR:1907, targeting the extracellular domain of EGFR, was used for the first time to assess its potential to detect HCC xenografts. By evaluating radio- or fluorescent-labeled Ac-Cys-ZEGFR:1907 as a probe for positron emission tomography (PET or optical imaging of HCC, subcutaneous EGFR-positive HCC xenografts were found to be successfully imaged by the PET probe. Thus, affibody-based PET imaging of EGFR provides a promising approach for detecting HCC in vivo.

  7. [11C]-MeJDTic: a novel radioligand for κ-opioid receptor positron emission tomography imaging

    International Nuclear Information System (INIS)

    Poisnel, Geraldine; Oueslati, Farhana; Dhilly, Martine; Delamare, Jerome; Perrio, Cecile; Debruyne, Daniele; Barre, Louisa

    2008-01-01

    Introduction: Radiopharmaceuticals that can bind selectively the κ-opioid receptor may present opportunities for staging clinical brain disorders and evaluating the efficiency of new therapies related to stroke, neurodegenerative diseases or opiate addiction. The N-methylated derivative of JDTic (named MeJDTic), which has been recently described as a potent and selective antagonist of κ-opioid receptor in vitro, was labeled with carbon-11 and evaluated for in vivo imaging the κ-opioid receptor in mice. Methods: [ 11 C]-MeJDTic was prepared by methylation of JDTic with [ 11 C]-methyl triflate. The binding of [ 11 C]-MeJDTic to κ-opioid receptor was investigated ex vivo by biodistribution and competition studies using nonfasted male CD1 mice. Results: [ 11 C]-MeJDTic exhibited a high and rapid distribution in peripheral organs. The uptake was maximal in lung where the κ receptor is largely expressed. [ 11 C]-MeJDTic rapidly crossed the blood-brain barrier and accumulated in the brain regions of interest (hypothalamus). The parent ligand remained the major radioactive compound in brain during the experiment. Chase studies with U50,488 (a κ referring agonist), morphine (a μ agonist) and naltrindole (a δ antagonist) demonstrated that this uptake was the result of specific binding to the κ-opioid receptor. Conclusion: These findings suggested that [ 11 C]-MeJDTic appeared to be a promising selective 'lead' radioligand for κ-opioid receptor PET imaging

  8. Fundamental study on brain receptor mapping by neuronuclear medicine imaging. Quantitation of receptor autoradiography in the rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Tsuji, Shiro

    1988-04-01

    The usefulness of autoradiography in the quantitation of the rat brain receptor was evaluated. H-3 spiperone, H-3 quinuclidinyl benzylate (QNB), H-3 muscimol, H-3 diprenorphine, H-3 ketanserin, and H-3 dihydroalprenolol hydrochloride were used for autoradiography. Satisfactory autoradiograms with these H-3 labeled ligants were obtained for incubation time, washing time, and binding curve. The video digitizer system was the most suitable in autoradiography. Using appropriate conditions for the ligand-receptor interaction, receptor autoradiography and in vitro receptor assay were concordant as for the the number of maximum binding sites (Bmax) of the muscarinic acetylcholine receptor and equilibrium dissociation constant (Kd) of its antagonist, H-3 QNB. Receptor autoradiography with high spatial resolution allowed the comparison of Bmax and Kd in the brain. To improve conventional Scatchard analysis, used in the estimation of Bmax and Kd, a new mathematical method was developed for estimating individual rate constants and Bmax on the basis of time courses of association and dissociation. Using the new mathematical method, apparent equilibrium dissociation rate constant was in good agreement with that from a non-isomerization model. Autoradiography may provide a clue for the basic data on brain receptor mapping by a promising emission computerized tomography in neuropsychiatric diseases. (Namekawa, K.).

  9. Asialoglycoprotein-receptor-targeted hepatocyte imaging using {sup 99m}Tc galactosylated chitosan

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eun-Mi [Department of Nuclear Medicine, Research Institute of Clinical Medicine, Chonbuk National University School of Medicine, Jeonju, Jeonbuk (Korea, Republic of); Jeong, Hwan-Jeong [Department of Nuclear Medicine, Research Institute of Clinical Medicine, Chonbuk National University School of Medicine, Jeonju, Jeonbuk (Korea, Republic of)]. E-mail: jayjeong@chonbuk.ac.kr; Kim, Se-Lim [Department of Nuclear Medicine, Research Institute of Clinical Medicine, Chonbuk National University School of Medicine, Jeonju, Jeonbuk (Korea, Republic of); Sohn, Myung-Hee [Department of Nuclear Medicine, Research Institute of Clinical Medicine, Chonbuk National University School of Medicine, Jeonju, Jeonbuk (Korea, Republic of); Nah, Jae-Woon [Division of Applied Materials Engineering, Department of Polymer Science and Engineering, Sunchon National University, Sunchon, Jeonnam (Korea, Republic of); Bom, Hee-Seung [Department of Nuclear Medicine, Chonnam National University School of Medicine, Gwangju (Korea, Republic of); Park, In-Kyu [School of Agricultural Biotechnology, Seoul National University, Seoul (Korea, Republic of); Cho, Chong-Su [School of Agricultural Biotechnology, Seoul National University, Seoul (Korea, Republic of)

    2006-05-15

    This study investigated the usefulness of {sup 99m}Tc hydrazinonicotinamide-galactosylated chitosan (HGC) in hepatocyte imaging. HGC was obtained by coupling the galactose moiety of both lactobionic acid and succinimidyl 6-hydrazinonicotinate hydrochloride (succinimidyl HYNIC). The coupled product was then radiolabeled with {sup 99m}Tc using stannous chloride and tricine as reducing agent and coligand, respectively. Labeling efficiency was >90% both in room temperature and in serum up to 24 h after injection. The hepatic uptake properties of {sup 99m}Tc HGC were studied in Balb/C mice. {sup 99m}Tc HGC and {sup 99m}Tc hydrazinonicotinamide chitosan (HC) were intravenously injected into mice, with receptor binding identified by coinjection with 9 and 14 mg of free galactose. Images were acquired with a {gamma}-camera. After injection via the tail vein of the mice, {sup 99m}Tc HGC showed high selectivity for the liver, while {sup 99m}Tc HC without a galactose group showed low liver uptake. In addition, the hepatic uptake of {sup 99m}Tc HGC was blocked by coinjection of free galactose. Tissue distribution was determined at three different times (10, 60 and 120 min). The liver accumulated 13.16{+-}2.72%, 16.11{+-}5.70% and 16.55{+-}2.28% of the injected dose per gram at 10, 60 and 120 min after injection, respectively. {sup 99m}Tc HGC showed specific and rapid targeting of hepatocytes. It is a promising receptor-specific radiopharmaceutical with potential applications in liver imaging for the evaluation of hepatocytic function.

  10. In vivo assessment of dopamine D-2 and serotonin S-2 receptors measured by C-11 N-methylspiperone (NMSP) in manic-depressive illness

    International Nuclear Information System (INIS)

    Wong, D.F.; Pearlson, G.; Wagner, H.N. Jr.

    1985-01-01

    The hypothesis has been suggested that either the dopaminergic or serotonergic neurotransmitter systems may be involved in manic-depressive illness (MD). The authors have studied 16 subjects with C-11 NMSP PET imaging. Two had never received neuroleptics; 4 were drug free for 1 month at the time of scanning; of these 3 were acutely manic; the rest were on stable lithium treatment. The dopamine and serotonin binding was estimated by the 43 min. caudate/cerebellum (Ca/Cb) and frontal/cerebellum (FC/Cb) ratios, respectively. No statistically significant difference was detected when compared to 44 age and sex matched controls. Based upon the variance in the normal data and the average age of the patient group studied, the probability of detecting a difference of >30% between patients and normals is >0.8. Hence, identification of receptor abnormalities if present will be improved with increased sample size of both normals and patients

  11. receptores

    Directory of Open Access Journals (Sweden)

    Salete Regina Daronco Benetti

    2006-01-01

    Full Text Available Se trata de un estudio etnográfico, que tuvo lo objetivo de interpretar el sistema de conocimiento y del significado atribuidos a la sangre referente a la transfusión sanguínea por los donadores y receptores de un banco de sangre. Para la colecta de las informaciones se observaron los participantes y la entrevista etnográfica se realizó el análisis de dominio, taxonómicos y temáticos. Los dominios culturales fueron: la sangre es vida: fuente de vida y alimento valioso; creencias religiosas: fuentes simbólicas de apoyos; donación sanguínea: un gesto colaborador que exige cuidarse, gratifica y trae felicidad; donación sanguínea: fuente simbólica de inseguridad; estar enfermo es una condición para realizar transfusión sanguínea; transfusión sanguínea: esperanza de vida; Creencias populares: transfusión sanguínea como riesgo para la salud; donadores de sangre: personas benditas; donar y recibir sangre: como significado de felicidad. Temática: “líquido precioso que origina, sostiene, modifica la vida, provoca miedo e inseguridad”.

  12. Comparison of benzodiazepine receptor and regional cerebral blood flow imagings of epileptiform foci in hippocampal kindled rabbits

    International Nuclear Information System (INIS)

    Kurokawa, Kenzo

    1993-01-01

    To compare the benzodiazepine (Bz) receptor imaging and regional cerebral blood flow (rCBF) imaging in the detection of epileptic foci, the distribution pattern of the Bz receptor and rCBF in hippocampal kindled rabbits was examined by a double tracer autoradiography using ethyl 7-[ 125 I]-5,6-dihydro-5-methyl-6-oxo-4H-imidazo [1, 5-a][1,4] benzodiazepine-3-carboxylate ( 125 I-Ro 16-0154) and 99m Tc-hexamethyl-propyleneamine oxime ( 99m Tc-HMPAO). In visual and quantitative analyses, 125 I-Ro 16-0154 accumulation in brain slices extracted after the completion of the kindling was markedly and extensively decreased in the kindled CA1 region mimicking a primary epileptic focus. 125 I-Ro 16-0154 accumulation was moderately decreased in the ipsilateral temporal lobe, dentate gyrus, CA2, CA4, and bilateral CA3 regions, regarded as the propagated sites of seizure discharges. 99m Tc-HMPAO accumulation was found to be decreased in the ipsilateral CA1, frontal, temporal and dentate gyri. However, the decrease was much more slight and less extensive than that in 125 I-Ro 16-0154 accumulation. These results suggest that Bz receptor imaging is much more sensitive in the detection of epileptic foci than rCBF imaging, and therefore that Bz receptor imaging is useful in clinical epilepsy. (author)

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

    Energy Technology Data Exchange (ETDEWEB)

    Cline, Gary W., E-mail: gary.cline@yale.edu [Yale University School of Medicine (United States); Zhao, Xiaojian [Yale University School of Medicine (United States); Jakowski, Amy B.; Soeller, Walter C.; Treadway, Judith L. [Pfizer Global Research and Development, Pfizer Inc., Groton CT (United States)

    2011-09-02

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

  14. Islet-selectivity of G-protein coupled receptor ligands evaluated for PET imaging of pancreatic β-cell mass

    International Nuclear Information System (INIS)

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

    2011-01-01

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

  15. Benzodiazepine receptor imaging with iomazenil SPECT in aphasic patients with cerebral infarction

    Energy Technology Data Exchange (ETDEWEB)

    Koshi, Yasuhiko; Kitamura, Shin; Ohyama, Masashi [Nippon Medical School, Tokyo (Japan)] (and others)

    1999-08-01

    To investigate the relationship between prognosis of aphasia and neuronal damage in the cerebral cortex, we evaluated the distribution of central-type benzodiazepine receptor (BZR) binding in post-stroke aphasics with [{sup 123}I]iomazenil and SPECT. We performed iomazenil SPECT in six aphasic patients (aged from 45 to 75 years; all right-handed) with unilateral left cerebral infarction. Three patients showed signs of Broca's aphasia and the other three Wernicke's aphasia. Cerebral blood flow (CBF) imaging was performed with [{sup 123}I]iodoamphetamine (IMP). The regions of interest (ROIs) on both images were set in the cerebral cortex, cerebellar cortex and language relevant area in both hemispheres. Three patients were classified in the mild prognosis group and the other three in the moderate prognosis group. The left language-relevant area was more closely concerned with the difference in aphasic symptoms than the right one in both BZR and CBF distribution, but the ipsilateral to the contralateral ratio (I/C ratio) in the language-relevant areas in the BZR distribution was significantly lower in the moderate prognosis group than in the mild prognosis group, although no difference was seen for these values between the two groups in the CBF distribution. These results suggest that BZR imaging, which makes possible an increase in neuronal cell viability in the cerebral cortex, is useful not only for clarifying the aphasic symptoms but also for evaluating the prognosis of aphasia in patients with cerebral infarction. (author)

  16. Benzodiazepine receptor imaging with iomazenil SPECT in aphasic patients with cerebral infarction

    International Nuclear Information System (INIS)

    Koshi, Yasuhiko; Kitamura, Shin; Ohyama, Masashi

    1999-01-01

    To investigate the relationship between prognosis of aphasia and neuronal damage in the cerebral cortex, we evaluated the distribution of central-type benzodiazepine receptor (BZR) binding in post-stroke aphasics with [ 123 I]iomazenil and SPECT. We performed iomazenil SPECT in six aphasic patients (aged from 45 to 75 years; all right-handed) with unilateral left cerebral infarction. Three patients showed signs of Broca's aphasia and the other three Wernicke's aphasia. Cerebral blood flow (CBF) imaging was performed with [ 123 I]iodoamphetamine (IMP). The regions of interest (ROIs) on both images were set in the cerebral cortex, cerebellar cortex and language relevant area in both hemispheres. Three patients were classified in the mild prognosis group and the other three in the moderate prognosis group. The left language-relevant area was more closely concerned with the difference in aphasic symptoms than the right one in both BZR and CBF distribution, but the ipsilateral to the contralateral ratio (I/C ratio) in the language-relevant areas in the BZR distribution was significantly lower in the moderate prognosis group than in the mild prognosis group, although no difference was seen for these values between the two groups in the CBF distribution. These results suggest that BZR imaging, which makes possible an increase in neuronal cell viability in the cerebral cortex, is useful not only for clarifying the aphasic symptoms but also for evaluating the prognosis of aphasia in patients with cerebral infarction. (author)

  17. MRI contrast agent for molecular imaging of the HER2/neu receptor using targeted magnetic nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Rasaneh, Samira; Rajabi, Hossein, E-mail: hrajabi@modares.ac.ir [Tarbiat Modares University, Department of Medical Physics (Iran, Islamic Republic of); Babaei, Mohammad Hossein [Nuclear Science and Technology Research Institute, Department of Radioisotope (Iran, Islamic Republic of); Akhlaghpoor, Shahram [Sina Hospital, Tehran Medical University, Noor Medical Imaging Center (Iran, Islamic Republic of)

    2011-06-15

    In this study, Trastuzumab modified Magnetic Nanoparticles (TMNs) were prepared as a new contrast agent for detecting HER2 (Human epidermal growth factor receptor-2) expression tumors by magnetic resonance imaging (MRI). TMNs were prepared based on iron oxide nanoparticles core and Trastuzumab modified dextran coating. The TMNs core and hydrodynamic size were determined by transmission electron microscopy and dynamic light scattering. TMNs stability and cytotoxicity were investigated. The ability of TMNs for HER2 detection were evaluated in breast carcinoma cell lines (SKBr3 and MCF7 cells) and tumor-bearing mice by MRI and iron uptake determination. The particles core and hydrodynamic size were 9 {+-} 2.5 and 41 {+-} 15 nm (size range: 15-87 nm), respectively. The molar antibody/nanoparticle ratio was 3.1-3.5. TMNs were non-toxic to the cells below the 30 {mu}g (Fe)/mL concentration and good stable up to 8 weeks in PBS buffer. TMNs could detect HER2 oncogenes in the cells surface with imagable contrast by MRI. The invivo study in mice bearing tumors indicated that TMNs possessed a good diagnostic ability as HER2 specific contrast agent by MRI. TMNs were demonstrated to be able to selectively accumulate in the tumor cells, with a proper signal enhancement in MRI T2 images. So, the complex may be considered for further investigations as an MRI contrast agent for detection of HER2 expression tumors in human.

  18. 99mTc labelled peptides for imaging of peripheral receptors

    International Nuclear Information System (INIS)

    Mustanser, J.; Anjum, A.

    2001-01-01

    Several peptides are being used as radiopharmaceuticals for receptor imaging scintigraphy. The peptide receptors are found in the tumours of various sites in the human body. Somatostatin is one of those, which is expressed by a variety of tumours say in brain cortex, medullary carcinoma of thyroid, adrenal glands, pancreas and gut. Therefore neuropeptides based on somatostatin analogues are labelled with different radionuclide, 123 I and 111 In. Efforts are underway to label RC-160 (an analogue of somatostatin) with 99m Tc because of its favourable radiation dosimetry, short half-life, low price, high count rate and better diagnostic efficacy. In this project various methods of labelling RC-160 with different radionuclides 125 I and 99m Tc have been studied in detail. Radioiodination of RC-160 was tried with 125 I using the iodogen method as directed and then with Chloramine T method. Labelling of RC-160 peptide with 99m Tc was done using two different aspects. Direct labelling with 99m Tc and indirect labelling with 99m Tc using double chelating agents. Radiochemical quality control was carried out applying instant thin layer chromatography using ITLC-SG strips in 85% of methanol. Later the HPLC analysis was used for its evaluation. To label RC-160 with 99m Tc the approach of direct labelling was attempted first. 46% labelling could be achieved with 95% of radiochemical purity. The biodistribution of 99m Tc-RC-160 complex in rats has also been studied to determine uptake in various sites of somatostatin receptors. Eventually, attempt was made to synthesize biomolecule by conjugating Boc protected RC-160 with benzoyl MAG-3. As a result 80% of Boc-RC-160 went under conjugation with benzoyl MAG-3. (author)

  19. Malignant Neuroleptic Syndrome following Deep Brain Stimulation Surgery of Globus Pallidus Pars Internus in Cerebral Palsy

    Directory of Open Access Journals (Sweden)

    Jae Meen Lee

    2016-02-01

    Full Text Available Neuroleptic malignant syndrome (NMS is a rare but potentially lethal outcome caused by sudden discontinuation or dose reduction of dopaminergic agents. We report an extremely rare case of NMS after deep brain stimulation (DBS surgery in a cerebral palsy (CP patient without the withdrawal of dopaminergic agents. A 19-year-old girl with CP was admitted for DBS due to medically refractory dystonia and rigidity. Dopaminergic agents were not stopped preoperatively. DBS was performed uneventfully under monitored anesthesia. Dopaminergic medication was continued during the postoperative period. She manifested spasticity and muscle rigidity, and was high fever resistant to anti-pyretic drugs at 2 h postoperative. At postoperative 20 h, she suffered cardiac arrest and expired, despite vigorous cardiopulmonary resuscitation. NMS should be considered for hyperthermia and severe spasticity in CP patients after DBS surgery, irrespective of continued dopaminergic medication.

  20. Neuroleptic malignant syndrome in an elderly with quetiapine: A case report and review of literature

    Directory of Open Access Journals (Sweden)

    Devakshi Dua

    2017-01-01

    Full Text Available Over the years, there is an increase in the prescription of antipsychotics among elderly patients, and these are used for various clinical indications such as psychotic disorders, affective disorders, behavioral and psychological symptoms of dementia and delirium. Quetiapine is one of the preferred antipsychotics among elderly because of its safety profile. However, quetiapine has been rarely been associated with the development of neuroleptic malignant syndrome (NMS among elderly. In this report, we discuss a case of NMS in a 70-year-old female, who developed symptoms of NMS at the dose of 200 mg/day, while quetiapine was being used along with lithium. A review of literature suggests that there are 12 cases of NMS reported in subjects older than 55 years of age.

  1. A Rare Case of Myxedema Coma with Neuroleptic Malignant Syndrome (NMS).

    Science.gov (United States)

    Dixit, Siddharth; Dutta, Manoj Kumar; Namdeo, Mayank

    2015-05-01

    Myxedema coma or hypothyroid crisis is an endocrine emergency and needs ICU management. Neuroleptic malignant syndrome (NMS) is another medical emergency which needs high degree of clinical suspicion else mortality can be high. There is a paradox in co existence of myxedema coma and NMS. While one is hypometabolic state another is hypermetabolic state and both can be precipitated by antipsychotics use. Hypothermia and flaccidity commonly expected in myxedema coma may mask fever and rigidity of classical NMS contributing to diagnostic problem and treatment delay. Scientific literature on coexistance of myxedema coma and NMS is sparse. We hereby report first case with coexisting myxedema coma and NMS in a patient of schizophrenia treated with antipsychotic, where classical symptoms of NMS were masked by myxedema coma. Prompt diagnosis and effective management by a team resulted in favourable outcome in our patient. This case is reported to alert intensive care physicians to atypical manifestations of NMS in presence of hypothyroidism.

  2. Effect of antidepressants and neuroleptics on phosphoinositide turnover in human platelets

    Energy Technology Data Exchange (ETDEWEB)

    Pandey, S.C.; Davis, J.M.; Schwertz, D.; Pandey, G.N. (Illinois State Psychiatric Inst., Chicago (United States))

    1990-02-26

    The authors previously reported that tricyclic antidepressants and iprindole inhibit thrombin-stimulated formation of inositol-1, 4 bisphosphate (IP2) and inositol-1,4,5 triphosphate (IP3) but do not cause any change in inositol-1 phosphate (IP1). In order to examine if this decrease in IP2 and IP3 formation by antidepressants is related to the inhibition of the enzyme phospholipase C (PLC), the authors determined the effects of antidepressants and neuroleptics on the levels of 3(H) phosphotidylinositol (PI), 3(H) PI-4 phosphate (PIP), 3(H) PI-4, 5 bisphosphate (PIP2) in human platelets. The implications of the findings and their relevance to the mode of action of antidepressants are discussed.

  3. Plasma prolactin and homovanillic acid as markers for psychopathology and abnormal movements after neuroleptic dose decrease.

    Science.gov (United States)

    Newcomer, J W; Riney, S J; Vinogradov, S; Csernansky, J G

    1992-01-01

    Plasma prolactin concentration (pPRL), plasma homovanillic acid concentration (pHVA), and symptomatology were measured in 24 male subjects with schizophrenia during maintenance haloperidol treatment. Fourteen subjects subsequently underwent 50 percent dose decreases under placebo-controlled, double-blind conditions. At baseline, a significant inverse correlation was found between pPRL and both tardive dyskinesia (TD) and "thinking disorder"; pPRL was directly correlated with negative symptoms. No such relationship was found with pHVA. In the patients who underwent a dose decrease, no relationship was found between baseline pPRL or pHVA and any clinical variable after the decrease. These data do not support the use of baseline pPRL or pHVA as markers of central dopamine function subsequent to a neuroleptic dose decrease.

  4. Síndrome neuroléptico maligno Neuroleptic malignant syndrome

    Directory of Open Access Journals (Sweden)

    Ricardo J. Toro

    1989-02-01

    Full Text Available

    El síndrome neuroléptico maligno (SNM es una complicación rara, idiosincrática y potencialmente fatal, relacionada con el uso de drogas que afectan el sistema dopaminérgico; su cuadro clínico consiste en síntomas extrapiramidales, signos de disfunción autonómica y trastornos en el estado de conciencia, asociados a leucocitosis ya cifras muy elevadas de creatina fosfoquinasa. Reportamos el caso de un hombre de 32 años que presentó un síndrome catatónico severo después del uso intrahospitalario de antipsicóticos potentes a altas dosis para el control de una depresión psicótica. Se discuten las características clínicas del paciente y los hallazgos comunes en el SNM.

    The Neuroleptic Malignant Syndrome (NMS Is a rare, idiosyncratic and potentially fatal complication of therapy with many drugs affecting the dopaminergic system; It Includes extrapyramidal symptoms, signs of autonomic dysfunction, disorders of consciousness, leucocytosis and an increase in serum creatine phosphokinase .We report the case of a 32 years old man, who developed a severe catatonic syndrome after receiving high doses of potent neuroleptics to control a psychotic depression. Clinical features of this case and common findings of NMS are discussed.

  5. 99m Tc-anti-epidermal growth factor receptor nanobody for tumor imaging.

    Science.gov (United States)

    Piramoon, Majid; Hosseinimehr, Seyed Jalal; Omidfar, Kobra; Noaparast, Zohreh; Abedi, Seyed Mohammad

    2017-04-01

    Nanobodies are important biomolecules for tumor targeting. In this study, we synthesized and labeled anti-epidermal growth factor receptor (EGFR) nanobody OA-cb6 with 99m Tc(CO) 3 + and evaluated its characteristics for targeting the EGFR in the A431 human epidermal carcinoma cell line. Nanobody radiolabeling was achieved with high yield and radiochemical purity, and the radioconjugate was stable. Biodistribution results in nude mice exhibited a favorable tumor-to-muscle ratio at 4-hr postinjection, and tumor location was visualized at 4 hr after injection of radiolabeled nanobody. Our result showed that the OA-cb6- 99m Tc-tricarbonyl radiolabeled nanobody is a promising radiolabeled biomolecule for tumor imaging in cancers with high EGFR overexpression. © 2016 John Wiley & Sons A/S.

  6. Technetium-99m spiperone dithiocarbamate: a potential radiopharmaceutical for dopamine receptor imaging with SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Ballinger, J R; Gulenchyn, K Y; Hassan, M N [Ottawa Civic Hospital (Canada). Div. of Nuclear Medicine and Neurology; Ottawa Univ., ON (Canada))

    1989-01-01

    Spiperone dithiocarbamate (SPDC) was prepared by reacting spiperone with carbon disulfide followed by sodium hydroxide. SPDC was labelled with {sup 99m}Tc by reduction of pertechnetate with formamidine sulfinic acid or sodium pertechnetate with formamidine sulfinic acid or sodium dithionite at alkaline pH, resulting in {similar to} 40% incorporation of {sup 99m}Tc. The lipophilic complex was conveniently isolated at high specific activity and high radiochemical purity by extraction into dichloromethane, which was then evaporated and the residue was redissolved in a 1:3 mixture of ethanol and saline containing 0.1mg/ml gentisic acid. Biodistribution studies following i.p. injection in rats showed low uptake of radioactivity in the brain, but striatum/cortex and striatum/cerebellum ratios were reduced by pretreatment with haloperidol. This agent may allow imaging of dopamine D-2 receptors using single-photon emission computed tomography (SPECT). (author).

  7. Anti-N-methyl-D-aspartate receptor encephalitis with an imaging-invisible ovarian teratoma: a case report.

    Science.gov (United States)

    Abdul-Rahman, Zainab M; Panegyres, Peter K; Roeck, Margareta; Hawkins, David; Bharath, Jude; Grolman, Paul; Neppe, Cliffe; Palmer, David

    2016-10-24

    Anti-N-methyl-D-aspartate receptor encephalitis is a recently discovered disease entity of paraneoplastic limbic encephalitis. It largely affects young women and is often associated with an ovarian teratoma. It is a serious yet treatable condition if diagnosed early. Its remedy involves immunotherapy and surgical removal of the teratoma of the ovaries. This case of anti-N-methyl-D-aspartate receptor encephalitis involves an early surgical intervention with bilateral oophorectomy, despite negative imaging evidence of a teratoma. A 25-year-old white woman with anti-N-methyl-D-aspartate receptor encephalitis presented with behavioral changes and seizures that were confirmed to be secondary to anti-N-methyl-D-aspartate receptor encephalitis. She required an admission to our intensive care unit for ventilator support and received a number of immunological therapies. Multiple imaging investigations showed no evidence of an ovarian teratoma; she had a bilateral oophorectomy 29 days after admission. Ovarian histology confirmed the presence of a teratoma with neuronal cells. A few days after the operation she began to show signs of improvement and, apart from mild short-term memory loss, she returned to normal function. Our patient is an example of teratoma-associated anti-N-methyl-D-aspartate receptor encephalitis, in which the teratoma was identified only microscopically. Her case highlights that even with negative imaging evidence of a teratoma, ovarian pathology should still be considered and explored.

  8. Radioiodinated SB 207710 as a radioligand in vivo: imaging of brain 5-HT{sub 4} receptors with SPET

    Energy Technology Data Exchange (ETDEWEB)

    Pike, Victor W. [MRC Cyclotron Unit, Imperial College School of Medicine, Hammersmith Hospital, Ducane Road, W12 0NN, London (United Kingdom); PET Radiopharmaceutical Sciences Section, Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Building 10, Room B3 C346A, 10 Center Drive, MD 20892-1003, Bethesda (United States); Halldin, Christer; Nobuhara, Kenji; Swahn, Carl-Gunnar; Karlsson, Per; Olsson, Hans; Larsson, Stig; Schnell, Per-Olof; Farde, Lars [Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institutet, Karolinska Hospital, 17176, Stockholm (Sweden); Hiltunen, Julka [MAP Medical Technologies, Oy, Tikkakoski (Finland); Mulligan, Rachel S. [MRC Cyclotron Unit, Imperial College School of Medicine, Hammersmith Hospital, Ducane Road, W12 0NN, London (United Kingdom); Institute of Psychiatry, SE 8AF, De Crespigny Park, Denmark Hill, London (United Kingdom); Centre for PET, Austin and Repatriation Medical Centre, Studley Road, Melbourne VIC 3084 (Australia); Hume, Susan P.; Hirani, Ella [MRC Cyclotron Unit, Imperial College School of Medicine, Hammersmith Hospital, Ducane Road, W12 0NN, London (United Kingdom); Imaging Research Solutions Ltd., Cyclotron Building, Hammersmith Hospital, Ducane Road, W12 0NN, London (United Kingdom); Whalley, Jaqueline [MRC Cyclotron Unit, Imperial College School of Medicine, Hammersmith Hospital, Ducane Road, W12 0NN, London (United Kingdom); Pilowsky, Lyn S. [Institute of Psychiatry, SE 8AF, De Crespigny Park, Denmark Hill, London (United Kingdom); Institute of Nuclear Medicine, Royal Free and University College, Medical School, Mortimer Street, W1N 8AA, London (United Kingdom); Ell, Peter J. [Institute of Nuclear Medicine, Royal Free and University College, Medical School, Mortimer Street, W1N 8AA, London (United Kingdom)

    2003-11-01

    Single-photon emission tomography (SPET) and positron emission tomography (PET), when coupled to suitable radioligands, are uniquely powerful for investigating the status of neurotransmitter receptors in vivo. The serotonin subtype-4 (5-HT{sub 4}) receptor has discrete and very similar distributions in rodent and primate brain. This receptor population may play a role in normal cognition and memory and is perhaps perturbed in some neuropsychiatric disorders. SB 207710 [(1-butyl-4-piperidinylmethyl)-8-amino-7-iodo-1,4-benzodioxan-5-carboxylate] is a selective high-affinity antagonist at 5-HT{sub 4} receptors. We explored radioiodinated SB 207710 as a possible radioligand for imaging 5-HT{sub 4} receptors in vivo. Rats were injected intravenously with iodine-125 labelled SB 207710, euthanised at known times and dissected to establish radioactivity content in brain tissues. Radioactivity entered brain but cleared rapidly and to a high extent from blood and plasma. Between 45 and 75 min after injection, the ratios of radioactivity concentration in each of 12 selected brain tissues to that in receptor-poor cerebellum correlated with previous measures of 5-HT{sub 4} receptor density distribution in vitro. The highest ratio was about 3.4 in striatum. SB 207710 was labelled with iodine-123 by an iododestannylation procedure. A cynomolgus monkey was injected intravenously with [{sup 123}I]SB 207710 and examined by SPET. Maximal whole brain uptake of radioactivity was 2.3% of the injected dose at 18 min after radioligand injection. Brain images acquired between 9 and 90 min showed high radioactivity uptake in 5-HT{sub 4} receptor-rich regions, such as striatum, and low uptake in receptor-poor cerebellum. At 169 min the ratio of radioactivity concentration in striatum to that in cerebellum was 4.0. In a second SPET experiment, the cynomolgus monkey was pretreated with a selective 5-HT{sub 4} receptor antagonist, SB 204070, at 20 min before [{sup 123}I]SB 207710 injection

  9. Image Restoration and Analysis of Influenza Virions Binding to Membrane Receptors Reveal Adhesion-Strengthening Kinetics.

    Directory of Open Access Journals (Sweden)

    Donald W Lee

    Full Text Available With the development of single-particle tracking (SPT microscopy and host membrane mimics called supported lipid bilayers (SLBs, stochastic virus-membrane binding interactions can be studied in depth while maintaining control over host receptor type and concentration. However, several experimental design challenges and quantitative image analysis limitations prevent the widespread use of this approach. One main challenge of SPT studies is the low signal-to-noise ratio of SPT videos, which is sometimes inevitable due to small particle sizes, low quantum yield of fluorescent dyes, and photobleaching. These situations could render current particle tracking software to yield biased binding kinetic data caused by intermittent tracking error. Hence, we developed an effective image restoration algorithm for SPT applications called STAWASP that reveals particles with a signal-to-noise ratio of 2.2 while preserving particle features. We tested our improvements to the SPT binding assay experiment and imaging procedures by monitoring X31 influenza virus binding to α2,3 sialic acid glycolipids. Our interests lie in how slight changes to the peripheral oligosaccharide structures can affect the binding rate and residence times of viruses. We were able to detect viruses binding weakly to a glycolipid called GM3, which was undetected via assays such as surface plasmon resonance. The binding rate was around 28 folds higher when the virus bound to a different glycolipid called GD1a, which has a sialic acid group extending further away from the bilayer surface than GM3. The improved imaging allowed us to obtain binding residence time distributions that reflect an adhesion-strengthening mechanism via multivalent bonds. We empirically fitted these distributions using a time-dependent unbinding rate parameter, koff, which diverges from standard treatment of koff as a constant. We further explain how to convert these models to fit ensemble-averaged binding data

  10. Development and evaluation of a novel radioiodinated vesamicol analog as a sigma receptor imaging agent.

    Science.gov (United States)

    Ogawa, Kazuma; Kanbara, Hiroya; Shiba, Kazuhiro; Kitamura, Yoji; Kozaka, Takashi; Kiwada, Tatsuto; Odani, Akira

    2012-09-28

    Sigma receptors are highly expressed in human tumors and should be appropriate targets for developing tumor imaging agents. Previously, we synthesized a vesamicol analog, (+)-2-[4-(4-iodophenyl)piperidino]cyclohexanol ((+)-pIV), with a high affinity for sigma receptors and prepared radioiodinated (+)-pIV. As a result, (+)-[125I]pIV showed high tumor uptake in biodistribution experiments. However, the accumulation of radioactivity in normal tissues, such as the liver, was high. We supposed that some parts of the accumulation of (+)-pIV in the liver should be because of its high lipophilicity, and prepared and evaluated a more hydrophilic radiolabeled vesamicol analog, (+)-4-[1-(2-hydroxycyclohexyl)piperidine-4-yl]-2-iodophenol ((+)-IV-OH). (+)-[125I]IV-OH was prepared by the chloramine T method from the precursor. The partition coefficient of (+)-[125I]IV-OH was measured. Biodistribution experiments were performed by intravenous administration of a mixed solution of (+)-[125I]IV-OH and (+)-[131I]pIV into DU-145 tumor-bearing mice. Blocking studies were performed by intravenous injection of (+)-[125I]IV-OH mixed with an excess amount of ligand into DU-145 tumor-bearing mice. The hydrophilicity of (+)-[125I]IV-OH was much higher than that of (+)-[125I]pIV. In biodistribution experiments, (+)-[125I]IV-OH and (+)-[131I]pIV showed high uptake in tumor tissues at 10-min post-injection. Although (+)-[131I]pIV tended to be retained in most tissues, (+)-[125I]IV-OH was cleared from most tissues. In the liver, the radioactivity level of (+)-[125I]IV-OH was significantly lower at all time points compared to those of (+)-[131I]pIV. In the blocking studies, co-injection of an excess amount of sigma ligands resulted in significant decreases of tumor/blood uptake ratios after injection of (+)-[125I]IV-OH. The results indicate that radioiodinated (+)-IV-OH holds a potential as a sigma receptor imaging agent.

  11. Near infrared spectral polarization imaging of prostate cancer tissues using Cybesin: a receptor-targeted contrast agent

    Science.gov (United States)

    Pu, Yang; Wang, W. B.; Tang, G. C.; Liang, Kexian; Achilefu, S.; Alfano, R. R.

    2013-03-01

    Cybesin, a smart contrast agent to target cancer cells, was investigated using a near infrared (NIR) spectral polarization imaging technique for prostate cancer detection. The approach relies on applying a contrast agent that can target cancer cells. Cybesin, as a small ICG-derivative dye-peptide, emit fluorescence between 750 nm and 900 nm, which is in the "tissue optical window". Cybesin was reported targeting the over-expressed bombesin receptors in cancer cells in animal model and the human prostate cancers over-expressing bombesin receptors. The NIR spectral polarization imaging study reported here demonstrated that Cybesin can be used as a smart optical biomarker and as a prostate cancer receptor targeted contrast agent.

  12. Biodistribution and dosimetry of iodine-123-labelled Z-MIVE: an oestrogen receptor radioligand for breast cancer imaging

    NARCIS (Netherlands)

    Rijks, L. J.; Busemann Sokole, E.; Stabin, M. G.; de Bruin, K.; Janssen, A. G.; van Royen, E. A.

    1998-01-01

    This study reports on the distribution and radiation dosimetry of iodine-123-labelled cis-11beta-methoxy-17alpha-iodovinyloestradiol (Z-[123I]MIVE), a promising radioligand for imaging of oestrogen receptors (ERs) in human breast cancer. Whole-body scans were performed up to 24 h after intravenous

  13. A randomised, blinded, placebo-controlled trial in dementia patients continuing or stopping neuroleptics (the DART-AD trial.

    Directory of Open Access Journals (Sweden)

    Clive Ballard

    2008-04-01

    Full Text Available BACKGROUND: There have been increasing concerns regarding the safety and efficacy of neuroleptics in people with dementia, but there are very few long-term trials to inform clinical practice. The aim of this study was to determine the impact of long-term treatment with neuroleptic agents upon global cognitive decline and neuropsychiatric symptoms in patients with Alzheimer disease. METHODS AND FINDINGS: DESIGN: Randomised, blinded, placebo-controlled parallel two-group treatment discontinuation trial. SETTING: Oxfordshire, Newcastle and Gateshead, London and Edinburgh, United Kingdom. PARTICIPANTS: Patients currently prescribed the neuroleptics thioridazine, chlorpromazine, haloperidol trifluoperazine or risperidone for behavioural or psychiatric disturbance in dementia for at least 3 mo. INTERVENTIONS: Continue neuroleptic treatment for 12 mo or switch to an identical placebo. OUTCOME MEASURES: Primary outcome was total Severe Impairment Battery (SIB score. Neuropsychiatric symptoms were evaluated with the Neuropsychiatric Inventory (NPI. RESULTS: 165 patients were randomised (83 to continue treatment and 82 to placebo, i.e., discontinue treatment, of whom 128 (78% commenced treatment (64 continue/64 placebo. Of those, 26 were lost to follow-up (13 per arm, resulting in 51 patients per arm analysed for the primary outcome. There was no significant difference between the continue treatment and placebo groups in the estimated mean change in SIB scores between baseline and 6 mo; estimated mean difference in deterioration (favouring placebo -0.4 (95% confidence interval [CI] -6.4 to 5.5, adjusted for baseline value (p = 0.9. For neuropsychiatric symptoms, there was no significant difference between the continue treatment and placebo groups (n = 56 and 53, respectively in the estimated mean change in NPI scores between baseline and 6 mo; estimated mean difference in deterioration (favouring continue treatment -2.4 (95% CI -8.2 to 3.5, adjusted for

  14. In vivo stem cell tracking with imageable nanoparticles that bind bioorthogonal chemical receptors on the stem cell surface.

    Science.gov (United States)

    Lee, Sangmin; Yoon, Hwa In; Na, Jin Hee; Jeon, Sangmin; Lim, Seungho; Koo, Heebeom; Han, Sang-Soo; Kang, Sun-Woong; Park, Soon-Jung; Moon, Sung-Hwan; Park, Jae Hyung; Cho, Yong Woo; Kim, Byung-Soo; Kim, Sang Kyoon; Lee, Taekwan; Kim, Dongkyu; Lee, Seulki; Pomper, Martin G; Kwon, Ick Chan; Kim, Kwangmeyung

    2017-09-01

    It is urgently necessary to develop reliable non-invasive stem cell imaging technology for tracking the in vivo fate of transplanted stem cells in living subjects. Herein, we developed a simple and well controlled stem cell imaging method through a combination of metabolic glycoengineering and bioorthogonal copper-free click chemistry. Firstly, the exogenous chemical receptors containing azide (-N 3 ) groups were generated on the surfaces of stem cells through metabolic glycoengineering using metabolic precursor, tetra-acetylated N-azidoacetyl-d-mannosamine(Ac 4 ManNAz). Next, bicyclo[6.1.0]nonyne-modified glycol chitosan nanoparticles (BCN-CNPs) were prepared as imageable nanoparticles to deliver different imaging agents. Cy5.5, iron oxide nanoparticles and gold nanoparticles were conjugated or encapsulated to BCN-CNPs for optical, MR and CT imaging, respectively. These imageable nanoparticles bound chemical receptors on the Ac 4 ManNAz-treated stem cell surface specifically via bioorthogonal copper-free click chemistry. Then they were rapidly taken up by the cell membrane turn-over mechanism resulting in higher endocytic capacity compared non-specific uptake of nanoparticles. During in vivo animal test, BCN-CNP-Cy5.5-labeled stem cells could be continuously tracked by non-invasive optical imaging over 15 days. Furthermore, BCN-CNP-IRON- and BCN-CNP-GOLD-labeled stem cells could be efficiently visualized using in vivo MR and CT imaging demonstrating utility of our stem cell labeling method using chemical receptors. These results conclude that our method based on metabolic glycoengineering and bioorthogonal copper-free click chemistry can stably label stem cells with diverse imageable nanoparticles representing great potential as new stem cell imaging technology. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Clinically compliant spatial and temporal imaging of chimeric antigen receptor T-cells.

    Science.gov (United States)

    Emami-Shahri, Nia; Foster, Julie; Kashani, Roxana; Gazinska, Patrycja; Cook, Celia; Sosabowski, Jane; Maher, John; Papa, Sophie

    2018-03-14

    The unprecedented efficacy of chimeric antigen receptor (CAR) T-cell immunotherapy of CD19 + B-cell malignancy has established a new therapeutic pillar of hematology-oncology. Nonetheless, formidable challenges remain for the attainment of comparable success in patients with solid tumors. To accelerate progress and rapidly characterize emerging toxicities, systems that permit the repeated and non-invasive assessment of CAR T-cell bio-distribution would be invaluable. An ideal solution would entail the use of a non-immunogenic reporter that mediates specific uptake of an inexpensive, non-toxic and clinically established imaging tracer by CAR T cells. Here we show the utility of the human sodium iodide symporter (hNIS) for the temporal and spatial monitoring of CAR T-cell behavior in a cancer-bearing host. This system provides a clinically compliant toolkit for high-resolution serial imaging of CAR T cells in vivo, addressing a fundamental unmet need for future clinical development in the field.

  16. Radiogenomic correlation in lung adenocarcinoma with epidermal growth factor receptor mutations: Imaging features and histological subtypes

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Su Jin [Seoul National University Bundang Hospital, Department of Radiology, Seongnam-si, Gyeonggi-do (Korea, Republic of); Hanyang University, Department of Radiology, School of Medicine, Seoul (Korea, Republic of); Kim, Tae Jung [Seoul National University Bundang Hospital, Department of Radiology, Seongnam-si, Gyeonggi-do (Korea, Republic of); Samsung Medical Center, Department of Radiology, Seoul (Korea, Republic of); Choi, Yo Won [Hanyang University, Department of Radiology, School of Medicine, Seoul (Korea, Republic of); Park, Jeong-Soo [Dankook Universicity, Department of Biochemistry, College of Medicine, Cheonan (Korea, Republic of); Chung, Jin-Haeng [Seoul National University Bundang Hospital, Department of Pathology, Seongnam-si, Gyeonggi-do (Korea, Republic of); Lee, Kyung Won [Seoul National University Bundang Hospital, Department of Radiology, Seongnam-si, Gyeonggi-do (Korea, Republic of)

    2016-10-15

    To correlate imaging features of resected lung adenocarcinoma with epidermal growth factor receptor (EGFR) mutation and the IASLC/ATS/ERS classification histological subtypes. In 250 consecutive patients with resected lung adenocarcinoma, EGFR mutation status was correlated with demographics, imaging features including ground-glass opacity (GGO) proportion and the IASLC/ATS/ERS classification histological subtypes. EGFR mutations were significantly more frequent in women (54.5 % vs. 38.1 %, p = 0.011) and in never-smokers (54.7 % vs. 35.3 %, p = 0.003). GGO proportion was significantly higher in tumours with EGFR mutation than in those without (30.3 ± 33.8 % vs. 19.0 ± 29.3 %, p = 0.005). EGFR mutation was significantly more frequent in tumours with GGO ≥ 50 % and tumours with any GGO (p = 0.026 and 0.008, respectively). Adenocarcinomas with exon 19 or 21 mutation showed significantly higher GGO proportion than that in EGFR wild-type tumours (p = 0.009 and 0.029, respectively). Absence of GGO was an independent predictor of negative EGFR mutation (odds ratio, 1.81; 95 % confidence interval, 1.16-3.04; p = 0.018). GGO proportion in adenocarcinomas with EGFR mutation was significantly higher than that in EGFR wild-type tumours, and the absence of GGO on CT was an independent predictor of negative EGFR mutation. (orig.)

  17. Somatostatin receptor scintigraphy and magnetic resonance imaging in recurrent medullary thyroid carcinoma: A comparative study

    International Nuclear Information System (INIS)

    Doerr, U.; Wuerstlin, S.; Frank-Raue, K.; Raue, F.; Hehrmann, R.; Iser, G.; Scholz, M.; Guhl, L.; Buhr, H.J.; Bihl, H.

    1993-01-01

    In a prospective study, 18 patients with recurrent medullary thyroid carcinoma (MTC) underwent magnetic resonance imaging (MRI) of the neck and mediastinum and somatostatin receptor scintigraphy (SRS) with 111 In-labeled pentetreotide. In nine patients with macroscopic MTC, 17 corresponding lesions were found on MRI and SRS; in addition, 13 suspicious lesions were seen on SRS only. Histological confirmation was available for 19 metastatic lesions, showing MRI to be true positive in 13 metastases, SRS in 18. In minimal residual disease (n=10), MRI and SRS were compared with the histological findings in three patients and with selective venous catheterization (SVC) in seven patients. Corresponding findings on MRI and SVC were seen in one of seven, whereas SRS and SVC showed concordant localization of tumor recurrence in five of seven. Histological examination demonstrated MTC tissue in one of three cases; MRI and SRS were false positive in one of three cases, while in the others the interpretation remained uncertain. In conclusion, SRS is a promising imaging modality for localization of MTC recurrence. MRI provides better spatial resolution and thus facilitates the planning of surgery for macroscopic metastases. In minimal residual disease, SRS turned out to be superior in detecting occult MTC recurrence, confirming SVC findings. (orig.)

  18. Somatostatin receptor expression in Merkel cell carcinoma as target for molecular imaging

    International Nuclear Information System (INIS)

    Buder, Kristina; Becker, Jürgen C; Lapa, Constantin; Kreissl, Michael C; Schirbel, Andreas; Herrmann, Ken; Schnack, Alexander; Bröcker, Eva-Bettina; Goebeler, Matthias; Buck, Andreas K

    2014-01-01

    Merkel cell carcinoma (MCC) is a rare cutaneous neoplasm with increasing incidence, aggressive behavior and poor prognosis. Somatostatin receptors (SSTR) are expressed in MCC and represent a potential target for both imaging and treatment. To non-invasively assess SSTR expression in MCC using PET and the radiotracers [ 68 Ga]DOTA-D-Phe 1 -Tyr 3 -octreotide (DOTATOC) or -octreotate (DOTATATE) as surrogate for tumor burden. In 24 patients with histologically proven MCC SSTR-PET was performed and compared to results of computed tomography (CT). SSTR-PET detected primary and metastatic MCC lesions. On a patient-based analysis, sensitivity of SSTR-PET was 73% for nodal metastases, 100% for bone, and 67% for soft-tissue metastases, respectively. Notably, brain metastases were initially detected by SSTR-PET in 2 patients, whereas liver and lung metastases were diagnosed exclusively by CT. SSTR-PET showed concordance to CT results in 20 out of 24 patients. Four patients (17%) were up-staged due to SSTR-PET and patient management was changed in 3 patients (13%). SSTR-PET showed high sensitivity for imaging bone, soft tissue and brain metastases, and particularly in combination with CT had a significant impact on clinical stage and patient management

  19. Synthesis and 125I labelling of a precursor for imaging nicotinic acetylcholine receptors

    International Nuclear Information System (INIS)

    Liu Yuxia; Liu Ning; Yang Yuanyou; Zan Liangbiao; Liao Jiali; Jin Jiannan; Sichuan Univ., Chengdu

    2006-01-01

    Nicotinic Acetylcholine Receptors (nAChRs) are involved in various pharmacological effects or diseases, such as Alzheimer's Disease, Parkinson's Disease and tobacco addiction. It will be very appealing to image nAChRs in vivo, diagnose and treat the above diseases, and probe the mechanism of nAChRs in tobacco addiction if the suitable radioactive labeled compound can be synthesized. In this study, (s)-5-(tri-butylstannyl)-3{[1-(tert-butoxycarbonyl)-2-azetidinyl]methoxy} pyridine, a precursor for imaging nAChRs, was synthesized with commercial 2-furfurylamine and (s)-2-azetidinecarboxylic acid as starting materials, and was further labeled with 125/123 I. The whole procedure for radiosynthesis needs 50-55 min and more than 30% of the 125 I are found in the purified 5-[ 125 I]-A-85380. Even staying for 3 days at room temperature in vitro, the purified 5-[ 125 I]-I-85380 can maintain its stability, with a radiochemical purity of more than 95%. (authors)

  20. SSTR-Mediated Imaging in Breast Cancer: Is There a Role for Radiolabeled Somatostatin Receptor Antagonists?

    Science.gov (United States)

    Dalm, Simone U; Haeck, Joost; Doeswijk, Gabriela N; de Blois, Erik; de Jong, Marion; van Deurzen, Carolien H M

    2017-10-01

    Recent studies have shown enhanced tumor targeting by novel somatostatin receptor (SSTR) antagonists compared with clinically widely used agonists. However, these results have been obtained mostly in neuroendocrine tumors, and only limited data are available for cancer types with lower SSTR expression, including breast cancer (BC). To date, two studies have reported higher binding of the antagonist than the agonist in BC, but in both studies only a limited number of cases were evaluated. In this preclinical study, we further investigated whether the application of an SSTR antagonist can improve SSTR-mediated BC imaging in a large panel of BC specimens. We also generated an in vivo BC mouse model and performed SPECT/MRI and biodistribution studies. Methods: Binding of 111 In-DOTA-Tyr 3 -octreotate (SSTR agonist) and 111 In-DOTA-JR11 (SSTR antagonist) to 40 human BC specimens was compared using in vitro autoradiography. SSTR2 immunostaining was performed to confirm SSTR2 expression of the tumor cells. Furthermore, binding of the radiolabeled SSTR agonist and antagonist was analyzed in tissue material from 6 patient-derived xenografts. One patient-derived xenograft, the estrogen receptor-positive model T126, was chosen to generate in vivo mouse models containing orthotopic breast tumors for in vivo SPECT/MRI and biodistribution studies after injection with 177 Lu-DOTA-Tyr 3 -octreotate or 177 Lu-DOTA-JR11. Results: 111 In-DOTA-JR11 binding to human BC tissue was significantly higher than 111 In-DOTA-Tyr 3 -octreotate binding ( P < 0.001). The median ratio of antagonist binding versus agonist binding was 3.39 (interquartile range, 2-5). SSTR2 immunostaining confirmed SSTR2 expression on the tumor cells. SPECT/MRI of the mouse model found better tumor visualization with the antagonist. This result was in line with the significantly higher tumor uptake of the radiolabeled antagonist than of the agonist as measured in biodistribution studies 285 min after radiotracer

  1. Downstream reporter gene imaging for signal transduction pathway of dopamine type 2 receptor

    International Nuclear Information System (INIS)

    Le, Uyenchi N.; Min, Jung Joon; Moon, Sung Min; Bom, Hee Seung

    2004-01-01

    The Dopamine 2 receptor (D2R) signal pathway regulates gene expression by phosphorylation of proteins including cAMP reponse element-binding protein (CREB), a transcription factor. In this study, we developed a reporter strategy using the GAL4 fusion CREB to assess the phosphorylation of CREB, one of the targets of the D2R signal transduction pathway. We used three plasmids: GAL4 fusion transactivator (pCMV-CREB), firefly luciferase reporter with GAL4 binding sites (pG5-FLUC), and D2R plasmid (pCMV-D2R). Group 1 293T cells were transiently transfected with pCMV-CREB and pG5-FLUC, and group 2 cells were transfected with all three plasmids. Transfected cells were stimulated with different concentrations of dopamine (0-200 M). For animal studies, group 1 and 2 cells (1x10 6 ) were subcutaneously injected on the left and right thigh of six nude mice, respectively. Dopamine stimiulation was performed with intraperitoneal injection of L-DOPA incombination with carbidopa, a peripheral DOPA decarboxylase inhibitor. Bioluminescence optical imaging studies were performed before and after L-DOPA injection. In cell culture studies, group 1 cells showed strong luciferase activity which implies direct activation of the signaling pathway due to growth factors contained in culture medium. Group 2 cells showed strong luciferase activity and a further increase after administration of dopamine. In animal studies, group 1 and 2 cells showed bioluminescence signal before L-DOPA injection, but signal from group 2 cells significantly increased 12 h after L-DOPA injection. The signal from group 1 cells disappeared thereafter, but group 2 cells continued to show signal until 36 h of L-DOPA injection. This study demonstrates imaging of the D2R signal transduction pathway and should be useful for noninvasive imaging of downstream effects of G-coupled protein pathways

  2. Radiosynthesis and initial evaluation of [18F]-FEPPA for PET imaging of peripheral benzodiazepine receptors

    International Nuclear Information System (INIS)

    Wilson, Alan A.; Garcia, Armando; Parkes, Jun; McCormick, Patrick; Stephenson, Karin A.; Houle, Sylvain; Vasdev, Neil

    2008-01-01

    Introduction: A novel [ 18 F]-radiolabelled phenoxyanilide, [ 18 F]-FEPPA, has been synthesized and evaluated, in vitro and ex vivo, as a potential positron emission tomography imaging agent for the peripheral benzodiazepine receptor (PBR). Methods: [ 18 F]-FEPPA and two other radiotracers for imaging PBR, namely [ 11 C]-PBR28 and [ 11 C]-PBR28-d3, were synthesised and evaluated in vitro and ex vivo as potential PBR imaging agents. Results: [ 18 F]-FEPPA is efficiently prepared in one step from its tosylate precursor and [ 18 F]-fluoride in high radiochemical yields and at high specific activity. FEPPA displayed a K i of 0.07 nM for PBR in rat mitochondrial membrane preparations and a suitable lipophilicity for brain penetration (log P of 2.99 at pH 7.4). Upon intravenous injection into rats, [ 18 F]-FEPPA showed moderate brain uptake [standard uptake value (SUV) of 0.6 at 5 min] and a slow washout (SUV of 0.35 after 60 min). Highest uptake of radioactivity was seen in the hypothalamus and olfactory bulb, regions previously reported to be enriched in PBR in rat brain. Analysis of plasma and brain extracts demonstrated that [ 18 F]-FEPPA was rapidly metabolized, but no lipophilic metabolites were observed in either preparation and only 5% radioactive metabolites were present in brain tissue extracts. Blocking studies to determine the extent of specific binding of [ 18 F]-FEPPA in rat brain were problematic due to large perturbations in circulating radiotracer and the lack of a reference region. Conclusions: Further evaluation of the potential of [ 18 F]-FEPPA will require the employment of rigorous kinetic models and/or appropriate animal models

  3. [11C]WAY-100635 PET imaging of 5-HT1A receptor binding in patients with temporal lobe epilepsy

    International Nuclear Information System (INIS)

    Sasai, Taeko; Matsuura, Masato; Itou, Shigeo; Suhara, Tetsuya; Yahata, Noriaki; Okubo, Yoshiro

    2006-01-01

    To understand the role of 5-HT in human temporal lobe epilepsy, here we measured 5-HT 1A receptor binding potential by positron emission tomography (PET) with [carbonyl- 11 C]WAY100635, a selective 5-HT 1A receptor antagonist, in patients with temporal lobe epilepsy and normal controls. Twelve patients with temporal lobe epilepsy and seventeen healthy controls participated in the study. For each subject, we conducted PET and magnetic resonance imaging (MRI), by which we measured the 5-HT 1A receptor binding potential, the R1-value, a relative indicator of cerebral blood flow in regions of interest, and the volume of gray matter. Patients with temporal lobe epilepsy showed significantly reduced 5-HT 1A receptor binding potential in the temporal lobe. The laterality of the reduction was coincided with the epileptogenic foci estimated by a scalp electroencephalography (EEG). In contrast, the R1-value and gray matter volume showed no difference between the patient and control groups. Our study revealed that 5-HT 1A receptor binding was reduced significantly at the epileptogenic foci. We suggest that PET imaging with [carbonyl- 11 C]WAY100635 is potentially a useful non-invasive method for determining the epileptogenic foci. (author)

  4. Imaging Agonist-Induced D2/D3 Receptor Desensitization and Internalization In Vivo with PET/fMRI.

    Science.gov (United States)

    Sander, Christin Y; Hooker, Jacob M; Catana, Ciprian; Rosen, Bruce R; Mandeville, Joseph B

    2016-04-01

    This study investigated the dynamics of dopamine receptor desensitization and internalization, thereby proposing a new technique for non-invasive, in vivo measurements of receptor adaptations. The D2/D3 agonist quinpirole, which induces receptor internalization in vitro, was administered at graded doses in non-human primates while imaging with simultaneous positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). A pronounced temporal divergence between receptor occupancy and fMRI signal was observed: occupancy remained elevated while fMRI responded transiently. Analogous experiments with an antagonist (prochlorperazine) and a lower-affinity agonist (ropinirole) exhibited reduced temporal dissociation between occupancy and function, consistent with a mechanism of desensitization and internalization that depends upon drug efficacy and affinity. We postulated a model that incorporates internalization into a neurovascular-coupling relationship. This model yielded in vivo desensitization/internalization rates (0.2/min for quinpirole) consistent with published in vitro measurements. Overall, these results suggest that simultaneous PET/fMRI enables characterization of dynamic neuroreceptor adaptations in vivo, and may offer a first non-invasive method for assessing receptor desensitization and internalization.

  5. In vivo characterization of radioiodinated (+)-2-[4-(4-iodophenyl) piperidino] cyclohexanol as a potential σ-1 receptor imaging agent

    International Nuclear Information System (INIS)

    Akhter, Nasima; Shiba, Kazuhiro; Ogawa, Kazuma; Kinuya, Seigo; Nakajima, Kenichi; Mori, Hirofumi

    2007-01-01

    In this study, the (+)-enantiomer of radioiodinated 2-[4-(4-iodophenyl)piperidino]cyclohexanol [(+)-[ 125 I]-p-iodovesamicol] [(+)-[ 125 I]pIV], which is reported to bind with high affinity to σ-1 receptors in vitro, was tested for its usefulness in imaging σ-1 receptors in the central nervous system (CNS) in vivo. In biodistribution studies, significant amounts (approximately 3% of the injected dose) of (+)-[ 125 I]pIV accumulated in rat brain, and its retention was prolonged. In blocking studies, the accumulation of (+)-[ 125 I]pIV in the rat brain was significantly reduced by the coadministration of σ-ligands such as pentazocine (5.0 μmol), haloperidol (0.5 μmol) or SA4503 (0.5 μmol). The blocking effect of pentazocine (selective σ-1 ligand) was similar to the blocking effects of SA4503 and haloperidol [nonselective σ (σ-1 and σ-2) ligands]. Ex vivo autoradiography of the rat brain at 45 min following intravenous injection of (+)-[ 125 I]pIV showed high localization in brain areas rich in σ-1 receptors. Thus, the distribution of (+)-[ 125 I]pIV was thought to bind to σ-1 receptors in the CNS in vivo. These results indicate that radioiodinated (+)-pIV may have the potential to image σ-1 receptors in vivo

  6. [Initial experiences with amisulpride, an in Germany novel, atypical neuroleptic drug in treatment of adolescents with psychiatric disorders].

    Science.gov (United States)

    Göpel, C; Marcus, A

    2001-08-01

    In addition to conventional antipsychotic drugs, during the past decade an increasing number of atypical neuroleptics has been introduced in the treatment of juvenile schizophrenic and schizoaffective disorders. In 1999 Germany legalized the benzamide amisulpride for the treatment of acute and chronic schizophrenic symptoms. Preliminary treatment results are reported here. Ten adolescent cases are presented with regard to the efficacy, side effects and dosage of amisulpride. Preliminary results on the use of amisulpride are promising. The rate of side effects is tolerable. Amisulprise seems to constitute a useful alternative in the treatment of juvenile schizophrenia for those who suffer from intolerable side effects of classical or atypical neuroleptics. Controlled studies are warranted to further clarify its efficacy and safety in the treatment of adolescents.

  7. [{sup 11}C]-MeJDTic: a novel radioligand for {kappa}-opioid receptor positron emission tomography imaging

    Energy Technology Data Exchange (ETDEWEB)

    Poisnel, Geraldine; Oueslati, Farhana; Dhilly, Martine; Delamare, Jerome [Groupe de Developpements Methodologiques en Tomographie par Emission de Positons, DSV/DRM UMR CEA 2E, Universite de Caen-Basse Normandie, Centre Cyceron, 14074 Caen Cedex (France); Perrio, Cecile [Groupe de Developpements Methodologiques en Tomographie par Emission de Positons, DSV/DRM UMR CEA 2E, Universite de Caen-Basse Normandie, Centre Cyceron, 14074 Caen Cedex (France)], E-mail: perrio@cyceron.fr; Debruyne, Daniele [Groupe de Developpements Methodologiques en Tomographie par Emission de Positons, DSV/DRM UMR CEA 2E, Universite de Caen-Basse Normandie, Centre Cyceron, 14074 Caen Cedex (France)], E-mail: debruyne@cyceron.fr; Barre, Louisa [Groupe de Developpements Methodologiques en Tomographie par Emission de Positons, DSV/DRM UMR CEA 2E, Universite de Caen-Basse Normandie, Centre Cyceron, 14074 Caen Cedex (France)

    2008-07-15

    Introduction: Radiopharmaceuticals that can bind selectively the {kappa}-opioid receptor may present opportunities for staging clinical brain disorders and evaluating the efficiency of new therapies related to stroke, neurodegenerative diseases or opiate addiction. The N-methylated derivative of JDTic (named MeJDTic), which has been recently described as a potent and selective antagonist of {kappa}-opioid receptor in vitro, was labeled with carbon-11 and evaluated for in vivo imaging the {kappa}-opioid receptor in mice. Methods: [{sup 11}C]-MeJDTic was prepared by methylation of JDTic with [{sup 11}C]-methyl triflate. The binding of [{sup 11}C]-MeJDTic to {kappa}-opioid receptor was investigated ex vivo by biodistribution and competition studies using nonfasted male CD1 mice. Results: [{sup 11}C]-MeJDTic exhibited a high and rapid distribution in peripheral organs. The uptake was maximal in lung where the {kappa} receptor is largely expressed. [{sup 11}C]-MeJDTic rapidly crossed the blood-brain barrier and accumulated in the brain regions of interest (hypothalamus). The parent ligand remained the major radioactive compound in brain during the experiment. Chase studies with U50,488 (a {kappa} referring agonist), morphine (a {mu} agonist) and naltrindole (a {delta} antagonist) demonstrated that this uptake was the result of specific binding to the {kappa}-opioid receptor. Conclusion: These findings suggested that [{sup 11}C]-MeJDTic appeared to be a promising selective 'lead' radioligand for {kappa}-opioid receptor PET imaging.

  8. The rapid synthesis of high purity [{sup 18}F]butyrophenone neuroleptics from nitro precursors for PET study

    Energy Technology Data Exchange (ETDEWEB)

    Hashizume, Kazunari; Hashimoto, Naoto; Kato, Hiroo; Cork, D G; Miyake, Yoshihiro [National Cardiovascular Center, Suita, Osaka (Japan)

    1995-04-01

    We have completed rapid syntheses of [{sup 18}F]butyrophenone neuroleptics ([{sup 18}F]haloperidol and [{sup 18}F]spiperone) from their nitro precursors in high radiochemical yields (up to 21%) by combining a one-step nitro-fluoro exchange reaction and a novel high performance liquid chromatography (HPLC) separation method. The synthesis time was ca. 95 min and both the radiochemical and chemical purities of the labeled products were over 99%. (author).

  9. Making Sense of the 'Chemical Revolution'. Patients' Voices on the Introduction of Neuroleptics in the 1950s.

    Science.gov (United States)

    Majerus, Benoît

    2016-01-01

    The so-called chemical revolution has produced a vast historiographical corpus. Yet the patient's voice remains surprisingly absent from these stories. Based on the archives of the Institut de Psychiatrie (Brussels), this paper traces the introduction of Largactil as recounted in patient letters, physician records and nurse notes. The paper thus contributes to the history of therapies from below, but also participates in the historiographical debate about whether the introduction of neuroleptics can indeed be considered a revolution.

  10. The gastrin/cholecystokinin-B receptor on prostate cells--a novel target for bifunctional prostate cancer imaging.

    Science.gov (United States)

    Sturzu, Alexander; Klose, Uwe; Sheikh, Sumbla; Echner, Hartmut; Kalbacher, Hubert; Deeg, Martin; Nägele, Thomas; Schwentner, Christian; Ernemann, Ulrike; Heckl, Stefan

    2014-02-14

    The means of identifying prostate carcinoma and its metastases are limited. The contrast agents used in magnetic resonance imaging clinical diagnostics are not taken up into the tumor cells, but only accumulate in the interstitial space of the highly vasculated tumor. We examined the gastrin/cholecystokinin-B receptor as a possible target for prostate-specific detection using the C-terminal seven amino acid sequence of the gastrin peptide hormone. The correct sequence and a scrambled control sequence were coupled to the fluorescent dye rhodamine and the magnetic resonance imaging contrast agent gadolinium (Gd)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). Expression analysis of the gastrin receptor mRNA was performed by reverse transcriptase polymerase chain reaction on PC3 prostate carcinoma cells, U373 glioma, U2OS osteosarcoma and Colo205 colon carcinoma cells. After having confirmed elevated expression of gastrin receptor in PC3 cells and very low expression of the receptor in Colo205 cells, these two cell lines were used to create tumor xenografts on nude mice for in vivo experiments. Confocal lasers scanning microscopy and magnetic resonance imaging showed a high specificity of the correct conjugate for the PC3 xenografts. Staining of the PC3 xenografts was much weaker with the scrambled conjugate while the Colo205 xenografts showed no marked staining with any of the conjugates. In vitro experiments comparing the correct and scrambled conjugates on PC3 cells by magnetic resonance relaxometry and fluorescence-activated cell sorting confirmed markedly higher specificity of the correct conjugate. The investigations show that the gastrin receptor is a promising tumor cell surface target for future prostate-cancer-specific imaging applications. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Imaging dopamine D3 receptors in the human brain with positron emission tomography, [11C]PHNO, and a selective D3 receptor antagonist.

    Science.gov (United States)

    Searle, Graham; Beaver, John D; Comley, Robert A; Bani, Massimo; Tziortzi, Andri; Slifstein, Mark; Mugnaini, Manolo; Griffante, Cristiana; Wilson, Alan A; Merlo-Pich, Emilio; Houle, Sylvain; Gunn, Roger; Rabiner, Eugenii A; Laruelle, Marc

    2010-08-15

    Dopamine D(3) receptors are involved in the pathophysiology of several neuropsychiatric conditions. [(11)C]-(+)-PHNO is a radiolabeled D(2) and D(3) agonist, suitable for imaging the agonist binding sites (denoted D(2HIGH) and D(3)) of these receptors with positron emission tomography (PET). PET studies in nonhuman primates documented that, in vivo, [(11)C]-(+)-PHNO displays a relative selectivity for D(3) compared with D(2HIGH) receptor sites and that the [(11)C]-(+)-PHNO signal is enriched in D(3) contribution compared with conventional ligands such as [(11)C] raclopride. To define the D(3) contribution (f(PHNO)(D3)) to [(11)C]-(+)-PHNO binding potential (BP(ND)) in healthy humans, 52 PET scans were obtained in 19 healthy volunteers at baseline and following oral administration of various doses of the selective D(3) receptor antagonist, GSK598809. The impact of GSK598809 on [(11)C]-(+)-PHNO was regionally selective. In dorsal regions of the striatum, GSK598809 did not significantly affect [(11)C]-(+)-PHNO BP(ND) (f(PHNO)(D3) approximately 0%). Conversely, in the substantia nigra, GSK598809 dose-dependently reduced [(11)C]-(+)-PHNO binding to nonspecific level (f(PHNO)(D3) approximately 100%). In ventral striatum (VST), globus pallidus and thalamus (THA), [(11)C]-(+)-PHNO BP(ND) was attributable to a combination of D(2HIGH) and D(3) receptor sites, with f(PHNO)(D3) of 26%, 67% and 46%, respectively. D(3) receptor binding potential (BP(ND)(D3)) was highest in globus pallidus (1.90) and substantial nigra (1.39), with lower levels in VST (.77) and THA (.18) and negligible levels in dorsal striatum. This study elucidated the pharmacologic nature of the [(11)C]-(+)-PHNO signal in healthy subjects and provided the first quantification of D(3) receptor availability with PET in the living human brain. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  12. Virus-resembling nano-structures for near infrared fluorescence imaging of ovarian cancer HER2 receptors

    Science.gov (United States)

    Guerrero, Yadir A.; Bahmani, Baharak; Singh, Sheela P.; Vullev, Valentine I.; Kundra, Vikas; Anvari, Bahman

    2015-10-01

    Ovarian cancer remains the dominant cause of death due to malignancies of the female reproductive system. The capability to identify and remove all tumors during intraoperative procedures may ultimately reduce cancer recurrence, and lead to increased patient survival. The objective of this study is to investigate the effectiveness of an optical nano-structured system for targeted near infrared (NIR) imaging of ovarian cancer cells that over-express the human epidermal growth factor receptor 2 (HER2), an important biomarker associated with ovarian cancer. The nano-structured system is comprised of genome-depleted plant-infecting brome mosaic virus doped with NIR chromophore, indocyanine green, and functionalized at the surface by covalent attachment of monoclonal antibodies against the HER2 receptor. We use absorption and fluorescence spectroscopy, and dynamic light scattering to characterize the physical properties of the constructs. Using fluorescence imaging and flow cytometry, we demonstrate the effectiveness of these nano-structures for targeted NIR imaging of HER2 receptors in vitro. These functionalized nano-materials may provide a platform for NIR imaging of ovarian cancer.

  13. Virus-resembling nano-structures for near infrared fluorescence imaging of ovarian cancer HER2 receptors

    International Nuclear Information System (INIS)

    Guerrero, Yadir A; Bahmani, Baharak; Vullev, Valentine I; Anvari, Bahman; Singh, Sheela P; Kundra, Vikas

    2015-01-01

    Ovarian cancer remains the dominant cause of death due to malignancies of the female reproductive system. The capability to identify and remove all tumors during intraoperative procedures may ultimately reduce cancer recurrence, and lead to increased patient survival. The objective of this study is to investigate the effectiveness of an optical nano-structured system for targeted near infrared (NIR) imaging of ovarian cancer cells that over-express the human epidermal growth factor receptor 2 (HER2), an important biomarker associated with ovarian cancer. The nano-structured system is comprised of genome-depleted plant-infecting brome mosaic virus doped with NIR chromophore, indocyanine green, and functionalized at the surface by covalent attachment of monoclonal antibodies against the HER2 receptor. We use absorption and fluorescence spectroscopy, and dynamic light scattering to characterize the physical properties of the constructs. Using fluorescence imaging and flow cytometry, we demonstrate the effectiveness of these nano-structures for targeted NIR imaging of HER2 receptors in vitro. These functionalized nano-materials may provide a platform for NIR imaging of ovarian cancer. (paper)

  14. In vitro and in vivo evaluation of [123I]IBZM: a potential CNS D-2 dopamine receptor imaging agent

    International Nuclear Information System (INIS)

    Kung, H.F.; Pan, S.; Kung, M.P.; Billings, J.; Kasliwal, R.; Reilley, J.; Alavi, A.

    1989-01-01

    In vitro binding characteristics of a CNS dopamine D-2 receptor imaging agent, (S)-N-[(1-ethyl-2-pyrrolidinyl)] methyl-2-hydroxy-3-iodo-6-methoxybenzamide [( 125 I]IBZM), was carried out in rats. Also brain images, as well as organ biodistribution were determined in a monkey following the administration of 123 I-labeled compound. The S-(-)-I[ 125 I]IBZM showed high specific dopamine D-2 receptor binding in rat striatum (Kd = 0.426 +/- 0.082 nM, Bmax = 480 +/- 22 fmol/mg of protein). Competition of various ligands for the IBZM binding displayed the following rank order of potency: spiperone greater than S(-)IBZM much greater than R(+)IBZM greater than or equal to S(-)BZM greater than dopamine greater than ketanserin greater than SCH-23390 much greater than propranolol, norepinephrine, serotonin. In vivo planar images of a monkey injected with [ 123 I]IBZM demonstrated a high concentration in basal ganglia of brain. The ratios of activity in the basal ganglia to cerebellum and the cortex to cerebellum in monkey brain were 4.93 and 1.44, respectively, at 120 min postinjection. These preliminary results indicate that [ 123 I]IBZM is a potentially promising imaging agent for the investigation of dopamine D-2 receptors in humans

  15. Multivariate cluster analysis of dynamic iodine-123 iodobenzamide SPET dopamine D{sub 2}receptor images in schizophrenia

    Energy Technology Data Exchange (ETDEWEB)

    Acton, P.D. [Inst. of Nuclear Medicine, Univ. Coll. London Medical School, London (United Kingdom); Pilowsky, L.S. [Institute of Psychiatry, London (United Kingdom); Costa, D.C. [Inst. of Nuclear Medicine, Univ. Coll. London Medical School, London (United Kingdom); Ell, P.J. [Inst. of Nuclear Medicine, Univ. Coll. London Medical School, London (United Kingdom)

    1997-02-01

    This paper describes the application of a multivariate statistical technique to investigate striatal dopamine D{sub 2}receptor concentrations measured by iodine-123 iodobenzamide ({sup 123}I-IBZM) single-photon emission tomography (SPET). This technique enables the automatic segmentation of dynamic nuclear medicine images based on the underlying time-activity curves present in the data. Once the time-activity curves have been extracted, each pixel can be mapped back on to the underlying distribution, considerably reducing image noise. Cluster analysis has been verified using computer simulations and phantom studies. The technique has been applied to SPET images of dopamine D {sub 2}receptors in a total of 20 healthy and 20 schizophrenic volunteers (22 male, 18 female), using the ligand {sup 123}I-IBZM. Following automatic image segmentation, the concentration of striatal dopamine D {sub 2}receptors shows a significant left-sided asymmetry in male schizophrenics compared with male controls. The mean left-minus-right laterality index for controls is -1.52 (95% CI -3.72-0.66) and for patients 4.04 (95% CI 1.07-7.01). Analysis of variance shows a case-by-sex-by-side interaction, with F=10.01, P=0.005. We can now demonstrate that the previously observed male sex-specific D {sub 2}receptor asymmetry in schizophrenia, which had failed to attain statistical significance, is valid. Cluster analysis of dynamic nuclear medicine studies provides a powerful tool for automatic segmentation and noise reduction of the images, removing much of the subjectivity inherent in region-of-interest analysis. The observed striatal D {sub 2}asymmetry could reflect long hypothesized disruptions in dopamine-rich cortico-striatal-limbic circuits in schizophrenic males. (orig.). With 4 figs., 2 tabs.

  16. Noninvasive imaging of transplanted living functional cells transfected with a reporter estrogen receptor gene

    Energy Technology Data Exchange (ETDEWEB)

    Takamatsu, Shinji [Biomedical Imaging Research Center, University of Fukui, 23-3 Shimoaizuki, Matsuoka, Yoshida, Fukui 910-1193 (Japan)]. E-mail: shinjit@fmsrsa.fukui-med.ac.jp; Furukawa, Takako [Biomedical Imaging Research Center, University of Fukui, 23-3 Shimoaizuki, Matsuoka, Yoshida, Fukui 910-1193 (Japan); Mori, Tetsuya [Biomedical Imaging Research Center, University of Fukui, 23-3 Shimoaizuki, Matsuoka, Yoshida, Fukui 910-1193 (Japan); Yonekura, Yoshiharu [Biomedical Imaging Research Center, University of Fukui, 23-3 Shimoaizuki, Matsuoka, Yoshida, Fukui 910-1193 (Japan); Fujibayashi, Yasuhisa [Biomedical Imaging Research Center, University of Fukui, 23-3 Shimoaizuki, Matsuoka, Yoshida, Fukui 910-1193 (Japan)

    2005-11-01

    The transplantation of functional cells such as dopaminergic cells into damaged tissue is now clinically ongoing, but at present the population of surviving cells at the transplantation site mostly cannot be noninvasively examined. To visualize surviving transplanted functional cells using a noninvasive method, we chose the estrogen receptor ligand binding domain (ERL) as a reporter molecule and 16{alpha}-[{sup 18}F]-fluoro-17{beta}-estradiol (FES) for its ligand. We used a mouse embryonic stem (ES) cell line for recipient cells as a model. To obtain ES cells that constitutively or inducibly express ERL, we transfected two types of expression vectors into EB5 parental ES cell line using the lipofection method and obtained about 30 clones for each of the two types of transfectants. Then, to examine the expression level of ERL, we performed Western blotting analysis. Ligand uptake experiments were carried out using [{sup 3}H]-estradiol with or without excessive unlabeled estradiol for control cells and ERL transfectants. Each selected clone was also used for in vivo positron emission tomography (PET) imaging studies involving FES in nude mice transplanted with control cells and ERL transfectants. In some of the clones transfected with the inducible-type ERL gene, protein was expressed much higher than in the controls. However, constitutive-type ERL gene-transfected ES cells showed no protein production in spite of their gene expression activity being considerably high. All clones also expressed equal levels of the Oct-3/4 gene, a marker of pluripotency, in comparison with the parental cells. Also, the specific uptake of [{sup 3}H]-estradiol was over 30 times higher in inducer-treated ERL-expressing ES cells compared to untreated control cells. Finally, by performing dynamic PET imaging, we successfully visualized ERL-expressing teratomas using FES.

  17. SPECT imaging of D{sub 2} dopamine receptors and endogenous dopamine release in mice

    Energy Technology Data Exchange (ETDEWEB)

    Jongen, Cynthia [University Medical Center Utrecht, Image Sciences Institute, Q0S.459, P.O. Box 85500, Utrecht (Netherlands); Bruin, Kora de; Booij, Jan [University of Amsterdam, Academic Medical Center, Department of Nuclear Medicine, Amsterdam (Netherlands); Beekman, Freek [University Medical Center Utrecht, Image Sciences Institute, Q0S.459, P.O. Box 85500, Utrecht (Netherlands); University Medical Center Utrecht, Department of Neuroscience and Pharmacology, Utrecht (Netherlands); Technical University Delft, Department R3, Section Radiation, Detection and Matter, Delft (Netherlands)

    2008-09-15

    The dopamine D{sub 2} receptor (D2R) is important in the mediation of addiction. [{sup 123}I]iodobenzamide (IBZM), a SPECT ligand for the D2R, has been used for in vivo studies of D2R availability in humans, monkeys, and rats. Although mouse models are important in the study of addiction, [{sup 123}I]IBZM has not been used in mice SPECT studies. This study evaluates the use of [{sup 123}I]IBZM for measuring D2R availability in mice. Pharmacokinetics of [{sup 123}I]IBZM in mice were studied with pinhole SPECT imaging after intravenous (i.v.) injection of [{sup 123}I]IBZM (20, 40, and 70 MBq). In addition, the ability to measure the release of endogenous dopamine after amphetamine administration with [{sup 123}I]IBZM SPECT was investigated. Thirdly, i.v. administration, the standard route of administration, and intraperitoneal (i.p.) administration of [{sup 123}I]IBZM were compared. Specific binding of [{sup 123}I]IBZM within the mouse striatum could be clearly visualized with SPECT. Peak specific striatal binding ratios were reached around 90 min post-injection. After amphetamine administration, the specific binding ratios of [{sup 123}I]IBZM decreased significantly (-27.2%; n=6; p=0.046). Intravenous administration of [{sup 123}I]IBZM led to significantly higher specific binding than i.p. administration of the same dose. However, we found that i.v. administration of a dose of 70 MBq [{sup 123}I]IBZM might result in acute ethanol intoxication because ethanol is used as a preparative aid for the routine production of [{sup 123}I]IBZM. Imaging of D2R availability and endogenous dopamine release in mice is feasible using [{sup 123}I]IBZM single pinhole SPECT. Using commercially produced [{sup 123}I]IBZM, a dose of 40 MBq injected i.v. can be recommended. (orig.)

  18. Multiparametric PET imaging in thyroid malignancy characterizing tumour heterogeneity: somatostatin receptors and glucose metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Traub-Weidinger, Tatjana [Medical University of Vienna, Division of Nuclear Medicine, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Medical University of Innsbruck, Department of Nuclear Medicine, Innsbruck (Austria); Putzer, Daniel; Bale, Reto [Medical University of Innsbruck, Department of Radiology, Innsbruck (Austria); Guggenberg, Elisabeth von; Dobrozemsky, Georg; Nilica, Bernhard; Kendler, Dorota; Virgolini, Irene Johanna [Medical University of Innsbruck, Department of Nuclear Medicine, Innsbruck (Austria)

    2015-12-15

    Radiolabelled somatostatin (SST) analogues have proven useful in diagnosing tumours positive for SST receptor (SSTR). As different subtypes of SSTR are expressed on the tumour cell surface, the choice of appropriate therapeutic SST analogue is crucial. We evaluated the SSTR status of thyroid cancer patients who had signs of progressive disease comparing different SSTR ligands for PET imaging to evaluate possible further therapeutic options. PET with {sup 68}Ga-radiolabelled SSTR ligands DOTA lanreotide (DOTA-LAN), DOTA-Tyr{sup 3} octreotide (DOTA-TOC) and {sup 18}F-FDG was performed in 31 patients with thyroid cancer (TC). These 31 patients comprised 18 with radioiodine non-avid differentiated TC (DTC) including 6 papillary TC (PTC), 8 follicular TC (FTC) and 4 oxyphilic TC (oxyTC), 5 with anaplastic TC (ATC), and 8 with medullary TC (MTC). The PET results were compared in a region-based evaluation. All patients underwent a PET study with {sup 68}Ga-DOTA-LAN, 28 patients with {sup 68}Ga-DOTA-TOC and 28 patients with {sup 18}F-FDG. A lack of SSTR expression was found in 13 of the 31 patients (42 %) with negative results with both SSTR tracers in 12 patients. Ambiguous results with both SSTR tracers were observed in one patient. High tracer uptake in SSTR PET images was seen in seven DTC patients (39 %; two PTC, three FTC, two oxyTC), in four ATC patients (80 %) and in six MTC patients (75 %). Lesions showing aerobic glycolysis on {sup 18}F-FDG PET were found in 24 of 28 patients (86 %) with corresponding positive results with {sup 68}Ga-DOTA-LAN in 35 % and with {sup 68}Ga-DOTA-TOC in 29 %. The heterogeneous SSTR profile of TC tumour lesions needs to be evaluated using different SSTR PET tracers to characterize more closely the SSTR subtype affinities in patients with progressive TC in order to further stratify therapy with SSTR therapeutics. (orig.)

  19. Noninvasive imaging of transplanted living functional cells transfected with a reporter estrogen receptor gene

    International Nuclear Information System (INIS)

    Takamatsu, Shinji; Furukawa, Takako; Mori, Tetsuya; Yonekura, Yoshiharu; Fujibayashi, Yasuhisa

    2005-01-01

    The transplantation of functional cells such as dopaminergic cells into damaged tissue is now clinically ongoing, but at present the population of surviving cells at the transplantation site mostly cannot be noninvasively examined. To visualize surviving transplanted functional cells using a noninvasive method, we chose the estrogen receptor ligand binding domain (ERL) as a reporter molecule and 16α-[ 18 F]-fluoro-17β-estradiol (FES) for its ligand. We used a mouse embryonic stem (ES) cell line for recipient cells as a model. To obtain ES cells that constitutively or inducibly express ERL, we transfected two types of expression vectors into EB5 parental ES cell line using the lipofection method and obtained about 30 clones for each of the two types of transfectants. Then, to examine the expression level of ERL, we performed Western blotting analysis. Ligand uptake experiments were carried out using [ 3 H]-estradiol with or without excessive unlabeled estradiol for control cells and ERL transfectants. Each selected clone was also used for in vivo positron emission tomography (PET) imaging studies involving FES in nude mice transplanted with control cells and ERL transfectants. In some of the clones transfected with the inducible-type ERL gene, protein was expressed much higher than in the controls. However, constitutive-type ERL gene-transfected ES cells showed no protein production in spite of their gene expression activity being considerably high. All clones also expressed equal levels of the Oct-3/4 gene, a marker of pluripotency, in comparison with the parental cells. Also, the specific uptake of [ 3 H]-estradiol was over 30 times higher in inducer-treated ERL-expressing ES cells compared to untreated control cells. Finally, by performing dynamic PET imaging, we successfully visualized ERL-expressing teratomas using FES

  20. SPECT imaging of D2 dopamine receptors and endogenous dopamine release in mice

    International Nuclear Information System (INIS)

    Jongen, Cynthia; Bruin, Kora de; Booij, Jan; Beekman, Freek

    2008-01-01

    The dopamine D 2 receptor (D2R) is important in the mediation of addiction. [ 123 I]iodobenzamide (IBZM), a SPECT ligand for the D2R, has been used for in vivo studies of D2R availability in humans, monkeys, and rats. Although mouse models are important in the study of addiction, [ 123 I]IBZM has not been used in mice SPECT studies. This study evaluates the use of [ 123 I]IBZM for measuring D2R availability in mice. Pharmacokinetics of [ 123 I]IBZM in mice were studied with pinhole SPECT imaging after intravenous (i.v.) injection of [ 123 I]IBZM (20, 40, and 70 MBq). In addition, the ability to measure the release of endogenous dopamine after amphetamine administration with [ 123 I]IBZM SPECT was investigated. Thirdly, i.v. administration, the standard route of administration, and intraperitoneal (i.p.) administration of [ 123 I]IBZM were compared. Specific binding of [ 123 I]IBZM within the mouse striatum could be clearly visualized with SPECT. Peak specific striatal binding ratios were reached around 90 min post-injection. After amphetamine administration, the specific binding ratios of [ 123 I]IBZM decreased significantly (-27.2%; n=6; p=0.046). Intravenous administration of [ 123 I]IBZM led to significantly higher specific binding than i.p. administration of the same dose. However, we found that i.v. administration of a dose of 70 MBq [ 123 I]IBZM might result in acute ethanol intoxication because ethanol is used as a preparative aid for the routine production of [ 123 I]IBZM. Imaging of D2R availability and endogenous dopamine release in mice is feasible using [ 123 I]IBZM single pinhole SPECT. Using commercially produced [ 123 I]IBZM, a dose of 40 MBq injected i.v. can be recommended. (orig.)

  1. Fluorescence lifetime FRET imaging of receptor-ligand complexes in tumor cells in vitro and in vivo

    Science.gov (United States)

    Rudkouskaya, Alena; Sinsuebphon, Nattawut; Intes, Xavier; Mazurkiewicz, Joseph E.; Barroso, Margarida

    2017-02-01

    To guide the development of targeted therapies with improved efficacy and accelerated clinical acceptance, novel imaging methodologies need to be established. Toward this goal, fluorescence lifetime Förster resonance energy transfer (FLIM-FRET) imaging assays capitalize on the ability of antibodies or protein ligands to bind dimerized membrane bound receptors to measure their target engagement levels in cancer cells. Conventional FLIM FRET microscopy has been widely applied at visible wavelengths to detect protein-protein interactions in vitro. However, operation at these wavelengths restricts imaging quality and ability to quantitate lifetime changes in in vivo small animal optical imaging due to high auto-fluorescence and light scattering. Here, we have analyzed the uptake of iron-bound transferrin (Tf) probes into human breast cancer cells using FLIM-FRET microscopy in the visible and near-infrared (NIR) range. The development of NIR FLIM FRET microscopy allows for the use of quantitative lifetime-based molecular assays to measure drug-target engagement levels at multiple scales: from in vitro microscopy to in vivo small animal optical imaging (macroscopy). This novel approach can be extended to other receptors, currently targeted in oncology. Hence, lifetime-based molecular imaging can find numerous applications in drug delivery and targeted therapy assessment and optimization.

  2. Serotonin-1A receptor imaging in recurrent depression: replication and literature review

    Energy Technology Data Exchange (ETDEWEB)

    Drevets, Wayne C. [Mood and Anxiety Disorders Program, MINH Molecular Imaging Branch, Bethesda, MD 20892 (United States); Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 19213 (United States); Department of Radiology, University of Pittsburgh, Pittsburgh, PA 19213 (United States)], E-mail: drevetsw@mail.nih.gov; Thase, Michael E. [Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 19213 (United States); Department of Psychiatry, University of Pennsylvania, School of Medicine and Philadelphia Veterans Affairs Medical Center, Philadelphia, PA 19104 (United States); Moses-Kolko, Eydie L. [Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 19213 (United States); Price, Julie [Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 19213 (United States); Department of Radiology, University of Pittsburgh, Pittsburgh, PA 19213 (United States); Frank, Ellen; Kupfer, David J. [Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 19213 (United States); Mathis, Chester [Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 19213 (United States); Department of Radiology, University of Pittsburgh, Pittsburgh, PA 19213 (United States)

    2007-10-15

    Introduction: Serotonin-1A receptor (5-HT{sub 1A}R) function appears to be decreased in major depressive disorder (MDD) based on physiological responses to 5-HT{sub 1A}R agonists in vivo and to 5-HT{sub 1A}R binding in brain tissues postmortem or antemortem. We have previously assessed 5-HT{sub 1A}R binding potential (BP) in depression using positron emission tomography (PET) and [carbonyl-{sup 11}C]WAY-100635, and we have demonstrated reduced 5-HT{sub 1A}R BP in the mesiotemporal cortex (MTC) and raphe in depressives with primary recurrent familial mood disorders (n=12) versus controls (n=8) [Drevets WC, Frank E, Price JC, Kupfer DJ, Holt D, Greer PJ, Huang Y, Gautier C, Mathis C. PET imaging of serotonin 1A receptor binding in depression. Biol Psychiatry 1999;46(10):1375-87]. These findings were replicated by some, but not other, studies performed in depressed samples that were more generally selected using criteria for MDD. In the current study, we attempted to replicate our previous findings in an independent sample of subjects selected according to the criteria for primary recurrent depression applied in our prior study. Methods: Using PET and [carbonyl-{sup 11}C]WAY-100635, 5-HT{sub 1A}R BP was assessed in 16 depressed subjects and 8 healthy controls. Results: Mean 5-HT{sub 1A}R BP was reduced by 26% in the MTC (P < .005) and by 43% in the raphe (P < .001) in depressives versus controls. Conclusions: These data replicate our original findings, which showed that BP was reduced by 27% in the MTC (P < .025) and by 42% in the raphe (P < .02) in depression. The magnitudes of these reductions in 5-HT{sub 1A}R binding were similar to those found postmortem in 5-HT{sub 1A}R mRNA concentrations in the hippocampus in MDD [Lopez JF, Chalmers DT, Little KY, Watson SJ. Regulation of serotonin 1A, glucocorticoid, and mineralocorticoid receptor in rat and human hippocampus: implications for neurobiology of depression. Biol Psychiatry 1998;43:547-73] and in 5-HT{sub 1A

  3. Serotonin-1A receptor imaging in recurrent depression: replication and literature review

    International Nuclear Information System (INIS)

    Drevets, Wayne C.; Thase, Michael E.; Moses-Kolko, Eydie L.; Price, Julie; Frank, Ellen; Kupfer, David J.; Mathis, Chester

    2007-01-01

    Introduction: Serotonin-1A receptor (5-HT 1A R) function appears to be decreased in major depressive disorder (MDD) based on physiological responses to 5-HT 1A R agonists in vivo and to 5-HT 1A R binding in brain tissues postmortem or antemortem. We have previously assessed 5-HT 1A R binding potential (BP) in depression using positron emission tomography (PET) and [carbonyl- 11 C]WAY-100635, and we have demonstrated reduced 5-HT 1A R BP in the mesiotemporal cortex (MTC) and raphe in depressives with primary recurrent familial mood disorders (n=12) versus controls (n=8) [Drevets WC, Frank E, Price JC, Kupfer DJ, Holt D, Greer PJ, Huang Y, Gautier C, Mathis C. PET imaging of serotonin 1A receptor binding in depression. Biol Psychiatry 1999;46(10):1375-87]. These findings were replicated by some, but not other, studies performed in depressed samples that were more generally selected using criteria for MDD. In the current study, we attempted to replicate our previous findings in an independent sample of subjects selected according to the criteria for primary recurrent depression applied in our prior study. Methods: Using PET and [carbonyl- 11 C]WAY-100635, 5-HT 1A R BP was assessed in 16 depressed subjects and 8 healthy controls. Results: Mean 5-HT 1A R BP was reduced by 26% in the MTC (P 1A R binding were similar to those found postmortem in 5-HT 1A R mRNA concentrations in the hippocampus in MDD [Lopez JF, Chalmers DT, Little KY, Watson SJ. Regulation of serotonin 1A, glucocorticoid, and mineralocorticoid receptor in rat and human hippocampus: implications for neurobiology of depression. Biol Psychiatry 1998;43:547-73] and in 5-HT 1A R-binding capacity in the raphe in depressed suicide victims [Arango V, Underwood MD, Boldrini M, Tamir H, Kassir SA, Hsiung S, Chen JJ, Mann JJ. Serotonin 1A receptors, serotonin transporter binding and serotonin transporter mRNA expression in the brainstem of depressed suicide victims. Neuropsychopharmacology 2001;25(6):892-903]. There

  4. Dialkoxyquinazolines: Screening Epidermal Growth Factor ReceptorTyrosine Kinase Inhibitors for Potential Tumor Imaging Probes

    Energy Technology Data Exchange (ETDEWEB)

    VanBrocklin, Henry F.; Lim, John K.; Coffing, Stephanie L.; Hom,Darren L.; Negash, Kitaw; Ono, Michele Y.; Hanrahan, Stephen M.; Taylor,Scott E.; Vanderpoel, Jennifer L.; Slavik, Sarah M.; Morris, Andrew B.; Riese II, David J.

    2005-09-01

    The epidermal growth factor receptor (EGFR), a long-standingdrug development target, is also a desirable target for imaging. Sixteendialkoxyquinazoline analogs, suitable for labeling with positron-emittingisotopes, have been synthesized and evaluated in a battery of in vitroassays to ascertain their chemical and biological properties. Thesecharacteristics provided the basis for the adoption of a selection schemato identify lead molecules for labeling and in vivo evaluation. A newEGFR tyrosine kinase radiometric binding assay revealed that all of thecompounds possessed suitable affinity (IC50 = 0.4 - 51 nM) for the EGFRtyrosine kinase. All of the analogs inhibited ligand-induced EGFRtyrosine phosphorylation (IC50 = 0.8 - 20 nM). The HPLC-estimatedoctanol/water partition coefficients ranged from 2.0-5.5. Four compounds,4-(2'-fluoroanilino)- and 4-(3'-fluoroanilino)-6,7-diethoxyquinazoline aswell as 4-(3'-chloroanilino)- and4-(3'-bromoanilino)-6,7-dimethoxyquinazoline, possess the bestcombination of characteristics that warrant radioisotope labeling andfurther evaluation in tumor-bearing mice.

  5. IGF1 Receptor Targeted Theranostic Nanoparticles for Targeted and Image-Guided Therapy of Pancreatic Cancer.

    Science.gov (United States)

    Zhou, Hongyu; Qian, Weiping; Uckun, Fatih M; Wang, Liya; Wang, Y Andrew; Chen, Hongyu; Kooby, David; Yu, Qian; Lipowska, Malgorzata; Staley, Charles A; Mao, Hui; Yang, Lily

    2015-08-25

    Overcoming resistance to chemotherapy is a major and unmet medical challenge in the treatment of pancreatic cancer. Poor drug delivery due to stromal barriers in the tumor microenvironment and aggressive tumor biology are additional impediments toward a more successful treatment of pancreatic cancer. In attempts to address these challenges, we developed IGF1 receptor (IGF1R)-directed, multifunctional theranostic nanoparticles for targeted delivery of therapeutic agents into IGF1R-expressing drug-resistant tumor cells and tumor-associated stromal cells. These nanoparticles were prepared by conjugating recombinant human IGF1 to magnetic iron oxide nanoparticles (IONPs) carrying the anthracycline doxorubicin (Dox) as the chemotherapeutic payload. Intravenously administered IGF1-IONPs exhibited excellent tumor targeting and penetration in an orthotopic patient-derived xenograft (PDX) model of pancreatic cancer featuring enriched tumor stroma and heterogeneous cancer cells. IGF1R-targeted therapy using the theranostic IGF1-IONP-Dox significantly inhibited the growth of pancreatic PDX tumors. The effects of the intratumoral nanoparticle delivery and therapeutic responses in the orthotopic pancreatic PDX tumors could be detected by magnetic resonance imaging (MRI) with IONP-induced contrasts. Histological analysis showed that IGF1R-targeted delivery of Dox significantly inhibited cell proliferation and induced apoptotic cell death of pancreatic cancer cells. Therefore, further development of IGF1R-targeted theranostic IONPs and MRI-guided cancer therapy as a precision nanomedicine may provide the basis for more effective treatment of pancreatic cancer.

  6. Benchmarking the performance of fixed-image receptor digital radiography systems. Part 2: system performance metric.

    Science.gov (United States)

    Lee, Kam L; Bernardo, Michael; Ireland, Timothy A

    2016-06-01

    This is part two of a two-part study in benchmarking system performance of fixed digital radiographic systems. The study compares the system performance of seven fixed digital radiography systems based on quantitative metrics like modulation transfer function (sMTF), normalised noise power spectrum (sNNPS), detective quantum efficiency (sDQE) and entrance surface air kerma (ESAK). It was found that the most efficient image receptors (greatest sDQE) were not necessarily operating at the lowest ESAK. In part one of this study, sMTF is shown to depend on system configuration while sNNPS is shown to be relatively consistent across systems. Systems are ranked on their signal-to-noise ratio efficiency (sDQE) and their ESAK. Systems using the same equipment configuration do not necessarily have the same system performance. This implies radiographic practice at the site will have an impact on the overall system performance. In general, systems are more dose efficient at low dose settings.

  7. The preparation of 99Tcm-GSA and its instant lyophilized kit for hepatic receptor imaging

    International Nuclear Information System (INIS)

    Mao Yilei; Dong Yinv; Yang Wenjiang; Zhang Xianzhong; Tang Zhigang; Wang Xuebin

    2008-01-01

    The ligand GSA (diethylenetriamine pentaacetic acid-galactosyl-human serum albumin) was synthesized by introducing bifunctional chelator DTPA (diethylenetriamine pentaacetic acid) to human serum albumin (HSA) via DTPA anhydride first, and then coupling galactosyl units (2-imino-2-methoxyethyl-thio-galactose) to DTPA-HSA. GSA was labeled with 99 Tc m by using SnCl 2 as reductant and the labeling conditions of 99 Tc m -GSA were optimized. Lyophilized kit of GSA was also developed for instant preparing of 99 Tc m - GSA. The labeling yields in excess of 96% by using both of liquid and lyophilized labeling methods. Biodistribution of 99 Tc m -GSA was investigated in both normal and liver-injury model mice. 99 Tc m -GSA showed high liver uptake in normal mice (>70%ID·g -1 at 30 min after injection). The liver uptake in liver-injury model mice is lower than that of in nor- mal mice (P=0.0324). The promising biological properties of 99 Tc m -GSA combined with the development of reliable and instant lyophilized GSA kit afford the opportunity of liver receptor imaging for routine clinical assessment of hepatocyte function. (authors)

  8. Dialkoxyquinazolines: Screening Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors for Potential Tumor Imaging Probes

    International Nuclear Information System (INIS)

    VanBrocklin, Henry F.; Lim, John K.; Coffing, Stephanie L.; Hom, Darren L.; Negash, Kitaw; Ono, Michele Y.; Hanrahan, Stephen M.; Taylor, Scott E.; Vanderpoel, Jennifer L.; Slavik, Sarah M.; Morris, Andrew B.; Riese II, David J.

    2005-01-01

    The epidermal growth factor receptor (EGFR), a long-standing drug development target, is also a desirable target for imaging. Sixteen dialkoxyquinazoline analogs, suitable for labeling with positron-emitting isotopes, have been synthesized and evaluated in a battery of in vitro assays to ascertain their chemical and biological properties. These characteristics provided the basis for the adoption of a selection schema to identify lead molecules for labeling and in vivo evaluation. A newEGFR tyrosine kinase radiometric binding assay revealed that all of the compounds possessed suitable affinity (IC50 = 0.4 - 51 nM) for the EGFR tyrosine kinase. All of the analogs inhibited ligand-induced EGFR tyrosine phosphorylation (IC50 = 0.8 - 20 nM). The HPLC-estimated octanol/water partition coefficients ranged from 2.0-5.5. Four compounds,4-(2'-fluoroanilino)- and 4-(3'-fluoroanilino)-6,7-diethoxyquinazoline as well as 4-(3'-chloroanilino)- and4-(3'-bromoanilino)-6,7-dimethoxyquinazoline, possess the best combination of characteristics that warrant radioisotope labeling and further evaluation in tumor-bearing mice

  9. Molecular imaging with 68Ga-SSTR PET/CT and correlation to immunohistochemistry of somatostatin receptors in neuroendocrine tumours

    International Nuclear Information System (INIS)

    Kaemmerer, Daniel; Haugvik, Sven-Petter; Hommann, Merten; Peter, Luisa; Lupp, Amelie; Schulz, Stefan; Saenger, Joerg; Prasad, Vikas; Kulkarni, Harshad; Baum, Richard Paul

    2011-01-01

    Somatostatin receptors (SSTR) are known for an overexpression in gastroenteropancreatic neuroendocrine tumours (GEP-NET). The aim of the present study was to find out if the receptor density predicted by the semi-quantitative parameters generated from the static positron emission tomography (PET/CT) correlated with the in vitro immunohistochemistry using a novel rabbit monoclonal anti-SSTR2A antibody (clone UMB-1) for specific SSTR2A immunohistochemistry and polyclonal antibodies for SSTR1 and 3-5. Overall 14 surgical specimens generated from 34 histologically documented GEP-NET patients were correlated with the preoperative 68 Ga-DOTA-NOC PET/CT. Quantitative assessment of the receptor density was done using the immunoreactive score (IRS) of Remmele and Stegner; the additional 4-point IRS classification for immunohistochemistry and standardized uptake values (SUV max and SUV mean ) were used for PET/CT. The IRS for SSTR2A and SSTR5 correlated highly significant with the SUV max on the PET/CT (p mean (p max on the 68 Ga-DOTA-NOC PET/CT scans is concordant with the affinity profile of 68 Ga-DOTA-NOC to the SSTR subtypes and demonstrates the excellent qualification of somatostatin analogues in the diagnostics of NET. This study correlating somatostatin receptor imaging using 68 Ga-DOTA-NOC PET/CT with immunohistochemically analysed SSTR also underlines the approval of therapy using somatostatin analogues, follow-up imaging as well as radionuclide therapy. (orig.)

  10. Development of an image analysis screen for estrogen receptor alpha (ERα) ligands through measurement of nuclear translocation dynamics.

    Science.gov (United States)

    Dull, Angie; Goncharova, Ekaterina; Hager, Gordon; McMahon, James B

    2010-11-01

    We have developed a robust high-content assay to screen for novel estrogen receptor alpha (ERα) agonists and antagonists by quantitation of cytoplasmic to nuclear translocation of an estrogen receptor chimera in 384-well plates. The screen utilizes a green fluorescent protein tagged-glucocorticoid/estrogen receptor (GFP-GRER) chimera which consisted of the N-terminus of the glucocorticoid receptor fused to the human ER ligand binding domain. The GFP-GRER exhibited cytoplasmic localization in the absence of ERα ligands, and translocated to the nucleus in response to stimulation with ERα agonists or antagonists. The BD Pathway 435 imaging system was used for image acquisition, analysis of translocation dynamics, and cytotoxicity measurements. The assay was validated with known ERα agonists and antagonists, and the Library of Pharmacologically Active Compounds (LOPAC 1280). Additionally, screening of crude natural product extracts demonstrated the robustness of the assay, and the ability to quantitate the effects of toxicity on nuclear translocation dynamics. The GFP-GRER nuclear translocation assay was very robust, with z' values >0.7, CVs screening of natural product extracts. This assay has been developed for future primary screening of synthetic, pure natural products, and natural product extracts libraries available at the National Cancer Institute at Frederick. Copyright © 2010 Elsevier Ltd. All rights reserved.

  11. Synthesis and Preliminary Evaluation of a 2-Oxoquinoline Carboxylic Acid Derivative for PET Imaging the Cannabinoid Type 2 Receptor

    Directory of Open Access Journals (Sweden)

    Linjing Mu

    2014-03-01

    Full Text Available Cannabinoid receptor subtype 2 (CB2 has been shown to be up-regulated in activated microglia and therefore plays an important role in neuroinflammatory and neurodegenerative diseases such as multiple sclerosis, amyotrophic lateral sclerosis and Alzheimer’s disease. The CB2 receptor is therefore considered as a very promising target for therapeutic approaches as well as for imaging. A promising 2-oxoquinoline derivative designated KP23 was synthesized and radiolabeled and its potential as a ligand for PET imaging the CB2 receptor was evaluated. [11C]KP23 was obtained in 10%–25% radiochemical yield (decay corrected and 99% radiochemical purity. It showed high stability in phosphate buffer, rat and mouse plasma. In vitro autoradiography of rat and mouse spleen slices, as spleen expresses a high physiological expression of CB2 receptors, demonstrated that [11C]KP23 exhibits specific binding towards CB2. High spleen uptake of [11C]KP23 was observed in dynamic in vivo PET studies with Wistar rats. In conclusion, [11C]KP23 showed promising in vitro and in vivo characteristics. Further evaluation with diseased animal model which has higher CB2 expression levels in the brain is warranted.

  12. Olanzapine-Induced Diabetic Ketoacidosis and Neuroleptic Malignant Syndrome with Rhabdomyolysis: A Case Report

    Directory of Open Access Journals (Sweden)

    Young Kyoung Sa

    2013-03-01

    Full Text Available Atypical antipsychotics have replaced conventional antipsychotics in the treatment of schizophrenia because they have less of a propensity to cause undesirable neurologic adverse events including extrapyramidal symptoms, tardive dyskinesia, and neuroleptic malignant syndrome (NMS. However, atypical antipsychotics have been known to result in various metabolic complications such as impaired glucose tolerance, diabetes and even diabetic ketoacidosis (DKA. In addition, a number of NMS cases have been reported in patients treated with atypical antipsychotics, although the absolute incidence of neurologic side effects is currently significantly low. Here, we report a patient who simultaneously developed DKA, acute renal failure and NMS with rhabdomyolysis after olanzapine treatment. Olanzapine-induced metabolic complications and NMS were dramatically improved with cessation of the olanzapine treatment and initiation of supportive management including fluid therapy, hemodialysis, and intensive glycemic control using insulin. At short-term follow-up, insulin secretion was markedly recovered as evidenced by a restoration of serum C-peptide level, and the patient no longer required any hypoglycemic medications. Despite the dramatic increase in the use of atypical antipsychotics treatment, individualized treatments along with careful monitoring may be prudent for high risk or vulnerable patients in order to avoid the development of metabolic side effects.

  13. Skeletal effects of central nervous system active drugs: anxiolytics, sedatives, antidepressants, lithium and neuroleptics.

    Science.gov (United States)

    Vestergaard, Peter

    2008-09-01

    Many central nervous system active drugs can alter postural balance, increasing the risk of fractures. Anxiolytics and sedatives include the benzodiazepines, and these have been associated with a limited increase in the risk of fractures, even at low doses, probably from an increased risk of falls. No systematic differences have been shown between benzodiazepines with long and short half-lives. Although the increase in risk of fractures was limited, care must still be taken when prescribing for older fall-prone subjects at risk of osteoporosis. Neuroleptics may be associated with a decrease in bone mineral density and a very limited increase in fracture risk. Antidepressants are associated with a dose-dependent increase in the risk of fractures. The increase in relative risk of fractures seems to be larger with selective serotonin reuptake inhibitors (SSRIs) than with tricyclic antidepressants. The reason for this is not known but may be linked to serotonin effects on bone cells and the risk of falls. With the wide use of SSRIs, more research is needed. Lithium is associated with a decrease in the risk of fractures. This may be linked to its effects on the Wnt glycoprotein family, which is a specialised signalling system for certain cell types.

  14. Paliperidone Inducing Concomitantly Syndrome of Inappropriate Antidiuretic Hormone, Neuroleptic Malignant Syndrome, and Rhabdomyolysis

    Directory of Open Access Journals (Sweden)

    Jaspinder Kaur

    2016-01-01

    Full Text Available Paliperidone, an active metabolite of risperidone, is a new atypical antipsychotic agent. Syndrome of inappropriate antidiuretic hormone (SIADH, neuroleptic malignant syndrome (NMS, and rhabdomyolysis are the uncommon side effects of psychotropic drugs. We report a case of 35-year-old male with schizoaffective disorder who was admitted for acute-on-chronic exacerbation of his psychotic disorder for which intramuscular paliperidone 234 mg injection was given. Two days later, the patient developed hyponatremic seizures secondary to SIADH which was treated with hypertonic saline. On the third day, he developed high grade fever and severe muscle rigidity with raised creatine phosphokinase (CPK and liver enzymes levels. He was treated with dantrolene 100 mg, bromocriptine 2.5 mg, and lorazepam 2 mg. Our patient required management of the three rare conditions following treatment with paliperidone. This case highlights the need for health care providers to be aware of the rare, potentially life threatening but preventable hyponatremia, NMS, and rhabdomyolysis as a possible adverse effect of paliperidone.

  15. [Applying Neuman's Systems Model to a neuroleptic malignant syndrome psychiatric patient and his caregiver].

    Science.gov (United States)

    Wang, Shu-Mi; Lai, Chien-Yu

    2010-04-01

    This article describes a nurse's experience using Neuman's Systems Model to care for a chronic psychiatric patient and his caregiver. The patient was diagnosed as suffering from neuroleptic malignant syndrome (NMS). Nursing care described in this article was administered from October 23 to December 4, 2007. The patient developed NMS in the third month of a three-month period of hospitalization, which endangered his life as well as the health of his caregiver. Nursing care was provided to the patient and his caregiver based on Neuman's Systems Model, which included assessments of intrapersonal, interpersonal, and extra-personal forces as well as of environmental factors affecting the health of the patient and his caregiver. The four nursing care issues identified included: existing self-care deficit, sensory/perceptual alteration, sleep pattern disturbance, and caregiver role strain. Following Neuman's systems model, primary, secondary, and tertiary prevention were used to strengthen the flexible lines of defense, internal lines of resistance, and supporting existing strengths of both patient and caregiver, as well as to conserve client system energy. Significant improvements in patient and caregiver abilities were apparent in nursing intervention outcomes. This experience shows the Neuman's systems model to be an efficient model in psychiatric nursing care.

  16. Olanzapine versus typical neuroleptics for schizophrenia: evaluation of social and economic costs

    Directory of Open Access Journals (Sweden)

    Giorgio Mariani

    2006-06-01

    Full Text Available An important number of publications is reporting results from health outcomes studies comparing atypical antipsychotics (AA with typical neuroleptics (TN over 1 year of observation. Our study has prolonged the period observation of the economical and social outcomes to 4 years: 31 patients with schizophrenia were observed retrospectively during two years of TN treatment and then followed during 2 more years of olanzapine treatment after naturalistic switch. The results show a general reduction of health care interventions (territory and hospital during the olanzapine treatment period. Global costs during olanzapine treatment were lower than during TN treatment (10506 euros with TN vs 6193 euros with olanzapine over 2 years. The social outcome, measured through the registration of the number of working days in the two periods of the study (retrospective with TN and prospective with olanzapine, was better during olanzapine treatment, probably due to increased patient compliance to the rehabilitative activities offered by the Department of Mental Health. In our experience, olanzapine appeared to dominate TN treatment, as its higher acquisition costs were offset by the reduction of territorial and nosocomial health care interventions over two years of observation, and associated with higher involvement in rehabilitative and social activities.

  17. Targeted functional imaging of estrogen receptors with 99mTc-GAP-EDL

    International Nuclear Information System (INIS)

    Takahashi, Nobukazu; Yang, David J.; Kohanim, Saady; Oh, Chang-Sok; Yu, Dong-Fang; Azhdarinia, Ali; Kurihara, Hiroaki; Kim, E.E.; Zhang, Xiaochun; Chang, Joe Y.

    2007-01-01

    To evaluate the feasibility of using 99m Tc-glutamate peptide-estradiol in functional imaging of estrogen receptor-positive [ER(+)] diseases. 3-Aminoethyl estradiol (EDL) was conjugated to glutamate peptide (GAP) to yield GAP-EDL. Cellular uptake studies of 99m Tc-GAP-EDL were conducted in ER(+) cell lines (MCF-7, 13762 and T47D). To demonstrate whether GAP-EDL increases MAP kinase activation, Western blot analysis of GAP-EDL was performed in 13762 cells. Biodistribution was conducted in nine rats with 13762 breast tumors at 0.5-4 h. Each rat was administered 99m Tc-GAP-EDL. Two animal models (rats and rabbits) were created to ascertain whether tumor uptake of 99m Tc-GAP-EDL was via an ER-mediated process. In the tumor model, breast tumor-bearing rats were pretreated with diethylstilbestrol (DES) 1 h prior to receiving 99m Tc-GAP-EDL. In the endometriosis model, part of the rabbit uterine tissue was dissected and grafted to the peritoneal wall. The rabbit was administered with 99m Tc-GAP-EDL. There was a 10-40% reduction in uptake of 99m Tc-GAP-EDL in cells treated with DES or tamoxifen compared with untreated cells. Western blot analysis showed an ERK1/2 phosphorylation process with GAP-EDL. Biodistribution studies showed that tumor uptake and tumor-to-muscle count density ratio in 99m Tc-GAP-EDL groups were significantly higher than those in 99m Tc-GAP groups at 4 h. Among 99m Tc-GAP-EDL groups, region of interest analysis of images showed that tumor-to muscle ratios were decreased in blocking groups. In the endometriosis model, the grafted uterine tissue could be visualized by 99m Tc-GAP-EDL. Cellular or tumor uptake of 99m Tc-GAP-EDL occurs via an ER-mediated process. 99m Tc-GAP-EDL is a useful agent for imaging functional ER(+) disease. (orig.)

  18. In vivo imaging of brain androgen receptors in rats: a [18F]FDHT PET study

    International Nuclear Information System (INIS)

    Khayum, M.A.; Doorduin, J.; Antunes, I.F.; Kwizera, C.; Zijlma, R.; Boer, J.A. den; Dierckx, R.A.J.O.; Vries, E.F.J. de

    2015-01-01

    Introduction: Steroid hormones like androgens play an important role in the development and maintenance of several brain functions. Androgens can act through androgen receptors (AR) in the brain. This study aims to demonstrate the feasibility of positron emission tomography (PET) with 16β-[ 18 F]fluoro-5α-dihydrotestosterone ([ 18 F]FDHT) to image AR expression in the brain. Methods: Male Wistar rats were either orchiectomized to inhibit endogenous androgen production or underwent sham-surgery. Fifteen days after surgery, rats were subjected to a 90-min dynamic [ 18 F]FDHT PET scan with arterial blood sampling. In a subset of orchiectomized rats, 1 mg/kg dihydrotestosterone was co-injected with the tracer in order to saturate the AR. Plasma samples were analyzed for the presence of radioactive metabolites by radio-TLC. Pharmacokinetic modeling was performed to quantify brain kinetics of the tracer. After the PET scan, the animals were terminated for ex-vivo biodistribution. Results: PET imaging and ex vivo biodistribution studies showed low [ 18 F]FDHT uptake in all brain regions, except pituitary. [ 18 F]FDHT uptake in the surrounding cranial bones was high and increased over time. [ 18 F]FDHT was rapidly metabolized in rats. Metabolism was significantly faster in orchiectomized rats than in sham-orchiectomized rats. Quantitative analysis of PET data indicated substantial spill-over of activity from cranial bones into peripheral brain regions, which prevented further analysis of peripheral brain regions. Logan graphical analysis and kinetic modeling using 1- and 2-tissue compartment models showed reversible and homogenously distributed tracer uptake in central brain regions. [ 18 F]FDHT uptake in the brain could not be blocked by endogenous androgens or administration of dihydrotestosterone. Conclusion: The results of this study indicate that imaging of AR availability in rat brain with [ 18 F]FDHT PET is not feasible. The low AR expression in the brain, the

  19. Targeted functional imaging of estrogen receptors with {sup 99m}Tc-GAP-EDL

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Nobukazu; Yang, David J.; Kohanim, Saady; Oh, Chang-Sok; Yu, Dong-Fang; Azhdarinia, Ali; Kurihara, Hiroaki; Kim, E.E. [The University of Texas M.D. Anderson Cancer Center, Division of Diagnostic Imaging, Houston, TX (United States); Zhang, Xiaochun; Chang, Joe Y. [The University of Texas M.D. Anderson Cancer Center, Division of Radiation Oncology, Houston, TX (United States)

    2007-03-15

    To evaluate the feasibility of using {sup 99m}Tc-glutamate peptide-estradiol in functional imaging of estrogen receptor-positive [ER(+)] diseases. 3-Aminoethyl estradiol (EDL) was conjugated to glutamate peptide (GAP) to yield GAP-EDL. Cellular uptake studies of {sup 99m}Tc-GAP-EDL were conducted in ER(+) cell lines (MCF-7, 13762 and T47D). To demonstrate whether GAP-EDL increases MAP kinase activation, Western blot analysis of GAP-EDL was performed in 13762 cells. Biodistribution was conducted in nine rats with 13762 breast tumors at 0.5-4 h. Each rat was administered {sup 99m}Tc-GAP-EDL. Two animal models (rats and rabbits) were created to ascertain whether tumor uptake of {sup 99m}Tc-GAP-EDL was via an ER-mediated process. In the tumor model, breast tumor-bearing rats were pretreated with diethylstilbestrol (DES) 1 h prior to receiving {sup 99m}Tc-GAP-EDL. In the endometriosis model, part of the rabbit uterine tissue was dissected and grafted to the peritoneal wall. The rabbit was administered with {sup 99m}Tc-GAP-EDL. There was a 10-40% reduction in uptake of {sup 99m}Tc-GAP-EDL in cells treated with DES or tamoxifen compared with untreated cells. Western blot analysis showed an ERK1/2 phosphorylation process with GAP-EDL. Biodistribution studies showed that tumor uptake and tumor-to-muscle count density ratio in {sup 99m}Tc-GAP-EDL groups were significantly higher than those in {sup 99m}Tc-GAP groups at 4 h. Among {sup 99m}Tc-GAP-EDL groups, region of interest analysis of images showed that tumor-to muscle ratios were decreased in blocking groups. In the endometriosis model, the grafted uterine tissue could be visualized by {sup 99m}Tc-GAP-EDL. Cellular or tumor uptake of {sup 99m}Tc-GAP-EDL occurs via an ER-mediated process. {sup 99m}Tc-GAP-EDL is a useful agent for imaging functional ER(+) disease. (orig.)

  20. Evaluation of transcriptional activity of the oestrogen receptor with sodium iodide symporter as an imaging reporter gene.

    Science.gov (United States)

    Kang, Joo Hyun; Chung, June-Key; Lee, Yong Jin; Kim, Kwang Il; Jeong, Jae Min; Lee, Dong Soo; Lee, Myung Chul

    2006-10-01

    Oestrogen receptors are ligand-dependent transcription factors whose activity is modulated either by oestrogens or by an alternative signalling pathway. Oestrogen receptors interact via a specific DNA-binding domain, the oestrogen responsive element (ERE), in the promoter region of sensitive genes. This binding leads to an initiation of gene expression and hormonal effects. To determine the transcriptional activity of the oestrogen receptor, we developed a molecular imaging system using sodium iodide symporter (NIS) as a reporter gene. The NIS reporter gene was placed under the control of an artificial ERE derived from pERE-TA-SEAP and named as pERE-NIS. pERE-NIS was transferred to MCF-7, human breast cancer cells, which highly expressed oestrogen receptor-alpha with lipofectamine. Stably expressing cells were generated by selection with G418 for 14 days. After treatment of 17beta-oestradiol and tamoxifen with serial doses, the (125)I uptake was measured for the determination of NIS expression. The inhibition of NIS activity was performed with 50 micromol x l(-1) potassium perchlorate. The MCF7/pERE-NIS treated with 17beta-oestradiol accumulated (125)I up to 70-80% higher than did non-treated cells. NIS expression was increased according to increasing doses of 17beta-oestradiol. MCF7/pERE-NIS treated with tamoxifen also accumulated (125)I up to 50% higher than did non-treated cells. Potassium perchlorate completely inhibited (125)I uptake. When MDA-MB231 cells, the oestrogen receptor-negative breast cancer cells, were transfected with pERE-NIS, (125)I uptake of MDA-MB-231/pERE-NIS did not increase. This pERE-NIS reporter system is sufficiently sensitive for monitoring transcriptional activity of the oestrogen receptor. Therefore, cis-enhancer reporter systems with ERE will be applicable to the development of a novel selective oestrogen receptor modulator with low toxicity and high efficacy.

  1. Cholinergic Receptor Binding in Alzheimer Disease and Healthy Aging: Assessment In Vivo with Positron Emission Tomography Imaging.

    Science.gov (United States)

    Sultzer, David L; Melrose, Rebecca J; Riskin-Jones, Hannah; Narvaez, Theresa A; Veliz, Joseph; Ando, Timothy K; Juarez, Kevin O; Harwood, Dylan G; Brody, Arthur L; Mandelkern, Mark A

    2017-04-01

    To compare regional nicotinic cholinergic receptor binding in older adults with Alzheimer disease (AD) and healthy older adults in vivo and to assess relationships between receptor binding and clinical symptoms. Using cross-sectional positron emission tomography (PET) neuroimaging and structured clinical assessment, outpatients with mild to moderate AD (N = 24) and healthy older adults without cognitive complaints (C group; N = 22) were studied. PET imaging of α4β2* nicotinic cholinergic receptor binding using 2-[ 18 F]fluoro-3-(2(S)azetidinylmethoxy)pyridine (2FA) and clinical measures of global cognition, attention/processing speed, verbal memory, visuospatial memory, and neuropsychiatric symptoms were used. 2FA binding was lower in the AD group compared with the C group in the medial thalamus, medial temporal cortex, anterior cingulate, insula/opercula, inferior caudate, and brainstem (p healthy older adults, lower receptor binding may be associated with slower processing speed. Cholinergic receptor binding in vivo may reveal links to other key brain changes associated with aging and AD and may provide a potential molecular treatment target. Published by Elsevier Inc.

  2. 124I-Epidepride: A PET radiotracer for extended imaging of dopamine D2/D3 receptors

    International Nuclear Information System (INIS)

    Pandey, Suresh; Venugopal, Archana; Kant, Ritu; Coleman, Robert; Mukherjee, Jogeshwar

    2014-01-01

    Objectives: A new radiotracer, 124 I-epidepride, has been developed for the imaging of dopamine D2/3 receptors (D2/3Rs). 124 I-Epidepride (half-life of 124 I = 4.2 days) allows imaging over extended periods compared to 18 F-fallypride (half-life of 18 F = 0.076 days) and may maximize visualization of D2/3Rs in the brain and pancreas (allowing clearance from adjacent organs). D2/3Rs are also present in pancreatic islets where they co-localize with insulin to produce granules and may serve as a surrogate marker for imaging diabetes. Methods: 124 I-Epidepride was synthesized using N-[[(2S)-1-ethylpyrrolidin-2-yl]methyl]-5-tributyltin-2, 3-dimethoxybenzamide and 124 I-iodide under no carrier added condition. Rats were used for in vitro and in vivo imaging. Brain slices were incubated with 124 I-epidepride (0.75 μCi/cc) and nonspecific binding measured with 10 μM haloperidol. Autoradiograms were analyzed by OptiQuant. 124 I-Epidepride (0.2 to 0.3 mCi, iv) was administered to rats and brain uptake at 3 hours, 24 hours, and 48 hours post injection was evaluated. Results: 124 I-Epidepride was obtained with 50% radiochemical yield and high radiochemical purity (> 95%). 124 I-Epidepride localized in the striatum with a striatum to cerebellum ratio of 10. Binding was displaced by dopamine and haloperidol. Brain slices demonstrated localization of 124 I-epidepride up until 48 hours in the striatum. However, the extent of binding was reduced significantly. Conclusions: 124 I-Epidepride is a new radiotracer suitable for extended imaging of dopamine D2/3 receptors and may have applications in imaging of receptors in the brain and monitoring pancreatic islet cell grafting

  3. Urokinase-type plasminogen activator receptor (uPAR) as a promising new imaging target

    DEFF Research Database (Denmark)

    Persson, Morten; Kjaer, Andreas

    2013-01-01

    modalities such as optical imaging, magnetic resonance imaging, single photon emission computer tomography (SPECT) and positron emission topography (PET). In this review, we will discuss recent advances in the development of uPAR-targeted imaging ligands according to imaging modality. In addition, we...... will discuss the potential future clinical application for uPAR imaging as a new imaging biomarker....

  4. Biodistribution and dosimetry in humans of two inverse agonists to image cannabinoid CB1 receptors using positron emission tomography

    International Nuclear Information System (INIS)

    Terry, Garth E.; Hirvonen, Jussi; Liow, Jeih-San; Seneca, Nicholas; Morse, Cheryl L.; Pike, Victor W.; Innis, Robert B.; Tauscher, Johannes T.; Schaus, John M.; Phebus, Lee; Felder, Christian C.; Halldin, Christer

    2010-01-01

    Cannabinoid subtype 1 (CB 1 ) receptors are found in nearly every organ in the body, may be involved in several neuropsychiatric and metabolic disorders, and are therefore an active target for pharmacotherapy and biomarker development. We recently reported brain imaging of CB 1 receptors with two PET radioligands: 11 C-MePPEP and 18 F-FMPEP-d 2 . Here we describe the biodistribution and dosimetry estimates for these two radioligands. Seven healthy subjects (four men and three women) underwent whole-body PET scans for 120 min after injection with 11 C-MePPEP. Another seven healthy subjects (two men and five women) underwent whole-body PET scans for 300 min after injection with 18 F-FMPEP-d 2 . Residence times were acquired from regions of interest drawn on tomographic images of visually identifiable organs for both radioligands and from radioactivity excreted in urine for 18 F-FMPEP-d 2 . The effective doses of 11 C-MePPEP and 18 F-FMPEP-d 2 are 4.6 and 19.7 μSv/MBq, respectively. Both radioligands demonstrated high uptake of radioactivity in liver, lung, and brain shortly after injection and accumulated radioactivity in bone marrow towards the end of the scan. After injection of 11 C-MePPEP, radioactivity apparently underwent hepatobiliary excretion only, while radioactivity from 18 F-FMPEP-d 2 showed both hepatobiliary and urinary excretion. 11 C-MePPEP and 18 F-FMPEP-d 2 yield an effective dose similar to other PET radioligands labeled with either 11 C or 18 F. The high uptake in brain confirms the utility of these two radioligands to image CB 1 receptors in brain, and both may also be useful to image CB 1 receptors in the periphery. (orig.)

  5. Synthesis and evaluation of new imaging agent for central nicotinic acetylcholine receptor α7 subtype

    International Nuclear Information System (INIS)

    Ogawa, Mikako; Nishiyama, Shingo; Tsukada, Hideo; Hatano, Kentaro; Fuchigami, Takeshi; Yamaguchi, Hiroshi; Matsushima, Yoshitaka; Ito, Kengo; Magata, Yasuhiro

    2010-01-01

    Introduction: The nicotinic acetylcholine receptor (nAChR) α7 subtype (α 7 nAChR) is one of the major nAChR subtypes in the brain. We synthesized C-11 labeled α 7 nAChR ligands, (R)-2-[ 11 C]methylamino-benzoic acid 1-aza-bicyclo[2.2.2]oct-3-yl ester ([ 11 C](R)-MeQAA) and its isomer (S)-[ 11 C]MeQAA, for in vivo investigation with positron emission tomography (PET). Then, the potential of (R)- and (S)-[ 11 C]MeQAA for in vivo imaging of α 7 nAChR in the brain was evaluated in mice and monkeys. Methods: The binding affinity for α 7 nAChR was measured using rat brain. Biodistribution and in vivo receptor blocking studies were undertaken in mice. Dynamic PET scans were performed in conscious monkeys. Results: The affinity for α 7 nAChR was 41 and 182 nM for (R)- and (S)-MeQAA, respectively. The initial uptake in the mouse brain was high ([ 11 C](R)-MeQAA: 7.68 and [ 11 C](S)-MeQAA: 6.65 %dose/g at 5 min). The clearance of [ 11 C](R)-MeQAA was slow in the hippocampus (α 7 nAChR-rich region) but was rapid in the cerebellum (α 7 nAChR-poor region). On the other hand, the clearance was fast for [ 11 C](S)-MeQAA in all regions. The brain uptake of [ 11 C](R)-MeQAA was decreased by methyllycaconitine (α 7 nAChR antagonist) treatment. In monkeys, α 7 nAChRs were highly distributed in the thalamus and cortex but poorly distributed in the cerebellum. The high accumulation was observed in the cortex and thalamus for [ 11 C](R)-MeQAA, while the uptake was rather homogeneous for [ 11 C](S)-MeQAA. Conclusions: [ 11 C](R)-MeQAA was successfully synthesized and showed high uptake to the brain. However, since the in vivo selectivity for α 7 nAChR was not enough, further PET kinetic analysis or structure optimization is needed for specific visualization of brain α 7 nAChRs in vivo.

  6. Fundamental considerations in the design of fluorine-18 labeled progestins and androgens as imaging agents for receptor-positive tumors of the breast and prostate

    International Nuclear Information System (INIS)

    Brandes, S.J.; Katzenellenbogen, J.A.

    1988-01-01

    A review is given of the structural and functional features which are important in the design and development of imaging agents for the progesterone receptor (PR) and the androgen receptor (AR) directed towards imaging receptor-positive tumors in the breast and prostate respectively. In particular the effects of various substituents on the biological activities and homologous receptor binding of progesterone, testosterone, nortestosterone and dihydrotestosterone are discussed. The effect of fluorine substitution on the affinities of progestins and androgens for their respective receptors is described. Other ligand systems that have high affinity for AR and PR and which may provide good bases for the design of fluorine-substituted imaging agents are also discussed. Finally, previous studies with radiolabelled progestins and androgens are described. (U.K.)

  7. Triple-color super-resolution imaging of live cells: resolving submicroscopic receptor organization in the plasma membrane.

    Science.gov (United States)

    Wilmes, Stephan; Staufenbiel, Markus; Lisse, Domenik; Richter, Christian P; Beutel, Oliver; Busch, Karin B; Hess, Samuel T; Piehler, Jacob

    2012-05-14

    In living color: efficient intracellular covalent labeling of proteins with a photoswitchable dye using the HaloTag for dSTORM super-resolution imaging in live cells is described. The dynamics of cellular nanostructures at the plasma membrane were monitored with a time resolution of a few seconds. In combination with dual-color FPALM imaging, submicroscopic receptor organization within the context of the membrane skeleton was resolved. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Time-Resolved Spectroscopy and Near Infrared Imaging for Prostate Cancer Detection: Receptor-targeted and Native Biomarker

    Science.gov (United States)

    Pu, Yang

    Optical spectroscopy and imaging using near-infrared (NIR) light provides powerful tools for non-invasive detection of cancer in tissue. Optical techniques are capable of quantitative reconstructions maps of tissue absorption and scattering properties, thus can map in vivo the differences in the content of certain marker chromophores and/or fluorophores in normal and cancerous tissues (for example: water, tryptophan, collagen and NADH contents). Potential clinical applications of optical spectroscopy and imaging include functional tumor detection and photothermal therapeutics. Optical spectroscopy and imaging apply contrasts from intrinsic tissue chromophores such as water, collagen and NADH, and extrinsic optical contrast agents such as Indocyanine Green (ICG) to distinguish disease tissue from the normal one. Fluorescence spectroscopy and imaging also gives high sensitivity and specificity for biomedical diagnosis. Recent developments on specific-targeting fluorophores such as small receptor-targeted dye-peptide conjugate contrast agent offer high contrast between normal and cancerous tissues hence provide promising future for early tumour detection. This thesis focus on a study to distinguish the cancerous prostate tissue from the normal prostate tissues with enhancement of specific receptor-targeted prostate cancer contrast agents using optical spectroscopy and imaging techniques. The scattering and absorption coefficients, and anisotropy factor of cancerous and normal prostate tissues were investigated first as the basis for the biomedical diagnostic and optical imaging. Understanding the receptors over-expressed prostate cancer cells and molecular target mechanism of ligand, two small ICG-derivative dye-peptides, namely Cypate-Bombesin Peptide Analogue Conjugate (Cybesin) and Cypate-Octreotate Peptide Conjugate (Cytate), were applied to study their clinical potential for human prostate cancer detection. In this work, the steady-state and time

  9. Imaging of D2 dopamine receptors of patients with Parkinson's disease using SPECT and 131I-IBZM

    International Nuclear Information System (INIS)

    Zhang Wei; Wang Jian; Jiang Yuping; Lu Chuanzhen

    2001-01-01

    Objective: To evaluate the usefulness of SPECT with 131 I-IBZM in imaging of D 2 Dopamine receptors in patients with Parkinson's disease (PD). Methods: Six patients which early unmedicated PD, six patients with moderate or advanced PD treated with long-term oral L-Dopa and Four control subjects were investigated with SPECT using 131 I-IBZM as dopamine receptor ligand. The ratio of basal ganglia to occipital cortex (BG/OC) and ratio of basal ganglia to frontal cortex (BG/FC) were calculated as semiquantitative parameter of striatal D 2 dopamine receptor's function. Results: The SPECT images revealed high uptake of IBZM in the basal ganglia. In the early unmedicated PD group, the BG/PC and BG/FC rates were significantly higher in the striatum contralateral to the parkinsonism. In the moderate or advanced PD group, no significant differences were observed bilaterally, and the BG/OC and the BG/FC rates in this group was lower than those of the control. Conclusion: 131 I-IBZM with SPECT imaging is useful in evaluating patients with Parkinson's disease

  10. PET/CT imaging of human somatostatin receptor 2 (hsstr2) as reporter gene for gene therapy

    International Nuclear Information System (INIS)

    Hofmann, M.; Gazdhar, A.; Weitzel, T.; Schmid, R.; Krause, T.

    2006-01-01

    Localized information on region-selective gene expression in small animals is widely obtained by use of reporter genes inducing light emission. Using these reporter genes for imaging deep inside the human body fluorescent probes are hindered by attenuation, scattering and possible fluorescence quenching. This can be overcome by use of radio-peptide receptors as reporter genes. Therefore, the feasibility of the somatostatin receptor 2 expression vector system for expression imaging was checked against a control vector containing luciferase gene. For in vivo transduction of vector DNA into the rat forelimb muscles the in vivo electroporation technique was chosen because of its high regio-selectivity. The gene expression was imaged by high-sensitive CCD camera (luciferase activity) and by PET/CT using a Ga-68-DOTATOC as radio peptide probe. The relative sstr2 expression was enhanced by gene transduction at maximum to a factor of 15. The PET/CT images could be fully quantified. The above demonstrated feasibility of radio-peptide PET/CT reporter gene imaging may serve in the future as a tool for full quantitative understanding of regional gene expression, especially in large animals and humans

  11. PET/CT imaging of human somatostatin receptor 2 (hsstr2) as reporter gene for gene therapy

    Energy Technology Data Exchange (ETDEWEB)

    Hofmann, M. [Molecular Imaging and Therapy Group (MIT-Bern), Clinic of Nuclear Medicine, Inselspital, Medical School Bern (Switzerland)]. E-mail: Michael.Hofmann@insel.ch; Gazdhar, A. [Division of Pulmonary Medicine, University Hospital Bern (Switzerland); Weitzel, T. [Molecular Imaging and Therapy Group (MIT-Bern), Clinic of Nuclear Medicine, Inselspital, Medical School Bern (Switzerland); Schmid, R. [Division of Thoracic Surgery, University Hospital Bern (Switzerland); Krause, T. [Molecular Imaging and Therapy Group (MIT-Bern), Clinic of Nuclear Medicine, Inselspital, Medical School Bern (Switzerland)

    2006-12-20

    Localized information on region-selective gene expression in small animals is widely obtained by use of reporter genes inducing light emission. Using these reporter genes for imaging deep inside the human body fluorescent probes are hindered by attenuation, scattering and possible fluorescence quenching. This can be overcome by use of radio-peptide receptors as reporter genes. Therefore, the feasibility of the somatostatin receptor 2 expression vector system for expression imaging was checked against a control vector containing luciferase gene. For in vivo transduction of vector DNA into the rat forelimb muscles the in vivo electroporation technique was chosen because of its high regio-selectivity. The gene expression was imaged by high-sensitive CCD camera (luciferase activity) and by PET/CT using a Ga-68-DOTATOC as radio peptide probe. The relative sstr2 expression was enhanced by gene transduction at maximum to a factor of 15. The PET/CT images could be fully quantified. The above demonstrated feasibility of radio-peptide PET/CT reporter gene imaging may serve in the future as a tool for full quantitative understanding of regional gene expression, especially in large animals and human000.

  12. Folic acid derivatives for PET imaging and therapy addressing folate receptor positive tumors

    Energy Technology Data Exchange (ETDEWEB)

    Schieferstein, Hanno

    2013-07-01

    Folic acid, also known as vitamin B9, is the oxidized form of 5,6,7,8-tetrahydrofolate, which serves as methyl- or methylene donor (C1-building blocks) during DNA synthesis. Under physiological conditions the required amount of 5,6,7,8-tetrahydrofolate for survival of the cell is accomplished through the reduced folate carrier (RFC). In contrast, the supply of 5,6,7,8-tetrahydrofolate is insufficient under pathophysiological conditions of tumors due to an increased proliferation rate. Consequently, many tumor cells exhibit an (over)expression of the folate receptor. This phenomenon has been applied to diagnostics (PET, SPECT, MR) to image FR-positive tumors and on the other hand to treat malignancies related to a FR (over)expression. Based on this concept, a new {sup 18}F-labeled folate for PET imaging has been developed and was evaluated in vivo using tumor-bearing mice. The incorporation of oligoethylene spacers into the molecular structure led to a significant enhancement of the pharmacokinetics in comparison to previously developed {sup 18}F-folates. The liver uptake could be reduced by one sixth by remaining a tumor uptake of 3%ID/g leading to better contrast ratios. Encouraged by these results, a clickable {sup 18}F-labeled serine-based prosthetic group has been synthesized, again with the idea to improve the metabolic and pharmacokinetic profile of hydrophilic radiotracers. Therefore, an alkyne-carrying azido-functionalized serine derivative for coupling to biomolecules was synthesized and a chlorine leaving group for {sup 18}F-labeling, which could be accomplished using a microwave-assisted synthesis, a [K is contained in 2.2.2]{sup +}/carbonate system in DMSO. Radiochemical yields of 77±6% could be achieved. The promising results obtained from the FR-targeting concept in the diagnostic field have been transferred to the boron neutron capture therapy. Therefore, a folate derivative was coupled to different boron clusters and cell uptake studies were

  13. Folic acid derivatives for PET imaging and therapy addressing folate receptor positive tumors

    International Nuclear Information System (INIS)

    Schieferstein, Hanno

    2013-01-01

    Folic acid, also known as vitamin B9, is the oxidized form of 5,6,7,8-tetrahydrofolate, which serves as methyl- or methylene donor (C1-building blocks) during DNA synthesis. Under physiological conditions the required amount of 5,6,7,8-tetrahydrofolate for survival of the cell is accomplished through the reduced folate carrier (RFC). In contrast, the supply of 5,6,7,8-tetrahydrofolate is insufficient under pathophysiological conditions of tumors due to an increased proliferation rate. Consequently, many tumor cells exhibit an (over)expression of the folate receptor. This phenomenon has been applied to diagnostics (PET, SPECT, MR) to image FR-positive tumors and on the other hand to treat malignancies related to a FR (over)expression. Based on this concept, a new 18 F-labeled folate for PET imaging has been developed and was evaluated in vivo using tumor-bearing mice. The incorporation of oligoethylene spacers into the molecular structure led to a significant enhancement of the pharmacokinetics in comparison to previously developed 18 F-folates. The liver uptake could be reduced by one sixth by remaining a tumor uptake of 3%ID/g leading to better contrast ratios. Encouraged by these results, a clickable 18 F-labeled serine-based prosthetic group has been synthesized, again with the idea to improve the metabolic and pharmacokinetic profile of hydrophilic radiotracers. Therefore, an alkyne-carrying azido-functionalized serine derivative for coupling to biomolecules was synthesized and a chlorine leaving group for 18 F-labeling, which could be accomplished using a microwave-assisted synthesis, a [K is contained in 2.2.2] + /carbonate system in DMSO. Radiochemical yields of 77±6% could be achieved. The promising results obtained from the FR-targeting concept in the diagnostic field have been transferred to the boron neutron capture therapy. Therefore, a folate derivative was coupled to different boron clusters and cell uptake studies were conducted. The synthesis of

  14. Quantification of GABAA receptors in the rat brain with [123I]Iomazenil SPECT from factor analysis-denoised images

    International Nuclear Information System (INIS)

    Tsartsalis, Stergios; Moulin-Sallanon, Marcelle; Dumas, Noé; Tournier, Benjamin B.; Ghezzi, Catherine; Charnay, Yves; Ginovart, Nathalie; Millet, Philippe

    2014-01-01

    Purpose: In vivo imaging of GABA A receptors is essential for the comprehension of psychiatric disorders in which the GABAergic system is implicated. Small animal SPECT provides a modality for in vivo imaging of the GABAergic system in rodents using [ 123 I]Iomazenil, an antagonist of the GABA A receptor. The goal of this work is to describe and evaluate different quantitative reference tissue methods that enable reliable binding potential (BP) estimations in the rat brain to be obtained. Methods: Five male Sprague–Dawley rats were used for [ 123 I]Iomazenil brain SPECT scans. Binding parameters were obtained with a one-tissue compartment model (1TC), a constrained two-tissue compartment model (2TC c ), the two-step Simplified Reference Tissue Model (SRTM2), Logan graphical analysis and analysis of delayed-activity images. In addition, we employed factor analysis (FA) to deal with noise in data. Results: BP ND obtained with SRTM2, Logan graphical analysis and delayed-activity analysis was highly correlated with BP F values obtained with 2TC c (r = 0.954 and 0.945 respectively, p c and SRTM2 in raw and FA-denoised images (r = 0.961 and 0.909 respectively, p ND values from raw images while scans of only 70 min are sufficient from FA-denoised images. These images are also associated with significantly lower standard errors of 2TC c and SRTM2 BP values. Conclusion: Reference tissue methods such as SRTM2 and Logan graphical analysis can provide equally reliable BP ND values from rat brain [ 123 I]Iomazenil SPECT. Acquisitions, however, can be much less time-consuming either with analysis of delayed activity obtained from a 20-minute scan 50 min after tracer injection or with FA-denoising of images

  15. Heterogeneity of triple-negative breast cancer: mammographic, US, and MR imaging features according to androgen receptor expression

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Min Sun; Song, Sung Eun; Kim, Won Hwa; Lee, Su Hyun; Moon, Woo Kyung [Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Park, So Yeon; Park, In-Ae [Seoul National University College of Medicine, Department of Pathology, Seoul (Korea, Republic of); Han, Wonshik; Noh, Dong-Young [Seoul National University College of Medicine, Department of Surgery, Seoul (Korea, Republic of)

    2014-09-16

    Our aim was to determine whether triple-negative breast cancers (TNBCs) with and without androgen receptor (AR) expression have distinguishing imaging features on mammography, breast ultrasound (US), and magnetic resonance (MR) imaging. AR expression was assessed immunohistochemically in 125 patients with TNBC from a consecutive series of 1,086 operable invasive breast cancers. Two experienced radiologists blinded to clinicopathological findings reviewed all imaging studies in consensus using the BI-RADS lexicon. The imaging and pathological features of 33 AR-positive TNBCs were compared with those of 92 AR-negative TNBCs. The presence of mammographic calcifications with or without a mass (p < 0.001), non-mass enhancement on MR imaging (p < 0.001), and masses with irregular shape or spiculated margins on US (p < 0.001 and p = 0.002) and MR imaging (p = 0.001 and p < 0.001) were significantly associated with AR-positive TNBC. Compared with AR-negative TNBC, AR-positive TNBC was more likely to have a ductal carcinoma in situ component (59.8 % vs. 90.9 %, p = 0.001) and low Ki-67 expression (30.4 % vs. 51.5 %, p = 0.030). AR-positive and AR-negative TNBCs have different imaging features, and certain imaging findings can be useful to predict AR status in TNBC. (orig.)

  16. Preclinical evaluation of a positron emitting progestin ([18F]fluoro-16 alpha-methyl-19-norprogesterone) for imaging progesterone receptor positive tumours with positron emission tomography

    NARCIS (Netherlands)

    Verhagen, Aalt; Luurtsema, Gert; PESSER, JW; DEGROOT, TJ; OOSTERHUIS, JW; Vaalburg, Willem; Wouda, S.

    Three 21-fluoro-progestins were investigated as potential imaging agents for the in vivo assessment of human progesterone receptor positive neoplasms with positron emission tomography. In competitive binding assays these compounds demonstrated high specificity, competing only for progesterone

  17. Transferrin receptor molecular imaging: targeting for diagnosis and monitoring of gene delivery

    International Nuclear Information System (INIS)

    Eun-Mi Kim; Hwan-Jeong Jeong; Jin-Hee Kim; Chang-Guhn Kim

    2004-01-01

    Objective: In this study, we investigated the targetability of Tf conjugated compounds to Tf-R expressed on cancer cells for detection and diagnosis and the usefulness of gamma probe-targeting delivery system on monitoring whether the gene complex bind to the cells specifically. Methods: For the detection and diagnosis of Tf-R positive cancer cells, Tf-chitosan conjugates were synthesized as previously described by Kircheis et al with some modifications. Succinimidyl 6-hydrazino nicotinate hydrochloride (HYNIC) was bound to Tf-chitosan conjugates. HYNIC-Tf-chitosan conjugates were labelled with 99mTc. In the monitoring of Tf-R specific gene delivery system, we used the HYNIC-Tf conjugated dendrimer. For tumor model, 5- to 6-week-old female BALB/c nude mice were injected subcutaneously in the left thigh with Ramos cells (human Burkitt's lymphoma). The gamma imagings were acquired after administration of 99mTc HYNIC-Tf conjugates and 99mTc HYNIC-Tf-DNA polyplexes via the tail vein of tumor bearing nude mice at 10, 30, 60, 90, and 120 min. To compare the image acquired with HYNIC-Tf conjugate, Ga-67 study was performed. To certify the expression of delivered gene via DNA polyplexes, 2 days after gene complex injection we inspected the expression of GFP in dissected tumor tissue. Results: Radiolabeling yields of both HYNIC-Tf conjugate and HYNIC-Tf-dendrimer gene complex were above 90% until 12hr. Uptake in the Ramos model of 99mTc HYNIC-Tf conjugate showed higher than those of Ga-67. A few minutes after injection 99mTc HYNIC-Tf conjugate localized mainly in the circulation (heart), kidneys, and tumor. At later times, radioactivity in tumor increased until 90 min. Pharmacokinetics of Ga-67 were different from those of 99mTc HYNIC-Tf conjugate. Tumor to nontumor ratio of Ga-67 was approximately 2 but in case of 99mTc HYNIC-Tf conjugate showed until 5. In Ramos lymphoma model, 99mTc HYNIC-Tf-DNA polyplexes accumulated the tumor site, and the gene expression of 99m

  18. Gd-EDDA/HYNIC-RGD as an MR molecular probe imaging integrin alphanubeta3 receptor-expressed tumor-MR molecular imaging of angiogenesis.

    Science.gov (United States)

    Huo, Tianlong; Du, Xiangke; Zhang, Sen; Liu, Xia; Li, Xubing

    2010-02-01

    The aim of this study is to develop a novel MR probe containing arginine-glycine-aspartic acid (RGD) motif for imaging integrin alphanubeta3 receptor-expressed tumor. Commercially available HYNIC-RGD conjugated with co-ligand EDDA was labeled with Gd(3+), and the mixture was isolated and purified by solid phase extract (SPE) to get the entire probe Gd-EDDA/HYNIC-RGD. Human hepatocellular carcinoma (HHCC) cell line BEL-7402 was cultured and the cells harvested and suspended in serum-free Dulbecco's modified Eagle medium (DMEM) were subcutaneously inoculated into athymic nude mice for tumor growth. In vitro cell binding assay to integrin alphanubeta3 receptor and cell viability experiments were conducted. The in vivo imaging of the three arms of xenografts were performed by MR scan with a dedicated animal coil at time points of 0, 30, 60, 90min and 24-h post-intravenous injection (p.i.). Three arms of nude mice then were sacrificed for histological examination to confirm the imaging results. Gd-EDDA/HYNIC-RGD was successfully isolated by SPE and validity was verified on signal enhancement through in vitro and in vivo experiments. The nude mice model bearing HHCC was well established. There was approx. 30% signal enhancement on T1WI FSE images at 90min post-intravenous injection of the Gd-EDDA/HYNIC-RGD compared with baseline, and the signal to time curve is straightforward over time in the span of 0-90min p.i., while the control arms do not show this tendency. Gd-EDDA/HYNIC-RGD has the potential to serve as an MR probe detecting integrin alphanubeta3 receptor-expressed tumor. Copyright (c) 2008 Elsevier Ireland Ltd. All rights reserved.

  19. Gd-EDDA/HYNIC-RGD as an MR molecular probe imaging integrin {alpha}{nu}{beta}3 receptor-expressed tumor-MR molecular imaging of angiogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Huo Tianlong [Peking University People' s Hospital, Radiology Department, 11 Xizhimen South Street, Xicheng District, Beijing 100044 (China)], E-mail: huotianlong@bjmu.edu.cn; Du Xiangke [Peking University People' s Hospital, Radiology Department, 11 Xizhimen South Street, Xicheng District, Beijing 100044 (China)], E-mail: duxk@263.net; Zhang Sen [Peking University People' s Hospital, Radiology Department, 11 Xizhimen South Street, Xicheng District, Beijing 100044 (China)], E-mail: skagerrak_s@yahoo.com.cn; Liu Xia [Peking University People' s Hospital, Radiology Department, 11 Xizhimen South Street, Xicheng District, Beijing 100044 (China)], E-mail: iamliuxia@126.com; Li Xubing [Peking University People' s Hospital, Radiology Department, 11 Xizhimen South Street, Xicheng District, Beijing 100044 (China)], E-mail: lixb@bjmu.edu.cn

    2010-02-15

    Rationale and objective: The aim of this study is to develop a novel MR probe containing arginine-glycine-aspartic acid (RGD) motif for imaging integrin {alpha}{nu}{beta}3 receptor-expressed tumor. Materials and methods: Commercially available HYNIC-RGD conjugated with co-ligand EDDA was labeled with Gd{sup 3+}, and the mixture was isolated and purified by solid phase extract (SPE) to get the entire probe Gd-EDDA/HYNIC-RGD. Human hepatocellular carcinoma (HHCC) cell line BEL-7402 was cultured and the cells harvested and suspended in serum-free Dulbecco's modified Eagle medium (DMEM) were subcutaneously inoculated into athymic nude mice for tumor growth. In vitro cell binding assay to integrin {alpha}{nu}{beta}3 receptor and cell viability experiments were conducted. The in vivo imaging of the three arms of xenografts were performed by MR scan with a dedicated animal coil at time points of 0, 30, 60, 90 min and 24-h post-intravenous injection (p.i.). Three arms of nude mice then were sacrificed for histological examination to confirm the imaging results. Results: Gd-EDDA/HYNIC-RGD was successfully isolated by SPE and validity was verified on signal enhancement through in vitro and in vivo experiments. The nude mice model bearing HHCC was well established. There was approx. 30% signal enhancement on T1WI FSE images at 90 min post-intravenous injection of the Gd-EDDA/HYNIC-RGD compared with baseline, and the signal to time curve is straightforward over time in the span of 0-90 min p.i., while the control arms do not show this tendency. Conclusion: Gd-EDDA/HYNIC-RGD has the potential to serve as an MR probe detecting integrin {alpha}{nu}{beta}3 receptor-expressed tumor.

  20. Gd-EDDA/HYNIC-RGD as an MR molecular probe imaging integrin ανβ3 receptor-expressed tumor-MR molecular imaging of angiogenesis

    International Nuclear Information System (INIS)

    Huo Tianlong; Du Xiangke; Zhang Sen; Liu Xia; Li Xubing

    2010-01-01

    Rationale and objective: The aim of this study is to develop a novel MR probe containing arginine-glycine-aspartic acid (RGD) motif for imaging integrin ανβ3 receptor-expressed tumor. Materials and methods: Commercially available HYNIC-RGD conjugated with co-ligand EDDA was labeled with Gd 3+ , and the mixture was isolated and purified by solid phase extract (SPE) to get the entire probe Gd-EDDA/HYNIC-RGD. Human hepatocellular carcinoma (HHCC) cell line BEL-7402 was cultured and the cells harvested and suspended in serum-free Dulbecco's modified Eagle medium (DMEM) were subcutaneously inoculated into athymic nude mice for tumor growth. In vitro cell binding assay to integrin ανβ3 receptor and cell viability experiments were conducted. The in vivo imaging of the three arms of xenografts were performed by MR scan with a dedicated animal coil at time points of 0, 30, 60, 90 min and 24-h post-intravenous injection (p.i.). Three arms of nude mice then were sacrificed for histological examination to confirm the imaging results. Results: Gd-EDDA/HYNIC-RGD was successfully isolated by SPE and validity was verified on signal enhancement through in vitro and in vivo experiments. The nude mice model bearing HHCC was well established. There was approx. 30% signal enhancement on T1WI FSE images at 90 min post-intravenous injection of the Gd-EDDA/HYNIC-RGD compared with baseline, and the signal to time curve is straightforward over time in the span of 0-90 min p.i., while the control arms do not show this tendency. Conclusion: Gd-EDDA/HYNIC-RGD has the potential to serve as an MR probe detecting integrin ανβ3 receptor-expressed tumor.

  1. Live Cell Imaging and 3D Analysis of Angiotensin Receptor Type 1a Trafficking in Transfected Human Embryonic Kidney Cells Using Confocal Microscopy.

    Science.gov (United States)

    Kadam, Parnika; McAllister, Ryan; Urbach, Jeffrey S; Sandberg, Kathryn; Mueller, Susette C

    2017-03-27

    Live-cell imaging is used to simultaneously capture time-lapse images of angiotensin type 1a receptors (AT1aR) and intracellular compartments in transfected human embryonic kidney-293 (HEK) cells following stimulation with angiotensin II (Ang II). HEK cells are transiently transfected with plasmid DNA containing AT1aR tagged with enhanced green fluorescent protein (EGFP). Lysosomes are identified with a red fluorescent dye. Live-cell images are captured on a laser scanning confocal microscope after Ang II stimulation and analyzed by software in three dimensions (3D, voxels) over time. Live-cell imaging enables investigations into receptor trafficking and avoids confounds associated with fixation, and in particular, the loss or artefactual displacement of EGFP-tagged membrane receptors. Thus, as individual cells are tracked through time, the subcellular localization of receptors can be imaged and measured. Images must be acquired sufficiently rapidly to capture rapid vesicle movement. Yet, at faster imaging speeds, the number of photons collected is reduced. Compromises must also be made in the selection of imaging parameters like voxel size in order to gain imaging speed. Significant applications of live-cell imaging are to study protein trafficking, migration, proliferation, cell cycle, apoptosis, autophagy and protein-protein interaction and dynamics, to name but a few.

  2. Radioiodinated ligands for dopamine receptors

    International Nuclear Information System (INIS)

    Kung, H.F.

    1994-01-01

    The dopamine receptor system is important for normal brain function; it is also the apparent action site for various neuroleptic drugs for the treatment of schizophrenia and other metal disorders. In the past few years radioiodinated ligands for single photon emission tomography (SPECT) have been successfully developed and tested in humans: [ 123 I]TISCH for D1 dopamine receptors; [ 123 I]IBZM, epidepride, IBF and FIDA2, four iodobenzamide derivatives, for D2/D3 dopamine receptors. In addition, [ 123 I]β-CIT (RTI-55) and IPT, cocaine derivatives, for the dopamine reuptake site are potentially useful for diagnosis of loss of dopamine neurons. The first iodinated ligand, (R)trans-7-OH-PIPAT, for D3 dopamine receptors, was synthesized and characterized with cloned cell lines (Spodoptera frugiperda, Sf9) expressing the D2 and D3 dopamine receptors and with rat basal forebrain membrane preparations. Most of the known iodobenzamides displayed similar potency in binding to both D2 and D3 dopamine receptors expressed in the cell lines. Initial studies appear to suggest that by fine tuning the structures it may be possible to develop agents specific for D2 and D3 dopamine receptors. It is important to investigate D2/D3 selectivity for this series of potent ligands

  3. Strategies for Imaging Androgen Receptor Signaling Pathway in Prostate Cancer: Implications for Hormonal Manipulation and Radiation Treatment

    Directory of Open Access Journals (Sweden)

    Gravina Giovanni Luca

    2013-01-01

    Full Text Available Prostate cancer (Pca is a heterogeneous disease; its etiology appears to be related to genetic and epigenetic factors. Radiotherapy and hormone manipulation are effective treatments, but many tumors will progress despite these treatments. Molecular imaging provides novel opportunities for image-guided optimization and management of these treatment modalities. Here we reviewed the advances in targeted imaging of key biomarkers of androgen receptor signaling pathways. A computerized search was performed to identify all relevant studies in Medline up to 2013. There are well-known limitations and inaccuracies of current imaging approaches for monitoring biological changes governing tumor progression. The close integration of molecular biology and clinical imaging could ease the development of new molecular imaging agents providing novel tools to monitor a number of biological events that, until a few years ago, were studied by conventional molecular assays. Advances in translational research may represent the next step in improving the oncological outcome of men with Pca who remain at high risk for systemic failure. This aim may be obtained by combining the anatomical properties of conventional imaging modalities with biological information to better predict tumor response to conventional treatments.

  4. Non-opiate [beta]-endorphin fragments and dopamine--III [gamma]-type endorphins and various neuroleptics counteract the hypoactivity elicited by injection of apomorphine into the nucleus accumbens

    NARCIS (Netherlands)

    Ree, J.M. van; Caffe, A.R.; Wolterink, G.

    1982-01-01

    The hypoactivity in rats induced by small doses of apomorphine, injected bilaterally into the nucleus accumbens area of the brain, could be antagonized by pretreatment with the neuroleptic-like neuropeptide des-enkephalin-γ-endorphin (DEγE, β-endorphin 6–17) as well as with the neuroleptic drugs

  5. Differential expression of growth factor receptors and membrane-bound tumor markers for imaging in male and female breast cancer.

    Directory of Open Access Journals (Sweden)

    Jeroen F Vermeulen

    Full Text Available INTRODUCTION: Male breast cancer accounts for 0.5-1% of all breast cancers and is generally diagnosed at higher stage than female breast cancers and therefore might benefit from earlier detection and targeted therapy. Except for HER2 and EGFR, little is known about expression of growth factor receptors in male breast cancer. We therefore investigated expression profiles of growth factor receptors and membrane-bound tumor markers in male breast cancer and gynecomastia, in comparison with female breast cancer. METHODS: Tissue microarrays containing 133 male breast cancer and 32 gynecomastia cases were stained by immunohistochemistry for a panel of membrane-bound targets and compared with data on 266 female breast cancers. RESULTS: Growth factor receptors were variably expressed in 4.5% (MET up to 38.5% (IGF1-R of male breast cancers. Compared to female breast cancer, IGF1-R and carbonic anhydrase 12 (CAXII were more frequently and CD44v6, MET and FGFR2 less frequently expressed in male breast cancer. Expression of EGFR, HER2, CAIX, and GLUT1 was not significantly different between male and female breast cancer. Further, 48.1% of male breast cancers expressed at least one and 18.0% expressed multiple growth factor receptors. Since individual membrane receptors are expressed in only half of male breast cancers, a panel of membrane markers will be required for molecular imaging strategies to reach sensitivity. A potential panel of markers for molecular imaging, consisting of EGFR, IGF1-R, FGFR2, CD44v6, CAXII, GLUT1, and CD44v6 was positive in 77% of male breast cancers, comparable to female breast cancers. CONCLUSIONS: Expression patterns of growth factor receptors and hypoxia membrane proteins in male breast cancer are different from female breast cancer. For molecular imaging strategies, a putative panel consisting of markers for EGFR, IGF1-R, FGFR2, GLUT1, CAXII, CD44v6 was positive in 77% of cases and might be considered for development of

  6. Relationship of neuromotor disturbances to psychosis symptoms in first-episode neuroleptic-naive schizophrenia patients.

    Science.gov (United States)

    Cortese, Leonardo; Caligiuri, Michael P; Malla, Ashok K; Manchanda, Rahul; Takhar, Jatinder; Haricharan, Raj

    2005-06-01

    From the very inception of the modern diagnostic scheme for psychotic disorders, abnormalities in motor function have been observed in these conditions. Despite convergence from multiple areas of research supporting the notion that multiple frontal-subcortical circuits regulate motor and limbic behavior, the precise relationship between motor abnormalities and psychopathology has not been elucidated. The goals of this study were to examine the prevalence of extrapyramidal signs (EPS) in first-episode schizophrenia patients and their relationships to three psychopathological dimensions (positive psychosis syndrome, negative syndrome, and disorganization). We assessed EPS using traditional observer-based as well as quantitative instrumental measures in 39 neuroleptic-naive first-episode schizophrenia subjects. Subjects were followed for 6 months after initiating antipsychotic treatment to examine the stability of motor-limbic relationships. Four main findings emerged from this study. First, depending on the measure used the prevalence of dyskinesia prior to treatment ranged from 13% to 20%. The prevalence of parkinsonism ranged from 18% to 28%. Second, severity of dyskinesia was associated with the positive psychotic syndrome; whereas parkinsonism was associated with the positive psychosis, negative syndrome and disorganization. Third, psychopathology improved significantly across all symptom dimensions following antipsychotic treatment, while EPS remained stable. This suggests that some motor abnormalities in schizophrenia may reflect trait characteristics. Fourth, abnormalities on the pre-treatment instrumental measure of parkinsonism predicted greater improvement on positive psychosis symptoms following treatment (p=0.008). Our findings support the notion that neuromotor disturbances may be a core feature of schizophrenia in a substantial proportion of patients and implicate multiple fronto-striatal circuits regulating limbic and neuromotor behavior in

  7. Acute Cocaine Induces Fast Activation of D1 Receptor and Progressive Deactivation of D2 Receptor Strial Neurons: In Vivo Optical Microprobe [Ca2+]i Imaging

    International Nuclear Information System (INIS)

    Du, C.; Luo, Z.; Volkow, N.D.; Heintz, N.; Pan, Y.; Du, C.

    2011-01-01

    Cocaine induces fast dopamine increases in brain striatal regions, which are recognized to underlie its rewarding effects. Both dopamine D1 and D2 receptors are involved in cocaine's reward but the dynamic downstream consequences of cocaine effects in striatum are not fully understood. Here we used transgenic mice expressing EGFP under the control of either the D1 receptor (D1R) or the D2 receptor (D2R) gene and microprobe optical imaging to assess the dynamic changes in intracellular calcium ([Ca 2+ ] i ) responses (used as marker of neuronal activation) to acute cocaine in vivo separately for D1R- versus D2R-expressing neurons in striatum. Acute cocaine (8 mg/kg, i.p.) rapidly increased [Ca 2+ ] i in D1R-expressing neurons (10.6 ± 3.2%) in striatum within 8.3 ± 2.3 min after cocaine administration after which the increases plateaued; these fast [Ca 2+ ] i increases were blocked by pretreatment with a D1R antagonist (SCH23390). In contrast, cocaine induced progressive decreases in [Ca 2+ ] i in D2R-expressing neurons (10.4 ± 5.8%) continuously throughout the 30 min that followed cocaine administration; these slower [Ca 2+ ] i decreases were blocked by pretreatment with a D2R antagonist (raclopride). Since activation of striatal D1R-expressing neurons (direct-pathway) enhances cocaine reward, whereas activation of D2R expressing neurons suppresses it (indirect-pathway) (Lobo et al., 2010), this suggests that cocaine's rewarding effects entail both its fast stimulation ofD1R (resulting in abrupt activation of direct-pathway neurons) and a slower stimulation of D2R (resulting in longer-lasting deactivation of indirect-pathway neurons). We also provide direct in vivo evidence of D2R and D1R interactions in the striatal responses to acute cocaine administration.

  8. A fundamental study on brain receptor mapping by neuronuclear medicine imaging

    International Nuclear Information System (INIS)

    Tsuji, Shiro

    1988-01-01

    The usefulness of autoradiography in the quantitation of the rat brain receptor was evaluated. H-3 spiperone, H-3 quinuclidinyl benzylate (QNB), H-3 muscimol, H-3 diprenorphine, H-3 ketanserin, and H-3 dihydroalprenolol hydrochloride were used for autoradiography. Satisfactory autoradiograms with these H-3 labeled ligants were obtained for incubation time, washing time, and binding curve. The video digitizer system was the most suitable in autoradiography. Using appropriate conditions for the ligand-receptor interaction, receptor autoradiography and in vitro receptor assay were concordant as for the the number of maximum binding sites (Bmax) of the muscarinic acetylcholine receptor and equilibrium dissociation constant (Kd) of its antagonist, H-3 QNB. Receptor autoradiography with high spatial resolution allowed the comparison of Bmax and Kd in the brain. To improve conventional Scatchard analysis, used in the estimation of Bmax and Kd, a new mathematical method was developed for estimating individual rate constants and Bmax on the basis of time courses of association and dissociation. Using the new mathematical method, apparent equilibrium dissociation rate constant was in good agreement with that from a non-isomerization model. Autoradiography may provide a clue for the basic data on brain receptor mapping by a promising emission computerized tomography in neuropsychiatric diseases. (Namekawa, K.)

  9. Evaluation of health resources expenditure in two groups of psychotic patients treated with olanzapine and typical neuroleptics in a Italian Mental Health Department in Calabria Region

    Directory of Open Access Journals (Sweden)

    Anna Caputo

    2008-01-01

    Full Text Available Numerous Italian and international trials have studied the global costs of treatment with olanzapine and typical neuroleptics. Our analysis confirms those results. In our study, treatment with olanzapine, as compared to typical neuroleptics, was associated with a greater reduction in emergency interventions (hospitalisations, with an increased use of rehabilitation services and with a small increase in the number of working days. The differences between the two groups for this variable were not great, while the differences in the assessment scores appeared important and statistically significant. The results of present study are relative to the practice of one Italian Mental Health Department and, for this reason, cannot be generalized. Anyway, they are another indication of increased efficiency of atypicals treatment over older neuroleptics in schizophrenia.

  10. Effects of acute and long-term typical or atypical neuroleptics on morphine-induced behavioural effects in mice.

    Science.gov (United States)

    Hollais, André W; Patti, Camilla L; Zanin, Karina A; Fukushiro, Daniela F; Berro, Laís F; Carvalho, Rita C; Kameda, Sonia R; Frussa-Filho, Roberto

    2014-03-01

    1. It has been suggested that the high prevalence of drug abuse in schizophrenics is related to chronic treatment with typical neuroleptics and dopaminergic supersensitivity that develops as a consequence. Within this context, atypical neuroleptics do not seem to induce this phenomenon. In the present study, we investigated the effects of acute administration or withdrawal from long-term administration of haloperidol and/or ziprasidone on morphine-induced open-field behaviour in mice. 2. In the first experiment, mice were given a single injection of haloperidol (1 mg/kg, i.p.) or several doses of ziprasidone (2, 4 or 6 mg/kg, i.p.) and motor activity was quantified by the open-field test. The aim of the second experiment was to verify the effects of an acute injection of haloperidol (1 mg/kg) or ziprasidone (6 mg/kg) on 20 mg/kg morphine-induced behaviours in the open-field test. In the third experiment, mice were treated with 1 mg/kg haloperidol and/or 2, 4 or 6 mg/kg ziprasidone for 20 days. Seventy-two hours after the last injection, mice were injected with 20 mg/kg, i.p., morphine and then subjected to the open-field test. Acute haloperidol or ziprasidone decreased spontaneous general activity and abolished morphine-induced locomotor stimulation. 3. Withdrawal from haloperidol or ziprasidone did not modify morphine-elicited behaviours in the open-field test. The results suggest that withdrawal from neuroleptic treatments does not contribute to the acute effect of morphine in schizophrenic patients. © 2014 Wiley Publishing Asia Pty Ltd.

  11. Preliminary studies of 99mTc-memantine derivatives for NMDA receptor imaging

    International Nuclear Information System (INIS)

    Zhou Xingqin; Zhang Jiankang; Yan Chenglong; Cao Guoxian; Zhang Rongjun; Cai Gangming; Jiang Mengjun; Wang Songpei

    2012-01-01

    Introduction: Novel technetium-labeled ligands, 99m Tc-NCAM and 99m Tc-NHAM were developed from the N-methyl-D-aspartate (NMDA) receptor agonist memantine as a lead compound by coupling with N 2 S 2 . This study evaluated the binding affinity and specificity of the ligands for the NMDA receptor. Methods: Ligand biodistribution and uptake specificity in the brain were investigated in mice. Binding affinity and specificity were determined by radioligand receptor binding assay. Three antagonists were used for competitive binding analysis. In addition, uptake of the complexes into SH-SY5Y nerve cells was evaluated. Results: The radiochemical purity of 99m Tc-labeled ligands was more than 95%. Analysis of brain regional uptake showed higher concentration in the frontal lobe and specific uptake in the hippocampus. 99m Tc-NCAM reached a higher target to nontarget ratio than 99m Tc-NHAM. The results indicated that 99m Tc-NCAM bound to a single site on the NMDA receptor with a K d of 701.21 nmol/l and a B max of 62.47 nmol/mg. Specific inhibitors of the NMDA receptor, ketamine and dizocilpine, but not the dopamine D 2 and 5HT 1A receptor partial agonist aripiprazole, inhibited specific binding of 99m Tc-NCAM to the NMDA receptor. Cell physiology experiments showed that NCAM can increase the viability of SH-SY5Y cells after glutamate-induced injury. Conclusions: The new radioligand 99m Tc-NCAM has good affinity for and specific binding to the NMDA receptor, and easily crosses the blood–brain barrier; suggesting that it might be a potentially useful tracer for NMDA receptor expression.

  12. [99mTc]O2-AMD3100 as a SPECT tracer for CXCR4 receptor imaging

    International Nuclear Information System (INIS)

    Hartimath, Siddesh V.; Domanska, Urszula M.; Walenkamp, Annemiek M.E.; Dierckx, Rudi A.J.O.; Vries, Erik F.J. de

    2013-01-01

    Purpose: CXCR4 plays an important role in HIV infection, tumor progression, neurogenesis, and inflammation. In-vivo imaging of CXCR4 could provide more insight in the role of this receptor in health and disease. The aim of this study was to investigate [ 99m Tc]O 2 -AMD3100 as a potential SPECT tracer for imaging of CXCR4. Method: AMD3100 was labelled with [ 99m Tc]pertechnetate. A cysteine challenge assay was performed to test the tracer stability. Heterologous and homologous receptor binding assay and internalization assay were performed in CXCR4 expressing Jurkat-T cells. Ex vivo biodistribution was studied in healthy mice at 30, 60, and 120 min after tracer injection. Tumor uptake of the tracer was determined by microSPECT imaging in nude mice xenografted with human PC-3 prostate tumor. Specificity of tracer uptake was determined by blocking studies using an excess of unlabelled AMD3100. Results: AMD3100 was labelled with technetium-99 m with a radiochemical yield of > 98%. The tracer was stable in PBS and mouse plasma for at least 6 h at 37 °C. Heterologous and homologous binding assays with AMD3100 showed IC 50 values of 240 ± 10 μM, and 92 ± 5 μM for [ 125 I]SDF-1α and [ 99m Tc]O 2 -AMD3100 respectively, with negligible receptor internalisation. The tracer showed high uptake in liver, lungs, spleen, thymus, intestine and bone. Blocking dose of AMD3100.8HCl (20 mg/kg) decreased the uptake in these organs (p 99m Tc]O 2 -AMD3100 showed specific tumor accumulation in mice bearing PC-3 xenografts model. Time activity curves (TAC) in AMD3100 pre-treated animals tracer showed 1.7 times less tumor uptake as compared to control animals (p 99m Tc]O 2 -AMD3100 is readily labelled, is stable in plasma and displays a favourable binding affinity for the CXCR4 receptors. [ 99m Tc O 2 -AMD3100 shows specific binding in organs with high CXCR4 expression and in CXCR4 positive tumors. These results justify further evaluation of this radiopharmaceutical as a potential

  13. Synthesis and evaluation of [11C]Cimbi-806 as a potential PET ligand for 5-HT7 receptor imaging

    DEFF Research Database (Denmark)

    Herth, Matthias Manfred; Hansen, Hanne Demant; Ettrup, Anders Janusz

    2012-01-01

    )-N,N-dimethylethanamine ([(11)C]Cimbi-806) as a radioligand for imaging brain 5-HT(7) receptors with positron emission tomography (PET). Precursor and reference compound was synthesized and subsequent (11)C-labelling with [(11)C]methyltriflate produced [(11)C]Cimbi-806 in specific activities ranging from 50 to 300 GBq...... of appropriate in vivo blocking with a 5-HT(7) receptor selective compounds renders the conclusion that [(11)C]Cimbi-806 is not an appropriate PET radioligand for imaging the 5-HT(7) receptor in vivo....

  14. Imaging the β-adrenergic receptor. II: [F-18]-fluoroalkyl derivatives of carazolol

    International Nuclear Information System (INIS)

    Kinsey, B.M.; Tewson, T.J.

    1990-01-01

    Carazolol is a ligand with one of the highest association constants known for the β-adrenergic receptor and presumably has one of the slowest rates of dissociation from the receptor. The authors have prepared a [F-18]-fluoroalkyl derivative of carazolol which the authors believe will be useful in the in vivo detection and measurement of the β-adrenergic receptor. The synthesis is based upon the formation of a hydrazole from cyclohexanedione and para-[2-hydroxyethyl]phenylhydrazine followed by Fischer indole synthesis, dehydrogenation and side chain addition to give the protected hydroxyethylcarazolol derivative 1

  15. Multifunctional molecular imaging probes for estrogen receptors. 99mTc labeled diethylstilbestrol (DES) conjugated, cuinp quantum dot nanoparticles (DESCIP)

    International Nuclear Information System (INIS)

    Payam Moharrami; Perihan Unak; Ozge Kozgus Guldu; Medine, E.I.; Gul Gumuser; Elvan Sayit Bilgin; Omer Aras

    2017-01-01

    A theranostic nanoparticle was synthesized based on diethylstilbestrol conjugated with phosphate, copper, and indium (DESCIP) and labelled with 99m Tc which can be used for SPECT imaging of ER-enriched cancers. In vitro biological activity of 99m Tc-DESCIP was examined in breast adenocarcinoma cells (MCF-7), prostatic carcinoma cells (PC-3), and pulmonary epithelial cells (A-549). In vivo lymph node imaging was performed in normal and receptor blocked female New Zealand rabbits. Results demonstrated that 99m Tc-DESCIP and DESCIP has potential for imaging ER-enriched tumors such as breast and prostate tumors, and their metastases in the lung, as well as improving management for their therapies. (author)

  16. Harnessing Integrative Omics to Facilitate Molecular Imaging of the Human Epidermal Growth Factor Receptor Family for Precision Medicine.

    Science.gov (United States)

    Pool, Martin; de Boer, H Rudolf; Hooge, Marjolijn N Lub-de; van Vugt, Marcel A T M; de Vries, Elisabeth G E

    2017-01-01

    Cancer is a growing problem worldwide. The cause of death in cancer patients is often due to treatment-resistant metastatic disease. Many molecularly targeted anticancer drugs have been developed against 'oncogenic driver' pathways. However, these treatments are usually only effective in properly selected patients. Resistance to molecularly targeted drugs through selective pressure on acquired mutations or molecular rewiring can hinder their effectiveness. This review summarizes how molecular imaging techniques can potentially facilitate the optimal implementation of targeted agents. Using the human epidermal growth factor receptor (HER) family as a model in (pre)clinical studies, we illustrate how molecular imaging may be employed to characterize whole body target expression as well as monitor drug effectiveness and the emergence of tumor resistance. We further discuss how an integrative omics discovery platform could guide the selection of 'effect sensors' - new molecular imaging targets - which are dynamic markers that indicate treatment effectiveness or resistance.

  17. Test-retest measurements of dopamine D_1-type receptors using simultaneous PET/MRI imaging

    International Nuclear Information System (INIS)

    Kaller, Simon; Patt, Marianne; Becker, Georg-Alexander; Luthardt, Julia; Meyer, Philipp M.; Werner, Peter; Barthel, Henryk; Bresch, Anke; Sabri, Osama; Rullmann, Michael; Girbardt, Johanna; Fritz, Thomas H.; Hesse, Swen

    2017-01-01

    The role of dopamine D_1-type receptor (D_1R)-expressing neurons in the regulation of motivated behavior and reward prediction has not yet been fully established. As a prerequisite for future research assessing D_1-mediated neuronal network regulation using simultaneous PET/MRI and D_1R-selective ["1"1C]SCH23390, this study investigated the stability of central D_1R measurements between two independent PET/MRI sessions under baseline conditions. Thirteen healthy volunteers (7 female, age 33 ± 13 yrs) underwent 90-min emission scans, each after 90-s bolus injection of 486 ± 16 MBq ["1"1C]SCH23390, on two separate days within 2-4 weeks using a PET/MRI system. Parametric images of D_1R distribution volume ratio (DVR) and binding potential (BP_N_D) were generated by a multi-linear reference tissue model with two parameters and the cerebellar cortex as receptor-free reference region. Volume-of-interest (VOI) analysis was performed with manual VOIs drawn on consecutive transverse MRI slices for brain regions with high and low D_1R density. The DVR varied from 2.5 ± 0.3 to 2.9 ± 0.5 in regions with high D_1R density (e.g. the head of the caudate) and from 1.2 ± 0.1 to 1.6 ± 0.2 in regions with low D_1R density (e.g. the prefrontal cortex). The absolute variability of the DVR ranged from 2.4% ± 1.3% to 5.1% ± 5.3%, while Bland-Altman analyses revealed very low differences in mean DVR (e.g. 0.013 ± 0.17 for the nucleus accumbens). Intraclass correlation (one-way, random) indicated very high agreement (0.93 in average) for both DVR and BP_N_D values. Accordingly, the absolute variability of BP_N_D ranged from 7.0% ± 4.7% to 12.5% ± 10.6%; however, there were regions with very low D_1R content, such as the occipital cortex, with higher mean variability. The test-retest reliability of D_1R measurements in this study was very high. This was the case not only for D_1R-rich brain areas, but also for regions with low D_1R density. These results will provide a solid base

  18. Smart dual-functional warhead for folate receptor-specific activatable imaging and photodynamic therapy.

    Science.gov (United States)

    Kim, Jisu; Tung, Ching-Hsuan; Choi, Yongdoo

    2014-09-21

    A smart dual-targeted theranostic agent becomes highly fluorescent and phototoxic only when its linker is cleaved by tumor-associated lysosomal enzyme cathepsin B after internalization into folate receptor-positive cancer cells.

  19. (/sup 76/Br)Bromolisuride: a new tool for quantitative in vivo imaging of D-2 dopamine receptors

    Energy Technology Data Exchange (ETDEWEB)

    Maziere, B; Loc' h, C; Stulzaft, O; Ottaviani, M; Comar, D; Maziere, M; Hantraye, P

    1986-08-15

    Bromolisuride, an ergoline derivative, was labeled with the positron emitter radionuclide, bromine 76. In vitro and in vivo binding and competition studies in rats demonstrated a high affinity (K/sub D/ = 0.3 nM) and a high specificity of this new radioligand for D-2 dopamine receptors. PET kinetic studies in baboons showed an accumulation of (/sup 76/Br)bromolisuride in the striatum which reached a maximum 30 min post-injection and which could be displaced by haloperidol. All these results indicated that this new ligand is certainly suitable for the non-invasive in vivo quantitative imaging of D-2 dopamine receptor sites in human brain. 20 refs.; 6 figs.; 1 table.

  20. Novel one-pot one-step synthesis of 2'-[(18)F]fluoroflumazenil (FFMZ) for benzodiazepine receptor imaging.

    Science.gov (United States)

    Yoon, Young Hyun; Jeong, Jae Min; Kim, Hyung Woo; Hong, Sung Hyun; Lee, Yun-Sang; Kil, Hee Sup; Chi, Dae Yoon; Lee, Dong Soo; Chung, June-Key; Lee, Myung Chul

    2003-07-01

    We describe the synthesis of 2'-[(18)F]fluoroflumazenil (FFMZ), which differs from the typically used [(18)F]fluoroethylflumazenil (FEFMZ) for benzodiazepine receptor imaging. For one-pot one-step labeling, the precursors, 2'-tosyloxyflumazenil (TFMZ) and 2'-mesyloxyflumazenil (MFMZ), were synthesized in three steps. The precursors were successfully labeled with no-carrier-added (18)F-fluoride which was activated by repeated azeotropic distillation with Kryptofix 2.2.2./potassium carbonate in MeCN. An automated system for labeling and purification of [(18)F]FFMZ was developed. Labeling efficiency and radiochemical purity of [(18)F]FFMZ after synthesis by the automated system were 68% and 98%, respectively. Specific binding of [(18)F]FFMZ to central benzodiazepine receptor of rats was demonstrated by phosphoimaging.

  1. Novel one-pot one-step synthesis of 2'-[18F]fluoroflumazenil (FFMZ) for benzodiazepine receptor imaging

    International Nuclear Information System (INIS)

    Young, Hyun Yoon; Jae, Min Jeong; Hyung, Woo Kim; Sung, Hyun Hong; Lee, Yun-Sang; Hee, Sup Kil; Dae, Yoon Chi; Dong, Soo Lee; Chung, June-Key; Myung, Chul Lee

    2003-01-01

    We describe the synthesis of 2'-[ 18 F]fluoroflumazenil (FFMZ), which differs from the typically used [ 18 F]fluoroethylflumazenil (FEFMZ) for benzodiazepine receptor imaging. For one-pot one-step labeling, the precursors, 2'-tosyloxyflumazenil (TFMZ) and 2'-mesyloxyflumazenil (MFMZ), were synthesized in three steps. The precursors were successfully labeled with no-carrier-added 18 F-fluoride which was activated by repeated azeotropic distillation with Kryptofix 2.2.2./potassium carbonate in MeCN. An automated system for labeling and purification of [ 18 F]FFMZ was developed. Labeling efficiency and radiochemical purity of [ 18 F]FFMZ after synthesis by the automated system were 68% and 98%, respectively. Specific binding of [ 18 F]FFMZ to central benzodiazepine receptor of rats was demonstrated by phosphoimaging

  2. Preliminary genetic imaging study of the association between estrogen receptor-α gene polymorphisms and harsh human maternal parenting.

    Science.gov (United States)

    Lahey, Benjamin B; Michalska, Kalina J; Liu, Chunyu; Chen, Qi; Hipwell, Alison E; Chronis-Tuscano, Andrea; Waldman, Irwin D; Decety, Jean

    2012-09-06

    A failure of neural changes initiated by the estrogen surge in late pregnancy to reverse the valence of infant stimuli from aversive to rewarding is associated with dysfunctional maternal behavior in nonhuman mammals. Estrogen receptor-α plays the crucial role in mediating these neural effects of estrogen priming. This preliminary study examines associations between estrogen receptor-α gene polymorphisms and human maternal behavior. Two polymorphisms were associated with human negative maternal parenting. Furthermore, hemodynamic responses in functional magnetic resonance imaging to child stimuli in neural regions associated with social cognition fully mediated the association between genetic variation and negative parenting. This suggests testable hypotheses regarding a biological pathway between genetic variants and dysfunctional human maternal parenting. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  3. Radioligands for brain 5-HT2 receptor imaging in vivo: why do we need them?

    International Nuclear Information System (INIS)

    Busatto, G.F.

    1996-01-01

    Recently, PET and SPET radiotracers with high specificity for 5-HT 2 receptors have been developed. These have been studied in baboons and humans with promising results, displaying a binding profile compatible with the brain distribution of 5-HT 2 receptors. It is predicted that studies with the newly developed 5-HT radioligands will substantially increase knowledge about the pharmacology of brain disorders. (orig./MG)

  4. Microultrasound Molecular Imaging of Vascular Endothelial Growth Factor Receptor 2 in a Mouse Model of Tumor Angiogenesis

    Directory of Open Access Journals (Sweden)

    Joshua J. Rychak

    2007-09-01

    Full Text Available High-frequency microultrasound imaging of tumor progression in mice enables noninvasive anatomic and functional imaging at excellent spatial and temporal resolution, although microultrasonography alone does not offer molecular scale data. In the current study, we investigated the use of microbubble ultrasound contrast agents bearing targeting ligands specific for molecular markers of tumor angiogenesis using high-frequency microultrasound imaging. A xenograft tumor model in the mouse was used to image vascular endothelial growth factor receptor 2 (VEGFR-2 expression with microbubbles conjugated to an anti-VEGFR-2 monoclonal antibody or an isotype control. Microultrasound imaging was accomplished at a center frequency of 40 MHz, which provided lateral and axial resolutions of 40 and 90 μm, respectively. The B-mode (two-dimensional mode acoustic signal from microbubbles bound to the molecular target was determined by an ultrasound-based destruction-subtraction scheme. Quantification of the adherent microbubble fraction in nine tumor-bearing mice revealed significant retention of VEGFR-2-targeted microbubbles relative to control-targeted microbubbles. These data demonstrate that contrast-enhanced microultrasound imaging is a useful method for assessing molecular expression of tumor angiogenesis in mice at high resolution.

  5. {sup 89}Zr-Onartuzumab PET imaging of c-MET receptor dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Pool, Martin; Kol, Arjan; Giesen, Danique; Vries, Elisabeth G.E. de [University of Groningen, Department of Medical Oncology, University Medical Center Groningen, Groningen (Netherlands); Terwisscha van Scheltinga, Anton G.T. [University of Groningen, Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, Groningen (Netherlands); Lub-de Hooge, Marjolijn N. [University of Groningen, Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, Groningen (Netherlands); University of Groningen, Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Groningen (Netherlands)

    2017-08-15

    c-MET and its ligand hepatocyte growth factor are often dysregulated in human cancers. Dynamic changes in c-MET expression occur and might predict drug efficacy or emergence of resistance. Noninvasive visualization of c-MET dynamics could therefore potentially guide c-MET-directed therapies. We investigated the feasibility of {sup 89}Zr-labelled one-armed c-MET antibody onartuzumab PET for detecting relevant changes in c-MET levels induced by c-MET-mediated epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib resistance or heat shock protein-90 (HSP90) inhibitor NVP-AUY-922 treatment in human non-small-cell lung cancer (NSCLC) xenografts. In vitro membrane c-MET levels were determined by flow cytometry. HCC827ErlRes, an erlotinib-resistant clone with c-MET upregulation, was generated from the exon-19 EGFR-mutant human NSCLC cell line HCC827. Mice bearing HCC827 and HCC827ErlRes tumours in opposite flanks underwent {sup 89}Zr-onartuzumab PET scans. The HCC827-xenografted mice underwent {sup 89}Zr-onartuzumab PET scans before treatment and while receiving biweekly intraperitoneal injections of 100 mg/kg NVP-AUY-922 or vehicle. Ex vivo, tumour c-MET immunohistochemistry was correlated with the imaging results. In vitro, membrane c-MET was upregulated in HCC827ErlRes tumours by 213 ± 44% in relation to the level in HCC827 tumours, while c-MET was downregulated by 69 ± 9% in HCC827 tumours following treatment with NVP-AUY-922. In vivo, {sup 89}Zr-onartuzumab uptake was 26% higher (P < 0.05) in erlotinib-resistant HCC827ErlRes than in HCC827 xenografts, while HCC827 tumour uptake was 33% lower (P < 0.001) following NVP-AUY-922 treatment. The results show that {sup 89}Zr-onartuzumab PET effectively discriminates relevant changes in c-MET levels and could potentially be used clinically to monitor c-MET status. (orig.)

  6. (-)-N-[(11)C]propyl-norapomorphine: a positron-labeled dopamine agonist for PET imaging of D(2) receptors.

    Science.gov (United States)

    Hwang, D R; Kegeles, L S; Laruelle, M

    2000-08-01

    Imaging neuroreceptors with radiolabeled agonists might provide valuable information on the in vivo agonist affinity states of receptors of interest. We report here the radiosynthesis, biodistribution in rodents, and imaging studies in baboons of [(11)C]-labeled (-)-N-propyl-norapomorphine [(-)-NPA]. (-)-[(11)C]NPA was prepared by reacting norapomorphine with [(11)C]propionyl chloride and a lithium aluminum hydride reduction. [(11)C]Propionyl chloride was prepared by reacting [(11)C]CO(2) with ethylmagnesium bromide, followed by reacting with phthaloyl chloride. The radiochemical yield of (-)-[(11)C]NPA was 2.5% at end of synthesis (EOS), and the synthesis time was 60 min. The specific activity was 1700+/-1900 mCi/micromol ( N=7; ranged 110-5200 mCi/micromol at EOS). Rodent biodistribution studies showed high uptake of [(11)C](-)-NPA in D(2) receptor-rich areas, and the striatum/cerebellum ratios were 1.7, 3.4, and 4.4 at 5 min, 30 min, and 60 min postinjection, respectively. Pretreating the animals with haloperidol (1 mg/kg) decreased the striatum/cerebellum ratio at 30 min postinjection to 1.3. (-)-[(11)C]NPA was also evaluated via baboon positron emission tomography (PET) studies. Under control conditions ( N=4), rapid uptake of the tracer was observed and the striatum/cerebellum ratio reached 2.86+/-0.15 at 45 min postinjection. Following haloperidol pretreatment (0.2 mg/kg IV), the striatum/cerebellum ratio was 1.29 at 45 min postinjection. The result demonstrated the existence of specific binding of this new tracer to the D(2) receptor. To our knowledge, the current finding of a striatum/cerebellum ratio of 2.8 in baboon was the highest reported with a radiolabeled D(2) agonist. (-)-[(11)C]NPA is a promising new D(2) agonist PET tracer for probing D(2) receptors in vivo using PET.

  7. SPET imaging of central muscarinic receptors with (R,R)[123I]-I-QNB: methodological considerations

    International Nuclear Information System (INIS)

    Norbury, R.; Travis, M.J.; Erlandsson, K.; Waddington, W.; Owens, J.; Ell, P.J.; Murphy, D.G.

    2004-01-01

    Investigations on the effect of normal healthy ageing on the muscarinic system have shown conflicting results. Also, in vivo determination of muscarinic receptor binding has been hampered by a lack of subtype selective ligands and differences in methods used for quantification of receptor densities. Recent in vitro and in vivo work with the muscarinic antagonist (R,R)-I-QNB indicates this ligand has selectivity for m 1 and m 4 muscarinic receptor subtypes. Therefore, we used (R,R)[ 123 I]-I-QNB and single photon emission tomography to study brain m 1 and m 4 muscarinic receptors in 25 healthy female subjects (11 younger subjects, age range 26-32 years and 14 older subjects, age range 57-82 years). Our aims were to ascertain the viability of tracer administration and imaging within the same day, and to evaluate whether normalization to whole brain, compared to normalization to cerebellum, could alter the clinical interpretation of results. Images were analyzed using the simplified reference tissue model and by two ratio methods: normalization to whole brain and normalization to cerebellum. Significant correlations were observed between kinetic analysis and normalization to cerebellum, but not to whole brain. Both the kinetic analysis and normalization to cerebellum showed age-related reductions in muscarinic binding in frontal, orbitofrontal, and parietal regions. Normalization to whole brain, however, failed to detect age-related changes in any region. Here we show that, for this radiotracer, normalizing to a region of negligible specific binding (cerebellum) significantly improves sensitivity when compared to global normalization

  8. Characterization with 3H-haloperidol of the dopamine receptor in the rat kidney particulate preparation

    International Nuclear Information System (INIS)

    Nakajima, Tohru; Kuruma, Isami

    1980-01-01

    The dopamine receptor of rat kidney particulate preparation was identified and characterized by the use of 3 H-haloperidol binding. Binding of 3 H-haloperidol to the kidney particulate preparation was slow and saturable. The dissociation constants (K sub(D)) were 0.41 nM and 5.88 nM, respectively, according to the model of two classes of independent binding sites. Maximal binding of high affinity site was obtained with 166 fmole/mg protein which was about 40% of the total receptor density. A wide variety of neuroleptics at specifically low concentrations in nanomolar range inhibited the 3 H-haloperidol binding. There was an excellent correlation between the affinity of numerous neuroleptics for the kidney particulate preparation and that for the brain striatum. (author)

  9. Tumor-associated macrophages in glioblastoma multiforme-a suitable target for somatostatin receptor-based imaging and therapy?

    Directory of Open Access Journals (Sweden)

    Constantin Lapa

    Full Text Available Glioblastoma multiforme (GBM is the most common primary brain tumor in adults. Tumor-associated macrophages (TAM have been shown to promote malignant growth and to correlate with poor prognosis. [1,4,7,10-tetraazacyclododecane-NN',N″,N'″-tetraacetic acid]-d-Phe1,Tyr3-octreotate (DOTATATE labeled with Gallium-68 selectively binds to somatostatin receptor 2A (SSTR2A which is specifically expressed and up-regulated in activated macrophages. On the other hand, the role of SSTR2A expression on the cell surface of glioma cells has not been fully elucidated yet. The aim of this study was to non-invasively assess SSTR2A expression of both glioma cells as well as macrophages in GBM.15 samples of patient-derived GBM were stained immunohistochemically for macrophage infiltration (CD68, proliferative activity (Ki67 as well as expression of SSTR2A. Anti-CD45 staining was performed to distinguish between resident microglia and tumor-infiltrating macrophages. In a subcohort, positron emission tomography (PET imaging using 68Ga-DOTATATE was performed and the semiquantitatively evaluated tracer uptake was compared to the results of immunohistochemistry.The amount of microglia/macrophages ranged from 50% in the tumor samples with the vast majority being resident microglial cells. A strong SSTR2A immunostaining was observed in endothelial cells of proliferating vessels, in neurons and neuropile. Only faint immunostaining was identified on isolated microglial and tumor cells. Somatostatin receptor imaging revealed areas of increased tracer accumulation in every patient. However, retention of the tracer did not correlate with immunohistochemical staining patterns.SSTR2A seems not to be overexpressed in GBM samples tested, neither on the cell surface of resident microglia or infiltrating macrophages, nor on the surface of tumor cells. These data suggest that somatostatin receptor directed imaging and treatment strategies are less promising in GBM.

  10. Preclinical evaluation of "1"1"1In-DOTA-Bombesin analogue for peptide receptor targeted imaging

    International Nuclear Information System (INIS)

    Salgueiro, C.; Castiglia, S.G. de; Tesan, F.; Salgueiro, M.J.

    2017-01-01

    Peptide receptors are very important targets for imaging and therapy. The bombesin family is becoming significant, in special the gastrine-releasing peptide receptor (GRPr) that has been found in Prostate and Breast tumors. The aim of this work is to label [DOTA-Pro1,Tyr4] BN with "1"1"1InCl3 and study its efficacy in normal and tumor animals. Radiolabeling experiences were made to find the best peptide : radionuclide relationship. The radiochemical purity was determined by Sep-pak C18 cartridge (Waters) and ITLC-SG using 50mM EDTA in 0.1M ammonium acetate (pH 5.5) and 3.5%(v/v) ammonia/methanol 1:1. Gamma imaging studies were made 24 hs after injection of the product in control rats. On the other hand gamma imaging studies were made at 24 hs in tumor bearing nude mice too. The tumor was induced by subcutaneous injection of PC3 cells. For biodistribution studies animals were sacrificed and blood, pancreas, intestine, kidneys, liver, lungs, femoral muscle and tumor were analyzed. The results were expressed as %ID/g of tissue. Radiolabeling experiments allowed us to obtain an stable product with >95% of radiochemical purity and 5.78MBq/nmol of specific activity, with a ratio of 13μg peptide per In-111 mCi. The normal and tumor animals imaging show physiological uptake in kidneys and a biodistribution according to bibliography. A specific uptake is evidenced in tumor. Our results show a radiochemical stable compound for 48 hs and suitable for GRPr imaging. (authors) [es

  11. In vivo type 2 cannabinoid receptor-targeted tumor optical imaging using a near infrared fluorescent probe.

    Science.gov (United States)

    Zhang, Shaojuan; Shao, Pin; Bai, Mingfeng

    2013-11-20

    The type 2 cannabinoid receptor (CB2R) plays a vital role in carcinogenesis and progression and is emerging as a therapeutic target for cancers. However, the exact role of CB2R in cancer progression and therapy remains unclear. This has driven the increasing efforts to study CB2R and cancers using molecular imaging tools. In addition, many types of cancers overexpress CB2R, and the expression levels of CB2R appear to be associated with tumor aggressiveness. Such upregulation of the receptor in cancer cells provides opportunities for CB2R-targeted imaging with high contrast and for therapy with low side effects. In the present study, we report the first in vivo tumor-targeted optical imaging using a novel CB2R-targeted near-infrared probe. In vitro cell fluorescent imaging and a competitive binding assay indicated specific binding of NIR760-mbc94 to CB2R in CB2-mid delayed brain tumor (DBT) cells. NIR760-mbc94 also preferentially labeled CB2-mid DBT tumors in vivo, with a 3.7-fold tumor-to-normal contrast enhancement at 72 h postinjection, whereas the fluorescence signal from the tumors of the mice treated with NIR760 free dye was nearly at the background level at the same time point. SR144528, a CB2R competitor, significantly inhibited tumor uptake of NIR760-mbc94, indicating that NIR760-mbc94 binds to CB2R specifically. In summary, NIR760-mbc94 specifically binds to CB2R in vitro and in vivo and appears to be a promising molecular tool that may have great potential for use in diagnostic imaging of CB2R-positive cancers and therapeutic monitoring as well as in elucidating the role of CB2R in cancer progression and therapy.

  12. Development of a Tc-99m labeled sigma-2 receptor-specific ligand as a potential breast tumor imaging agent

    International Nuclear Information System (INIS)

    Choi, Seok-Rye; Yang, Biao; Ploessl, Karl; Chumpradit, Sumalee; Wey, Shiaw-Pyng; Acton, Paul D.; Wheeler, Kenneth; Mach, Robert H.; Kung, Hank F.

    2001-01-01

    A novel in vivo imaging agent, 99m Tc labeled [(N-[2-((3'-N'-propyl-[3,3,1]aza-bicyclononan-3α-yl)(2''-methoxy-5- methyl-phenylcarbamate) (2-mercaptoethyl)amino)acetyl]-2-aminoethanethiolato] technetium(V) oxide), [ 99m Tc]2, displaying specific binding towards sigma-2 receptors was prepared and characterized. In vitro binding assays showed that the rhenium surrogate of [ 99m Tc]2, Re-2, displayed excellent binding affinity and selectivity towards sigma-2 receptors (K i = 2,723 and 22 nM for sigma-1 and sigma-2 receptor, respectively). Preparation of [ 99m Tc]2 was achieved by heating the S-protected starting material, 1, in the presence of acid, reducing agent (stannous glucoheptonate) and sodium [ 99m Tc]pertechnetate. The lipophilic racemic mixture was successfully prepared in 10 to 50% yield and the radiochemical purity was >98%. Separation of the isomers, peak A and peak B, was successfully achieved by using a chiralpak AD column eluted with an isocratic solvent (n-hexane/isopropanol; 3:1; v/v). The peak A and peak B appear to co-elute with the isomers of the surrogate, Re-2, under the same HPLC condition. Biodistribution studies in tumor bearing mice (mouse mammary adenocarcinoma, cell line 66, which is known to over-express sigma-2 receptors) showed that the racemic [ 99m Tc]2 localized in the tumor. Uptake in the tumor was 2.11, 1.30 and 1.11 %dose/gram at 1, 4 and 8 hr post iv injection, respectively, suggesting good uptake and retention in the tumor cells. The tumor uptake was significantly, but incompletely, blocked (about 25-30% blockage) by co-injection of 'cold' (+)pentazocine or haloperidol (1 mg/Kg). A majority of the radioactivity localized in the tumor tissue was extractable (>60%), and the HPLC analysis showed that it is the original compound, racemic [ 99m Tc]2 (>98% pure). The distribution of the purified peak A and peak B was determined in the same tumor bearing mice at 4 hr post iv injection. The tumor uptake was similar for both isomers

  13. Temporal changes in serum creatine kinase concentration and degree of muscle rigidity in 24 patients with neuroleptic malignant syndrome

    Directory of Open Access Journals (Sweden)

    Nisijima K

    2013-06-01

    Full Text Available Koichi Nisijima, Katutoshi ShiodaDepartment of Psychiatry, Jichi Medical University, Tochigi, JapanAbstract: Neuroleptic malignant syndrome (NMS is a dangerous adverse response to antipsychotic drugs. It is characterized by the four major clinical symptoms of hyperthermia, severe muscle rigidity, autonomic dysfunction, and altered mental state. Serum creatine kinase (CK elevation occurs in over 90% of NMS cases. In the present study, the detailed temporal changes in serum CK and degree of muscle rigidity, and the relationship between CK concentration and degree of muscle rigidity over the time course from fever onset, were evaluated in 24 affected patients. The results showed that serum CK peaked on day 2 after onset of fever and returned to within normal limits at day 12. Mild muscle rigidity was observed before the onset of fever in 17 of 24 cases (71%. Muscle rigidity was gradually exacerbated and worsened until day 4 after onset of fever. These findings confirm physicians' empirical understanding of serum CK concentrations and muscle rigidity in NMS based on data accumulated from numerous patients with the syndrome, and they indicate that serum CK may contribute to the early detection of NMS.Keywords: neuroleptic malignant syndrome, creatine kinase, muscle rigidity

  14. Revealing dynamically-organized receptor ion channel clusters in live cells by a correlated electric recording and super-resolution single-molecule imaging approach.

    Science.gov (United States)

    Yadav, Rajeev; Lu, H Peter

    2018-03-28

    The N-methyl-d-aspartate (NMDA) receptor ion-channel is activated by the binding of ligands, along with the application of action potential, important for synaptic transmission and memory functions. Despite substantial knowledge of the structure and function, the gating mechanism of the NMDA receptor ion channel for electric on-off signals is still a topic of debate. We investigate the NMDA receptor partition distribution and the associated channel's open-close electric signal trajectories using a combined approach of correlating single-molecule fluorescence photo-bleaching, single-molecule super-resolution imaging, and single-channel electric patch-clamp recording. Identifying the compositions of NMDA receptors, their spatial organization and distributions over live cell membranes, we observe that NMDA receptors are organized inhomogeneously: nearly half of the receptor proteins are individually dispersed; whereas others exist in heterogeneous clusters of around 50 nm in size as well as co-localized within the diffraction limited imaging area. We demonstrate that inhomogeneous interactions and partitions of the NMDA receptors can be a cause of the heterogeneous gating mechanism of NMDA receptors in living cells. Furthermore, comparing the imaging results with the ion-channel electric current recording, we propose that the clustered NMDA receptors may be responsible for the variation in the current amplitude observed in the on-off two-state ion-channel electric signal trajectories. Our findings shed new light on the fundamental structure-function mechanism of NMDA receptors and present a conceptual advancement of the ion-channel mechanism in living cells.

  15. Synthesis and biological evaluation of carbon-11- and fluorine-18-labeled 2-oxoquinoline derivatives for type 2 cannabinoid receptor positron emission tomography imaging

    International Nuclear Information System (INIS)

    Evens, Nele; Muccioli, Giulio G.; Houbrechts, Nele; Lambert, Didier M.; Verbruggen, Alfons M.; Van Laere, Koen; Bormans, Guy M.

    2009-01-01

    Introduction: The type 2 cannabinoid (CB 2 ) receptor is part of the endocannabinoid system and has been suggested as a mediator of several central and peripheral inflammatory processes. Imaging of the CB 2 receptor has been unsuccessful so far. We synthesized and evaluated a carbon-11- and a fluorine-18-labeled 2-oxoquinoline derivative as new PET tracers with high specificity and affinity for the CB 2 receptor. Methods: Two 2-oxoquinoline derivatives were synthesized and radiolabeled with either carbon-11 or fluorine-18. Their affinity and selectivity for the human CB 2 receptor were determined. Biological evaluation was done by biodistribution, radiometabolite and autoradiography studies in mice. Results: In vitro studies showed that both compounds are high affinity CB 2 -specific inverse agonists. Biodistribution study of the tracers in mice showed a high in vivo initial brain uptake and fast brain washout, in accordance with the low CB 2 receptor expression levels in normal brain. A persistently high in vivo binding to the spleen was observed, which was inhibited by pretreatment with two structurally unrelated CB 2 selective inverse agonists. In vitro autoradiography studies with the radioligands confirmed CB 2 -specific binding to the mouse spleen. Conclusion: We synthesized two novel CB 2 receptor PET tracers that show high affinity/selectivity for CB 2 receptors. Both tracers show favourable characteristics as radioligands for central and peripheral in vivo visualization of the CB 2 receptor and are promising candidates for primate and human CB 2 PET imaging.

  16. Brain imaging of serotonin 4 receptors in humans with [11C]SB207145-PET

    DEFF Research Database (Denmark)

    Marner, Lisbeth; Gillings, Nic; Madsen, Karine

    2010-01-01

    Pharmacological stimulation of the serotonin 4 (5-HT(4)) receptor has shown promise for treatment of Alzheimer's disease and major depression. A new selective radioligand, [(11)C]SB207145, for positron emission tomography (PET) was used to quantify brain 5-HT(4) receptors in sixteen healthy......(max) was in accordance with post-mortem brain studies (Spearman's r=0.83, p=0.04), and the regional binding potentials, BP(ND), were on average 2.6 in striatum, 0.42 in prefrontal cortex, and 0.91 in hippocampus. We found no effect of sex but a decreased binding with age (p=0.046). A power analysis showed that, given......-HT(4) receptor binding in human brain can be reliably assessed with [(11)C]SB207145, which is encouraging for future PET studies of drug occupancy or patients with neuropsychiatric disorders....

  17. Dual-purpose linker for alpha helix stabilization and imaging agent conjugation to glucagon-like peptide-1 receptor ligands.

    Science.gov (United States)

    Zhang, Liang; Navaratna, Tejas; Liao, Jianshan; Thurber, Greg M

    2015-02-18

    Peptides display many characteristics of efficient imaging agents such as rapid targeting, fast background clearance, and low non-specific cellular uptake. However, poor stability, low affinity, and loss of binding after labeling often preclude their use in vivo. Using glucagon-like peptide-1 receptor (GLP-1R) ligands exendin and GLP-1 as a model system, we designed a novel α-helix-stabilizing linker to simultaneously address these limitations. The stabilized and labeled peptides showed an increase in helicity, improved protease resistance, negligible loss or an improvement in binding affinity, and excellent in vivo targeting. The ease of incorporating azidohomoalanine in peptides and efficient reaction with the dialkyne linker enable this technique to potentially be used as a general method for labeling α helices. This strategy should be useful for imaging beta cells in diabetes research and in developing and testing other peptide targeting agents.

  18. A radiogallium-DOTA-based bivalent peptidic ligand targeting a chemokine receptor, CXCR4, for tumor imaging.

    Science.gov (United States)

    Sano, Kohei; Masuda, Ryo; Hisada, Hayato; Oishi, Shinya; Shimokawa, Kenta; Ono, Masahiro; Fujii, Nobutaka; Saji, Hideo; Mukai, Takahiro

    2014-03-01

    We have developed a novel radiogallium (Ga)-DOTA-based bivalent peptidic ligand targeting a chemokine receptor, CXCR4, for tumor imaging. A CXCR4 imaging probe with two CXCR4 antagonists (Ac-TZ14011) on Ga-DOTA core, Ga-DOTA-TZ2, was synthesized, and the affinity and binding to CXCR4 was evaluated in CXCR4 expressing cells in vitro. The affinity of Ga-DOTA-TZ2 for CXCR4 was 20-fold greater than the corresponding monovalent probe, Ga-DOTA-TZ1. (67)Ga-DOTA-TZ2 showed the significantly higher accumulation in CXCR4-expressing tumor cells compared with (67)Ga-DOTA-TZ1, suggesting the bivalent effect enhances its binding to CXCR4. The incorporation of two CXCR4 antagonists to Ga-DOTA could be effective in detecting CXCR4-expressing tumors. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Synthesis of 99mTc-oxybutynin for M3-receptor-mediated imaging of urinary bladder

    International Nuclear Information System (INIS)

    Moustapha, M.E.; Benha University, Benha; Motaleb, M.A.; Ibrahim, I.T.

    2011-01-01

    Radiolabeling of oxybutynin, a muscarinic acetylcholine (mACh) receptor antagonist agent with 99m Tc is of considerable interest for imaging of urinary bladder. This study is aimed to optimize radiolabeling yield of oxybutynin with 99m Tc using SnCl 2 x 2H 2 O as a reducing agent with respect to factors that affect the reaction conditions such as oxybutynin amount, stannous chloride amount, reaction time and pH of the reaction mixture. In vitro stability of the radiolabeled complex was checked and it was found to be stable for up to 8 h. 99m Tc-oxybutynin was injected via subcutaneous and intravenous administration routes into normal Sprague-Dawley rats. Biodistribution studies have revealed that 99m Tc-oxybutynin exhibits high affinity and specificity for the muscarinic M 3 subtype located on the smooth muscle of urinary bladder relative to the M 1 and M 2 subtypes of the G protein coupled receptor (GPCR) superfamily. In vivo uptake of subcutaneous 99m Tc-oxybutynin in urinary bladder was 19.6 ± 0.42% ID at 0.5 h, whereas in intravenous administration route the accumulation in the urinary bladder was found to be 9.4 ± 0.31% ID at 0.5 h post injection. Administration of cold oxybutynin effectively blocked urinary bladder uptake and further confirms the high specificity of this complex for the M 3 receptor. (author)

  20. [18F]fluoromethylated phenyl-pyrroles and 7-azaindole analog as potential dopamine D4 receptor imaging agents

    International Nuclear Information System (INIS)

    Ji, D. Y.; Oh, S. Z.; Choi, Y. S.; Lee, K. C.; Kim, S. E.; Choi, Y.; Lee, K. H.; Kim, B. T.

    1997-01-01

    An association between the dopamine D 4 receptor and schizophrenia was recently suggested and the D 4 receptor antagonists may thus have potential in elucidating the role of the receptor in schizophrenic patients. The purpose of this study was to develop some of these antagonists as potential dopamine D 4 receptor imaging agents for PET. We have prepared 1-(3-[ 18 F]fluoromethylphenyl)-3-([4-(pyridin-2-yl)piperazin-1-yl)methyl) pyrrole (1), 1-(3-[ 18 F]fluoromethylphenyl)-3-([4-(pyridin-2-yl)piperazin-1-yl)methyl) pyrrole (2), and 3-([4-(4-[ 18 F]fluoro methylbenzyl)piperazin-1-yl)methyl)-1H-pyrrolo(2,3,-b)pyridine (3) as potential imaging agents for the dopamine D 4 receptor for PET. The compounds [ 18 F]1 and [ 18 F]2 were prepared by coupling of (3-[ 18 F]fluoromethylphenyl)-pyrrol-1- yl-3-aldehyde and the piperazine moiety in the presence of NaBH 3 CN. The [ 18 F]fluorinated aldehyde was obtained in 60-85% yield by the displacement of the corresponding mesylate with F-18-(THF, 90 .deg. C, 5 min). HPLC purification (Alltech Econosil C-18 columm, 250 x 10 mm, 35: 65 = 0.1M NH 4 CI 2 H : CH 3 OH, 4 ml/min, t R =26.6 min) gave the [ 18 F]1 and [ 18 F]2 in 7-12% yield. In the case of azaindole 3, a methlene link was inserted between the piperazinyl and a fluoromethyl phenyl group. Radiochemical synthesis of the [ 18 F]3 was carried out by coupling of the piperazne moiety and [ 18 F]fluoromethylbenzyl mesylate in the presence of NEt 3 (3:1-CH 3 CN: DMF, 120 .deg. C, 30 min). Purification was carried out by HPLC using a C-18 column (Alltech Econosil, 50 x 10 mm, 100% 0.1M NH 4 CO 2 H for 5 min followed by 40:60=0.1 M NH 4 CO 2 H : MeOH, 4 ml/min t R =28.7 min). The time of synthesis including HPLC purification was 100 min. The overall yield of [ 18 F]3 was 10-15% with a radiochemical purity better than 97% and a specific activity greater than 1000 ci/mmol

  1. Imaging evidence for endothelin ETA/ETB receptor heterodimers in isolated rat mesenteric resistance arteries

    DEFF Research Database (Denmark)

    Kapsokalyvas, Dimitrios; Schiffers, Paul M H; Maij, Nathan

    2014-01-01

    AIMS: In engineered cells, endothelin ETA and ETB receptors can heterodimerize. We tested whether this can also be observed in native tissue. MAIN METHODS: Rat mesenteric resistance arteries (rMRA) were maintained in organ culture for 24h to upregulate ETB-mediated contractions in addition to the...

  2. Gastrin-releasing peptide receptor imaging in human breast carcinoma versus immunohistochemistry

    NARCIS (Netherlands)

    de Wiele, Christophe Van; Phonteyne, Philippe; Pauwels, Patrick; Goethals, Ingeborg; Van den Broecke, Rudi; Cocquyt, Veronique; Dierckx, Rudi Andre

    This study reports on the uptake of (99m)Tc-RP527 by human breast carcinoma and its relationship to gastrin-releasing peptide receptor (GRIP-R) expression as measured by immunohistochemistry (IHC). Methods: Nine patients referred because of a clinical diagnosis suggestive of breast carcinoma and 5

  3. Live cell imaging unveils multiple domain requirements for in vivo dimerization of the glucocorticoid receptor

    DEFF Research Database (Denmark)

    Presman, Diego M; Ogara, M Florencia; Stortz, Martín

    2014-01-01

    Glucocorticoids are essential for life, but are also implicated in disease pathogenesis and may produce unwanted effects when given in high doses. Glucocorticoid receptor (GR) transcriptional activity and clinical outcome have been linked to its oligomerization state. Although a point mutation wi...

  4. PET Imaging of Steroid Receptor Expression in Breast and Prostate Cancer

    NARCIS (Netherlands)

    Hospers, G. A. P.; Helmond, F. A.; Dierckx, R. A.; de Vries, Emma; de Vries, Erik

    2008-01-01

    The vast majority of breast and prostate cancers express specific receptors for steroid hormones, which play a pivotal role in tumor progression. Because of the efficacy of endocrine therapy combined with its relatively mild side-effects, this intervention has nowadays become the treatment of choice

  5. Imaging of persistent cAMP signaling by internalized G protein-coupled receptors.

    Science.gov (United States)

    Calebiro, Davide; Nikolaev, Viacheslav O; Lohse, Martin J

    2010-07-01

    G protein-coupled receptors (GPCRs) are the largest family of plasma membrane receptors. They mediate the effects of several endogenous cues and serve as important pharmacological targets. Although many biochemical events involved in GPCR signaling have been characterized in great detail, little is known about their spatiotemporal dynamics in living cells. The recent advent of optical methods based on fluorescent resonance energy transfer allows, for the first time, to directly monitor GPCR signaling in living cells. Utilizing these methods, it has been recently possible to show that the receptors for two protein/peptide hormones, the TSH and the parathyroid hormone, continue signaling to cAMP after their internalization into endosomes. This type of intracellular signaling is persistent and apparently triggers specific cellular outcomes. Here, we review these recent data and explain the optical methods used for such studies. Based on these findings, we propose a revision of the current model of the GPCR-cAMP signaling pathway to accommodate receptor signaling at endosomes.

  6. SPECT imaging of D2 dopamine receptors and endogenous dopamine release in mice

    NARCIS (Netherlands)

    Jongen, C.; De Bruin, K.; Beekman, F.J.; Booij, J.

    2008-01-01

    Purpose: The dopamine D2 receptor (D2R) is important in the mediation of addiction. [123I]iodobenzamide (IBZM), a SPECT ligand for the D2R, has been used for in vivo studies of D2R availability in humans, monkeys, and rats. Although mouse models are important in the study of addiction, [123I]IBZM

  7. In vivo imaging of GABAA receptors using sequential whole-volume iodine-123 iomazenil single-photon emission tomography

    International Nuclear Information System (INIS)

    Busatto, G.F.; Pilowsky, L.S.; Costa, D.C.; Ell, P.J.; Lingford-Hughes, A.; Kerwin, R.W.

    1995-01-01

    Using a brain-dedicated triple-headed single-photon emission tomography (SPET) system, a sequential whole-volume imaging protocol has been devised to evaluate the regional distribution of iodine-123 iomazenil binding to GABA A receptors in the entire brain. The protocol was piloted in eight normal volunteers (seven males and one female; mean age, 24.8±3.9 years). The patterns obtained were largely compatible with the known distribution of GABA A receptors in the brain as reported in autoradiographic studies, with cerebral cortical regions, particularly the occipital and frontal cortices, displaying the highest 123 I-iomazenil uptake. Measures of time to peak uptake and tracer washout rates presented with the same pattern of regional variation, with later times to peak and slower washout rates in cortical regions compared to other brain areas. Semiquantitative analysis of the data using white matter/ventricle regions as reference demonstrated a plateau of specific 123 I-iomazenil binding in neocortical and cerebellar regions from 60-75 min onwards. These data demonstrate the feasibility of sequential, dynamic whole-volume 123 I-iomazenil SPET imaging. The protocol may be particularly useful in the investigation of neuropsychiatric conditions which are likely to involve more than one focus of GABA abnormalities, such as anxiety disorders and schizophrenia. (orig.)

  8. Cyclopentadienyl tricarbonyl complexes of 99mTc for the in vivo imaging of the serotonin 5-HT 1a receptor in the brain

    International Nuclear Information System (INIS)

    Saidi, Mouldi; Trabelsi, Adel; MEKNI, Abdelkader; Kretzschmar, M.; Sefert, S.; Bergmann, R.; Pietzsch, H.-J.

    2005-01-01

    The present interest in the 5-HT 1a receptor is due to its implicated role in several major neuropsychiatric disorders such as depression, eating disorders and anxiety. For the diagnosis of these pathophysiological processes it is important to have radioligands in hand able to specifically bind on the 5-HT 1a receptor in order to allow brain imaging. due to the optimal radiation properties of 99mTc there is a considerable interest in the development of 99mTc radiopharmaceuticals for imaging serotonergic CNS receptors using single-photon emission tomography (SPET). Here we introduce two cyclopentadienyl technitium tricarbonyl conjugates of piperidine derivatives which show high accumulation of radioactivity in brain areas rich in 5-HT 1a receptors

  9. Synthesis, radiolabeling and bioevaluation of a novel arylpiperazine derivative containing triazole as a 5-HT1A receptor imaging agents

    International Nuclear Information System (INIS)

    Hassanzadeh, Leila; Erfani, Mostafa; Najafi, Reza; Shafiei, Mohammad; Amini, Mohsen; Shafiee, Abbass; Ebrahimi, Seyed Esmaeil Sadat

    2013-01-01

    Introduction: It has been recognized that serotonin plays a main role in various pathological conditions such as anxiety, depression, aggressiveness, schizophrenia, suicidal behavior, panic and autism. 1-(2-Methoxyphenyl) piperazine pharmacophore, a fragment of the true 5-HT 1A antagonist WAY100635, is found in numerous selective 5-HT 1A imaging agents. In this paper, we have reported the synthesis of a novel derivative of 1-(2-methoxyphenyl) piperazine that is labeled with 99m Tc (CO) 3 via click chemistry. Methods: The bidentate alkyne, propargylglycine was reacted with phenyl piperazine triazole derivative in the presence of a catalytic amount of Cu (I) to form tridentate ligand. The ligand was radiolabeled with the precursor [ 99m Tc] [(H 2 O) 3 (CO) 3 ] + and characterized by HPLC. The bioevaluation of radio labeled ligand was carried out in rats. Results: Triazole complex was labeled by 99m Tc-tricarbonyl and its radiochemical yield was more than > 95% which was determined by HPLC. In vivo stability studies in human serum albumin show a 93% ratio of complex after a 24 h period. The calculated partition coefficient (logP) was 0.34 ± 0.02. Receptor binding assays indicated about 70% specific binding of radioligand to 5-HT 1A receptors. Biodistribution studies have shown brain hippocampus uptake of 0.40 ± 0.08 %ID/g at 30 min post injection. Conclusions: Results indicate that this 99m Tc-tricabonyl-arylpiperazine derivative has specific binding to 5-HT 1A receptors and presented suitable characters for its use as a CNS imaging agent

  10. Bromine-77-labeled estrogen receptor-binding radiopharmaceuticals for breast tumor imaging

    International Nuclear Information System (INIS)

    McElvany, K.D.

    1985-01-01

    Two derivatives of 16α-bromoestradiol, both with and without an 11β-methoxy substituent, have been labeled with bromine-77 and evaluated as potential breast tumor imaging agents. Extensive characterization of these radiotracers in animal models has demonstrated their effective concentration in estrogen target tissues. Preliminary clinical studies have demonstrated the potential of radiolabeled estrogens for breast tumor imaging; however, the suboptimal decay properties of bromine-77 limit the utility of these agents in imaging studies. These results with 77 -Br-labeled estrogens suggest that estrogen derivatives labeled with other radionuclides should provide enhanced image resolution with various imaging devices. Although the decay characteristics of bromine-77 are such that it is not ideally suited to imaging with conventional gamma cameras, it may be a useful radionuclide for therapeutic applications

  11. Quantitative Time-Resolved Fluorescence Imaging of Androgen Receptor and Prostate-Specific Antigen in Prostate Tissue Sections.

    Science.gov (United States)

    Krzyzanowska, Agnieszka; Lippolis, Giuseppe; Helczynski, Leszek; Anand, Aseem; Peltola, Mari; Pettersson, Kim; Lilja, Hans; Bjartell, Anders

    2016-05-01

    Androgen receptor (AR) and prostate-specific antigen (PSA) are expressed in the prostate and are involved in prostate cancer (PCa). The aim of this study was to develop reliable protocols for reproducible quantification of AR and PSA in benign and malignant prostate tissue using time-resolved fluorescence (TRF) imaging techniques. AR and PSA were detected with TRF in tissue microarrays from 91 PCa patients. p63/ alpha-methylacyl-CoA racemase (AMACR) staining on consecutive sections was used to categorize tissue areas as benign or cancerous. Automated image analysis was used to quantify staining intensity. AR intensity was significantly higher in AMACR+ and lower in AMACR- cancer areas as compared with benign epithelium. The PSA intensity was significantly lower in cancer areas, particularly in AMACR- glands. The AR/PSA ratio varied significantly in the AMACR+ tumor cells as compared with benign glands. There was a trend of more rapid disease progression in patients with higher AR/PSA ratios in the AMACR- areas. This study demonstrates the feasibility of developing reproducible protocols for TRF imaging and automated image analysis to study the expression of AR and PSA in benign and malignant prostate. It also highlighted the differences in AR and PSA protein expression within AMACR- and AMACR+ cancer regions. © 2016 The Histochemical Society.

  12. In vivo binding and autoradiographic imaging of (+)-3-[125I]Iodo-MK-801 to the NMDA receptor-channel complex in rat brain

    International Nuclear Information System (INIS)

    Gibson, R.E.; Burns, H.D.; Thorpe, H.H.; Waisi Eng; Ransom, R.; Solomon, H.

    1992-01-01

    Radioiodinated (+)-3-Iodo-MK-801 is a high affinity radioligand for the N-methyl-D-aspartate (NMDA) receptor-channel complex. We have demonstrated in vivo localization in the CNS of rat which is stereoselective and blocked by coinjection of unlabeled MK-801. Autoradiography indicates localization in vivo which is in concordance with in vitro autoradiographic studies. These results indicate that radioiodinated (+)-3-Iodo-MK-801 is a useful probe for in vitro and in vivo autoradiographic studies and suggest that radioligands for the NMDA receptor may be developed which will provide in vivo images of receptor distribution in man. (author)

  13. Anti-N-methyl-D-aspartate receptor encephalitis concomitant with multifocal subcortical white matter lesions on magnetic resonance imaging: a case report and review of the literature.

    Science.gov (United States)

    Wang, Rui-Jin; Chen, Bu-Dong; Qi, Dong

    2015-07-08

    Anti-N-methyl-D-aspartate receptor encephalitis is a severe autoimmune disorder characterized by severe psychiatric symptoms, seizures, decreased consciousness, autonomic dysregulation, and dyskinesias. Multifocal subcortical white matter lesions on fluid-attenuated inversion recovery and diffuse weighted images have rarely been reported in previous literature, and serial magnetic resonance imaging changes after plasma exchange have not been presented before. A previously healthy 24-year-old Chinese woman presented with acute psychiatric symptoms characterized by fear and agitation followed by decreased consciousness, dyskinesias, and seizures. Magnetic resonance imaging revealed hyperintense lesions on fluid-attenuated inversion recovery and diffuse weighted images in bilateral subcortical white matter. Cerebrospinal fluid analysis revealed a mild pleocytosis with lymphocytic predominance. Protein and glucose levels were normal. Aquaporin-4 antibodies in serum and cerebrospinal fluid were negative. Identification of anti-N-methyl-D-aspartate receptor antibodies in serum and cerebrospinal fluid confirmed the diagnosis of anti-N-methyl-D-aspartate receptor encephalitis. She was initially treated with combined intravenous immunoglobulin and methylprednisolone without improvement. Plasma exchange was then initiated with good response; the patient made a full recovery after several cycles of plasma exchange. Repeat magnetic resonance imaging performed 1 month after plasma exchange showed partial resolution of the hyperintense lesions in bilateral subcortical white matter, and follow-up magnetic resonance imaging 2 months after plasma exchange showed complete resolution. Anti-N-methyl-D-aspartate receptor encephalitis may be concomitant with multifocal subcortical white matter lesions. Such lesions may resolve after appropriate immunotherapy.

  14. Novel Chemical Strategies for Labeling Small Molecule Ligands for Androgen, Progestin, and Peroxisome Proliferator-Activated Receptors for Imaging Prostate and Breast Cancer and the Heart

    International Nuclear Information System (INIS)

    Katzenellenbogen, John A.

    2007-01-01

    Summary of Progress The specific aims of this project can be summarized as follows: Aim 1: Prepare and evaluate radiolabeled ligands for the peroxisome proliferator-activated receptor γ (PPARγ), a new nuclear hormone receptor target for tumor imaging and hormone therapy. Aim 2: Prepare steroids labeled with a cyclopentadienyl tricarbonyl technetium or rhenium unit. Aim 3: Prepare and evaluate other organometallic systems of novel design as ligand mimics and halogenated ligands for nuclear hormone receptor-based tumor imaging. As is described in detail in the report, we made excellent progress on all three of these aims; the highlights of our progress are the following: (1) we have prepared the first fluorine-18 labeled analogs of ligands for the PPARγ receptor and used these in tissue distribution studies in rats; (2) we have developed three new methods for the synthesis of cyclopentadienyltricarbonyl rhenium and technetium (CpRe(CO)3 and CpTc(CO)3) systems and we have adapted these to the synthesis of steroids labeled with these metals, as well as ligands for other receptor systems; (3) we have prepared a number of fluorine-18 labeled steroidal and non-steroidal androgens and measured their tissue distribution in rats; (4) we have prepared iodine and bromine-labeled progestins with high progesterone receptor binding affinity; and (5) we have prepared inorganic metal tricarbonyl complexes and steroid receptor ligands in which the metal tricarbonyl unit is an integral part off the ligand core

  15. Nuclear Imaging of Prostate Cancer with Gastrin-Releasing-Peptide-Receptor Targeted Radiopharmaceuticals

    NARCIS (Netherlands)

    Ananias, H. J. K.; de Jong, I. J.; Dierckx, R. A.; van de Wiele, C.; Helfrich, W.; Elsinga, P. H.

    2008-01-01

    Prostate cancer is one of the most common causes of cancer in men. Evaluating the different stages of prostate cancer with conventional imaging techniques still proves difficult. Nuclear imaging might provide a technique that is able to evaluate prostate cancer, but clinical application has been

  16. Analysis of fluorescently labeled substance P analogs: binding, imaging and receptor activation

    Directory of Open Access Journals (Sweden)

    Simmons Mark A

    2001-06-01

    Full Text Available Abstract Background Substance P (SP is a peptide neurotransmitter found in central and peripheral nerves. SP is involved in the control of smooth muscle, inflammation and nociception. The amino acid sequence of SP is Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2. Five different forms of fluorescently labeled SP have recently been synthesized, in which Alexa 488, BODIPY Fl, fluorescein, Oregon Green 488 or tetramethylrhodamine has been covalently linked to SP at Lys3. Here, these novel analogs are characterized as to their ligand binding, receptor activation and fluorescence labeling properties. Results Competition binding studies, using radiolabeled [125I] SP, revealed that all of the labeled forms of SP, except for Alexa 488-SP, effectively competed with radiolabeled SP for binding at the rat SP receptor. With the exception of Alexa 488-SP, all of the SP analogs produced Ca++ elevations and fluorescence labeling of the SP receptor expressed in Chinese hamster ovary cells. In SP-responsive neurons, BODIPY Fl-SP and Oregon Green 488-SP were as effective as unlabeled SP in producing a reduction of the M-type K+ current. Fluorescein-SP produced variable results, while tetramethylrhodamine-SP was less potent and Alexa 488-SP was less effective on intact neurons. Conclusions The above results show that fluorescent labeling of SP altered the biological activity and the binding properties of the parent peptide. Oregon Green 488 and BODIPY FL-SP are the most useful fluorophores for labeling SP without affecting its biological activity. Given these results, these probes can now be utilized in further investigations of the mechanisms of SPR function, including receptor localization, internalization and recycling.

  17. Clone and expression of human transferrin receptor gene: a marker gene for magnetic resonance imaging

    International Nuclear Information System (INIS)

    Li Li; Liu Lizhi; Lv Yanchun; Liu Xuewen; Cui Chunyan; Wu Peihong; Liu Qicai; Ou Shanxing

    2007-01-01

    Objective: To clone human transferrin receptor (hTfR) gene and construct expression vector producing recombination protein. Methods: Human transferrin receptor gene cDNA was amplified by RT-PCR from human embryonic liver and lung tissue. Recombinant pcDNA3-hTfR and pEGFP-Cl-hTfR plasmids were constructed and confirmed by DNA sequencing. These plasmids were stably transfected into the HEK293 cells. The protein expression in vitro was confirmed by Western Blot. The efficiency of expression and the location of hTfR were also investigated by fluorescence microscopy and confocal fluorescence microscopy. Results: The full length cDNA of hTfR gene (2332 bp) was cloned and sequenced. The hTfR (190 000) was overexpressed in transfected HEK293 cells by Western blot analysis. Fluorescence micrographs displayed that the hTfR was expressed at high level and located predominantly in the cell surface. Conclusions: Human transferrin receptor (hTfR) gene has been successfully cloned and obtained high-level expression in HEK293 cells, and the recombination protein of hTfR distributed predominantly in the cell membrane. (authors)

  18. Development and labeling of EP-00652218 analogues, NK1 receptors antagonist, for PET and SPECT imaging

    International Nuclear Information System (INIS)

    Bagot-Gueret, C.

    2001-12-01

    The aim of this work was the synthesis and radiosynthesis of compounds labelled either with a positron emitter (fluorine-18, t 1/2 = 109 minutes) or with a gamma emitter (iodine-123, t 1/2 = 16.2 hours), for Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) studies. EP-00652218 is a novel potent antagonist, with a sub-nano-molar affinity towards the NK 1 receptors. In order to develop ligands that could be used either in PET or SPECT, we undertook the synthesis of poly-halogenated analogues of EP-00652218. Compound 17 was synthesized through two different synthetic pathways. A series of original compounds has been obtained from compound 17 by halogen exchanges on the naphthyridone or the benzene ring. These molecules were tested to determine their in vitro affinity towards NK 1 receptors. Compound 21 was labelled with fluorine-18 in 135 minutes and with a 20% radiochemical yield. Compound 26 was radioiodinated following reaction with Na 125 I (t 1/2 = 60.14 days) in a 18% radiochemical yield. Despite expectation, these analogues of EP-00652218 exhibited an insufficient affinity for NK 1 receptors (IC 50 = 10 -7 M) and thus unlikely usable for in vivo studies with PET and SPECT. (author)

  19. (-)-N-[11C]propyl-norapomorphine: a positron-labeled dopamine agonist for PET imaging of D2 receptors

    International Nuclear Information System (INIS)

    Hwang, Dah-Ren; Kegeles, Lawrence S.; Laruelle, Marc

    2000-01-01

    Imaging neuroreceptors with radiolabeled agonists might provide valuable information on the in vivo agonist affinity states of receptors of interest. We report here the radiosynthesis, biodistribution in rodents, and imaging studies in baboons of [ 11 C]-labeled (-)-N-propyl-norapomorphine [(-)-NPA]. (-)-[ 11 C]NPA was prepared by reacting norapomorphine with [ 11 C]propionyl chloride and a lithium aluminum hydride reduction. [ 11 C]Propionyl chloride was prepared by reacting [ 11 C]CO 2 with ethylmagnesium bromide, followed by reacting with phthaloyl chloride. The radiochemical yield of (-)-[ 11 C]NPA was 2.5% at end of synthesis (EOS), and the synthesis time was 60 min. The specific activity was 1700±1900 mCi/μmol ( N=7; ranged 110-5200 mCi/μmol at EOS). Rodent biodistribution studies showed high uptake of [ 11 C](-)-NPA in D 2 receptor-rich areas, and the striatum/cerebellum ratios were 1.7, 3.4, and 4.4 at 5 min, 30 min, and 60 min postinjection, respectively. Pretreating the animals with haloperidol (1 mg/kg) decreased the striatum/cerebellum ratio at 30 min postinjection to 1.3. (-)-[ 11 C]NPA was also evaluated via baboon positron emission tomography (PET) studies. Under control conditions ( N=4), rapid uptake of the tracer was observed and the striatum/cerebellum ratio reached 2.86±0.15 at 45 min postinjection. Following haloperidol pretreatment (0.2 mg/kg IV), the striatum/cerebellum ratio was 1.29 at 45 min postinjection. The result demonstrated the existence of specific binding of this new tracer to the D 2 receptor. To our knowledge, the current finding of a striatum/cerebellum ratio of 2.8 in baboon was the highest reported with a radiolabeled D 2 agonist. (-)-[ 11 C]NPA is a promising new D 2 agonist PET tracer for probing D 2 receptors in vivo using PET

  20. Molecular imaging of σ receptors: synthesis and evaluation of the potent σ1 selective radioligand [18F]fluspidine

    International Nuclear Information System (INIS)

    Fischer, Steffen; Hiller, Achim; Deuther-Conrad, Winnie; Scheunemann, Matthias; Steinbach, Joerg; Brust, Peter; Wiese, Christian; Grosse Maestrup, Eva; Schepmann, Dirk; Wuensch, Bernhard

    2011-01-01

    Neuroimaging of σ 1 receptors in the human brain has been proposed for the investigation of the pathophysiology of neurodegenerative and psychiatric diseases. However, there is a lack of suitable 18 F-labelled PET radioligands for that purpose. The selective σ 1 receptor ligand [ 18 F]fluspidine (1'-benzyl-3-(2-[ 18 F]fluoroethyl)-3H-spiro[[2]benzofuran-1,4'-piperidine]) was synthesized by nucleophilic 18 F - substitution of the tosyl precursor. In vitro receptor binding affinity and selectivity were assessed by radioligand competition in tissue homogenate and autoradiographic approaches. In female CD-1 mice, in vivo properties of [ 18 F]fluspidine were evaluated by ex vivo brain section imaging and organ distribution of intravenously administered radiotracer. Target specificity was validated by organ distribution of [ 18 F]fluspidine after treatment with 1 mg/kg i.p. of the σ receptor antagonist haloperidol or the emopamil binding protein (EBP) inhibitor tamoxifen. In vitro metabolic stability and in vivo metabolism were investigated by LC-MS n and radio-HPLC analysis. [ 18 F]Fluspidine was obtained with a radiochemical yield of 35-45%, a radiochemical purity of ≥ 99.6% and a specific activity of 150-350 GBq/μmol (n = 6) within a total synthesis time of 90-120 min. In vitro, fluspidine bound specifically and with high affinity to σ 1 receptors (K i = 0.59 nM). In mice, [ 18 F]fluspidine rapidly accumulated in brain with uptake values of 3.9 and 4.7%ID/g and brain to blood ratios of 7 and 13 at 5 and 30 min after intravenous application of the radiotracer, respectively. By ex vivo autoradiography of brain slices, resemblance between binding site occupancy of [ 18 F]fluspidine and the expression of σ 1 receptors was shown. The radiotracer uptake in the brain as well as in peripheral σ 1 receptor expressing organs was significantly inhibited by haloperidol but not by tamoxifen. Incubation with rat liver microsomes led to a fast biotransformation of

  1. Characterization with /sup 3/H-haloperidol of the dopamine receptor in the rat kidney particulate preparation

    Energy Technology Data Exchange (ETDEWEB)

    Nakajima, T; Kuruma, I [Nippon Roche Research Center, Kanagawa (Japan)

    1980-12-01

    The dopamine receptor of rat kidney particulate preparation was identified and characterized by the use of /sup 3/H-haloperidol binding. Binding of /sup 3/H-haloperidol to the kidney particulate preparation was slow and saturable. The dissociation constants (K sub(D)) were 0.41 nM and 5.88 nM, respectively, according to the model of two classes of independent binding sites. Maximal binding of high affinity site was obtained with 166 fmole/mg protein which was about 40% of the total receptor density. A wide variety of neuroleptics at specifically low concentrations in nanomolar range inhibited the /sup 3/H-haloperidol binding. There was an excellent correlation between the affinity of numerous neuroleptics for the kidney particulate preparation and that for the brain striatum.

  2. Olanzapine-induced neuroleptic malignant syndrome in a patient with bipolar affective disorder: Does quetiapine holds the solution?

    Directory of Open Access Journals (Sweden)

    Praveen Tripathi

    2013-01-01

    Full Text Available Neuroleptic Malignant Syndrome (NMS is a rare, severe and life threatening condition induced by antipsychotic medications. It is commonly encountered with the use of first generation antipsychotics, however cases of NMS have been reported with the use of second generation antipsychotics like Olanzapine, Risperidone, Paliperidone, Aripiprazole, Ziprasidone, Amisulpride, Quetiapine and Clozapine, though the incidence of such reports is rare. Due to decreased use of first generation antipsychotics, NMS is reported less frequently now a days. In this case report- we highlight the management issues of a patient suffering from bipolar affective disorder, who had developed NMS following intramuscular injection of haloperidol, which was withdrawn and olanzapine was given later on. The patient had again developed NMS with olanzapine. Finally the patient was managed with modified electroconvulsive therapy and discharged on Lithium carbonate and Quetiapine.

  3. Catatonia, neuroleptic malignant syndrome, and cotard syndrome in a 22-year-old woman: a case report.

    Science.gov (United States)

    Weiss, C; Santander, J; Torres, R

    2013-01-01

    The following case study describes a 22-year-old woman with depression and symptoms of psychosis who developed neuroleptic malignant syndrome after using Risperidone, thus requiring life support equipment and Bromocriptine, later recovering after seven days. From a psychiatric and neurological point of view, however, the persistence of catatonic syndrome and Cotard syndrome delusions was observed, based on assertions such as "I do not have a heart," "my heart is not beating," "I can not breathe," "I am breaking apart," "I have no head" (ideas of negation) and statements about the patient being responsible for the "death of the whole world" (ideas of enormity). Brain NMR revealed leukoencephalopathy, interpreted as scar lesions caused by perinatal neurological damage, after discarding other pathologies. The patient responded well to electroconvulsive therapy after 11 sessions. Organic vulnerability to these syndromes, as well as their coexistence and clinical differentiation is discussed in the light of the data observed.

  4. [Treatment of attention deficit disorders in adulthood using psychostimulants and low-dose neuroleptics--a critical case report].

    Science.gov (United States)

    Schmidt, L G; Schlünder, M; Reischies, F M

    1988-03-01

    Psychiatric research and therapy recently evinced increasing interest in patients suffering from attention deficit disorder. "Attention deficit disorder" is a category of mental disorders listed in DSM III, with a separate diagnostic subgroup for attention deficit disorders persisting in adults who had been hyperkinetic in childhood ("attention deficit disorder-residual type"); however, this does not feature in a corresponding manner in the ICD 9 version. Since there are practically no therapy studies in existence within the ICD range that can be relevant for such disorders, we studied the treatment of an adult patient with the psychostimulant fenetylline under clinical conditions and found a significant improvement in attention performance. However, on integration in a long-term day-clinic rehabilitation programme we found that low-dose neuroleptic treatment was on the whole of greater benefit than fenetylline treatment.

  5. Neurokinin-3 Receptor Binding in Guinea Pig, Monkey, and Human Brain: In Vitro and in Vivo Imaging Using the Novel Radioligand, [18F]Lu AF10628.

    Science.gov (United States)

    Varnäs, Katarina; Finnema, Sjoerd J; Stepanov, Vladimir; Takano, Akihiro; Tóth, Miklós; Svedberg, Marie; Møller Nielsen, Søren; Khanzhin, Nikolay A; Juhl, Karsten; Bang-Andersen, Benny; Halldin, Christer; Farde, Lars

    2016-08-01

    Previous autoradiography studies have suggested a marked interspecies variation in the neuroanatomical localization and expression levels of the neurokinin 3 receptor, with high density in the brain of rat, gerbil, and guinea pig, but at the time offered no conclusive evidence for its presence in the human brain. Hitherto available radioligands have displayed low affinity for the human neurokinin 3 receptor relative to the rodent homologue and may thus not be optimal for cross-species analyses of the expression of this protein. A novel neurokinin 3 receptor radioligand, [(18)F]Lu AF10628 ((S)-N-(cyclobutyl(3-fluorophenyl)methyl)-8-fluoro-2-((3-[(18)F]-fluoropropyl)amino)-3-methyl-1-oxo-1,2-dihydroisoquinoline-4-carboxamide), was synthesized and used for autoradiography studies in cryosections from guinea pig, monkey, and human brain as well as for positron emission tomography studies in guinea pig and monkey. The results confirmed previous observations of interspecies variation in the neurokinin 3 receptor brain localization with more extensive distribution in guinea pig than in primate brain. In the human brain, specific binding to the neurokinin 3 receptor was highest in the amygdala and in the hypothalamus and very low in other regions examined. Positron emission tomography imaging showed a pattern consistent with that observed using autoradiography. The radioactivity was, however, found to accumulate in skull bone, which limits the use of this radioligand for in vivo quantification of neurokinin 3 receptor binding. Species differences in the brain distribution of neurokinin 3 receptors should be considered when using animal models for predicting human neurokinin 3 receptor pharmacology. For positron emission tomography imaging of brain neurokinin 3 receptors, additional work is required to develop a radioligand with more favorable in vivo properties. © The Author 2016. Published by Oxford University Press on behalf of CINP.

  6. IGF-1 receptor targeted nanoparticles for image-guided therapy of stroma-rich and drug resistant human cancer.

    Science.gov (United States)

    Zhou, Hongyu; Qian, Weiping; Uckun, Fatih M; Zhou, Zhiyang; Wang, Liya; Wang, Andrew; Mao, Hui; Yang, Lily

    2016-04-17

    Low drug delivery efficiency and drug resistance from highly heterogeneous cancer cells and tumor microenvironment represent major challenges in clinical oncology. Growth factor receptor, IGF-1R, is overexpressed in both human tumor cells and tumor associated stromal cells. The level of IGF-1R expression is further up-regulated in drug resistant tumor cells. We have developed IGF-1R targeted magnetic iron oxide nanoparticles (IONPs) carrying multiple anticancer drugs into human tumors. This IGF-1R targeted theranostic nanoparticle delivery system has an iron core for non-invasive MR imaging, amphiphilic polymer coating to ensure the biocompatibility as well as for drug loading and conjugation of recombinant human IGF-1 as targeting molecules. Chemotherapy drugs, Doxorubicin (Dox), was encapsulated into the polymer coating and/or conjugated to the IONP surface by coupling with the carboxyl groups. The ability of IGF1R targeted theranostic nanoparticles to penetrate tumor stromal barrier and enhance tumor cell killing has been demonstrated in human pancreatic cancer patient tissue derived xenograft (PDX) models. Repeated systemic administrations of those IGF-1R targeted theranostic IONP carrying Dox led to breaking the tumor stromal barrier and improved therapeutic effect. Near infrared (NIR) optical and MR imaging enabled noninvasive monitoring of nanoparticle-drug delivery and therapeutic responses. Our results demonstrated that IGF-1R targeted nanoparticles carrying multiple drugs are promising combination therapy approaches for image-guided therapy of stroma-rich and drug resistant human cancer, such as pancreatic cancer.

  7. Assessment of chitosan-affected metabolic response by peroxisome proliferator-activated receptor bioluminescent imaging-guided transcriptomic analysis.

    Directory of Open Access Journals (Sweden)

    Chia-Hung Kao

    Full Text Available Chitosan has been widely used in food industry as a weight-loss aid and a cholesterol-lowering agent. Previous studies have shown that chitosan affects metabolic responses and contributes to anti-diabetic, hypocholesteremic, and blood glucose-lowering effects; however, the in vivo targeting sites and mechanisms of chitosan remain to be clarified. In this study, we constructed transgenic mice, which carried the luciferase genes driven by peroxisome proliferator-activated receptor (PPAR, a key regulator of fatty acid and glucose metabolism. Bioluminescent imaging of PPAR transgenic mice was applied to report the organs that chitosan acted on, and gene expression profiles of chitosan-targeted organs were further analyzed to elucidate the mechanisms of chitosan. Bioluminescent imaging showed that constitutive PPAR activities were detected in brain and gastrointestinal tract. Administration of chitosan significantly activated the PPAR activities in brain and stomach. Microarray analysis of brain and stomach showed that several pathways involved in lipid and glucose metabolism were regulated by chitosan. Moreover, the expression levels of metabolism-associated genes like apolipoprotein B (apoB and ghrelin genes were down-regulated by chitosan. In conclusion, these findings suggested the feasibility of PPAR bioluminescent imaging-guided transcriptomic analysis on the evaluation of chitosan-affected metabolic responses in vivo. Moreover, we newly identified that downregulated expression of apoB and ghrelin genes were novel mechanisms for chitosan-affected metabolic responses in vivo.

  8. IGF-1 receptor targeted nanoparticles for image-guided therapy of stroma-rich and drug resistant human cancer

    Science.gov (United States)

    Zhou, Hongyu; Qian, Weiping; Uckun, Fatih M.; Zhou, Zhiyang; Wang, Liya; Wang, Andrew; Mao, Hui; Yang, Lily

    2016-05-01

    Low drug delivery efficiency and drug resistance from highly heterogeneous cancer cells and tumor microenvironment represent major challenges in clinical oncology. Growth factor receptor, IGF-1R, is overexpressed in both human tumor cells and tumor associated stromal cells. The level of IGF-1R expression is further up-regulated in drug resistant tumor cells. We have developed IGF-1R targeted magnetic iron oxide nanoparticles (IONPs) carrying multiple anticancer drugs into human tumors. This IGF-1R targeted theranostic nanoparticle delivery system has an iron core for non-invasive MR imaging, amphiphilic polymer coating to ensure the biocompatibility as well as for drug loading and conjugation of recombinant human IGF-1 as targeting molecules. Chemotherapy drugs, Doxorubicin (Dox), was encapsulated into the polymer coating and/or conjugated to the IONP surface by coupling with the carboxyl groups. The ability of IGF1R targeted theranostic nanoparticles to penetrate tumor stromal barrier and enhance tumor cell killing has been demonstrated in human pancreatic cancer patient tissue derived xenograft (PDX) models. Repeated systemic administrations of those IGF-1R targeted theranostic IONP carrying Dox led to breaking the tumor stromal barrier and improved therapeutic effect. Near infrared (NIR) optical and MR imaging enabled noninvasive monitoring of nanoparticle-drug delivery and therapeutic responses. Our results demonstrated that IGF-1R targeted nanoparticles carrying multiple drugs are promising combination therapy approaches for image-guided therapy of stroma-rich and drug resistant human cancer, such as pancreatic cancer.

  9. Nociceptive thermal threshold testing in horses – effect of neuroleptic sedation and neuroleptanalgesia at different stimulation sites

    Science.gov (United States)

    2013-01-01

    Background Aim of the study was to compare the effect of neuroleptic sedation with acepromazine and neuroleptanalgesia with acepromazine and buprenorphine on thermal thresholds (TT) obtained at the nostrils and at the withers. The study was carried out as a randomized, blinded, controlled trial with cross-over design. Thermal thresholds were determined by incremental contact heat applied to the skin above the nostril (N) or the withers (W). Eleven horses were treated with saline (S), acepromazine (0.05 mg/kg) (ACE) or acepromazine and buprenorphine (0.0075 mg/kg) (AB) intravenously (IV). Single stimulations were performed 15 minutes prior and 15, 45, 75, 105, 165, 225, 285, 405 and 525 minutes after treatment. Sedation score, gastrointestinal auscultation score and occurrence of skin lesions were recorded. Data were analysed with analysis of variance for repeated measurements. Results There were no significant differences in TT between N and W with all treatments. The TT remained constant after S and there was no difference in TT between S and ACE. After AB there was a significant increase above baseline in TT until 405 minutes after treatment. Restlessness occurred 30–90 minutes after AB in 7 horses. All horses had reduced to absent borborygmi after AB administration for 165 to 495 minutes. Conclusion Thermal stimulation at both described body areas gives comparable results in the assessment of cutaneous anti-nociception in horses. There is no differential influence of neuroleptic sedation or neuroleptanalgesia on TTs obtained at N or W. Buprenorphine combined with acepromazine has a long lasting anti-nociceptive effect associated with the typical opioid induced side effects in horses. PMID:23837730

  10. Functional magnetic resonance imaging reveals different neural substrates for the effects of orexin-1 and orexin-2 receptor antagonists.

    Directory of Open Access Journals (Sweden)

    Alessandro Gozzi

    Full Text Available Orexins are neuro-modulatory peptides involved in the control of diverse physiological functions through interaction with two receptors, orexin-1 (OX1R and orexin-2 (OX2R. Recent evidence in pre-clinical models points toward a putative dichotomic role of the two receptors, with OX2R predominantly involved in the regulation of the sleep/wake cycle and arousal, and the OX1R being more specifically involved in reward processing and motivated behaviour. However, the specific neural substrates underlying these distinct processes in the rat brain remain to be elucidated. Here we used functional magnetic resonance imaging (fMRI in the rat to map the modulatory effect of selective OXR blockade on the functional response produced by D-amphetamine, a psychostimulant and arousing drug that stimulates orexigenic activity. OXR blockade was produced by GSK1059865 and JNJ1037049, two novel OX1R and OX2R antagonists with unprecedented selectivity at the counter receptor type. Both drugs inhibited the functional response to D-amphetamine albeit with distinct neuroanatomical patterns: GSK1059865 focally modulated functional responses in striatal terminals, whereas JNJ1037049 induced a widespread pattern of attenuation characterised by a prominent cortical involvement. At the same doses tested in the fMRI study, JNJ1037049 exhibited robust hypnotic properties, while GSK1059865 failed to display significant sleep-promoting effects, but significantly reduced drug-seeking behaviour in cocaine-induced conditioned place preference. Collectively, these findings highlight an essential contribution of the OX2R in modulating cortical activity and arousal, an effect that is consistent with the robust hypnotic effect exhibited by JNJ1037049. The subcortical and striatal pattern observed with GSK1059865 represent a possible neurofunctional correlate for the modulatory role of OX1R in controlling reward-processing and goal-oriented behaviours in the rat.

  11. Synthesis and Biological Evaluation of Thiophene-Based Cannabinoid Receptor Type 2 Radiotracers for PET Imaging

    Directory of Open Access Journals (Sweden)

    Ahmed Haider

    2016-07-01

    Full Text Available Over the past two decades, our understanding of the endocannabinoid system has greatly improved due to the wealth of results obtained from exploratory studies. Currently, two cannabinoid receptor subtypes have been well characterized. The cannabinoid receptor type 1 (CB1 is widely expressed in the central nervous system, while the levels of the cannabinoid receptor type 2 (CB2 in the brain and spinal cord of healthy individuals are relatively low. However, recent studies demonstrated a CB2 upregulation on activated microglia upon neuroinflammation, an indicator of neurodegeneration. Our research group aims to develop a suitable positron emission tomography (PET tracer to visualize the CB2 receptor in patients suffering from neurodegenerative diseases. Herein we report two novel thiophene-based 11C-labeled PET ligands designated [11C]AAT-015 and [11C]AAT-778. The reference compounds were synthesized using Gewald reaction conditions to obtain the aminothiophene intermediates, followed by amide formation. Saponification of the esters provided their corresponding precursors. Binding affinity studies revealed Ki values of 3.3 ± 0.5 nM (CB2 and 1.0 ± 0.2 µM (CB1 for AAT-015. AAT-778 showed similar Ki values of 4.3 ± 0.7 nM (CB2 and 1.1 ± 0.1 µM (CB1. Radiosynthesis was carried out under basic conditions using [11C]iodomethane as methylating agent. After semi-preparative HPLC purification both radiolabeled compounds were obtained in 99% radiochemical purity and the radiochemical yields ranged from 12 to 37%. Specific activity was between 96 - 449 GBq/µmol for both tracers. In order to demonstrate CB2 specificity of [11C]AAT-015 and [11C]AAT-778, we carried out autoradiography studies using CB2-positive mouse/rat spleen tissues. The obtained results revealed unspecific binding in spleen tissue that was not blocked by an excess of CB2-specific ligand GW402833. For in vivo analysis, [11C]AAT-015 was administered to healthy rats via tail

  12. Radioligand imaging of α4β2* nicotinic acetylcholine receptors in Alzheimer’s disease and Parkinson’s disease

    International Nuclear Information System (INIS)

    Meyer, P. M.; Tiepolt, S.; Barthel, H.; Hesse, S.; Sabri, O.

    2014-01-01

    The α4β2 * nicotinic acetylcholine receptors (α4β2 * -nAChR) are highly abundant in the human brain. As neuromodulators they play an important role in cognitive functions such as memory, learning and attention as well as mood and motor function. Post mortem studies suggest that abnormalities of α4β2 * -nAChRs are closely linked to histopathological hallmarks of Alzheimer’s disease (AD), such as amyloid aggregates/oligomers and tangle pathology and of Parkinson’s disease (PD) such as Lewy body pathology and the nigrostriatal dopaminergic deficit. In this review we summarize and discuss nicotinic receptor imaging findings of 2-[18F]FA-85380 PET, [ 11 C]nicotine PET and 5-[ 123 I]IA-85380 SPECT studies investigating α4β2 * -nAChR binding in vivo and their relationship to mental dysfunction in the brain of patients with AD and patients out of the spectrum of Lewy body disorders such as PD and Lewy body dementia (DLB). Furthermore, recent developments of novel α4β2*-nAChR-specific PET radioligands, such as (-)[ 18 F]Flubatine or [ 18 F]AZAN are summarized. We conclude that α4β2*-nAChR-specific PET might become a biomarker for early diagnostics and drug developments in patients with AD, DLB and PD, even at early or prodromal stages.

  13. Kit formulated asialoglycoprotein receptor targeting tracer based on copolymer for liver SPECT imaging

    International Nuclear Information System (INIS)

    Liu, Chang; Guo, Zhide; Zhang, Pu; Song, Manli; Zhao, Zuoquan; Wu, Xiaowei; Zhang, Xianzhong

    2014-01-01

    Introduction: Specific targeting of galactose-carrying molecule to ASGP-R in normal hepatocytes has been demonstrated before. In this study, galactosyl polystyrene was synthesized from controllable ratio of functional monomers and radio-labelled with 99m Tc by formulated kit for SPECT imaging of hepatic function. Methods: p(VLA-co-VNI)(46:54) was synthesized by free-radical copolymerization initiated by AIBN, purified by dialysis, lyophilized to kit with Tricine and TPPTS as co-ligands for 99m Tc labeling. Radiotracer 99m Tc-p(VLA-co-VNI)(46:54)(Tricine)(TPPTS) was prepared and evaluated by in vitro stability, in vivo metabolism, ex vivo biodistribution and microSPECT/CT imaging in normal KM mice. MicroSPECT/CT and microMRI imaging were also performed in C57BL/b6 mice with xenograft hepatic carcinoma for hepatic function evaluation. Results: 99m Tc-p(VLA-co-VNI)(46:54)(Tricine)(TPPTS) was obtained in high radio chemical purity (RCP) (> 99%) by using instant kit without further purification and excellent in vitro and in vivo stability. The result of biodistribution showed that liver had high uptake (90.49 ± 10.68 ID%/g) at 30 min after injection and was blocked significantly by cold copolymer. MicroSPECT imaging in normal KM mice at 1 h and 4 h after injection showed good liver retention and targeting properties. Significant defect of activity was observed in the tumor site which was confirmed by MRI imaging. Conclusion: 99m Tc-p(VLA-co-VNI)(46:54)(Tricine)(TPPTS) with lower ratio of targeting moiety has no observable effect on the specific binding affinity and liver uptake. This makes it possible to introduce more imaging units for multi-modality imaging. Furthermore, the instant kit preparation of 99m Tc-labeling provides great potential for the evaluation of hepatocyte function in clinical application

  14. Testing the validity of a receptor kinetic model via TcNGA functional imaging of liver transplant recipients. Final report

    International Nuclear Information System (INIS)

    Stadalnik, R.C.

    1993-01-01

    The author had accomplished the expertise for I-125-HSA plasma volume, galactose clearance for determination of hepatic plasma flow as well as finalizing the kinetic model. They have just completed modifying the microscale Scatchard assay for greater precision of receptor measurement using only 5--10 mg of liver tissue. In addition, he determined during the past year that the most practical method and clinically reasonable measurement of liver volume was to measure the transplanted liver in vivo using Tc-NGA images in the anterior, posterior, and right lateral projections, using the method of Rollo and DeLand. Direct measurement of liver weight obtained during transplant operation was not reliable due to variability of fluid retention in the donor liver secondary to ischemia, preservation fluid, etc., which thereby did not reflect an accurate liver weight which is needed in the kinetic analysis comparison, i.e., V h (hepatic plasma volume)

  15. Live cell imaging unveils multiple domain requirements for in vivo dimerization of the glucocorticoid receptor.

    Directory of Open Access Journals (Sweden)

    Diego M Presman

    2014-03-01

    Full Text Available Glucocorticoids are essential for life, but are also implicated in disease pathogenesis and may produce unwanted effects when given in high doses. Glucocorticoid receptor (GR transcriptional activity and clinical outcome have been linked to its oligomerization state. Although a point mutation within the GR DNA-binding domain (GRdim mutant has been reported as crucial for receptor dimerization and DNA binding, this assumption has recently been challenged. Here we have analyzed the GR oligomerization state in vivo using the number and brightness assay. Our results suggest a complete, reversible, and DNA-independent ligand-induced model for GR dimerization. We demonstrate that the GRdim forms dimers in vivo whereas adding another mutation in the ligand-binding domain (I634A severely compromises homodimer formation. Contrary to dogma, no correlation between the GR monomeric/dimeric state and transcriptional activity was observed. Finally, the state of dimerization affected DNA binding only to a subset of GR binding sites. These results have major implications on future searches for therapeutic glucocorticoids with reduced side effects.

  16. Segregation of lipids near acetylcholine-receptor channels imaged by cryo-EM

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    Nigel Unwin

    2017-07-01

    Full Text Available Rapid communication at the chemical synapse depends on the action of ion channels residing in the postsynaptic membrane. The channels open transiently upon the binding of a neurotransmitter released from the presynaptic nerve terminal, eliciting an electrical response. Membrane lipids also play a vital but poorly understood role in this process of synaptic transmission. The present study examines the lipid distribution around nicotinic acetylcholine (ACh receptors in tubular vesicles made from postsynaptic membranes of the Torpedo ray, taking advantage of the recent advances in cryo-EM. A segregated distribution of lipid molecules is found in the outer leaflet of the bilayer. Apparent cholesterol-rich patches are located in specific annular regions next to the transmembrane helices and also in a more extended `microdomain' between the apposed δ subunits of neighbouring receptors. The particular lipid distribution can be interpreted straightforwardly in relation to the gating movements revealed by an earlier time-resolved cryo-EM study, in which the membranes were exposed briefly to ACh. The results suggest that in addition to stabilizing the protein, cholesterol may play a mechanical role by conferring local rigidity to the membrane so that there is productive coupling between the extracellular and membrane domains, leading to opening of the channel.

  17. Imaging benzodiazepine receptors in man with C-11-suriclone and positron emission tomography

    International Nuclear Information System (INIS)

    Frost, J.J.; Dannals, R.F.; Ravert, H.T.; Wilson, A.A.; Links, J.M.; Trifiletti, R.; Snyder, S.H.; Wagner, H.N. Jr.

    1985-01-01

    Suriclone is a potent cyclopyrrolone, anti-anxiety drug which binds to the benzodiazepine receptor complex (BZR) with high affinity. Suriclone binds to a site on the BZR distinct from the site where benzodiazepines bind. The K/sub D/ of suriclone at 37oC is 0.03 nM. C-11-suriclone (SUR) was synthesized by reacting C-CH3I with the appropriate amine precursor. SUR (1 μg/kg) was injected IV into a baboon alone or with 1 mg/kg of Ro-151788, a benzodiazepine antagonist, and serial PET scans of the brain were obtained. High radioactivity concentrations were observed in the cerebral cortex and cerebellum which contain high densities of BZR, intermediate concentrations in thalamus and low concentrations in the striatum. When Ro-151788 was given a uniform distribution of radioactivity was observed; the radioactivity was reduced to ca. 25% of control values in the brain which was contained within the PET slice. SUR (0.2 μg/kg) was next administered to a human subject. From 30-60 minutes after injection high radioactivity concentrations were observed in the cerebral cortex and cerebellum, intermediate concentrations in the thalamus and a low concentration in the caudate. Radioactivity in the cerebral cortex and cerebellum decreased slowly with time, implying that binding of SUR to a high affinity site had occurred. These results demonstrate utility of SUR for measuring binding to the benzodiazepine receptor complex non-invasively in man

  18. Experimental study of 99mTc-NGA--a imaging agent of hepatic asialo-glycoprotein receptor

    International Nuclear Information System (INIS)

    Zhang Rongjun; Jin Jian; Liang Gaolin; Wan Weixing; Li Wenxin; Tao Yonghui; Hu Mingyang

    2001-01-01

    Galactosyl neo-glycol-albumin (NGA), a specific ligand of asialo-glycoprotein receptor (ASGPR), was synthesized and identified. FITC-HSA and FITC-NGA was prepared by the method of Marshal. NGA was labeled directly with Na 99m TcO 4 . Contrasted with FITC-HSA, FITC-NGA was analyzed with flow cytometry (FCM). The results of FCM analysis showed that the amounts of ASGPR on the surface of normal hepatic cells, chronic injured ones and carcinoma ones was different obviously. Their values of MIF were 228.7, 5.81 and 1.13 respectively. The worse the hepatic cell was injured, the lower the values of MIF decreased. The amounts of ASGPR on the surface of per normal hepatic cell was about 8 x 10 6 . The ASGPRs on 1 x 10 6 hepatic cells can be saturated by 0.4 μg FITC-NGA, and the combination of ASGPR with FITC-NGA can be inhibited by 50 times amounts of NGA. It showed that NGA is a specific ligand of ASGPR. Biodistribution in mice showed that 99m Tc-NGA could be up taken specifically by liver of mice, and had the characteristic of saturation. The radioactivities of other organs were all low, and that of intestinal tract increased with time. The liver imaging of normal and model animals showed that the rates of blood clearance of normal animals were higher than that of liver injured model animal and the imaging could be inhibited by excessive NGA; The simple kinetics analysis indicated that comparing the normal animals and the model animals, the time-radioactivity curves of both hearts and livers were obviously different. The values of receptor index (LHL15) were 0.980 +- 0.010 and 0.949 +- 0.025 (n = 6), respectively

  19. On the clinical impact of cerebral dopamine D2 receptor scintigraphy

    International Nuclear Information System (INIS)

    Larisch, R.; Klimke, A.

    1998-01-01

    The present review describes findings and clinical indications for the dopamine D 2 receptor scintigraphy. Methods for the examination of D 2 receptors are positron emission tomography (PET) using 11 C- or 18 F-labelled butyrophenones or benzamides or single photon emission tomography (SPECT) using 123 I-iodobenzamide (IBZM) respectively. The most important indication in neurology is the differential diagnosis of Parkinsonism: Patients with early Parkinson's disease show an increased D 2 receptor binding (D 2 -RB) compared to control subjects. However, patients suffering from Steele-Richardson-Olszewski-Syndrome or Multiple System Atrophy show a decreased D 2 -RB and are generally non-responsive to treatment. Postsynaptic blockade of D 2 receptors results in a drug induced Parkinsonian syndrome, which can be diagnosed by D 2 scintigraphy. Further possible indications occur in psychiatry: The assessment of receptor occupancy is useful in schizophrenic patients treated with neuroleptics. Additionally, D 2 receptor scintigraphy might help to clarify the differential diagnosis between neuroleptic malignant syndrome and lethal catatonia. The method might be useful for supervising neurobiochemical changes in drug dependency and during withdrawal. Assessment of dopamine D 2 receptor binding can simplify the choice of therapy in depressive disorder: Patients showing a low D 2 binding are likely to improve following an antidepressive drug treatment whereas sleep deprivation is promising in patients with high D 2 binding. (orig.) [de

  20. DOTA-PESIN, a DOTA-conjugated bombesin derivative designed for the imaging and targeted radionuclide treatment of bombesin receptor-positive tumours

    International Nuclear Information System (INIS)

    Zhang, Hanwen; Maecke, Helmut R.; Schuhmacher, Jochen; Eisenhut, Michael; Waser, Beatrice; Reubi, Jean Claude; Wild, Damian

    2007-01-01

    We aimed at designing and developing a novel bombesin analogue, DOTA-PEG 4 -BN(7-14) (DOTA-PESIN), with the goal of labelling it with 67/68 Ga and 177 Lu for diagnosis and radionuclide therapy of prostate and other human cancers overexpressing bombesin receptors. The 8-amino acid peptide bombesin (7-14) was coupled to the macrocyclic chelator DOTA via the spacer 15-amino-4,7,10,13-tetraoxapentadecanoic acid (PEG 4 ). The conjugate was complexed with Ga(III) and Lu(III) salts. The GRP receptor affinity and the bombesin receptor subtype profile were determined in human tumour specimens expressing the three bombesin receptor subtypes. Internalisation and efflux studies were performed with the human GRP receptor cell line PC-3. Xenografted nude mice were used for biodistribution. [Ga III /Lu III ]-DOTA-PESIN showed good affinity to GRP and neuromedin B receptors but no affinity to BB3. [ 67 Ga/ 177 Lu]-DOTA-PESIN internalised rapidly into PC-3 cells whereas the efflux from PC-3 cells was relatively slow. In vivo experiments showed a high and specific tumour uptake and good retention of [ 67 Ga/ 177 Lu]-DOTA-PESIN. [ 67 Ga/ 177 Lu]-DOTA-PESIN highly accumulated in GRP receptor-expressing mouse pancreas. The uptake specificity was demonstrated by blocking tumour uptake and pancreas uptake. Fast clearance was found from blood and all non-target organs except the kidneys. High tumour-to-normal tissue ratios were achieved, which increased with time. PET imaging with [ 68 Ga]-DOTA-PESIN was successful in visualising the tumour at 1 h post injection. Planar scintigraphic imaging showed that the 177 Lu-labelled peptide remained in the tumour even 3 days post injection. The newly designed ligands have high potential with regard to PET and SPECT imaging with 68/67 Ga and targeted radionuclide therapy with 177 Lu. (orig.)

  1. In vivo quantitative imaging of dopamine receptors in human brain using positron emission tomography and (XWBr)bromospiperone

    Energy Technology Data Exchange (ETDEWEB)

    Maziere, B; Loc' h, C; Barton, J -C; Sgouropoulos, P; Duquesnoy, N; Antona, R d' ; Cambon, H

    1985-08-27

    The brain regional distribution and kinetics of (XWBr)bromospiperone, a derivative of a neuroleptic (spiperone) labeled with the positron emitter bromine-76, were studied by time-of-flight tomography after i.v. injection in man. In a control subject the kinetic distribution study showed an accumulation of radioactivity which reached a maximum 3 h postinjection in the frontal cortex and cerebellum regions and 4-5 h postinjection in the basal ganglia. Thereafter the striatal activity remained essentially constant over a period of 25 h. In a group of 13 control subjects, the mean value for the striatum-to-cerebellum ratio, at 4.5 h postinjection, was 1.84 (S.D. 0.21). In two schizophrenics treated with high doses of haloperidol, this ratio was found to be only 1.22. These data indicate that radiolabeled bromospiperone is very suitable for human pharmacological or pathological investigations of the central dopaminergic system. (Auth.). 20 refs.; 3 figs.; 1 table.

  2. The Z-isomer of 11 beta-methoxy-17 alpha-[123I]iodovinylestradiol is a promising radioligand for estrogen receptor imaging in human breast cancer

    NARCIS (Netherlands)

    Rijks, L. J.; Boer, G. J.; Endert, E.; de Bruin, K.; Janssen, A. G.; van Royen, E. A.

    1997-01-01

    The potential of both stereoisomers of 11 beta-methoxy-17 alpha-[123I] iodovinylestradiol (E- and Z-[123I]MIVE) as suitable radioligands for imaging of estrogen receptor (ER)-positive human breast tumours was studied. The 17 alpha-[123I]iodovinylestradiol derivatives were prepared stereospecifically

  3. 111In-cetuximab-F(ab')2 SPECT imaging for quantification of accessible epidermal growth factor receptors (EGFR) in HNSCC xenografts

    NARCIS (Netherlands)

    Dijk, L.K. van; Hoeben, B.A.W.; Stegeman, H.; Kaanders, J.H.A.M.; Franssen, G.M.; Boerman, O.C.; Bussink, J.

    2013-01-01

    BACKGROUND AND PURPOSE: Immunohistochemical epidermal growth factor receptor (EGFR) expression does not correlate with treatment response in head and neck squamous cell carcinomas (HNSCC). Aim was to apply the tracer (111)In-cetuximab-F(ab')2 for EGFR microSPECT imaging and to investigate if tracer

  4. Synthesis and in vivo evaluation of a PET radioligand for imaging the endothelin-A receptor

    Energy Technology Data Exchange (ETDEWEB)

    Mathews, William B. [Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, MD 21287 (United States)]. E-mail: bmathews@petscan.nm.jhu.edu; Zober, Tamas G. [Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, MD 21287 (United States); Ravert, Hayden T. [Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, MD 21287 (United States); Scheffel, Ursula [Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, MD 21287 (United States); Hilton, John [Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, MD 21287 (United States); Sleep, Darryl [Abbott Laboratories, Abbott Park, IL 60064 (United States); Dannals, Robert F. [Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, MD 21287 (United States); Szabo, Zsolt [Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, MD 21287 (United States)

    2006-01-15

    The endothelin-A receptor ligand Atrasentan (ABT-627) was radiolabeled by {sup 11}C-methylaton of the desmethyl precursor in phenolate form. In mice, the highest uptake of [{sup 11}C]ABT-627 was in the liver, kidneys and lungs. No significant binding was observed in mouse brain or heart. PET studies in a baboon, however, showed accumulation in the myocardium and lungs with a tissue/blood equilibrium reached at 40 min postinjection. Between 35 and 75 min, the heart/blood and lung/blood ratios were 1.72 and 1.31, respectively. Pretreatment with a 0.39 mg/kg dose of unlabeled ABT-627 inhibited the uptake of the tracer by 53-54% in both the myocardium and lungs at 65 min.

  5. Development of Fluorinated Non-Peptidic Ghrelin Receptor Ligands for Potential Use in Molecular Imaging

    Directory of Open Access Journals (Sweden)

    Rareş-Petru Moldovan

    2017-04-01

    Full Text Available The ghrelin receptor (GhrR is a widely investigated target in several diseases. However, the current knowledge of its role and distribution in the brain is limited. Recently, the small and non-peptidic compound (S-6-(4-bromo-2-fluorophenoxy-3-((1-isopropylpiperidin-3-ylmethyl-2-methylpyrido[3,2-d]pyrimidin-4(3H-one ((S-9 has been described as a GhrR ligand with high binding affinity. Here, we describe the synthesis of fluorinated derivatives, the in vitro evaluation of their potency as partial agonists and selectivity at GhrRs, and their physicochemical properties. These results identified compounds (S-9, (R-9, and (S-16 as suitable parent molecules for 18F-labeled positron emission tomography (PET radiotracers to enable future investigation of GhrR in the brain.

  6. 99mTc labelled peptide for imaging of peripheral receptors

    International Nuclear Information System (INIS)

    Mishra, A.K.; Mishra, P.; Chuttani, K.; Sharma, R.K.; Lazar Mathew, T.

    2001-01-01

    Conjugates of somatostatin analogues, RC-160 with different bifunctional chelators to label with 99m Tc, were synthesized. Conjugates with hydrazinonicotinamide (HYNIC) and compounds (benzoyl MAG-3 and CITC-DTPA) were prepared on a small scale with high purity and evaluated as different types of chelators on RC-160. Stability studies performed under physiological conditions showed high stability. Peptide conjugates could be labelled at high specific activities (307inCi/umol) with 99m Tc and different transchelator were used for the HYNIC conjugates. The resulting radiolabelled with ( 99m Tc and 1251) complexes were highly stable and showed binding affinity to somatostatin receptors in the nanomolar range. The radioconjugates were administered to rabbits and mice in order to study their in vivo stability, biokinetics and biodistribution. (author)

  7. Synthesis and in vivo evaluation of a PET radioligand for imaging the endothelin-A receptor

    International Nuclear Information System (INIS)

    Mathews, William B.; Zober, Tamas G.; Ravert, Hayden T.; Scheffel, Ursula; Hilton, John; Sleep, Darryl; Dannals, Robert F.; Szabo, Zsolt

    2006-01-01

    The endothelin-A receptor ligand Atrasentan (ABT-627) was radiolabeled by 11 C-methylaton of the desmethyl precursor in phenolate form. In mice, the highest uptake of [ 11 C]ABT-627 was in the liver, kidneys and lungs. No significant binding was observed in mouse brain or heart. PET studies in a baboon, however, showed accumulation in the myocardium and lungs with a tissue/blood equilibrium reached at 40 min postinjection. Between 35 and 75 min, the heart/blood and lung/blood ratios were 1.72 and 1.31, respectively. Pretreatment with a 0.39 mg/kg dose of unlabeled ABT-627 inhibited the uptake of the tracer by 53-54% in both the myocardium and lungs at 65 min

  8. Kit formulated asialoglycoprotein receptor targeting tracer based on copolymer for liver SPECT imaging.

    Science.gov (United States)

    Liu, Chang; Guo, Zhide; Zhang, Pu; Song, Manli; Zhao, Zuoquan; Wu, Xiaowei; Zhang, Xianzhong

    2014-08-01

    Specific targeting of galactose-carrying molecule to ASGP-R in normal hepatocytes has been demonstrated before. In this study, galactosyl polystyrene was synthesized from controllable ratio of functional monomers and radio-labelled with (99m)Tc by formulated kit for SPECT imaging of hepatic function. p(VLA-co-VNI)(46:54) was synthesized by free-radical copolymerization initiated by AIBN, purified by dialysis, lyophilized to kit with Tricine and TPPTS as co-ligands for (99m)Tc labeling. Radiotracer (99m)Tc-p(VLA-co-VNI)(46:54)(Tricine)(TPPTS) was prepared and evaluated by in vitro stability, in vivo metabolism, ex vivo biodistribution and microSPECT/CT imaging in normal KM mice. MicroSPECT/CT and microMRI imaging were also performed in C57BL/b6 mice with xenograft hepatic carcinoma for hepatic function evaluation. (99m)Tc-p(VLA-co-VNI)(46:54)(Tricine)(TPPTS) was obtained in high radio chemical purity (RCP) (>99%) by using instant kit without further purification and excellent in vitro and in vivo stability. The result of biodistribution showed that liver had high uptake (90.49±10.68 ID%/g) at 30 min after injection and was blocked significantly by cold copolymer. MicroSPECT imaging in normal KM mice at 1h and 4h after injection showed good liver retention and targeting properties. Significant defect of activity was observed in the tumor site which was confirmed by MRI imaging. (99m)Tc-p(VLA-co-VNI)(46:54)(Tricine)(TPPTS) with lower ratio of targeting moiety has no observable effect on the specific binding affinity and liver uptake. This makes it possible to introduce more imaging units for multi-modality imaging. Furthermore, the instant kit preparation of (99m)Tc-labeling provides great potential for the evaluation of hepatocyte function in clinical application. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. (/sup 3/H)Haloperidol labels brain dopamine receptors after its injection into the internal carotid artery of the rat

    Energy Technology Data Exchange (ETDEWEB)

    D' Ambrosio, A; Zivkovic, B; Bartholini, G [Research Department, Synthelabo-L.E.R.S., Paris (France)

    1982-04-29

    Pulse injection of (/sup 3/H)haloperidol (0.1 ..mu..Ci; 0.003 ..mu..g) into the internal carotid artery of the rat specifically labelled dopamine receptors in striatum and olfactory tubercle, as indicated by the kinetics of, and the effects of neuroleptic drugs on, the ligand disposition. The described method may prove useful for labelling brain receptors with ligands which readily cross the blood-brain barrier but which do not selectively mark their receptors if injected systemically.

  10. [3H]Haloperidol labels brain dopamine receptors after its injection into the internal carotid artery of the rat

    International Nuclear Information System (INIS)

    D'Ambrosio, A.; Zivkovic, B.; Bartholini, G.

    1982-01-01

    Pulse injection of [ 3 H]haloperidol (0.1 μCi; 0.003 μg) into the internal carotid artery of the rat specifically labelled dopamine receptors in striatum and olfactory tubercle, as indicated by the kinetics of, and the effects of neuroleptic drugs on, the ligand disposition. The described method may prove useful for labelling brain receptors with ligands which readily cross the blood-brain barrier but which do not selectively mark their receptors if injected systemically. (Auth.)

  11. Receptor mapping in psychiatric patients with SPECT

    International Nuclear Information System (INIS)

    Schlegel, S.

    1997-01-01

    This paper summarizes some data of our studies with the single-photon-emission-computerized tomography (SPECT), focussing on the dopamine-D2- and the benzodiazepine receptor mapping. Benzodiazepine receptors: Central benzodiazepine receptors (BZr) can be visualized with iomazenil which is an analogue of the benzodiazepine antagonist flumazenil, labeled with 123-iodine. Since the involvement of the BZr system is discussed in the pathogenesis of anxiety and depression, patients with these disorders were investigated. A third study investigated the BZr-occupancy during benzodiazepine treatment (lorazepam). Results: (a) Patients with panic disorders had lower iomazenil uptake values compared to epileptic patients. (b) Depressed patients showed a positive correlation between severity of illness and frontal uptake. (c) BZr occupancy during lorazepam treatment was measurable, but not associated with lorazepam plasma levels. Dopamine-D2-receptors: With 123-I-iodobenzamide (IBZM), and iodine-labeled dopamine receptor ligand, the D2 receptor density can be measured by a semiquantitative approach (striatum/frontal cortex=ST/FC). Therefore, we investigated the D2-receptor occupancy during treatment with typical and atypical neuroleptics in relationship to dosages (normalized with different formulas of chlorpromazine equivalents), side effects, and prolactin plasma levels. Results: Dependent on the selected formula for chlorpromazine equivalents, the ST/FC ratio was correlated with dosages. Side effects and prolactin plasma levels showed a negative association with lower ST/FC ratios. (orig.) [de

  12. OctreoScan 111 for imaging of a somatostatin receptor-positive islet cell tumor in rat

    International Nuclear Information System (INIS)

    Bruns, C.; Stolz, B.; Albert, R.; Marbach, P.; Pless, J.

    1993-01-01

    We report here the in vitro characterization of SDZ 215-811 and the in vivo imaging of a islet cell tumor gown in rats using [ 111 In]SDZ 215-811. In vitro autoradiographies revelaed a high density of SRIF receptors on the pancreatic tumor tissue. As early as 5 min after intravenous injection of [ 111 In]SDZ 215-811 into tumour-bearing rats, the tumors were clearly localized by gamma-camera scintigraphy. Even 24 h post injection, the islet cell tumor was still detectable. The radioligand was mainly cleared from the circulation via the Kidneys, with a rapid α-phase (t 1/2 =5.6 min) and a slow elimination phase (t 1/2 =7.3 h). Biodistribution studies revealed a relatively high accumulation of radioactivity in the kidneys, but low uptake into the liver and the intestine. High uptake of [ 111 In]SDZ 215-811 was observed for the tumor tissue (0.92±0.07% ID/g; 1 h post injection). Interestingly, a tumor load of 0.14±0.01% ID/g was still measured after 24 h. The tumor/blood ratio was 4.93 after 24 h, indicating specific accumulation of radioactivity in the islet cell tumour. [ 111 In]SDZ 215-811 appears to be sensitive and specific ligand for SRIF receptorpositive tumors and offers an easy procedure for scintigraphic imaging of such tumors in man. (orig.)

  13. MR imaging and T2 measurements in peripheral nerve repair with activation of Toll-like receptor 4 of neurotmesis

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Xiang; Zhang, Fang; Lu, Liejing; Li, Haojiang; Wen, Xuehua; Shen, Jun [Sun Yat-Sen University, Department of Radiology, Sun Yat-Sen Memorial Hospital, Guangzhou, Guangdong (China)

    2014-05-15

    To investigate the role of MR imaging in neurotmesis combined with surgical repair and Toll-like receptor 4 (TLR4) activation. Forty-eight rats received subepineurial microinjection of the TLR4 agonist lipopolysaccharide (LPS, n = 24) or phosphate buffered saline (PBS, n = 24) immediately after surgical repair of the transected sciatic nerve. Sequential fat-suppressed T2-weighted imaging and quantitative T2 measurements were obtained at 3, 7, 14 and 21 days after surgery, with histologic assessments performed at regular intervals. T2 relaxation times and histological quantification of the distal stumps were measured and compared. The distal stumps of transected nerves treated with LPS or PBS both showed persistent enlargement and hyperintense signal. T2 values of the distal stumps showed a rapid rise to peak level followed by a rapid decline pattern in nerves treated with LPS, while exhibiting a slow rise to peak value followed by a slow decline in nerves treated with PBS. Nerves treated with LPS exhibited more prominent macrophage recruitment, faster myelin debris clearance and more pronounced nerve regeneration. Nerves treated with TLR4 activation had a characteristic pattern of T2 value change over time. Longitudinal T2 measurements can be used to detect the enhanced repair effect associated with TLR4 activation in the surgical repair of neurotmesis. (orig.)

  14. Imaging for metabotropic glutamate receptor subtype 1 in rat and monkey brains using PET with [18F]FITM.

    Science.gov (United States)

    Yamasaki, Tomoteru; Fujinaga, Masayuki; Maeda, Jun; Kawamura, Kazunori; Yui, Joji; Hatori, Akiko; Yoshida, Yuichiro; Nagai, Yuji; Tokunaga, Masaki; Higuchi, Makoto; Suhara, Tetsuya; Fukumura, Toshimitsu; Zhang, Ming-Rong

    2012-04-01

    In this study, we evaluate the utility of 4-[(18)F]fluoro-N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methylbenzamide ([(18)F]FITM) as a positron emission tomography (PET) ligand for imaging of the metabotropic glutamate receptor subtype 1 (mGluR1) in rat and monkey brains. In vivo distribution of [(18)F]FITM in brains was evaluated by PET scans with or without the mGluR1-selective antagonist (JNJ16259685). Kinetic parameters of monkey PET data were obtained using the two-tissue compartment model with arterial blood sampling. In PET studies in rat and monkey brains, the highest uptake of radioactivity was in the cerebellum, followed by moderate uptake in the thalamus, hippocampus and striatum. The lowest uptake of radioactivity was detected in the pons. These uptakes in all brain regions were dramatically decreased by pre-administration of JNJ16259685. In kinetic analysis of monkey PET, the highest volume of distribution (V(T)) was detected in the cerebellum (V(T) = 11.5). [(18)F]FITM has an excellent profile as a PET ligand for mGluR1 imaging. PET with [(18)F]FITM may prove useful for determining the regional distribution and density of mGluR1 and the mGluR1 occupancy of drugs in human brains.

  15. Biokinetics and dosimetry of 99m Tc-EDDA/HYNIC-[Lys3]-bombesin in humans: imaging of GRP receptors

    International Nuclear Information System (INIS)

    Santos C, C.L.; Ferro F, G.; Murphy, C.A de; Cardena, E.; Pichardo R, P.

    2007-01-01

    Full text: Bombesin (BN) receptor subtype 2 (GRP-r) is over-expressed on various human tumors including breast, prostate, small cell lung and pancreatic cancer. Recently we reported the 99- mTc-EDDA/HYNIC-[Lys 3 ]-Bombesin ( 99m Tc-HYNIC-BN) complex as a new radiopharmaceutical with high stability in human serum, specific cell GRP-receptor binding and rapid internalization. The aim of this study was to evaluate the 99m Tc-HYNIC-BN biokinetics and dosimetry in 5-healthy and 3-breast cancer women. Whole-body images were acquired at 20, 90, 180 min and 24 h after 99m Tc-HYNIC-BN administration. Regions of interest (ROIs) were drawn around source' organs on each time frame. The same set of ROIs was used for all 8 scans and the cpm of each ROI was converted to activity using the conjugate view counting method. The image sequence was used to extrapolate 99m Tc-HYNIC-BN time activity curves in each organ, to calculate the total number of disintegrations (N) that occurred in the source regions. N data were the input for the OLINDA/EXM code to calculate internal radiation dose estimates. Images showed a rapid radiopharmaceutical blood clearance with predominantly renal excretion and minimal hepatobiliary elimination. 99m Tc-HYNIC-BN exhibited high in vivo affinity for GRP-r over-expression successfully visualized in breast cancer lesions and well differentiated from GRP-r expression in lungs and airways with normal GRP-r density (ratio 3:1). The equivalent doses for a study using 370 MBq were 7.38±1.68, 0.59±0.08, 2.07±0.60, 0.58±0.1, 0.75±0.09 and 0.43±0.07 mSv for kidneys, liver, lungs, ovaries, pancreas and red marrow respectively. The effective dose was 1.64±0.25 mSv which is comparable with the doses known for most of the 99m Tc radiopharmaceutical studies in nuclear medicine. (Author)

  16. Iodine-123 N-methyl-4-iododexetimide: a new radioligand for single-photon emission tomographic imaging of myocardial muscarinic receptors

    International Nuclear Information System (INIS)

    Hicks, R.J.; Kassiou, M.; Eu, P.; Katsifis, A.G.; Garra, M.; Power, J.; Najdovski, L.; Lambrecht, R.M.

    1995-01-01

    Cardiac muscarinic receptor ligands suitable for positron emission tomography have previously been characterised. Attempts to develop radioligands of these receptors suitable for single-photon emission tomographic (SPET) imaging have not been successful due to high lung retention and high non-specific binding of previously investigated potential tracers. The purpose of this study was to evaluate the biodistribution and in vivo imaging characteristics of a new radiopharmaceutical, [ 123 I]N-methyl-4-iododexetimide. Biodistribution studies performed in rats showed high cardiac uptake (2.4% ID/g) 10 min after injection with a heart to lung activity ratio of 5:1. Specificity and stereoselectivity of cardiac binding were demonstrated using blocking experiments in rats. Dynamic imaging studies in anaesthetised greyhounds demonstrated rapid and high myocardial uptake and low lung binding with stable heart to lung activity ratios of >2.5:1 between 10 and 30 min, making SPET imaging feasible. Administration of an excess of an unlabelled muscarinic antagonist, methyl-quinuclidinyl benzylate rapidly displaced myocardial activity to background levels and the pharmacologically inactive enantiomer, [ 123 I]N-methyl-4-iodolevetimide, had no detectable cardiac uptake, indicating specific and stereoselective muscarinic receptor binding. SPET revealed higher activity in the inferior than in the anterior wall, this being consistent with previously described regional variation of cardiac parasympathetic innervation. [ 123 I]N-methyl-4-iododexetimide shows promise as an imaging agent for muscarinic receptor distribution in the heart and may be helpful in evaluating diverse cardiac diseases associated with altered muscarinic receptor function, including heart failure and diabetic heart disease. (orig.)

  17. A comparison of the diagnostic utility of two image receptors for panoramic radiography.

    Science.gov (United States)

    Carmichael, F A; Hirschmann, P N; Scaife, B; Sheard, L; Mackenzie, A

    2000-01-01

    To compare the diagnostic utility of two screen-film systems for panoramic radiography, one based on green and the other on ultraviolet light. Two hundred consecutive adult patients with teeth in all four quadrants requiring panoramic radiographs were randomly allocated to one of two groups. One group was imaged with OGA L (CEA AB, Strängnäs, Sweden) film using Lanex Regular (Eastman Kodak, Rochester, NY, USA) screens (the Lanex group). The other group was imaged using Ultra-Vision (Dupont UK Limited, Hertfordshire, UK) film and screens (the Ultra-vision group). Two different panoramic machines were used, a Planmeca (Planmeca OY, Helsinki, Finland) and Cranex (Soredex Orion Corporation, Helsinki, Finland). The radiographs were evaluated by two radiographers for overall quality and any faults recorded. Two dental radiologists evaluated the crestal and apical areas of every standing tooth on a 4-point scale. The likelihood of getting a high-quality image with the different films was modelled using logistic regression, adjusting for the radiologist and the area of the tooth being examined. Inter- and intra-examiner agreement was calculated using Kappa and weighted Kappa where appropriate. The radiographers recorded no significant differences in positioning errors between the two groups of film. However, the films produced on the Cranex were less likely to be recorded as excellent. The radiologists' interexaminer agreement for the lower molars and upper incisors was only moderate at best (kappa = 0.56). No significant differences were found between the likelihood of the two types of film providing a high-quality image. Crestal areas were more likely to be scored well than apical areas. There were no differences in ease of discerning apical and crestal areas between the two screen-film systems. There was only poor to moderate agreement between the two radiologists. Ultra-Vision can be recommended as an alternative to existing rare earth systems for panoramic

  18. Novel mixed ligand technetium complexes as 5-HT1A receptor imaging agents

    International Nuclear Information System (INIS)

    Leon, A.; Rey, A.; Mallo, L.; Pirmettis, I.; Papadopoulos, M.; Leon, E.; Pagano, M.; Manta, E.; Incerti, M.; Raptopoulou, C.; Terzis, A.; Chiotellis, E.

    2002-01-01

    The synthesis, characterization and biological evaluation of two novel 3 + 1 mixed ligand 99m Tc-complexes, bearing the 1-(2-methoxyphenylpiperazine) moiety, a fragment of the true 5-HT 1A antagonist WAY 100635, is reported. Complexes at tracer level 99m TcO[(CH 3 CH 2 ) 2 NCH 2 CH 2 N(CH 2 CH 2 S) 2 ][o-CH 3 OC 6 H 4 N(CH 2 CH 2 ) 2 NCH 2 CH 2 S], 99m Tc-1, and 99m TcO[((CH 3 ) 2 CH) 2 NCH 2 CH 2 N(CH 2 CH 2 S) 2 ][o-CH 3 OC 6 H 4 N (CH 2 CH 2 ) 2 NCH 2 CH 2 S], 99m Tc-2, were prepared using 99m Tc-glucoheptonate as precursor. For structural characterization, the analogous oxorhenium complexes, Re-1 and Re-2, were prepared by ligand exchange reaction using ReOCl 3 (PPh 3 ) 2 as precursor, and characterized by elemental analysis and spectroscopic methods. Complex Re-1 was further characterized by crystallographic analysis. Labeling was performed with high yield (>85%) and radiochemical purity (>90%) using very low ligand concentration. The structure of 99m Tc complexes was established by comparative HPLC using the well-characterized oxorhenium analogues as references. In vitro binding assays demonstrated the affinity of these complexes for 5-HT 1A receptors (IC 50 : 67 and 45 nM for Re-1 and Re-2 respectively). Biological studies in mice showed the ability of 99m Tc-1 and 99m Tc-2 complexes to cross the intact blood-brain barrier (1.4 and 0.9% dose/g, respectively at 1 min post-inj.). The distribution of these complexes in various regions in rat brain is inhomogeneous. The highest ratio between areas reach and poor in 5-HT 1A receptors was calculated for complex Tc-1 at 60 min p.i. (hippocampus/cerebellum = 1.7).

  19. Novel mixed ligand technetium complexes as 5-HT1A receptor imaging agents.

    Science.gov (United States)

    León, A; Rey, A; Mallo, L; Pirmettis, I; Papadopoulos, M; León, E; Pagano, M; Manta, E; Incerti, M; Raptopoulou, C; Terzis, A; Chiotellis, E

    2002-02-01

    The synthesis, characterization and biological evaluation of two novel 3 + 1 mixed ligand 99mTc-complexes, bearing the 1-(2-methoxyphenylpiperazine) moiety, a fragment of the true 5-HT1A antagonist WAY 100635, is reported. Complexes at tracer level 99mTcO[(CH3CH2)2NCH2CH2N(CH2CH2S)2][o-CH3OC6H4N(CH2CH2)2NCH2CH2S], 99mTc-1, and 99mTcO[((CH3)2CH)2NCH2CH2N(CH2CH2S)2][o-CH3OC6H4N (CH2CH2)2NCH2CH2S], 99mTc-2, were prepared using 99mTc-glucoheptonate as precursor. For structural characterization, the analogous oxorhenium complexes, Re-1 and Re-2, were prepared by ligand exchange reaction using ReOCl3(PPh3)2 as precursor, and characterized by elemental analysis and spectroscopic methods. Complex Re-1 was further characterized by crystallographic analysis. Labeling was performed with high yield (>85%) and radiochemical purity (>90%) using very low ligand concentration. The structure of 99mTc complexes was established by comparative HPLC using the well-characterized oxorhenium analogues as references. In vitro binding assays demonstrated the affinity of these complexes for 5-HT1A receptors (IC50 : 67 and 45 nM for Re-1 and Re-2 respectively). Biological studies in mice showed the ability of 99mTc-1 and 99mTc-2 complexes to cross the intact blood-brain barrier (1.4 and 0.9% dose/g, respectively at 1 min post-inj.). The distribution of these complexes in various regions in rat brain is inhomogeneous. The highest ratio between areas reach and poor in 5-HT1A receptors was calculated for complex Tc-1 at 60 min p.i. (hippocampus/cerebellum = 1.7).

  20. Novel mixed ligand technetium complexes as 5-HT{sub 1A} receptor imaging agents

    Energy Technology Data Exchange (ETDEWEB)

    Leon, A.; Rey, A. E-mail: arey@bilbo.edu.uy; Mallo, L.; Pirmettis, I.; Papadopoulos, M.; Leon, E.; Pagano, M.; Manta, E.; Incerti, M.; Raptopoulou, C.; Terzis, A.; Chiotellis, E

    2002-02-01

    The synthesis, characterization and biological evaluation of two novel 3 + 1 mixed ligand {sup 99m}Tc-complexes, bearing the 1-(2-methoxyphenylpiperazine) moiety, a fragment of the true 5-HT{sub 1A} antagonist WAY 100635, is reported. Complexes at tracer level {sup 99m}TcO[(CH{sub 3}CH{sub 2}){sub 2}NCH{sub 2}CH{sub 2}N(CH{sub 2}CH{sub 2}S){sub 2}][o-CH{sub 3}OC{sub 6}H{sub 4}N(CH{sub 2}CH{sub 2}){sub 2}NCH{sub 2}= CH{sub 2}S], {sup 99m}Tc-1, and {sup 99m}TcO[((CH{sub 3}){sub 2}CH){sub 2}NCH{sub 2}CH{sub 2}N(CH{sub 2}CH{sub 2}S){sub 2}][o-CH{sub 3}OC{sub 6}H{sub 4}N (CH{sub 2}CH{sub 2}){sub 2}NCH{sub 2}CH{sub 2}S], {sup 99m}Tc-2, were prepared using {sup 99m}Tc-glucoheptonate as precursor. For structural characterization, the analogous oxorhenium complexes, Re-1 and Re-2, were prepared by ligand exchange reaction using ReOCl{sub 3}(PPh{sub 3}){sub 2} as precursor, and characterized by elemental analysis and spectroscopic methods. Complex Re-1 was further characterized by crystallographic analysis. Labeling was performed with high yield (>85%) and radiochemical purity (>90%) using very low ligand concentration. The structure of {sup 99m}Tc complexes was established by comparative HPLC using the well-characterized oxorhenium analogues as references. In vitro binding assays demonstrated the affinity of these complexes for 5-HT{sub 1A} receptors (IC{sub 50} : 67 and 45 nM for Re-1 and Re-2 respectively). Biological studies in mice showed the ability of {sup 99m}Tc-1 and {sup 99m}Tc-2 complexes to cross the intact blood-brain barrier (1.4 and 0.9% dose/g, respectively at 1 min post-inj.). The distribution of these complexes in various regions in rat brain is inhomogeneous. The highest ratio between areas reach and poor in 5-HT{sub 1A} receptors was calculated for complex Tc-1 at 60 min p.i. (hippocampus/cerebellum = 1.7)

  1. In Vivo Imaging of Cerebral Dopamine D3 Receptors in Alcoholism

    Science.gov (United States)

    Erritzoe, David; Tziortzi, Andri; Bargiela, David; Colasanti, Alessandro; Searle, Graham E; Gunn, Roger N; Beaver, John D; Waldman, Adam; Nutt, David J; Bani, Massimo; Merlo-Pich, Emilio; Rabiner, Eugenii A; Lingford-Hughes, Anne

    2014-01-01

    Animal studies support the role of the dopamine D3 receptor (DRD3) in alcohol reinforcement or liking. Sustained voluntary alcohol drinking in rats has been associated with an upregulation of striatal DRD3 gene expression and selective blockade of DRD3 reduces ethanol preference, consumption, and cue-induced reinstatement. In vivo measurement of DRD3 in the living human brain has not been possible until recently owing to a lack of suitable tools. In this study, DRD3 status was assessed for the first time in human alcohol addiction. Brain DRD3 availability was compared between 16 male abstinent alcohol-dependent patients and 13 healthy non-dependent age-matched males using the DRD3-preferring agonist positron emission tomography (PET) radioligand [11C]PHNO with and without blockade with a selective DRD3 antagonist (GSK598809 60 mg p.o.). In striatal regions of interest, where the [11C]PHNO PET signal represents primarily DRD2 binding, no differences were seen in [11C]PHNO binding between the groups at baseline. However, baseline [11C]PHNO binding was higher in alcohol-dependent patients in hypothalamus (VT: 16.5±4 vs 13.7±2.9, p=0.040), a region in which the [11C]PHNO signal almost entirely reflects DRD3 availability. The reductions in regional receptor binding (VT) following a single oral dose of GSK598809 (60 mg) were consistent with those observed in previous studies across all regions. There were no differences in regional changes in VT following DRD3 blockade between the two groups, indicating that the regional fractions of DRD3 are similar in the two groups, and the increased [11C]PHNO binding in the hypothalamus in alcohol-dependent patients is explained by elevated DRD3 in this group. Although we found no difference between alcohol-dependent patients and controls in striatal DRD3 levels, increased DRD3 binding in the hypothalamus of alcohol-dependent patients was observed. This may be relevant to the development of future therapeutic strategies to

  2. Radiosynthesis and initial evaluation of [{sup 18}F]-FEPPA for PET imaging of peripheral benzodiazepine receptors

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, Alan A. [PET Centre, Centre for Addiction and Mental Health, Toronto, Ontario, M5T 1R8 (Canada); Department of Psychiatry, University of Toronto, Toronto, Ontario, M5T 1R8 (Canada)], E-mail: alan.wilson@camhpet.ca; Garcia, Armando; Parkes, Jun [PET Centre, Centre for Addiction and Mental Health, Toronto, Ontario, M5T 1R8 (Canada); McCormick, Patrick [PET Centre, Centre for Addiction and Mental Health, Toronto, Ontario, M5T 1R8 (Canada); Institute of Medical Science, University of Toronto, Toronto, Ontario, M5S 1A8 (Canada); Stephenson, Karin A. [PET Centre, Centre for Addiction and Mental Health, Toronto, Ontario, M5T 1R8 (Canada); Houle, Sylvain; Vasdev, Neil [PET Centre, Centre for Addiction and Mental Health, Toronto, Ontario, M5T 1R8 (Canada); Department of Psychiatry, University of Toronto, Toronto, Ontario, M5T 1R8 (Canada)

    2008-04-15

    Introduction: A novel [{sup 18}F]-radiolabelled phenoxyanilide, [{sup 18}F]-FEPPA, has been synthesized and evaluated, in vitro and ex vivo, as a potential positron emission tomography imaging agent for the peripheral benzodiazepine receptor (PBR). Methods: [{sup 18}F]-FEPPA and two other radiotracers for imaging PBR, namely [{sup 11}C]-PBR28 and [{sup 11}C]-PBR28-d3, were synthesised and evaluated in vitro and ex vivo as potential PBR imaging agents. Results: [{sup 18}F]-FEPPA is efficiently prepared in one step from its tosylate precursor and [{sup 18}F]-fluoride in high radiochemical yields and at high specific activity. FEPPA displayed a K{sub i} of 0.07 nM for PBR in rat mitochondrial membrane preparations and a suitable lipophilicity for brain penetration (log P of 2.99 at pH 7.4). Upon intravenous injection into rats, [{sup 18}F]-FEPPA showed moderate brain uptake [standard uptake value (SUV) of 0.6 at 5 min] and a slow washout (SUV of 0.35 after 60 min). Highest uptake of radioactivity was seen in the hypothalamus and olfactory bulb, regions previously reported to be enriched in PBR in rat brain. Analysis of plasma and brain extracts demonstrated that [{sup 18}F]-FEPPA was rapidly metabolized, but no lipophilic metabolites were observed in either preparation and only 5% radioactive metabolites were present in brain tissue extracts. Blocking studies to determine the extent of specific binding of [{sup 18}F]-FEPPA in rat brain were problematic due to large perturbations in circulating radiotracer and the lack of a reference region. Conclusions: Further evaluation of the potential of [{sup 18}F]-FEPPA will require the employment of rigorous kinetic models and/or appropriate animal models.

  3. Validation of quantitative brain dopamine D2 receptor imaging with a conventional single-head SPET camera

    International Nuclear Information System (INIS)

    Nikkinen, P.; Liewendahl, K.; Savolainen, S.; Launes, J.

    1993-01-01

    Phantom measurements were performed with a conventional single-head single-photon emission tomography (SPET) camera in order to validate the relevance of the basal ganglia/frontal cortex iodine-123 iodobenzamide (IBZM) uptake ratios measured in patients. Inside a cylindrical phantom (diameter 22 cm), two cylinders with a diameter of 3.3 cm were inserted. The activity concentrations of the cylinders ranged from 6.0 to 22.6 kBq/ml and the cylinder/background activity ratios varied from 1.4 to 3.8. From reconstructed SPET images the cylinder/background activity ratios were calculated using three different regions of interest (ROIs). A linear relationship between the measured activity ratio and the true activity ratio was obtained. In patient studies, basal ganglia/frontal cortex IBZM uptake ratios determined from the reconstructed slices using attentuation correction prior to reconstruction were 1.30 ±0.03 in idiopathic Parkinson's disease (n = 9), 1,33 ±0.09 in infantile and juvenile neuronal ceroid lipofuscinosis (n = 7) and 1.34 ±0.05 in narcolepsy (n = 8). Patients with Huntington's disease had significantly lower ratios (1.09 ±0.04, n = 5). The corrected basal ganglia/frontal cortex ratios, determined using linear regression, were about 80 % higher. The use of dual-window scatter correction increased the measured ratios by about 10 %. Although comprehensive correction methods can further improve the resolution in SPET images, the resolution of the SPET system used by us (1.5 - 2 cm) will determine what is achievable in basal ganglia D2 receptor imaging. (orig.)

  4. Validation of quantitative brain dopamine D2 receptor imaging with a conventional single-head SPET camera

    Energy Technology Data Exchange (ETDEWEB)

    Nikkinen, P [Helsinki Univ. (Finland). Dept. of Clinical Chemistry; Liewendahl, K [Helsinki Univ. (Finland). Dept. of Clinical Chemistry; Savolainen, S [Helsinki Univ. (Finland). Dept. of Physics; Launes, J [Helsinki Univ. (Finland). Dept. of Neurology

    1993-08-01

    Phantom measurements were performed with a conventional single-head single-photon emission tomography (SPET) camera in order to validate the relevance of the basal ganglia/frontal cortex iodine-123 iodobenzamide (IBZM) uptake ratios measured in patients. Inside a cylindrical phantom (diameter 22 cm), two cylinders with a diameter of 3.3 cm were inserted. The activity concentrations of the cylinders ranged from 6.0 to 22.6 kBq/ml and the cylinder/background activity ratios varied from 1.4 to 3.8. From reconstructed SPET images the cylinder/background activity ratios were calculated using three different regions of interest (ROIs). A linear relationship between the measured activity ratio and the true activity ratio was obtained. In patient studies, basal ganglia/frontal cortex IBZM uptake ratios determined from the reconstructed slices using attentuation correction prior to reconstruction were 1.30 [+-]0.03 in idiopathic Parkinson's disease (n = 9), 1,33 [+-]0.09 in infantile and juvenile neuronal ceroid lipofuscinosis (n = 7) and 1.34 [+-]0.05 in narcolepsy (n = 8). Patients with Huntington's disease had significantly lower ratios (1.09 [+-]0.04, n = 5). The corrected basal ganglia/frontal cortex ratios, determined using linear regression, were about 80 % higher. The use of dual-window scatter correction increased the measured ratios by about 10 %. Although comprehensive correction methods can further improve the resolution in SPET images, the resolution of the SPET system used by us (1.5 - 2 cm) will determine what is achievable in basal ganglia D2 receptor imaging. (orig.)

  5. Guideline for PET/CT imaging of neuroendocrine neoplasms withGa-DOTA-conjugated somatostatin receptor targeting peptides andF-DOPA

    DEFF Research Database (Denmark)

    Bozkurt, Murat Fani; Virgolini, Irene; Balogova, Sona

    2017-01-01

    PURPOSE & METHODS: Neuroendocrine neoplasms are a heterogenous group of tumours, for which nuclear medicine plays an important role in the diagnostic work-up as well as in the targeted therapeutic options. This guideline is aimed to assist nuclear medicine physicians in recommending, performing......, reporting and interpreting the results of somatostatin receptor (SSTR) PET/CT imaging using68Ga-DOTA-conjugated peptides, as well as18F-DOPA imaging for various neuroendocrine neoplasms. RESULTS & CONCLUSION: The previous procedural guideline by EANM regarding the use PET/CT tumour imaging with68Ga...

  6. New detection of brain dopamine receptors with [3H]dihydroergocryptine

    International Nuclear Information System (INIS)

    Tittler, M.; Weinreich, P.; Seeman, P.

    1977-01-01

    Because dihydroergocryptine (DHE) and closely related ergots are dopamine-mimetic agonists, we tested [ 3 H]DHE as a possible ligand for [ 3 H]dopamine receptors in the calf caudate. In order to avoid [ 3 H]DHE from tagging α-adrenergic receptors, an excess of 500 nM phentolamine was used to block these sites, permitting the dopamine receptors to be measured separately. Specific binding of [ 3 H]DHE was defined as total binding minus that occurring in the presence of 1 μM (+)-butaclamol. Excess phentolamine reduced the specific binding of [ 3 H]DHE from 328 down to 138 fmol/mg, the difference presumably representing α-receptors. The K/sub D/ for [ 3 H]DHE was 0.55 nM (with or without phentolamine), and this high affinity site was blocked (in the presence of phentolamine) by 250 nM apomorphine, 650 nM dopamine, and 1200 nM (-)-norepinephrine, indicating that [ 3 H]DHE was binding to dopamine receptors. All neuroleptics blocked specific [ 3 H]DHE binding in direct relation to the clinical potency of the neuroleptic. The displacement of specific [ 3 H]DHE binding by dopamine or by norepinephrine (in the presence of phentolamine) revealed two subsets of dopamine receptors

  7. Triazolam-induced modulation of muscarinic acetylcholine receptor in living brain slices as revealed by a new positron-based imaging technique

    International Nuclear Information System (INIS)

    Murata, T.; Matsumura, K.; Onoe, H.; Watanabe, Y.; Sihver, S.; Sihver, W.; Langstroem, B.; Bergstroem, M.; Yonekura, Y.

    1997-01-01

    The effect of triazolam, a potent benzodiazepine (BZ) agonist, on muscarinic acetylcholinergic receptor (mAChR) binding was investigated in living brain slices by use of a novel positron-based imaging technique. Fresh rat brain slices were incubated with [ 11 C]N-methyl-4-piperidylbenzilate ([ 11 C]NMPB), a mAChR antagonist, in oxygenated Krebs-Ringer solution at 37 degree C. During incubation, time-resolved imaging of [ 11 C]NMPB binding in the slices was constructed on the storage phosphor screens. Addition of triazolam (1 μM) plus muscimol (30 μM), a GABA A receptor agonist, to the incubation mixture decreased the specific binding of [ 11 C]NMPB. Ro15-1788, a BZ receptor antagonist, prevented this effect, indicating that the effect was exerted through the GABA A /BZ receptor complex. These results demonstrated that stimulation of the GABA A /BZ receptor lowers the affinity of the mAChR for its ligand, which may underlie the BZ-induced amnesia, a serious clinical side effect of BZ. No such effect in the P2-fraction instead implies that the integrity of the neuronal cells and/or their environment is prerequisite for the modulation of mAChR by GABA A /BZ stimulation. (author)

  8. Change of central cholinergic receptors following lesions of nucleus basalis magnocellularis in rats: search for an imaging index suitable for the early detection of Alzheimer's disease

    International Nuclear Information System (INIS)

    Ogawa, Mikako; Iida, Yasuhiko; Nakagawa, Masaki; Kuge, Yugi; Kawashima, Hidekazu; Tominaga, Akiko; Ueda, Masashi; Magata, Yasuhiro; Saji, Hideo

    2006-01-01

    Cholinergic system in the central nervous system is involved in the memory function. Thus, because the dysfunction of cholinergic system that project to the cerebral cortex from nucleus basalis of Meynert (nbM) would be implicated in the memory function deficits in Alzheimer's disease (AD), evaluating cholinergic function may be useful for the early detection of AD. In this study, because the nucleus basalis magnocellularis (NBM) in rats is equivalent to nbM in human, we investigated the change in cholinergic receptors in the frontal cortex of rats with unilateral lesion to the NBM to find an appropriate index for the early detection of AD using techniques of nuclear medicine. The right NBM was injected with ibotenic acid. [ 18 F]FDG-PET images were obtained 3 days later. Some rats were sacrificed at 1 week, whereas others were subjected to a second [ 18 F]FDG-PET at 4 weeks then sacrificed for membrane preparation. The prepared membranes were subjected to radioreceptor assays to measure the density of nicotinic and muscarinic acetylcholine receptors. Glucose metabolism had decreased on the damaged side compared to the control side at 3 days, but at 4 weeks, there was no difference between the sides. Nicotinic acetylcholine receptors had significantly decreased in density compared to the control side at both 1 and 4 weeks. However, muscarinic receptors were not affected. These results suggested that neuronal dysfunction in AD could be diagnosed at an early stage by imaging nicotinic acetylcholine receptors

  9. Current applications of PET imaging of sex hormone receptors with a fluorinated analogue of estradiol or of testosterone

    International Nuclear Information System (INIS)

    Talbot, J-N.; Montravers, F.; Huchet, V.; Michaud, L.; Ohnona, J.; Balogova, S.; Kerrou, K.; Gligorov, V.; Lotz, P.; Nataf, V.; Cussenot, O.; Darai, E.

    2015-01-01

    Currently, the most frequent approach in the oncologic applications of positron emission tomography (PET) is detecting the hypermetabolic activity of the cancer tissue. A more specific approach, which may be complementary, is detecting the overexpression of receptors. In this review article, we aim to evaluate the results that are currently available for PET imaging of the sex hormone receptors in clinical oncology. The indication of PET and now PET/CT has been more disputed in breast carcinoma than in many other primary cancers (e.g., lung, head and neck, colorectal, lymphoma). 18 F-fluorodeoxyglucose (FDG), the glucose analogue for PET imaging, has a limited sensitivity to detect the primary breast tumors in case of lobular or in situ forms or small sized tumors localised on systematic mammography, and to identify minimal node invasion in the axilla. Using 16α-( 18 F]fluoro-17β-estradiol (FES), a fluorinated estradiol analogue, PET is able to detect the over-expression of the oestrogen receptor (ER) in lesions, at a whole-body level. FES and FDG appear complementary for a better diagnostic performance in staging locally advanced breast cancer or restaging recurrent or metastatic breast cancer. Another potential indication is predicting the response to starting or resuming hormone therapy in patients with metastatic breast cancer, in relation with the ER status of all lesions revealed by FES PET. In two retrospective studies, FDG PET was also able to predict the response to hormone therapy, on basis of a metabolic flare, observed either after 7-10 days of treatment or during an estradiol challenge. A prospective comparison of those approaches is warranted. One study reported predicting response to neoadjuvant chemotherapy thanks to a low value of FES SUV m ax or FES/FDG SUV max ratio. The presence of ER in uterine tumors, including the benign ones, in ovarian cancers or even in meningiomas, may have therapeutic consequences and FES PET could have a clinical

  10. Comparison of intravenous and intraperitoneal [{sup 123}I]IBZM injection for dopamine D2 receptor imaging in mice

    Energy Technology Data Exchange (ETDEWEB)

    Meyer, Philipp T. [Department of Neurology, University Hospital Aachen, 52074 Aachen (Germany); Department of Nuclear Medicine, University Hospital Aachen, 52074 Aachen (Germany)], E-mail: pmeyer@ukaachen.de; Salber, Dagmar [C. and O. Vogt Institute of Brain Research, University Hospital Duesseldorf, 40225 Duesseldorf (Germany); Schiefer, Johannes [Department of Neurology, University Hospital Aachen, 52074 Aachen (Germany); Cremer, Markus [Institute of Neurosciences and Biophysics - Medicine, Research Center Juelich, 52425 Juelich (Germany); Schaefer, Wolfgang M. [Department of Nuclear Medicine, University Hospital Aachen, 52074 Aachen (Germany); Kosinski, Christoph M. [Department of Neurology, University Hospital Aachen, 52074 Aachen (Germany); Langen, Karl-Josef [Institute of Neurosciences and Biophysics - Medicine, Research Center Juelich, 52425 Juelich (Germany)

    2008-07-15

    Introduction: Intraperitoneal (IP) injection represents an attractive alternative route of radiotracer administration for small animal imaging, e.g., for longitudinal studies in transgenic mouse models. We explored the cerebral kinetics of the reversible dopamine D2 receptor ligand [{sup 123}I]IBZM after IP injection in mice. Methods: Cerebral [{sup 123}I]IBZM kinetics were assessed by ex vivo autoradiography in mice sacrificed between 30 and 200 min after IP or intravenous (IV) injection. The striatum-to-cerebellum (S/C) uptake ratio at 140 min was evaluated in wild-type mice and R6/2 transgenic mice (a Huntington's disease model) in comparison with in vitro autoradiography using [{sup 3}H]raclopride. Results: [{sup 123}I]IBZM uptake was slower and lower after IP injection [maximum uptake in striatum 5.6% injected dose per gram (ID/g) at 60 min] than IV injection (10.5%ID/g at 30 min). Between 60 and 120 min, striatal (cerebellar) uptake after IP injection reached 63% (91%) of the uptake after IV injection. The S/C uptake ratio increased to 15.5 at 200 min after IP injection, which corresponds to 87% of the IV injection value (17.8). Consistent with in vitro [{sup 3}H]raclopride autoradiography, the S/C ratio given by ex vivo [{sup 123}I]IBZM autoradiography (140 min after IP injection) was significantly reduced in R6/2 mice. Conclusions: Although IP injection resulted in slower kinetics, relevant measures of dopamine D2 receptor availability were comparable. Thus, IP injection represents a promising route of tracer administration for small animal [{sup 123}I]IBZM SPECT. This should considerably simplify the implementation of longitudinal small animal neuroimaging studies, e.g., in transgenic mouse models.

  11. Small-animal PET imaging of the type 1 and type 2 cannabinoid receptors in a photothrombotic stroke model

    International Nuclear Information System (INIS)

    Vandeputte, Caroline; Casteels, Cindy; Koole, Michel; Gerits, Anneleen; Struys, Tom; Veghel, Daisy van; Evens, Nele; Bormans, Guy; Dresselaers, Tom; Himmelreich, Uwe; Lambrichts, Ivo; Laere, Koen van

    2012-01-01

    Recent ex vivo and pharmacological evidence suggests involvement of the endocannabinoid system in the pathophysiology of stroke, but conflicting roles for type 1 and 2 cannabinoid receptors (CB 1 and CB 2 ) have been suggested. The purpose of this study was to evaluate CB 1 and CB 2 receptor binding over time in vivo in a rat photothrombotic stroke model using PET. CB 1 and CB 2 microPET imaging was performed at regular time-points up to 2 weeks after stroke using [ 18 F]MK-9470 and [ 11 C]NE40. Stroke size was measured using MRI at 9.4 T. Ex vivo validation was performed via immunostaining for CB 1 and CB 2 . Immunofluorescent double stainings were also performed with markers for astrocytes (GFAP) and macrophages/microglia (CD68). [ 18 F]MK-9470 PET showed a strong increase in CB 1 binding 24 h and 72 h after stroke in the cortex surrounding the lesion, extending to the insular cortex 24 h after surgery. These alterations were consistently confirmed by CB 1 immunohistochemical staining. [ 11 C]NE40 did not show any significant differences between stroke and sham-operated animals, although staining for CB 2 revealed minor immunoreactivity at 1 and 2 weeks after stroke in this model. Both CB 1 + and CB 2 + cells showed minor immunoreactivity for CD68. Time-dependent and regionally strongly increased CB 1 , but not CB 2 , binding are early consequences of photothrombotic stroke. Pharmacological interventions should primarily aim at CB 1 signalling as the role of CB 2 seems minor in the acute and subacute phases of stroke. (orig.)

  12. Small-animal PET imaging of the type 1 and type 2 cannabinoid receptors in a photothrombotic stroke model

    Energy Technology Data Exchange (ETDEWEB)

    Vandeputte, Caroline; Casteels, Cindy; Koole, Michel; Gerits, Anneleen [KU Leuven, Division of Nuclear Medicine, Leuven (Belgium); KU Leuven, Molecular Small Animal Imaging Center, MoSAIC, Leuven (Belgium); Struys, Tom [Hasselt University, Laboratory of Histology, Biomedical Research Institute, Hasselt (Belgium); KU Leuven, Biomedical NMR Unit, Leuven (Belgium); Veghel, Daisy van; Evens, Nele; Bormans, Guy [KU Leuven, Molecular Small Animal Imaging Center, MoSAIC, Leuven (Belgium); KU Leuven, Laboratory of Radiopharmacy, Leuven (Belgium); Dresselaers, Tom; Himmelreich, Uwe [KU Leuven, Molecular Small Animal Imaging Center, MoSAIC, Leuven (Belgium); KU Leuven, Biomedical NMR Unit, Leuven (Belgium); Lambrichts, Ivo [Hasselt University, Laboratory of Histology, Biomedical Research Institute, Hasselt (Belgium); Laere, Koen van [KU Leuven, Division of Nuclear Medicine, Leuven (Belgium); KU Leuven, Molecular Small Animal Imaging Center, MoSAIC, Leuven (Belgium); UZ Leuven, Division of Nuclear Medicine, Leuven (Belgium)

    2012-11-15

    Recent ex vivo and pharmacological evidence suggests involvement of the endocannabinoid system in the pathophysiology of stroke, but conflicting roles for type 1 and 2 cannabinoid receptors (CB{sub 1} and CB{sub 2}) have been suggested. The purpose of this study was to evaluate CB{sub 1} and CB{sub 2} receptor binding over time in vivo in a rat photothrombotic stroke model using PET. CB{sub 1} and CB{sub 2} microPET imaging was performed at regular time-points up to 2 weeks after stroke using [{sup 18}F]MK-9470 and [{sup 11}C]NE40. Stroke size was measured using MRI at 9.4 T. Ex vivo validation was performed via immunostaining for CB{sub 1} and CB{sub 2}. Immunofluorescent double stainings were also performed with markers for astrocytes (GFAP) and macrophages/microglia (CD68). [{sup 18}F]MK-9470 PET showed a strong increase in CB{sub 1} binding 24 h and 72 h after stroke in the cortex surrounding the lesion, extending to the insular cortex 24 h after surgery. These alterations were consistently confirmed by CB{sub 1} immunohistochemical staining. [{sup 11}C]NE40 did not show any significant differences between stroke and sham-operated animals, although staining for CB{sub 2} revealed minor immunoreactivity at 1 and 2 weeks after stroke in this model. Both CB{sub 1} {sup +} and CB{sub 2} {sup +} cells showed minor immunoreactivity for CD68. Time-dependent and regionally strongly increased CB{sub 1}, but not CB{sub 2}, binding are early consequences of photothrombotic stroke. Pharmacological interventions should primarily aim at CB{sub 1} signalling as the role of CB{sub 2} seems minor in the acute and subacute phases of stroke. (orig.)

  13. Tratamento farmacológico de acatisia induzida por antipsicóticos Pharmacological treatment of neuroleptic-induced akathisia

    Directory of Open Access Journals (Sweden)

    Adriano Resende Lima

    2001-06-01

    Full Text Available INTRODUÇÃO: A acatisia induzida por antipsicóticos é um transtorno de movimento relacionado ao sistema motor e caracterizado por sensação subjetiva de inquietude interna, irritabilidade ou disforia que podem ser intensas. Associa-se à sensação física e objetiva de desassossego e a movimentos não discinéticos. Esse efeito adverso pode predispor à pobre adesão ao tratamento e, conseqüentemente, favorecer recaídas. Assim, a escolha do melhor tratamento contribui para o alívio do sofrimento dos pacientes e favorece o melhor prognóstico. OBJETIVOS: Avaliar a eficácia e a tolerabilidade dos betabloqueadores, benzodiazepínicos e anticolinérgicos, comparados ao placebo e entre si, no tratamento de acatisia induzida por antipsicóticos, independente de idade ou diagnóstico psiquiátrico. MÉTODOS: Todos os estudos controlados, obtidos a partir das estratégias de busca que compararam betabloqueadores de ação central, benzodiazepínicos ou anticolinérgicos ao placebo e entre si, independente de sexo, idade ou diagnóstico psiquiátrico, foram considerados para esta atualização. Até março de 1999, foram consultadas sete bases de dados eletrônicos, sendo também examinadas as referências bibliográficas dos artigos selecionados. RESULTADOS: São apresentados 22 estudos controlados, sendo 13 comparando betabloqueadores, benzodiazepínicos e anticolinérgicos ao placebo e nove comparando diretamente as intervenções entre si. CONCLUSÕES: As três intervenções farmacológicas demonstraram eficácia superior comparadas ao placebo. Betabloqueadores de ação central mostraram-se mais eficazes, quando comparados a betabloqueadores de ação periférica, benzodiazepínicos e anticolinérgicos.INTRODUCTION: Neuroleptic-induced akathisia is a movement disorder related to the motor system characterized by complaints of inner restlessness, mental uneasiness, or dysphoria, all of which can be intense. Restlessness and non

  14. Synthesis and evaluation of [125I]I-TSA as a brain nicotinic acetylcholine receptor α7 subtype imaging agent

    International Nuclear Information System (INIS)

    Ogawa, Mikako; Tatsumi, Ryo; Fujio, Masakazu; Katayama, Jiro; Magata, Yasuhiro

    2006-01-01

    Introduction: Some in vitro investigations have suggested that the nicotinic acetylcholine receptor (nAChR) α 7 subtype is implicated in Alzheimer's disease, schizophrenia and others. Recently, we developed (R)-3'-(5-bromothiophen-2-yl)spiro[1-azabicyclo[2.2.2]octane-3,5'-[1',3'] oxazolidin]-2'-one (Br-TSA), which has a high affinity and selectivity for α 7 nAChRs. Therefore we synthesized (R)-3'-(5-[ 125 I]iodothiophen-2-yl)spiro[1-azabicyclo[2.2.2]octane-3,5'- [1',3']oxazolidin]-2'-one ([ 125 I]I-TSA) and evaluated its potential for the in vivo detection of α 7 nAChR in brain. Methods: In vitro binding affinity of I-TSA was measured in rat brain homogenates. Radioiodination was accomplished by a Br-I exchange reaction. Biodistribution studies were undertaken in mice by tail vein injection of [ 125 I]I-TSA. In vivo receptor blocking studies were carried out by treating mice with methyllycaconitine (MLA; 5 nmol/5 μl, i.c.v.) or nonradioactive I-TSA (50 μmol/kg, i.v.). Results: I-TSA exhibited a high affinity and selectivity for the α 7 nAChR (K i for α 7 nAChR=0.54 nM). Initial uptake in the brain was high (4.42 %dose/g at 5 min), and the clearance of radioactivity was relatively slow in the hippocampus (α 7 nAChR-rich region) and was rather rapid in the cerebellum (α 7 nAChR poor region). The hippocampus to cerebellum uptake ratio was 0.9 at 5 min postinjection, but it was increased to 1.8 at 60 min postinjection. Although the effect was not statistically significant, administration of I-TSA and MLA decreased the accumulation of radioactivity in hippocampus. Conclusion: Despite its high affinity and selectivity, [ 125 I]I-TSA does not appear to be a suitable tracer for in vivo α 7 nAChR receptor imaging studies due to its high nonspecific binding. Further structural optimization is needed

  15. Plasma homovanillic acid, plasma anti-D1 and -D2 dopamine-receptor activity, and negative symptoms in chronically mediated schizophrenia.

    Science.gov (United States)

    Suzuki, E; Kanba, S; Nibuya, M; Koshikawa, H; Nakaki, T; Yagi, G

    1992-02-15

    We have investigated the relationship between the concentration of homovanillic acid in human plasma (pHVA) and plasma anti-D1 and anti-D2 dopamine receptor activity in chronic schizophrenic patients whose neuroleptic dosage was changed. The change in pHVA level correlated with that in anti-D1, not anti-D2 activity, thus suggesting that the neuroleptic-induced changes in pHVA concentration may be associated with the blocking of D1- as well as D2- receptors. The change of scores on the Scale for the Assessment of Negative Symptoms did not significantly correlate with changes in anti-D1 or anti-D2 activity, but did so correlated with the change in pHVA level.

  16. 99m Tc- la bed somatostatin analogs for imaging somatostatin-receptor-positive tumors

    International Nuclear Information System (INIS)

    Gandomkar, M.; Najafi, R.; Shafiei, A.; Sadat Ebrahimi, E.; Babaie, M.H.; Rabani, M.

    2002-01-01

    Over the least few years, 111 In-DTPA- Octreotide has found widespread clinical applicability, especially in oncology. However limitation, especially concerning availability, imaging properties, and costs, remain and have stimulated research on radiolabeling with many alternative radionuclides. The purpose of this investigation was to labeling somatostatin analogs with 99 m Tc and evaluate their suitability as an agents for in vivo use. Octreotide and Tyr-3-Octreotide were labeled by 99 mTc with direct and indirect methods. Sodium ascorbate and sodium dithionite were used for reduction of cystine bridge and HYNIC was used as bifunctional agents and different co ligands used for labeling by 99 mTc. Yield of labeling, purity, stability, internalisation, binding affinity and biodistribution of peptide conjugates were studied. Direct labeling of octreotide was simple, rapid, efficient and yield was good (%60). K d for binding affinity as high (10 -9 ) but stability was low. Labeling for HYNIC-Tyr-Octreotide had a high yield (>%90), good stability, internalisation and biodistribution. with more experimental work and some improve this peptide-based radiopharmaceuticals can be employed in all nuclear medicine centers as a useful agent for imaging of tumors

  17. Image-receptor performance: a comparison of Trophy RVG UI sensor and Kodak Ektaspeed Plus film.

    Science.gov (United States)

    Ludlow, J; Mol, A

    2001-01-01

    Objective. This study compares the physical characteristics of the RVG UI sensor (RVG) with Ektaspeed Plus film. Dose-response curves were generated for film and for each of 6 available RVG modes. An aluminum step-wedge was used to evaluate exposure latitude. Spatial resolution was assessed by using a line-pair test tool. Latitude and resolution were assessed by observers for both modalities. The RVG was further characterized by its modulation transfer function. Exposure latitude was equal for film and RVG in the periodontal mode. Other gray scale modes demonstrated much lower latitude. The average maximum resolution was 15.3 line-pairs per millimeter (lp/mm) for RVG in high-resolution mode, 10.5 lp/mm for RVG in low-resolution mode, and 20 lp/mm for film (P <.0001). Modulation transfer function measurements supported the subjective assessments. In periodontal mode, the RVG UI sensor demonstrates exposure latitude similar to that of Ektaspeed Plus film. Film images exhibit significantly higher spatial resolution than the RVG images acquired in high-resolution mode.

  18. Preclinical evaluation and quantification of [(18)F]MK-9470 as a radioligand for PET imaging of the type 1 cannabinoid receptor in rat brain

    OpenAIRE

    Casteels, Cindy; Koole, Michel; Celen, Sofie; Bormans, Guy; Van Laere, Koen

    2012-01-01

    PURPOSE: [(18)F]MK-9470 is an inverse agonist for the type 1 cannabinoid (CB1) receptor allowing its use in PET imaging. We characterized the kinetics of [(18)F]MK-9470 and evaluated its ability to quantify CB1 receptor availability in the rat brain. METHODS: Dynamic small-animal PET scans with [(18)F]MK-9470 were performed in Wistar rats on a FOCUS-220 system for up to 10 h. Both plasma and perfused brain homogenates were analysed using HPLC to quantify radiometabolites. Displacement and blo...

  19. PET imaging detection of macrophages with a formyl peptide receptor antagonist

    International Nuclear Information System (INIS)

    Zhang, Yi; Kundu, Bijoy; Zhong, Min; Huang, Tao; Li, Jing; Chordia, Mahendra D.; Chen, Mei-Hua; Pan, Dongfeng; He, Jiang; Shi, Weibin

    2015-01-01

    Macrophages are a major inflammatory cell type involved in the development and progression of many important chronic inflammatory diseases. We previously found that apolipoprotein E-deficient (Apoe −/− ) mice with the C57BL/6 (B6) background develop type 2 diabetes mellitus (T2DM) and accelerated atherosclerosis when fed a Western diet and that there are increased macrophage infiltrations in pancreatic islets and aorta. The formyl peptide receptor 1 (FPR1) is abundantly expressed on the surface of macrophages. The purpose of this study was to evaluate the applicability of cinnamoyl-F-(D)L-F-(D)L-F (cFLFLF), a natural FPR1 antagonist, to detection of macrophages in the pancreatic islets and aorta. 64 Cu labeled cFLFLF and 18 F-fluorodeoxyglucose (FDG) were administered to mice with or without T2DM. Diabetic mice showed an increased 18 FDG uptake in the subcutaneous fat compared with control mice, but pancreatic uptake was minimal for either group. In contrast, diabetic mice exhibited visually noticeable more cFLFLF- 64 Cu retention in pancreas and liver than control mice. The heart and pancreas isolated from diabetic mice contained more macrophages and showed stronger PET signals than those of control mice. Flow cytometry analysis revealed the presence of macrophages but not neutrophils in pancreatic islets. Real-time PCR analysis revealed much higher FPR1 expression in pancreatic islets of diabetic over control mice. Autoradiography and immunohistochemical analysis confirmed abundant FPR1 expression in atherosclerotic lesions. Thus, 64 Cu-labeled cFLFLF peptide is a more effective PET agent for detecting macrophages compared to FDG

  20. Design of the Magnetic Resonance Imaging Evaluation of Mineralocorticoid Receptor Antagonism in Diabetic Atherosclerosis (MAGMA) Trial.

    Science.gov (United States)

    Rajagopalan, Sanjay; Alaiti, M Amer; Broadwater, Kylene; Goud, Aditya; Gaztanaga, Juan; Connelly, Kim; Fares, Anas; Shirazian, Shayan; Kreatsoulas, Catherine; Farkouh, Michael; Dobre, Mirela; Fink, Jeffrey C; Weir, Matthew R

    2017-09-01

    Mineralocorticoid receptor (MR) activation plays an essential role in promoting inflammation, fibrosis, and target organ damage. Currently, no studies are investigating MR antagonism in patients with type 2 diabetes mellitus (T2DM) with chronic kidney disease, at high risk for cardiovascular complications, who are otherwise not candidates for MR antagonism by virtue of heart failure. Further, there is limited information on candidate therapies that may demonstrate differential benefit from this therapy. We hypothesized that MR antagonism may provide additional protection from atherosclerosis progression in higher-risk patients who otherwise may not be candidates for such a therapeutic approach. In this double-blind, randomized, placebo-controlled trial, subjects with T2DM with chronic kidney disease (≥ stage 3) will be randomized in a 1:1 manner to placebo or spironolactone (12.5 mg with eventual escalation to 25 mg daily over a 4-week period). The co-primary efficacy endpoint will be percentage change in total atheroma volume in thoracic aorta and left ventricular mass at 52 weeks in patients treated with spironolactone vs placebo. Secondary outcomes include 24-hour mean systolic blood pressure, central aortic blood pressure, and insulin resistance (HOMA-IR) at 6 weeks. A novel measure in the study will be changes in candidate miRNAs that regulate expression of NR3C2 (MR gene) as well as measuring monocyte/macrophage polarization in response to therapy with spironolactone. We envision that our strategy of simultaneously probing the effects of a drug combined with analysis of mechanisms of action and predictive response will likely provide key information with which to design event-based trials. © 2017 Wiley Periodicals, Inc.

  1. Image-derived and arterial blood sampled input functions for quantitative PET imaging of the angiotensin II subtype 1 receptor in the kidney

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Tao; Tsui, Benjamin M. W.; Li, Xin; Vranesic, Melin; Lodge, Martin A.; Gulaldi, Nedim C. M.; Szabo, Zsolt, E-mail: zszabo@jhmi.edu [Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins School of Medicine, Baltimore, Maryland 21287 (United States)

    2015-11-15

    Purpose: The radioligand {sup 11}C-KR31173 has been introduced for positron emission tomography (PET) imaging of the angiotensin II subtype 1 receptor in the kidney in vivo. To study the biokinetics of {sup 11}C-KR31173 with a compartmental model, the input function is needed. Collection and analysis of arterial blood samples are the established approach to obtain the input function but they are not feasible in patients with renal diseases. The goal of this study was to develop a quantitative technique that can provide an accurate image-derived input function (ID-IF) to replace the conventional invasive arterial sampling and test the method in pigs with the goal of translation into human studies. Methods: The experimental animals were injected with [{sup 11}C]KR31173 and scanned up to 90 min with dynamic PET. Arterial blood samples were collected for the artery derived input function (AD-IF) and used as a gold standard for ID-IF. Before PET, magnetic resonance angiography of the kidneys was obtained to provide the anatomical information required for derivation of the recovery coefficients in the abdominal aorta, a requirement for partial volume correction of the ID-IF. Different image reconstruction methods, filtered back projection (FBP) and ordered subset expectation maximization (OS-EM), were investigated for the best trade-off between bias and variance of the ID-IF. The effects of kidney uptakes on the quantitative accuracy of ID-IF were also studied. Biological variables such as red blood cell binding and radioligand metabolism were also taken into consideration. A single blood sample was used for calibration in the later phase of the input function. Results: In the first 2 min after injection, the OS-EM based ID-IF was found to be biased, and the bias was found to be induced by the kidney uptake. No such bias was found with the FBP based image reconstruction method. However, the OS-EM based image reconstruction was found to reduce variance in the subsequent

  2. Biodistribution and receptor imaging studies of insulin labelled with radioiodine in mice bearing H22 hepatocellular cacinoma

    International Nuclear Information System (INIS)

    Tang Gongshun; Kuang Anren; Liang Zenlu

    2004-01-01

    Objectives: It has been demonstrated that insulin receptor of hepatocellular carcinoma cells is overexpression. The biodistribution of 125I-insulin and receptor imaging studies of 131I-insulin in mice bearing solid liver tumor comprised of hepatic carcinoma H22 cells were performed to develop insulin as a carder of radioiodine. Methods: 1 )Insulin was radiolabeled with iodine-125 or iodine-131 using a Chloramines T method. Twenty mice bearing tumor were divided into 4 groups (n = 5 each) randomly. They were killed at 5, 15, 30, 60 min after 125I-insulin administered intravenously. The percentage of injected dose of 125I-insulin per gram of tissue(%ID/gdis) in mice bearing tumor were determined. 2) Another ten mice bearing tumor were selected to be as a inhibition group. They received cold insulin 2 mg intravenously 2 min ahead of administration of 125I-insulin and they were killed at 30 min (n=5) and 60 rain (n=5) randomly post 125I-insulin injection. The %ID/ginh and the inhibited rates[(%ID/gdis-%iD/ginh) %ID/gdis 100%] were obtained. 3) One tumor-mouse received 7.4 Mbq 13II-insulin intravenously, another received cold insulin 2 mg injection before 13II-insulin injection. Whole body images were carded out and the radioactivity ratios of tumor/normal were accounted at 60 min. Results: 1) The radiochemical purities of 125I-insulin and 13II-insulin were 96.7%-98.9%. The tumors uptake of the 125I-insulin increased gradually, its peak (%ID/gdis) was 3.44% 0.42% at 30 min, when the normal tissues uptake decreased sharply post-injection. The radioactivity ratio of the tumor/blood and tumor/muscle reached to 1.44 and 3.62 respectively at 60 min. 2)The tumor-inhibition rate was 32.07% at 30 min and 37.42% at 60 min. 3) A high radioactivity accumulation in tumor region could be seen in the mouse at 60 min post 131I-insulin injection. The radioactivity ratio of the tumor/normal tissue was 2.13 and it declined to 1.37 after received insulin 2 mg intervention. Conclusions

  3. [¹¹C]-(+)-PHNO PET imaging of dopamine D(2/3) receptors in Parkinson's disease with impulse control disorders.

    Science.gov (United States)

    Payer, Doris E; Guttman, Mark; Kish, Stephen J; Tong, Junchao; Strafella, Antonio; Zack, Martin; Adams, John R; Rusjan, Pablo; Houle, Sylvain; Furukawa, Yoshiaki; Wilson, Alan A; Boileau, Isabelle

    2015-02-01

    Dopamine agonist medications with high affinity for the D3 dopamine receptor are commonly used to treat Parkinson's disease, and have been associated with pathological behaviors categorized under the umbrella of impulse control disorders (ICD). The aim of this study was to investigate whether ICD in Parkinson's patients are associated with greater D3 dopamine receptor availability. We used positron emission tomography (PET) radioligand imaging with the D3 dopamine receptor preferring agonist [¹¹C]-(+)-propyl-hexahydro-naphtho-oxazin (PHNO) in Parkinson's patients with (n = 11) and without (n = 21) ICD, and age-, sex-, and education-matched healthy control subjects (n = 18). Contrary to hypotheses, [¹¹C]-(+)-PHNO binding in D3 -rich brain areas was not elevated in Parkinson's patients with ICD compared with those without; instead, [¹¹C]-(+)-PHNO binding in ventral striatum was 20% lower (P = 0.011), correlating with two measures of ICD severity (r = -0.8 and -0.9), which may reflect higher dopamine tone in ventral striatum. In dorsal striatum, where [¹¹C]-(+)-PHNO binding is associated with D2 receptor levels, [¹¹C]-(+)-PHNO binding was elevated across patients compared with controls. We conclude that although D3 dopamine receptors have been linked to the occurrence of ICD in Parkinson's patients. Our findings do not support the hypothesis that D3 receptor levels are elevated in Parkinson's patients with ICD. We also did not find ICD-related abnormalities in D2 receptor levels. Our findings argue against the possibility that differences in D2/3 receptor levels can account for the development of ICD in PD; however, we cannot rule out that differences in dopamine levels (particularly in ventral striatum) may be involved. © 2015 International Parkinson and Movement Disorder Society.

  4. Quantitative single-photon emission tomography for cerebral flow and receptor distribution imaging

    International Nuclear Information System (INIS)

    Budinger, T.F.

    1985-01-01

    Recently there has been renewed interest in single-photon emission tomography for two major reasons. First, correction methods have been devised for attenuation compensation, nonuniform resolution, and scattered radiation. Second, new radiopharmaceuticals with 1-5% uptake in the brain provide adequate statistics for quantitative imaging of flow using properly designed single-photon tomographic instruments. The lack of commercially available instruments designed specifically to optimize sensitivity for a resolution finer than 15 mm full width at half maximum (FWHM) seems now to be the major deterrent to the widespread use of single-photon emission tomography. But it appears now that some development in this respect also might lead to a widespread renewed interest in single-photon tomography of the brain. Major activities of the past few years can be placed in three distinct categories of instrumentation and methodology

  5. Radiation dosimetry of iodine-123 HEAT, an alpha-1 receptor imaging agent

    International Nuclear Information System (INIS)

    Thomas, K.D.; Greer, D.M.; Couch, M.W.; Williams, C.M.

    1987-01-01

    Biologic distribution data in the rat were obtained for the alpha-1 adrenoceptor imaging agent (+/-) 2-[beta-(iodo-4-hydroxyphenyl)ethylaminomethyl]tetralone (HEAT) labeled with [ 123 I]. The major excretory routes were through the liver (67%) and the kidney (33%). Internal radiation absorbed dose estimates to nine source organs, total body, the GI tract, gonads, and red bone marrow were calculated for the human using the physical decay data for [ 123 I]. The critical organ was found to be the lower large intestine, receiving 1.1 rad per mCi of [ 123 I]HEAT administered. The total-body dose was found to be 58 mrad per mCi

  6. EGF receptor targeted tumor imaging with biotin-PEG-EGF linked to 99mTc-HYNIC labeled avidin and streptavidin

    International Nuclear Information System (INIS)

    Jung, Kyung-Ho; Park, Jin Won; Paik, Jin-Young; Quach, Cung Hoa Thien; Choe, Yearn Seong; Lee, Kyung-Han

    2012-01-01

    Introduction: As direct radiolabeled peptides suffer limitations for in vivo imaging, we investigated the usefulness of radioloabeled avidin and streptavidin as cores to link peptide ligands for targeted tumor imaging. Methods: Human epidermal growth factor (EGF) was site specifically conjugated with a single PEG-biotin molecule and linked to 99m Tc-HYNIC labeled avidin-FITC (Av) or streptavidin-Cy5.5 (Sav). Receptor targeting was verified in vitro, and in vivo pharmacokinetic and biodistribution profiles were studied in normal mice. Scintigraphic imaging was performed in MDA-MB-468 breast tumor xenografted nude mice. Results: Whereas both 99m Tc-Av-EGF and 99m Tc-Sav-EGF retained receptor-specific binding in vitro, the two probes substantially diverged in pharmacokinetic and biodistribution behavior in vivo. 99m Tc-Av-EGF was rapidly eliminated from the circulation with a T1/2 of 4.3 min, and showed intense hepatic accumulation but poor tumor uptake (0.6%ID/gm at 4 h). 99m Tc-Sav-EGF displayed favorable in vivo profiles of longer circulation (T1/2β, 51.5 min) and lower nonspecific uptake that resulted in higher tumor uptake (3.8 %ID/gm) and clear tumor visualization at 15 h. Conclusion: 99m Tc-HYNIC labeled streptavidin linked with growth factor peptides may be useful as a protein-ligand complex for targeted imaging of tumor receptors.

  7. Striatal adenosine A2A receptor-mediated positron emission tomographic imaging in 6-hydroxydopamine-lesioned rats using [18F]-MRS5425

    International Nuclear Information System (INIS)

    Bhattacharjee, Abesh Kumar; Lang Lixin; Jacobson, Orit; Shinkre, Bidhan; Ma Ying; Niu Gang; Trenkle, William C.; Jacobson, Kenneth A.; Chen Xiaoyuan; Kiesewetter, Dale O.

    2011-01-01

    Introduction: A 2A receptors are expressed in the basal ganglia, specifically in striatopallidal GABAergic neurons in the striatum (caudate-putamen). This brain region undergoes degeneration of presynaptic dopamine projections and depletion of dopamine in Parkinson's disease. We developed an 18 F-labeled A 2A analog radiotracer ([ 18 F]-MRS5425) for A 2A receptor imaging using positron emission tomography (PET). We hypothesized that this tracer could image A 2A receptor changes in the rat model for Parkinson's disease, which is created following unilateral injection of the monoaminergic toxin 6-hydroxydopamine (6-OHDA) into the substantia nigra. Methods: [ 18 F]-MRS5425 was injected intravenously in anesthetized rats, and PET imaging data were collected. Image-derived percentage injected doses per gram (%ID/g) in regions of interest was measured in the striatum of normal rats and in rats unilaterally lesioned with 6-OHDA after intravenous administration of saline (baseline), D 2 agonist quinpirole (1.0 mg/kg) or D 2 antagonist raclopride (6.0 mg/kg). Results: Baseline %ID/g reached a maximum at 90 s and maintained plateau for 3.5 min, and then declined slowly thereafter. In 6-OHDA-lesioned rats, %ID/g was significantly higher in the lesioned side compared to the intact side, and the baseline total %ID/g (data from both hemispheres were combined) was significantly higher compared to quinpirole stimulation starting from 4.5 min until the end of acquisition at 30 min. Raclopride did not produce any change in uptake compared to baseline or between the hemispheres. Conclusion: Thus, increase of A 2A receptor-mediated uptake of radioactive MRS5425 could be a superior molecular target for Parkinson's imaging.

  8. Striatal adenosine A{sub 2A} receptor-mediated positron emission tomographic imaging in 6-hydroxydopamine-lesioned rats using [{sup 18}F]-MRS5425

    Energy Technology Data Exchange (ETDEWEB)

    Bhattacharjee, Abesh Kumar; Lang Lixin; Jacobson, Orit [Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892 (United States); Shinkre, Bidhan [Chemical Biology Unit, Laboratory of Cell Biochemistry and Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 (United States); Ma Ying [Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892 (United States); Niu Gang [Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892 (United States); Department of Radiology and Imaging Sciences, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892 (United States); Trenkle, William C. [Chemical Biology Unit, Laboratory of Cell Biochemistry and Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 (United States); Jacobson, Kenneth A. [Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 (United States); Chen Xiaoyuan [Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892 (United States); Kiesewetter, Dale O., E-mail: dk7k@nih.gov [Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892 (United States)

    2011-08-15

    Introduction: A{sub 2A} receptors are expressed in the basal ganglia, specifically in striatopallidal GABAergic neurons in the striatum (caudate-putamen). This brain region undergoes degeneration of presynaptic dopamine projections and depletion of dopamine in Parkinson's disease. We developed an {sup 18}F-labeled A{sub 2A} analog radiotracer ([{sup 18}F]-MRS5425) for A{sub 2A} receptor imaging using positron emission tomography (PET). We hypothesized that this tracer could image A{sub 2A} receptor changes in the rat model for Parkinson's disease, which is created following unilateral injection of the monoaminergic toxin 6-hydroxydopamine (6-OHDA) into the substantia nigra. Methods: [{sup 18}F]-MRS5425 was injected intravenously in anesthetized rats, and PET imaging data were collected. Image-derived percentage injected doses per gram (%ID/g) in regions of interest was measured in the striatum of normal rats and in rats unilaterally lesioned with 6-OHDA after intravenous administration of saline (baseline), D{sub 2} agonist quinpirole (1.0 mg/kg) or D{sub 2} antagonist raclopride (6.0 mg/kg). Results: Baseline %ID/g reached a maximum at 90 s and maintained plateau for 3.5 min, and then declined slowly thereafter. In 6-OHDA-lesioned rats, %ID/g was significantly higher in the lesioned side compared to the intact side, and the baseline total %ID/g (data from both hemispheres were combined) was significantly higher compared to quinpirole stimulation starting from 4.5 min until the end of acquisition at 30 min. Raclopride did not produce any change in uptake compared to baseline or between the hemispheres. Conclusion: Thus, increase of A{sub 2A} receptor-mediated uptake of radioactive MRS5425 could be a superior molecular target for Parkinson's imaging.

  9. Synthesis, radiolabelling, and evaluation of [11C]PB212 as a radioligand for imaging sigma-1 receptors using PET.

    Science.gov (United States)

    Spinelli, Francesco; Haider, Ahmed; Toscano, Annamaria; Pati, Maria Laura; Keller, Claudia; Berardi, Francesco; Colabufo, Nicola Antonio; Abate, Carmen; Ametamey, Simon M

    2018-01-01

    The Sigma-1 receptor (Sig-1R) has been described as a pluripotent modulator of distinct physiological functions and its involvement in various central and peripheral pathological disorders has been demonstrated. However, further investigations are required to understand the complex role of the Sig-1R as a molecular chaperon. A specific PET radioligand would provide a powerful tool in Sig-1R related studies. As part of our efforts to develop a Sig-1R PET radioligand that shows antagonistic properties, we investigated the suitability of 1-(4-(6-methoxynaphthalen-1-yl)butyl)-4-methylpiperidine (designated PB212) for imaging Sig-1R. PB212 is a Sig-1R antagonist and exhibits subnanomolar affinity ( K i = 0.030 nM) towards Sig-1R as well as good to excellent selectivity over Sig-2R. The radiolabelling of [ 11 C]PB212 was accomplished by O-methylation of the phenolic precursor using [ 11 C]MeI. In vitro autoradiography with [ 11 C]PB212 on WT and Sig-1R KO mouse brain tissues revealed high non-specific binding, however using rat spleen tissues from CD1 mice and Wistar rats, high specific binding was observed. The spleen is known to have a high expression of Sig-1R. In vivo PET experiments in Wistar rats also showed high accumulation of [ 11 C]PB212 in the spleen. Injection of Sig-1R binding compounds, haloperidol (1 mg/kg) or fluspidine (1 mg/kg) shortly before [ 11 C]PB212 administration induced a drastic reduction of radiotracer accumulation, confirming the specificity of [ 11 C]PB212 towards Sig-1R in the spleen. The results obtained herein indicate that although [ 11 C]PB212 is not suitable for imaging Sig-1R in the brain, it is a promising candidate for the detection and quantification of Sig-1Rs in the periphery.

  10. A stable neurotensin-based radiopharmaceutical for targeted imaging and therapy of neurotensin receptor-positive tumours

    International Nuclear Information System (INIS)

    Garcia-Garayoa, Elisa; Blaeuenstein, Peter; Blanc, Alain; Maes, Veronique; Tourwe, Dirk; Schubiger, P.A.

    2009-01-01

    Neurotensin (NT) and its high affinity receptor (NTR1) are involved in several neoplastic processes. Thus, NT-based radiopharmaceuticals are potential tracers for targeted diagnosis and therapy of NTR-positive tumours. A new analogue based on NT(8-13), NT-XIX, with the three enzymatic cleavage sites stabilised, was synthesised and tested. The synthesis was performed by Boc strategy. Labelling with 99m Tc/ 188 Re was performed using the tricarbonyl technique. Metabolic stability was tested in vitro and in vivo. NT-XIX was further characterised in vitro in HT-29 cells and in vivo in nude mice with HT-29 xenografts. NT-XIX showed much longer half-lives than non-stabilised analogues. Binding to NTR1 was highly specific, although the affinity was lower than that of natural NT. Bound activity rapidly internalised into HT-29 cells and 50% remained trapped after 24 h. In the time-course biodistribution, the highest uptake was found in the tumour at all p.i. times. In vivo uptake was specific, and accumulation of activity in the kidneys was low. Radioactivity clearance from healthy organs was faster than that from the tumour, resulting in improved tumour-to-tissue ratios and good SPECT/CT imaging. Treatment with 188 Re-NT-XIX (30 MBq, in three or four fractions) decreased tumour growth by 50% after 3 weeks. The high in vivo stability and the favourable in vivo behaviour makes NT-XIX an excellent candidate for the imaging and therapy of NTR1-positive tumours. (orig.)

  11. Initial clinical experiences with dopamine D2 receptor imaging by means of 2'-iodospiperone and single-photon emission computed tomography

    International Nuclear Information System (INIS)

    Yonekura, Yoshiharu; Saji, Hideo; Iwasaki, Yasushi

    1995-01-01

    Dopamine D 2 receptor imaging was performed with 123 I labeled 2'-iodospiperone (2'-ISP) and single-photon emission computed tomography (SPECT) in 9 patients: 4 with idiopathic Parkinson's disease, 2 with parkinsonism, 1 with Wilson's disease and 2 with pituitary tumor, and the results were compared with the data for 9 normal subjects. Following an intravenous injection of 123 I-2'-ISP, early (within 30 min) and late (between 2 and 4 hr) SPECT images were obtained by means of a multi-detector SPECT scanner or a rotating gamma camera. In normal subjects, early SPECT images demonstrated uniform distribution of radioactivity in the cerebral gray matter and cerebellum reflecting regional cerebral blood flow, whereas late SPECT images showed high radioactivity only in the basal ganglia. All the patients with Parkinson's disease also demonstrated symmetrical basal ganglia uptake in the late SPECT images, but it was diminished in parkinsonism and Wilson's disease. One patient with a growth hormone-producing pituitary tumor had a positive uptake in the tumor. These preliminary clinical data demonstrated that 2'-ISP can be used for SPECT imaging of D 2 dopamine receptors and may be of clinical value for the diagnosis and planning of the treatment of neurological diseases. (author)

  12. Initial clinical experiences with dopamine D{sub 2} receptor imaging by means of 2`-iodospiperone and single-photon emission computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Yonekura, Yoshiharu [Fukui Medical Schoool, Matsuoka (Japan). Biomedical Imaging Research Center; Saji, Hideo; Iwasaki, Yasushi [and others

    1995-08-01

    Dopamine D{sub 2} receptor imaging was performed with {sup 123}I labeled 2`-iodospiperone (2`-ISP) and single-photon emission computed tomography (SPECT) in 9 patients: 4 with idiopathic Parkinson`s disease, 2 with parkinsonism, 1 with Wilson`s disease and 2 with pituitary tumor, and the results were compared with the data for 9 normal subjects. Following an intravenous injection of {sup 123}I-2`-ISP, early (within 30 min) and late (between 2 and 4 hr) SPECT images were obtained by means of a multi-detector SPECT scanner or a rotating gamma camera. In normal subjects, early SPECT images demonstrated uniform distribution of radioactivity in the cerebral gray matter and cerebellum reflecting regional cerebral blood flow, whereas late SPECT images showed high radioactivity only in the basal ganglia. All the patients with Parkinson`s disease also demonstrated symmetrical basal ganglia uptake in the late SPECT images, but it was diminished in parkinsonism and Wilson`s disease. One patient with a growth hormone-producing pituitary tumor had a positive uptake in the tumor. These preliminary clinical data demonstrated that 2`-ISP can be used for SPECT imaging of D{sub 2} dopamine receptors and may be of clinical value for the diagnosis and planning of the treatment of neurological diseases. (author).

  13. [7α-18F]fluoro-17α-methyl-5α-dihydrotestosterone: a ligand for androgen receptor-mediated imaging of prostate cancer

    International Nuclear Information System (INIS)

    Garg, Pradeep K.; Labaree, David C.; Hoyte, Robert M.; Hochberg, Richard B.

    2001-01-01

    We have synthesized a 18 F-labeled androgen, [7α- 18 F]fluoro-17α-methyl-5α-dihydrotestosterone, in a no-carrier-added radiosynthesis by exchange of 18 F- (tetrabutylammonium fluoride) with the 7β-tosyloxy of 17α-methyl-5α-dihydrotestosterone. The nonradioactive steroid binds with high affinity and specificity to the androgen receptor and binds poorly, if at all, to other steroid receptors and plasma sex hormone binding globulin. The 7α- 18 F-androgen concentrates markedly in the prostate of rats by an androgen receptor-dependent mechanism. It is likely that [7α- 18 F]fluoro-17α-methyl-5α-dihydrotestosterone will be an excellent positron emission tomography imaging agent for prostate cancer

  14. Imaging and measuring the biophysical properties of Fc gamma receptors on single macrophages using atomic force microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Li, Mi [State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang 110016 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Liu, Lianqing, E-mail: lqliu@sia.cn [State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang 110016 (China); Xi, Ning [Department of Mechanical and Biomedical Engineering, City University of Hong Kong, Hong Kong (China); Wang, Yuechao [State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang 110016 (China); Xiao, Xiubin [Department of Lymphoma, Affiliated Hospital of Military Medical Academy of Sciences, Beijing 100071 (China); Zhang, Weijing, E-mail: zhangwj3072@163.com [Department of Lymphoma, Affiliated Hospital of Military Medical Academy of Sciences, Beijing 100071 (China)

    2013-09-06

    Highlights: •Nanoscale cellular ultra-structures of macrophages were observed. •The binding affinities of FcγRs were measured directly on macrophages. •The nanoscale distributions of FcγRs were mapped on macrophages. -- Abstract: Fc gamma receptors (FcγR), widely expressed on effector cells (e.g., NK cells, macrophages), play an important role in clinical cancer immunotherapy. The binding of FcγRs to the Fc portions of antibodies that are attached to the target cells can activate the antibody-dependent cell-mediated cytotoxicity (ADCC) killing mechanism which leads to the lysis of target cells. In this work, we used atomic force microscopy (AFM) to observe the cellular ultra-structures and measure the biophysical properties (affinity and distribution) of FcγRs on single macrophages in aqueous environments. AFM imaging was used to obtain the topographies of macrophages, revealing the nanoscale cellular fine structures. For molecular interaction recognition, antibody molecules were attached onto AFM tips via a heterobifunctional polyethylene glycol (PEG) crosslinker. With AFM single-molecule force spectroscopy, the binding affinities of FcγRs were quantitatively measured on single macrophages. Adhesion force mapping method was used to localize the FcγRs, revealing the nanoscale distribution of FcγRs on local areas of macrophages. The experimental results can improve our understanding of FcγRs on macrophages; the established approach will facilitate further research on physiological activities involved in antibody-based immunotherapy.

  15. Technetium labeled WH701 for its potential use to image TNF-receptor-positive hepatocarcinoma

    International Nuclear Information System (INIS)

    Xia Jinsong; Wu Hua; Xiang Yan

    2004-01-01

    Objective: In this investigation, TNF analogs (WH701) was labeled with technetium (A number of TNF analogs had been selected and synthesized in our lab using random phage-display peptides library ) and pharmacokinetics and feasibility studies were performed for its potential use as diagnostic radiopharmaceutical. Methods WH701 was radiolabeled with 99m Tc then the complexes were characterized by thin layer chromatography. In vitro stability of the radiolabeled WH701 was examined simultaneity. Biodistribution and tumor uptake studies were also conducted to determine its in vivo characteristics. Results: The peptide analog WH701 permitted efficient incorporation of 99m Tc. The preparation of 99m Tc-WH701 was stable in vitro. Studies in vivo suggested that the biological activity of the peptide was not compromised. The agent was cleared rapidly from the blood and excreted mainly from kidney. The labeled peptide was shown in the nude mouse model to localize rapidly and specifically in site of tumor. Conclusions: The TNF analogue peptide WH701 can be radiolabeled with 99m Tc without loss of affinity, and the 99m Tc-WH701 shows radiochemical stability for an extended period of time in vitro. The high specific tumor uptake, rapid blood clearance, and predominantly renal excretion make 99m Tc-WH701 a promising candidate for tumor imaging. This agent is worthy of further investigation.

  16. Technetium labeled WH701 for its potential use to image TNF-receptor-positive hepatocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Jinsong, Xia; Hua, Wu; Yan, Xiang [Department of Nuclear Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China)

    2004-07-01

    Objective: In this investigation, TNF analogs (WH701) was labeled with technetium (A number of TNF analogs had been selected and synthesized in our lab using random phage-display peptides library ) and pharmacokinetics and feasibility studies were performed for its potential use as diagnostic radiopharmaceutical. Methods WH701 was radiolabeled with {sup 99m}Tc then the complexes were characterized by thin layer chromatography. In vitro stability of the radiolabeled WH701 was examined simultaneity. Biodistribution and tumor uptake studies were also conducted to determine its in vivo characteristics. Results: The peptide analog WH701 permitted efficient incorporation of {sup 99m}Tc. The preparation of {sup 99m}Tc-WH701 was stable in vitro. Studies in vivo suggested that the biological activity of the peptide was not compromised. The agent was cleared rapidly from the blood and excreted mainly from kidney. The labeled peptide was shown in the nude mouse model to localize rapidly and specifically in site of tumor. Conclusions: The TNF analogue peptide WH701 can be radiolabeled with {sup 99m}Tc without loss of affinity, and the {sup 99m}Tc-WH701 shows radiochemical stability for an extended period of time in vitro. The high specific tumor uptake, rapid blood clearance, and predominantly renal excretion make {sup 99m}Tc-WH701 a promising candidate for tumor imaging. This agent is worthy of further investigation.

  17. Catatonia, Neuroleptic Malignant Syndrome, and Cotard Syndrome in a 22-Year-Old Woman: A Case Report

    Directory of Open Access Journals (Sweden)

    C. Weiss

    2013-01-01

    Full Text Available The following case study describes a 22-year-old woman with depression and symptoms of psychosis who developed neuroleptic malignant syndrome after using Risperidone, thus requiring life support equipment and Bromocriptine, later recovering after seven days. From a psychiatric and neurological point of view, however, the persistence of catatonic syndrome and Cotard syndrome delusions was observed, based on assertions such as “I do not have a heart,” “my heart is not beating,” “I can not breathe,” “I am breaking apart,” “I have no head” (ideas of negation and statements about the patient being responsible for the “death of the whole world” (ideas of enormity. Brain NMR revealed leukoencephalopathy, interpreted as scar lesions caused by perinatal neurological damage, after discarding other pathologies. The patient responded well to electroconvulsive therapy after 11 sessions. Organic vulnerability to these syndromes, as well as their coexistence and clinical differentiation is discussed in the light of the data observed.

  18. Neuroleptic malignant syndrome: A review of the clinical/diagnostic features and report of a case without fever

    Directory of Open Access Journals (Sweden)

    Okwudili Obayi

    2017-01-01

    Full Text Available Neuroleptic malignant syndrome (NMS is an uncommon but potentially fatal idiosyncratic reaction characterized by the development of altered consciousness, hyperthermia, autonomic dysfunction, and muscular rigidity on exposure to antipsychotic (or some other psychotropic medications. It is a medical emergency that requires early prompt identification and intervention. Fever is a predominant symptom in NMS. However, there have been reports that the classical high temperature usually associated with NMS may, on rare occasions, be absent. Case presentation This review and case report focus on the clinical/diagnostic features of NMS and a report of an unusual case without the classical high grade fever in a 27- year old male patient with schizophrenia who had been on high doses of multiple typical and atypical antipsychotic drugs. Conclusion This case report serves to remind clinicians of the essential features in the diagnosis of NMS and supports earlier reports that the classical high temperature usually associated with NMS may, on rare occasions, be absent and that would not exclude the diagnosis.

  19. Vitamin B6 versus mianserin and placebo in acute neuroleptic-induced akathisia: a randomized, double-blind, controlled study.

    Science.gov (United States)

    Miodownik, Chanoch; Lerner, Vladimir; Statsenko, Nikolay; Dwolatzky, Tzvi; Nemets, Boris; Berzak, Elina; Bergman, Joseph

    2006-01-01

    Treatment strategies against acute neuroleptic-induced akathisia (NIA) include anticholinergic (antimuscarinic) agents, dopamine agonists, GABAergic agents, beta-blockers, benzodiazepines, and serotonin antagonists. However, many patients who have acute akathisia fail to respond. In previous studies, mianserin and vitamin B6 were found to be effective in the treatment of acute akathisia. The purpose of this study was to compare the efficacy of B(6), mianserin and placebo in the treatment of acute NIA. Sixty schizophrenia and schizoaffective inpatients who have NIA were randomly divided to receive vitamin B(6) 1,200 mg/d, mianserin 15 mg/d, or placebo for 5 days, in a double-blind design. The Barnes Akathisia Rating Scale, Brief Psychiatric Rating Scale, and Clinical Global Impression were used to assess the severity of NIA and psychotic symptoms. The assessment was made at baseline and daily for the duration of the study. Compared with the placebo group, the vitamin B(6)-treated and mianserin-treated patients showed a significant improvement in the subjective (P vitamin B(6) group (13/23, 56%) as well as in the mianserin groups (13/20, 65%), and in only one patient in the placebo group (1/17, 6%; P vitamin B(6) and mianserin suggests that the pathophysiology of acute NIA is heterogeneous with the various subtypes of acute NIA responding differently to the various pharmacological approaches.

  20. A retrospective analysis of cases with neuroleptic malignant syndrome and an evaluation of risk factors for mortality.

    Science.gov (United States)

    Sahin, Aynur; Cicek, Mustafa; Gonenc Cekic, Ozgen; Gunaydin, Mucahit; Aykut, Demet Saglam; Tatli, Ozgur; Karaca, Yunus; Arici, Mualla Aylin

    2017-12-01

    Neuroleptic malignant syndrome (NMS) is a neurological emergency rarely encountered in clinical practice but with a high mortality rate. Cases associated with atypical antipsychotic use or termination of dopamine agonists have been seen in recent years. The purpose of this study was to assess the presence of risk factors for mortality by investigating all clinical and laboratory characteristics of cases with NMS. This descriptive, cross-sectional study retrospectively investigated all clinical and laboratory characteristics by scanning the ICD-10 codes of patients presenting to the XXXX Faculty of Medicine Emergency Department and diagnosed with NMS between 2006 and 2016. Patients were divided into surviving and non-surviving groups, and the data elicited were subjected to statistical comparisons. The mean age of the 18 patients diagnosed with NMS was 46.9 ± 4.8 years, and 50% were women. In addition to antipsychotics among the drugs leading to NMS, the syndrome also developed as a result of levodopa withdrawal in three patients and metoclopramide use in one patient. Statistically significant differences were determined between the surviving and non-surviving patients in terms of blood pressure, blood urea nitrogen (BUN), creatine kinase (CK) and mean platelet volume (MPV) values (p ≤ 0.05). In this study the most common agent that cause NMS was atypical antipsychotics. Also advanced age, increased blood pressure and serum CK, BUN and MPV values were identified as potential risk factors for mortality in NMS.

  1. Characterization of high specific activity [16 alpha-123I]Iodo-17 beta-estradiol as an estrogen receptor-specific radioligand capable of imaging estrogen receptor-positive tumors

    International Nuclear Information System (INIS)

    Pavlik, E.J.; Nelson, K.; Gallion, H.H.; van Nagell, J.R. Jr.; Donaldson, E.S.; Shih, W.J.; Spicer, J.A.; Preston, D.F.; Baranczuk, R.J.; Kenady, D.E.

    1990-01-01

    16 alpha-[123I]Iodo-17 beta-estradiol (16 alpha-[123I]E2) has been characterized for use as a selective radioligand for estrogen receptor (ERc) that is capable of generating in situ images of ERc-positive tumors. High specific activity 16 alpha-[123I]E2 (7,500-10,000 Ci/mmol) was used in all determinations. Radiochemical purity was determined by thin layer chromatography, and the selectivity of radioligand for ERc was evaluated using size exclusion high performance liquid chromatography on ERc prepared from rodent uteri. Efficiencies of radioidination approaching 100% were achieved, and excellent receptor selectivity was obtained even when the efficiency of radioiodination was as low as 10%. Low radiochemical purity was always associated with poor selectivity for ERc. No new radioligand species was generated during the course of radiodecay; however, reduced binding over time, even when increased activity was used to compensate for radiodecay, indicated that the formation of a radioinert competitor does occur. 16 alpha-[123I]E2 demonstrated stable, high affinity binding to ERc and was concentrated by ERc-positive tissues. After injecting 16 alpha-[123I]E2 in vivo, images of ERc-containing tissues were obtained, including rabbit reproductive tract and dimethylbenzanthracene-induced tumors. The demonstrations of ERc selectivity and image formation both indicate that 16 alpha-[123I]E2 should have promise as a useful new radiopharmaceutical for imaging ERc-positive cancers

  2. Improved delineation of human dopamine receptors using [18F]-N-methylspiroperidol and PET

    International Nuclear Information System (INIS)

    Arnett, C.D.; Wolf, A.P.; Shiue, C.Y.; Fowler, J.S.; MacGregor, R.R.; Christman, D.R.; Smith, M.R.

    1986-01-01

    The brain uptake of [18F]-N-methylspiroperidol, a butyrophenone neuroleptic with high selectivity for the dopamine receptor, has been measured in three normal human volunteers using positron emission tomography for times up to 12 hr postinjection. These studies demonstrated two unique findings concerning the in vivo distribution of this neuroleptic: (a) it is tightly bound to dopamine D-2 receptors in the caudate-putamen brain regions, and (b) these regions are the only large brain structures which exhibit appreciable long-term retention. In addition, radioactivity clears rapidly from plasma, and the percentage of unchanged [18F]-N-methylspiroperidol in plasma declines rapidly. These results suggest that this compound binds irreversibly to dopamine D-2 receptors, and that there are few if any dopamine D-2 receptors in the human frontal cortex. These studies emphasize not only the importance of characterizing neurotransmitter receptors in living human brain using a ligand labeled with a positron emitting nuclide of sufficiently long half-life to allow monitoring of brain radioactivity distribution for several hours after the injection of radioligand, but also of accurately determining the amount of unchanged tracer in plasma for tracer kinetic modeling

  3. Insulinoma imaging with glucagon-like peptide-1 receptor targeting probe (18)F-FBEM-Cys (39)-exendin-4.

    Science.gov (United States)

    Xu, Yuping; Pan, Donghui; Xu, Qing; Zhu, Chen; Wang, Lizhen; Chen, Fei; Yang, Runlin; Luo, Shineng; Yang, Min

    2014-09-01

    Glucagon-like peptide-1 receptor (GLP-1R) is a specific target for insulinomas imaging since it is overexpressed in the tumor. Exendin-4 exhibits high affinity for the GLP-1R. In this study, a novel (18)F-labeled exendin-4 analog, (18)F-FBEM-Cys(39)-exendin-4, was synthesized and its potentials for GLP-1R imaging were also evaluated. (18)F-FBEM was synthesized by coupling (18)F-fluorobenzoic acid ((18)F-FBA) with N-(2-aminoethyl) maleimide, and the reaction conditions were optimized. Cys(39)-exendin-4 was then conjugated with (18)F-FBEM to obtain (18)F-FBEM-Cys(39)-exendin-4. The GLP-1R targeting potential and pharmacokinetic profile of the tracer were analyzed in INS-1 insulinoma and MDA-MB-435 breast tumor model, respectively. Under the optimal conditions, the yield of radiolabeled (18)F-FBEM was 49.1 ± 2.0 % (based on (18)F-FBA, non-decay corrected). The yield of (18)F-FBEM-Cys(39)-exendin-4 was 35.1 ± 2.6 % (based on the starting (18)F-FBEM, non-decay corrected). The radiochemical purity of (18)F-FBEM-Cys(39)-exendin-4 is >95 %, and the specific activity was at least 35 GBq/μmol. The GLP-1R-positive INS-1 insulinoma xenograft was clearly visible with good contrast to background, whereas GLP-1R-negative MDA-MB435 breast tumor was barely visible. Low levels of radioactivity were also detected at pancreas and lungs due to few GLP-1R expressions. GLP-1R binding specificity was demonstrated by reduced INS-1 tumor uptake of the tracer after coinjection with an excess of unlabeled Cys(39)-exendin-4 at 1 h postinjection. The thiol-reactive reagent, (18)F-FBEM, was prepared with high yield and successfully conjugated to Cys(39)-exendin-4. Favorable preclinical data showing specific and effective tumor targeting by (18)F-FBEM-Cys(39)-exendin-4 suggest that the tracer may be a potential probe for insulinomas imaging.

  4. Development of an inflammation imaging tracer, 111In-DOTA-DAPTA, targeting chemokine receptor CCR5 and preliminary evaluation in an ApoE-/- atherosclerosis mouse model.

    Science.gov (United States)

    Wei, Lihui; Petryk, Julia; Gaudet, Chantal; Kamkar, Maryam; Gan, Wei; Duan, Yin; Ruddy, Terrence D

    2018-02-07

    Chemokine receptor 5 (CCR5) plays an important role in atherosclerosis. Our objective was to develop a SPECT tracer targeting CCR5 for imaging plaque inflammation by radiolabeling D-Ala-peptide T-amide (DAPTA), a CCR5 antagonist, with 111 In. 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) conjugated DAPTA (DOTA-DAPTA) was labeled with 111 In. Cell uptake studies were conducted in U87-CD4-CCR5 and U87-MG cells. Biodistribution was determined in C57BL/6 mice. Autoradiography, en face and Oil Red O (ORO) imaging studies were performed in ApoE -/- mice. DOTA-DAPTA was radiolabeled with 111 In with high radiochemical purity (> 98%) and specific activity (70 MBq·nmol). 111 In-DOTA-DAPTA exhibited fast blood and renal clearance and high spleen uptake. The U87-CD4-CCR5 cells had significantly higher uptake in comparison to the U87-MG cells. The cell uptake was reduced by three times with DAPTA, indicating the receptor specificity of the uptake. Autoradiographic images showed significantly higher lesion uptake of 111 In-DOTA-DAPTA in ApoE -/- mice than that in C57BL/6 mice. The tracer uptake in 4 month old ApoE -/- high fat diet (HFD) mice with blocking agent was twofold lower than the same mice without the blocking agent, demonstrating the specificity of the tracer for the CCR5 receptor. 111 In-DOTA-DAPTA, specifically targeting chemokine receptor CCR5, is a potential SPECT agent for imaging inflammation in atherosclerosis.

  5. Biodistribution and dosimetry in humans of two inverse agonists to image cannabinoid CB{sub 1} receptors using positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Terry, Garth E. [National Institute of Mental Health, Molecular Imaging Branch, Bethesda, MD (United States); Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Stockholm (Sweden); Hirvonen, Jussi; Liow, Jeih-San; Seneca, Nicholas; Morse, Cheryl L.; Pike, Victor W.; Innis, Robert B. [National Institute of Mental Health, Molecular Imaging Branch, Bethesda, MD (United States); Tauscher, Johannes T.; Schaus, John M.; Phebus, Lee; Felder, Christian C. [Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN (United States); Halldin, Christer [Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Stockholm (Sweden)

    2010-08-15

    Cannabinoid subtype 1 (CB{sub 1}) receptors are found in nearly every organ in the body, may be involved in several neuropsychiatric and metabolic disorders, and are therefore an active target for pharmacotherapy and biomarker development. We recently reported brain imaging of CB{sub 1} receptors with two PET radioligands: {sup 11}C-MePPEP and {sup 18}F-FMPEP-d{sub 2}. Here we describe the biodistribution and dosimetry estimates for these two radioligands. Seven healthy subjects (four men and three women) underwent whole-body PET scans for 120 min after injection with {sup 11}C-MePPEP. Another seven healthy subjects (two men and five women) underwent whole-body PET scans for 300 min after injection with {sup 18}F-FMPEP-d{sub 2}. Residence times were acquired from regions of interest drawn on tomographic images of visually identifiable organs for both radioligands and from radioactivity excreted in urine for {sup 18}F-FMPEP-d{sub 2}. The effective doses of {sup 11}C-MePPEP and {sup 18}F-FMPEP-d{sub 2} are 4.6 and 19.7 {mu}Sv/MBq, respectively. Both radioligands demonstrated high uptake of radioactivity in liver, lung, and brain shortly after injection and accumulated radioactivity in bone marrow towards the end of the scan. After injection of {sup 11}C-MePPEP, radioactivity apparently underwent hepatobiliary excretion only, while radioactivity from {sup 18}F-FMPEP-d{sub 2} showed both hepatobiliary and urinary excretion. {sup 11}C-MePPEP and {sup 18}F-FMPEP-d{sub 2} yield an effective dose similar to other PET radioligands labeled with either {sup 11}C or {sup 18}F. The high uptake in brain confirms the utility of these two radioligands to image CB{sub 1} receptors in brain, and both may also be useful to image CB{sub 1} receptors in the periphery. (orig.)

  6. Synthesis and evaluation of new imaging agent for central nicotinic acetylcholine receptor {alpha}{sub 7} subtype

    Energy Technology Data Exchange (ETDEWEB)

    Ogawa, Mikako [Photon Medical Research Center, Hamamatsu University School of Medicine, Hamamatsu (Japan); Nishiyama, Shingo; Tsukada, Hideo [PET Center, Central Research Laboratory, Hamamatsu Photonics K.K., Hamamatsu (Japan); Hatano, Kentaro [National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, Obu (Japan); Fuchigami, Takeshi [Photon Medical Research Center, Hamamatsu University School of Medicine, Hamamatsu (Japan); Yamaguchi, Hiroshi [National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, Obu (Japan); Molecular Imaging Frontier Research Center, Hamamatsu University School of Medicine, Hamamatsu (Japan); Matsushima, Yoshitaka [Department of Chemistry, Hamamatsu University School of Medicine, Hamamatsu (Japan); Ito, Kengo [National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, Obu (Japan); Magata, Yasuhiro [Photon Medical Research Center, Hamamatsu University School of Medicine, Hamamatsu (Japan); Molecular Imaging Frontier Research Center, Hamamatsu University School of Medicine, Hamamatsu (Japan)], E-mail: magata@hama-med.ac.jp

    2010-04-15

    Introduction: The nicotinic acetylcholine receptor (nAChR) {alpha}7 subtype ({alpha}{sub 7} nAChR) is one of the major nAChR subtypes in the brain. We synthesized C-11 labeled {alpha}{sub 7} nAChR ligands, (R)-2-[{sup 11}C]methylamino-benzoic acid 1-aza-bicyclo[2.2.2]oct-3-yl ester ([{sup 11}C](R)-MeQAA) and its isomer (S)-[{sup 11}C]MeQAA, for in vivo investigation with positron emission tomography (PET). Then, the potential of (R)- and (S)-[{sup 11}C]MeQAA for in vivo imaging of {alpha}{sub 7} nAChR in the brain was evaluated in mice and monkeys. Methods: The binding affinity for {alpha}{sub 7} nAChR was measured using rat brain. Biodistribution and in vivo receptor blocking studies were undertaken in mice. Dynamic PET scans were performed in conscious monkeys. Results: The affinity for {alpha}{sub 7} nAChR was 41 and 182 nM for (R)- and (S)-MeQAA, respectively. The initial uptake in the mouse brain was high ([{sup 11}C](R)-MeQAA: 7.68 and [{sup 11}C](S)-MeQAA: 6.65 %dose/g at 5 min). The clearance of [{sup 11}C](R)-MeQAA was slow in the hippocampus ({alpha}{sub 7} nAChR-rich region) but was rapid in the cerebellum ({alpha}{sub 7} nAChR-poor region). On the other hand, the clearance was fast for [{sup 11}C](S)-MeQAA in all regions. The brain uptake of [{sup 11}C](R)-MeQAA was decreased by methyllycaconitine ({alpha}{sub 7} nAChR antagonist) treatment. In monkeys, {alpha}{sub 7} nAChRs were highly distributed in the thalamus and cortex but poorly distributed in the cerebellum. The high accumulation was observed in the cortex and thalamus for [{sup 11}C](R)-MeQAA, while the uptake was rather homogeneous for [{sup 11}C](S)-MeQAA. Conclusions: [{sup 11}C](R)-MeQAA was successfully synthesized and showed high uptake to the brain. However, since the in vivo selectivity for {alpha}{sub 7} nAChR was not enough, further PET kinetic analysis or structure optimization is needed for specific visualization of brain {alpha}{sub 7} nAChRs in vivo.

  7. Functional antagonistic properties of clozapine at the 5-HT3 receptor.

    Science.gov (United States)

    Hermann, B; Wetzel, C H; Pestel, E; Zieglgänsberger, W; Holsboer, F; Rupprecht, R

    1996-08-23

    The atypical neuroleptic clozapine is thought to exert its psychopharmacological actions through a variety of neurotransmitter receptors. It binds preferentially to D4 and 5-HT2 receptors; however, little is known on it's interaction with the 5-HT3 receptor. Using a cell line stably expressing the 5-HT3 receptor, whole-cell voltage-clamp analysis revealed functional antagonistic properties of clozapine at low nanomolar concentrations in view of a binding affinity in the upper nanomolar range. Because the concentration of clozapine required for an interaction with the 5-HT3 receptor can be achieved with therapeutical doses, functional antagonistic properties at this ligand-gated ion channel may contribute to its unique psychopharmacological profile.

  8. In vivo imaging of oxidative stress in the kidney of diabetic mice and its normalization by angiotensin II type 1 receptor blocker

    International Nuclear Information System (INIS)

    Sonta, Toshiyo; Inoguchi, Toyoshi; Matsumoto, Shingo; Yasukawa, Keiji; Inuo, Mieko; Tsubouchi, Hirotaka; Sonoda, Noriyuki; Kobayashi, Kunihisa; Utsumi, Hideo; Nawata, Hajime

    2005-01-01

    This study was undertaken to evaluate oxidative stress in the kidney of diabetic mice by electron spin resonance (ESR) imaging technique. Oxidative stress in the kidney was evaluated as organ-specific reducing activity with the signal decay rates of carbamoyl-PROXYL probe using ESR imaging. The signal decay rates were significantly faster in corresponding image pixels of the kidneys of streptozotocin-induced diabetic mice than in those of controls. This technique further demonstrated that administration of angiotensin II type 1 receptor blocker (ARB), olmesartan (5 mg/kg), completely restored the signal decay rates in the diabetic kidneys to control values. In conclusion, this study provided for the first time the in vivo evidence for increased oxidative stress in the kidneys of diabetic mice and its normalization by ARB as evaluated by ESR imaging. This technique would be useful as a means of further elucidating the role of oxidative stress in diabetic nephropathy

  9. Biokinetics and dosimetry in patients of 99mTc-HYNIC-Lys3-Bombesin: images of GRP receptors

    International Nuclear Information System (INIS)

    Santos C, C. L.

    2007-01-01

    The bombesin (BN) receptor subtype 2 (GRP-r) is expressed in several normal human tissues and is over-expressed in various human tumors including breast, prostate, small cell lung and pancreatic cancer. Recently [ 99m Tc]EDDA/HYNIC-Lys 3 -bombesin ( 99m Tc-HYNIC-BN) was reported as a radiopharmaceutical with high stability in human serum, specific cell GRP-r binding and rapid cell internalization. The aim of this study was to evaluate the feasibility of using 99m Tc-HYNIC-BN to image GRP-r and to assess the radiopharmaceutical biokinetics and dosimetry in 4 breast cancer patients and in 7 healthy women. Methods: Whole-body images were acquired at 20, 90, 180 min and 24 h after 99m Tc-HYNIC-BN administration. Regions of interest (ROIs) were drawn around source organs on each time frame. The same set of ROIs was used for all 11 scans and the cpm of each ROI was converted to activity using the conjugate view counting method. The image sequence was used to extrapolate 99m Tc-HYNIC-BN time-activity curves in each organ in order to calculate the total number of disintegrations (N) that occurred in the source regions, according with MIRD methodology. N data were the input for the OLINDA/EXM code to calculate internal radiation dose estimates. Results: Images showed a rapid radiopharmaceutical blood clearance with renal excretion as predominant route. 99m Tc-HYNIC-BN exhibited high in vivo affinity for GRP-r over-expression successfully visualized in cancer mammary glands and well differentiated from the ubiquitous GRP-r expression in normal breast, lungs and airways. There was no statistically significant difference (p > 0.05) in the radiation absorbed doses between cancer patients and healthy women. The average equivalent doses (n=11) for a study using 740 MBq were 24.8 +- 8.8 mSv (kidneys), 7.3 +- 1.8 mSv (lungs), 6.5 +- 4.0 mSv (breast) 2.0 +- 0.3 mSv (pancreas), 1.6 +- 0.3 mSv (liver), 1.2 +- 0.2 mSv (ovaries) and 1.0 +- 0.2 mSv (red marrow). The mean effective dose

  10. Aptamer-conjugated PEGylated quantum dots targeting epidermal growth factor receptor variant III for fluorescence imaging of glioma

    Directory of Open Access Journals (Sweden)

    Tang J

    2017-05-01

    Full Text Available Jiaze Tang,1 Ning Huang,1 Xiang Zhang,1,2 Tao Zhou,3 Ying Tan,1,4 Jiangli Pi,5 Li Pi,1 Si Cheng,6 Huzhi Zheng,5 Yuan Cheng1 1Department of Neurosurgery, The Second Affiliated Hospital of Chongqing Medical University, 2Chongqing Key Laboratory of Ultrasound Molecular Imaging, Institute of Ultrasound Imaging, 3Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, 4Institute of Life Sciences, Chongqing Medical University, 5Key Laboratory on Luminescent and Real-Time Analytical Chemistry, Ministry of Education, College of Chemistry and Chemical Engineering, Southwest University, 6Department of Orthopaedics, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China Abstract: The extent of resection is a significant prognostic factor in glioma patients. However, the maximum safe resection level is difficult to determine due to the inherent infiltrative character of tumors. Recently, fluorescence-guided surgery has emerged as a new technique that allows safe resection of glioma. In this study, we constructed a new kind of quantum dot (QD-labeled aptamer (QD-Apt nanoprobe by conjugating aptamer 32 (A32 to the QDs surface, which can specially bind to the tumors. A32 is a single-stranded DNA capable of binding to the epidermal growth factor receptor variant III (EGFRvIII specially distributed on the surface of glioma cells. To detect the expression of EGFRvIII in human brain tissues, 120 specimens, including 110 glioma tissues and 10 normal brain tissues, were examined by immunohistochemistry, and the results showed that the rate of positive expression of EGFRvIII in the glioma tissues was 41.82%, and 0.00% in normal brain tissues. Besides, the physiochemical properties of QD-Apt nanoparticles (NPs were thoroughly characterized. Biocompatibility of the NPs was evaluated, and the results suggested that the QD-Apt was nontoxic in vivo and vitro. Furthermore, the use of the QD-Apt in labeling

  11. DOTA-PESIN, a DOTA-conjugated bombesin derivative designed for the imaging and targeted radionuclide treatment of bombesin receptor-positive tumours

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Hanwen; Maecke, Helmut R. [University Hospital Basel, Division of Radiological Chemistry, Department of Radiology, Basel (Switzerland); Schuhmacher, Jochen; Eisenhut, Michael [German Cancer Research Centre, Department of Radiopharmaceutical Chemistry, Heidelberg (Germany); Waser, Beatrice; Reubi, Jean Claude [University of Berne, Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, P.O. Box 62, Berne (Switzerland); Wild, Damian [University Hospital, Clinic and Institute of Nuclear Medicine, Department of Radiology, Basel (Switzerland)

    2007-08-15

    We aimed at designing and developing a novel bombesin analogue, DOTA-PEG{sub 4}-BN(7-14) (DOTA-PESIN), with the goal of labelling it with {sup 67/68}Ga and {sup 177}Lu for diagnosis and radionuclide therapy of prostate and other human cancers overexpressing bombesin receptors. The 8-amino acid peptide bombesin (7-14) was coupled to the macrocyclic chelator DOTA via the spacer 15-amino-4,7,10,13-tetraoxapentadecanoic acid (PEG{sub 4}). The conjugate was complexed with Ga(III) and Lu(III) salts. The GRP receptor affinity and the bombesin receptor subtype profile were determined in human tumour specimens expressing the three bombesin receptor subtypes. Internalisation and efflux studies were performed with the human GRP receptor cell line PC-3. Xenografted nude mice were used for biodistribution. [Ga{sup III}/Lu{sup III}]-DOTA-PESIN showed good affinity to GRP and neuromedin B receptors but no affinity to BB3. [{sup 67}Ga/{sup 177}Lu]-DOTA-PESIN internalised rapidly into PC-3 cells whereas the efflux from PC-3 cells was relatively slow. In vivo experiments showed a high and specific tumour uptake and good retention of [{sup 67}Ga/{sup 177}Lu]-DOTA-PESIN. [{sup 67}Ga/{sup 177}Lu]-DOTA-PESIN highly accumulated in GRP receptor-expressing mouse pancreas. The uptake specificity was demonstrated by blocking tumour uptake and pancreas uptake. Fast clearance was found from blood and all non-target organs except the kidneys. High tumour-to-normal tissue ratios were achieved, which increased with time. PET imaging with [{sup 68}Ga]-DOTA-PESIN was successful in visualising the tumour at 1 h post injection. Planar scintigraphic imaging showed that the {sup 177}Lu-labelled peptide remained in the tumour even 3 days post injection. The newly designed ligands have high potential with regard to PET and SPECT imaging with {sup 68/67}Ga and targeted radionuclide therapy with {sup 177}Lu. (orig.)

  12. Co-targeting androgen receptor and DNA for imaging and molecular radiotherapy of prostate cancer: in vitro studies.

    Science.gov (United States)

    Han, Guang; Kortylewicz, Zbigniew P; Enke, Thomas; Baranowska-Kortylewicz, Janina

    2014-12-01

    The androgen receptor (AR) axis, the key growth and survival pathway in prostate cancer, remains a prime target for drug development. 5-Radioiodo-3'-O-(17β-succinyl-5α-androstan-3-one)-2'-deoxyuridin-5'-yl phosphate (RISAD-P) is the AR-seeking reagent developed for noninvasive assessment of AR and proliferative status, and for molecular radiotherapy of prostate cancer with Auger electron-emitting radionuclides. RISAD-P radiolabeled with 123I, 124I, and 125I were synthesized using a common stannylated precursor. The cellular uptake, subcellular distribution, and radiotoxicity of 123I-, 124I-, and (125) IRISAD-P were measured in LNCaP, DU145, and PC-3 cell lines expressing various levels of AR. The uptake of RISAD-P by prostate cancer cells is proportional to AR levels and independent of the radionuclide. The intracellular accumulation of radioactivity is directly proportional to the extracellular concentration of RISAD-P and the duration of exposure. Initially, RISAD-P is trapped in the cytoplasm. Within 24 hr, radioactivity is associated exclusively with DNA. The RISAD-P radiotoxicity is determined by the radionuclide; however, the cellular responses are directly proportional to the AR expression levels. LNCaP cells expressing high levels of AR are killed at the rate of up to 60% per day after a brief 1 hr RISAD-P treatment. For the first time, the AR expression in PC-3 and DU 145 cells, generally reported as AR-negative, was quantitated by the ultra sensitive RISAD-P-based method. RISAD-P is a theranostic drug, which targets AR. Its subcellular metabolite participates in DNA synthesis. RISAD-P is a promising candidate for imaging of the AR expression and tumor proliferation as well as molecular radiotherapy of prostate cancer. © 2014 Wiley Periodicals, Inc.

  13. Actin cytoskeleton-dependent Rab GTPase-regulated angiotensin type I receptor lysosomal degradation studied by fluorescence lifetime imaging microscopy

    Science.gov (United States)

    Li, Hewang; Yu, Peiying; Sun, Yuansheng; Felder, Robin A.; Periasamy, Ammasi; Jose, Pedro A.

    2010-09-01

    The dynamic regulation of the cellular trafficking of human angiotensin (Ang) type 1 receptor (AT1R) is not well understood. Therefore, we investigated the cellular trafficking of AT1R-enhanced green fluorescent protein (EGFP) (AT1R-EGFP) heterologously expressed in HEK293 cells by determining the change in donor lifetime (AT1R-EGFP) in the presence or absence of acceptor(s) using fluorescence lifetime imaging-fluorescence resonance energy transfer (FRET) microscopy. The average lifetime of AT1R-EGFP in our donor-alone samples was ~2.33 ns. The basal state lifetime was shortened slightly in the presence of Rab5 (2.01+/-0.10 ns) or Rab7 (2.11+/-0.11 ns) labeled with Alexa 555, as the acceptor fluorophore. A 5-min Ang II treatment markedly shortened the lifetime of AT1R-EGFP in the presence of Rab5-Alexa 555 (1.78+/-0.31 ns) but was affected minimally in the presence of Rab7-Alexa 555 (2.09+/-0.37 ns). A 30-min Ang II treatment further decreased the AT1R-EGFP lifetime in the presence of both Rab5- and Rab7-Alexa 555. Latrunculin A but not nocodazole pretreatment blocked the ability of Ang II to shorten the AT1R-EGFP lifetime. The occurrence of FRET between AT1R-EGFP (donor) and LAMP1-Alexa 555 (acceptor) with Ang II stimulation was impaired by photobleaching the acceptor. These studies demonstrate that Ang II-induced AT1R lysosomal degradation through its association with LAMP1 is regulated by Rab5/7 via mechanisms that are dependent on intact actin cytoskeletons.

  14. Aptamer-conjugated PEGylated quantum dots targeting epidermal growth factor receptor variant III for fluorescence imaging of glioma.

    Science.gov (United States)

    Tang, Jiaze; Huang, Ning; Zhang, Xiang; Zhou, Tao; Tan, Ying; Pi, Jiangli; Pi, Li; Cheng, Si; Zheng, Huzhi; Cheng, Yuan

    2017-01-01

    The extent of resection is a significant prognostic factor in glioma patients. However, the maximum safe resection level is difficult to determine due to the inherent infiltrative character of tumors. Recently, fluorescence-guided surgery has emerged as a new technique that allows safe resection of glioma. In this study, we constructed a new kind of quantum dot (QD)-labeled aptamer (QD-Apt) nanoprobe by conjugating aptamer 32 (A32) to the QDs surface, which can specially bind to the tumors. A32 is a single-stranded DNA capable of binding to the epidermal growth factor receptor variant III (EGFRvIII) specially distributed on the surface of glioma cells. To detect the expression of EGFRvIII in human brain tissues, 120 specimens, including 110 glioma tissues and 10 normal brain tissues, were examined by immunohistochemistry, and the results showed that the rate of positive expression of EGFRvIII in the glioma tissues was 41.82%, and 0.00% in normal brain tissues. Besides, the physiochemical properties of QD-Apt nanoparticles (NPs) were thoroughly characterized. Biocompatibility of the NPs was evaluated, and the results suggested that the QD-Apt was nontoxic in vivo and vitro. Furthermore, the use of the QD-Apt in labeling glioma cell lines and human brain glioma tissues, and target gliomas in situ was also investigated. We found that not only could QD-Apt specially bind to the U87-EGFRvIII glioma cells but also bind to human glioma tissues in vitro. Fluorescence imaging in vivo with orthotopic glioma model mice bearing U87-EGFRvIII showed that QD-Apt could penetrate the blood-brain barrier and then selectively accumulate in the tumors through binding to EGFRvIII, and consequently, generate a strong fluorescence, which contributed to the margins of gliomas that were visualized clearly, and thus, help the surgeons realize the maximum safe resection of glioma. In addition, QD-Apt can also be applied in preoperative diagnosis and postoperative examination of glioma

  15. Synthesis and In Vitro Evaluation of Oxindole Derivatives as Potential Radioligands for 5-HT7 Receptor Imaging with PET

    DEFF Research Database (Denmark)

    Herth, Matthias Manfred; Volk, Balázs; Pallagi, Katalin

    2012-01-01

    The most recently discovered serotonin (5-HT) receptor subtype, 5-HT(7), is considered to be associated with several CNS disorders. Noninvasive in vivo positron emission tomography (PET) studies of cerebral 5-HT(7) receptors could provide a significant advance in the understanding of the neurobio...

  16. Positron Emission Tomographic Imaging of the Cannabinoid Type 1 Receptor System with [11C]OMAR ([11C]JHU75528: Improvements in Image Quantification Using Wild-Type and Knockout Mice

    Directory of Open Access Journals (Sweden)

    Raúl Herance

    2011-11-01

    Full Text Available In this study, we assessed the feasibility of using positron emission tomography (PET and the tracer [11C]OMAR ([11C]JHU75528, an analogue of rimonabant, to study the brain cannabinoid type 1 (CB1 receptor system. Wild-type (WT andCB1 knockout (KO animals were imaged at baseline and after pretreatment with blocking doses of rimonabant. Brain uptake in WT animals was higher (50% than in KO animals in baseline conditions. After pretreatment with rimonabant, WT uptake lowered to the level of KO animals. The results of this study support the feasibility of using PET with the radiotracer [11C]JHU75528 to image the brain CB1 receptor system in mice. In addition, this methodology can be used to assess the effect of new drugs in preclinical studies using genetically manipulated animals.

  17. Preparation and evaluation of 99mTc-EDDA/HYNIC-[Lys 3]-bombesin for imaging gastrin-releasing peptide receptor-positive tumours.

    Science.gov (United States)

    Ferro-Flores, Guillermina; Arteaga de Murphy, Consuelo; Rodriguez-Cortés, Jeanette; Pedraza-López, Martha; Ramírez-Iglesias, María Teresa

    2006-04-01

    Bombesin is a peptide that was initially isolated from frog skin and which belongs to a large group of neuropeptides with many biological functions. The human equivalent is gastrin-releasing peptide (GRP), whose receptors are over-expressed in a variety of malignant tumours. To prepare a HYNIC-[Lys 3]-bombesin analogue that could be easily labelled with 99mTc from lyophilized kit formulations and to evaluate its potential as an imaging agent for GRP receptor-positive tumours. HYNIC was conjugated to the epsilon-amino group of Lys 3 residue at the N-terminal region of bombesin via succinimidyl-N-Boc-HYNIC at pH 9.0. 99mTc labelling was performed by addition of sodium pertechnetate solution and 0.2 M phosphate buffer pH 7.0 to a lyophilized formulation. Stability studies were carried out by reversed phase HPLC and ITLC-SG analyses in serum and cysteine solutions. In-vitro internalization was tested using human prostate cancer PC-3 cells with blocked and non-blocked receptors. Biodistribution and tumour uptake were determined in PC-3 tumour-bearing nude mice. 99mTc-EDDA/HYNIC-[Lys 3]-bombesin was obtained with radiochemical purities >93% and high specific activity ( approximately 0.1 GBq.nmol). Results of in-vitro studies demonstrated a high stability in serum and cysteine solutions, specific cell receptor binding and rapid internalization. Biodistribution data showed a rapid blood clearance, with predominantly renal excretion and specific binding towards GRP receptor-positive tissues such as pancreas and PC-3 tumours. 99mTc-EDDA/HYNIC-[Lys 3]-bombesin obtained from lyophilized kit formulations has promising characteristics for the diagnosis of malignant tumours that over-express the GRP receptor.

  18. A Mixed Presentation of Serotonin Syndrome vs Neuroleptic Malignant Syndrome in a 12-Year-Old Boy.

    Science.gov (United States)

    Sun, Christie; Sweet, Hannah; Minns, Alicia B; Shapiro, Desiree; Jenkins, Willough

    2018-04-24

    Neuroleptic malignant syndrome (NMS) and serotonin syndrome (SS) are serious medical conditions associated with commonly prescribed psychiatric medications. Although the mechanisms differ, they can be clinically difficult to distinguish. We report a case of a pediatric patient with complicated psychiatric history that developed features of both syndromes in the setting of polypharmacy. A 12-year-old boy with a history of developmental delay, attention-deficit hyperactivity disorder, and posttraumatic stress disorder presented to the emergency department with behavior changes consisting of delayed reactions, gait instability, drooling, and slowed movements. Ten days before presentation, his outpatient psychiatrist had made multiple medication changes including discontinuation of cyproheptadine (an appetite stimulant) and initiation of aripiprazole. On arrival, the patient was noted to be tachycardia and hypertensive for age. He was disoriented, intermittently agitated, and tremulous with increased tonicity, clonus in the lower extremities, and mydriasis. He was supportively treated with lorazepam and intravenous fluids while discontinuing potential offending agents. His course was complicated by hypertension and agitation managed with dexmedetomidine infusion and benzodiazepines. His mental status, tremors, and laboratory values began to improve over the next 2 days, and eventually transitioned to the inpatient psychiatric unit on hospital day 7. Diagnosis of NMS or SS can be difficult when there is overlap between syndromes, particularly in the setting of multiple potential offending agents or underlying developmental delay. In addition, pediatric patients may present atypically as compared with adult patients with the same condition. The use of antipsychotic medications for young children with behavioral problems has risen dramatically in the last decade, increasing their risk for developing SS or NMS.

  19. Context-dependent efficacy of a counter-conditioning strategy with atypical neuroleptic drugs in mice previously sensitized to cocaine.

    Science.gov (United States)

    Oliveira-Lima, A J; Marinho, Eav; Santos-Baldaia, R; Hollais, A W; Baldaia, M A; Talhati, F; Ribeiro, L T; Wuo-Silva, R; Berro, L F; Frussa-Filho, R

    2017-02-06

    We have previously demonstrated that treatment with ziprasidone and aripiprazole selectively inhibit the development of behavioral sensitization to cocaine in mice. We now investigate their effects on a counter-conditioning strategy in mice and the importance of the treatment environment for this phenomenon. Evaluate the context-specificity of ziprasidone and aripiprazole on conditioned locomotion to cocaine and cocaine-induced hyperlocomotion and behavioral sensitization in a counter-conditioning strategy in mice. Animals were sensitized with saline or cocaine injections in the open-field apparatus in a 15-day intermittent treatment and subsequently treated with vehicle, 5mg/kg ziprasidone or 0.1mg/kg aripiprazole paired to the open-field or the home-cage for 4 alternate days. Mice were then challenged with saline and cocaine in the open-field apparatus on subsequent days. While treatment with ziprasidone decreased spontaneous locomotion and conditioned locomotion alike, treatment with aripiprazole specifically attenuated the expression of conditioned hyperlocomotion to cocaine. Ziprasidone and aripiprazole had no effects on cocaine-induced conditioned hyperlocomotion observed during saline challenge after drug withdrawal. Treatment with either ziprasidone or aripiprazole when previously given in the cocaine-paired environment attenuated the subsequent expression of behavioral sensitization to cocaine. Animals treated with aripiprazole in the open-field, but not in the home-cage, showed a blunted response to cocaine when receiving a cocaine challenge for the first time. Both neuroleptic drugs showed a context-dependent effectiveness in attenuating long-term expression of cocaine-induced behavioral sensitization when administered in the cocaine-associated environment, with aripiprazole also showing effectiveness in blocking the expression of acute cocaine effects. Copyright © 2016. Published by Elsevier Inc.

  20. A retrospective analysis of cases with neuroleptic malignant syndrome and an evaluation of risk factors for mortality

    Directory of Open Access Journals (Sweden)

    Aynur Sahin

    2017-12-01

    Full Text Available Objective: Neuroleptic malignant syndrome (NMS is a neurological emergency rarely encountered in clinical practice but with a high mortality rate. Cases associated with atypical antipsychotic use or termination of dopamine agonists have been seen in recent years. The purpose of this study was to assess the presence of risk factors for mortality by investigating all clinical and laboratory characteristics of cases with NMS. Material and methods: This descriptive, cross-sectional study retrospectively investigated all clinical and laboratory characteristics by scanning the ICD-10 codes of patients presenting to the XXXX Faculty of Medicine Emergency Department and diagnosed with NMS between 2006 and 2016. Patients were divided into surviving and non-surviving groups, and the data elicited were subjected to statistical comparisons. Results: The mean age of the 18 patients diagnosed with NMS was 46.9 ± 4.8 years, and 50% were women. In addition to antipsychotics among the drugs leading to NMS, the syndrome also developed as a result of levodopa withdrawal in three patients and metoclopramide use in one patient. Statistically significant differences were determined between the surviving and non-surviving patients in terms of blood pressure, blood urea nitrogen (BUN, creatine kinase (CK and mean platelet volume (MPV values (p ≤ 0.05. Conclusion: In this study the most common agent that cause NMS was atypical antipsychotics. Also advanced age, increased blood pressure and serum CK, BUN and MPV values were identified as potential risk factors for mortality in NMS.

  1. Antipsychotic dose escalation as a trigger for Neuroleptic Malignant Syndrome (NMS: literature review and case series report

    Directory of Open Access Journals (Sweden)

    Langan Julie

    2012-11-01

    Full Text Available Abstract Background “Neuroleptic malignant syndrome” (NMS is a potentially fatal idiosyncratic reaction to any medication which affects the central dopaminergic system. Between 0.5% and 1% of patients exposed to antipsychotics develop the condition. Mortality rates may be as high as 55% and many risk factors have been reported. Although rapid escalation of antipsychotic dose is thought to be an important risk factor, to date it has not been the focus of a published case series or scientifically defined. Description We aimed to identify cases of NMS and review risk factors for its development with a particular focus on rapid dose escalation in the 30 days prior to onset. A review of the literature on rapid dose escalation was undertaken and a pragmatic definition of “rapid dose escalation” was made. NMS cases were defined using DSM-IV criteria and systematically identified within a secondary care mental health service. A ratio of titration rate was calculated for each NMS patient and “rapid escalators” and “non rapid escalators” were compared. 13 cases of NMS were identified. A progressive mean dose increase 15 days prior to the confirmed episode of NMS was observed (241.7 mg/day during days 1–15 to 346.9 mg/day during days 16–30 and the mean ratio of dose escalation for NMS patients was 1.4. Rapid dose escalation was seen in 5/13 cases and non rapid escalators had markedly higher daily cumulative antipsychotic dose compared to rapid escalators. Conclusions Rapid dose escalation occurred in less than half of this case series (n = 5, 38.5%, although there is currently no consensus on the precise definition of rapid dose escalation. Cumulative antipsychotic dose – alongside other known risk factors - may also be important in the development of NMS.

  2. Analysis of PETT images in psychiatric disorders

    International Nuclear Information System (INIS)

    Brodie, J.D.; Gomez-Mont, F.; Volkow, N.D.; Corona, J.F.; Wolf, A.P.; Wolkin, A.; Russell, J.A.G.; Christman, D.; Jaeger, J.

    1983-01-01

    A quantitative method is presented for studying the pattern of metabolic activity in a set of Positron Emission Transaxial Tomography (PETT) images. Using complex Fourier coefficients as a feature vector for each image, cluster, principal components, and discriminant function analyses are used to empirically describe metabolic differences between control subjects and patients with DSM III diagnosis for schizophrenia or endogenous depression. We also present data on the effects of neuroleptic treatment on the local cerebral metabolic rate of glucose utilization (LCMRGI) in a group of chronic schizophrenics using the region of interest approach. 15 references, 4 figures, 3 tables

  3. Analysis of PETT images in psychiatric disorders

    Energy Technology Data Exchange (ETDEWEB)

    Brodie, J.D.; Gomez-Mont, F.; Volkow, N.D.; Corona, J.F.; Wolf, A.P.; Wolkin, A.; Russell, J.A.G.; Christman, D.; Jaeger, J.

    1983-01-01

    A quantitative method is presented for studying the pattern of metabolic activity in a set of Positron Emission Transaxial Tomography (PETT) images. Using complex Fourier coefficients as a feature vector for each image, cluster, principal components, and discriminant function analyses are used to empirically describe metabolic differences between control subjects and patients with DSM III diagnosis for schizophrenia or endogenous depression. We also present data on the effects of neuroleptic treatment on the local cerebral metabolic rate of glucose utilization (LCMRGI) in a group of chronic schizophrenics using the region of interest approach. 15 references, 4 figures, 3 tables.

  4. In-vivo characteristics of high and low specific activity radioiodinated (+)-2-[4-(4-iodophenyl) piperidino] cyclohexanol [(+)-pIV] for imaging sigma-1 receptor in brain

    International Nuclear Information System (INIS)

    Akhter, Nasima; Kinuya, Seigo; Nakajima, Kenichi; Shiba, Kazuhiro; Ogawa, Kazuma; Mori, Hirofumi

    2007-01-01

    Full text: In this study, (+)-enantiomer of radioiodinated 2-[4-(4- iodophenyl)piperidino]cyclohexanol ((+)-[ 125 I]-p- iodovesamicol) [(+)-[ 125 I]pIV], which is reported to bind with high affinity to the sigma-1 receptor both in vitro and in vivo, was tested to compare the in vivo characteristics between high and low specific activity (+)-[ 125 I]pIV to image sigma-1 receptor in the central nervous system. In the biodistribution study, no significant difference was observed between two methods. Accumulation of (+)- [ 125 I]pIV in rat brain was significant (approximately 3% of the injected dose) and its retention was prolonged. In the blocking study, the accumulation of (+)-[ 125 I] pIV in the rat brain was significantly reduced by the co-administration of sigma ligands such as pentazocine, haloperidol or SA4503 in both methods. But the blocking effect was relatively stronger in the study using high specific activity radioiodinated (+)pIV. Though, the distribution of high and low specific activity (+)-[ 125 I] pIV was more or less similar to bind to sigma-1 receptor in the central nervous system in vivo, high specific activity radioiodinated (+) pIV might have a better specificity to bind sigma-1 receptor in brain. (author)

  5. Evaluation of radiolabeled ML04, a putative irreversible inhibitor of epidermal growth factor receptor, as a bioprobe for PET imaging of EGFR-overexpressing tumors

    International Nuclear Information System (INIS)

    Abourbeh, Galith; Dissoki, Samar; Jacobson, Orit; Litchi, Amir; Daniel, Revital Ben; Laki, Desirediu; Levitzki, Alexander; Mishani, Eyal

    2007-01-01

    Overexpression of epidermal growth factor receptor (EGFR) has been implicated in tumor development and malignancy. Evaluating the degree of EGFR expression in tumors could aid in identifying patients for EGFR-targeted therapies and in monitoring treatment. Nevertheless, no currently available assay can reliably quantify receptor content in tumors. Radiolabeled inhibitors of EGFR-TK could be developed as bioprobes for positron emission tomography imaging. Such imaging agents would not only provide a noninvasive quantitative measurement of EGFR content in tumors but also serve as radionuclide carriers for targeted radiotherapy. The potency, reversibility, selectivity and specific binding characteristics of ML04, an alleged irreversible inhibitor of EGFR, were established in vitro. The distribution of the F-18-labeled compound and the extent of EGFR-specific tumor uptake were evaluated in tumor-bearing mice. ML04 demonstrated potent, irreversible and selective inhibition of EGFR, combined with specific binding to the receptor in intact cells. In vivo distribution of the radiolabeled compound revealed tumor/blood and tumor/muscle activity uptake ratios of about 7 and 5, respectively, 3 h following administration of a radiotracer. Nevertheless, only minor EGFR-specific uptake of the compound was detected in these studies, using either EGFR-negative tumors or blocking studies as controls. To improve the in vivo performance of ML04, administration via prolonged intravenous infusion is proposed. Detailed pharmacokinetic characterization of this bioprobe could assist in the development of a kinetic model that would afford accurate measurement of EGFR content in tumors

  6. Application of gamma-aminobutyric acid type A-benzodiazepine receptor imaging for study of neuropsychiatric disorders

    International Nuclear Information System (INIS)

    Bao Weiqi; Qiu Chun; Guan Yihui

    2012-01-01

    Gamma-aminobutyric acid type A-benzodiazepine receptors are heterogeneous polypeptide pentamers widely spread in the central nervous system on the neuron membrane. Different subunit combinations educe various neuro-inhibitory pharmacological effects such as sedative, hypnosis, anticonvulsion and anxiolysis. PET can be utilized to study the binding of the receptors in vivo. PET radioligands of gamma-aminobutyric acid type A-benzodiazepine receptors can be classified into 3 types: antagonists,agonists and reverse agonists, of which antagonist radiotracer 11 C-flumazenil is the most commonly applied in epilepsy, anxiety disorders, depression, vegetative state,addiction and other neuro-psychiatric disorders. (authors)

  7. Guideline for PET/CT imaging of neuroendocrine neoplasms with {sup 68}Ga-DOTA-conjugated somatostatin receptor targeting peptides and {sup 18}F-DOPA

    Energy Technology Data Exchange (ETDEWEB)

    Bozkurt, Murat Fani [Hacettepe University Faculty of Medicine Department of Nuclear Medicine, Ankara (Turkey); Virgolini, Irene; Decristoforo, Clemens [Medical University Innsbruck, Department of Nuclear Medicine, Innsbruck (Austria); Balogova, Sona [Comenius University and St. Elisabeth Oncology Institute, Department of Nuclear Medicine, Bratislava (Slovakia); Tenon Hospital AP-HP and Universite Pierre et Marie Curie, Department of Nuclear Medicine, Paris (France); Beheshti, Mohsen [St. Vincent' s Hospital, PET-CT Center, Department of Nuclear Medicine and Endocrinology, Linz (Austria); Paracelsus Medical University, Department of Nuclear Medicine, Salzburg (Austria); Rubello, Domenico [Santa Maria della Misericordia Hospital, Department of Nuclear Medicine, PET Center and Medical Physics and Radiology, Rovigo (Italy); Ambrosini, Valentina; Fanti, Stefano [University of Bologna, Department of Experimental, Diagnostic and Specialty Medicine-DIMES, Bologna (Italy); Kjaer, Andreas [National University Hospital and University of Copenhagen, Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, Copenhagen (Denmark); Delgado-Bolton, Roberto [San Pedro Hospital and Centre for Biomedical Research of La Rioja (CIBIR), Department of Diagnostic Imaging (Radiology) and Nuclear Medicine, Logrono (Spain); Kunikowska, Jolanta [Medical University of Warsaw, Nuclear Medicine, Warsaw (Poland); Oyen, Wim J.G. [Institute of Cancer Research and Royal Marsden NHS Foundation Trust, London (United Kingdom); Chiti, Arturo [Humanitas University, Nuclear Medicine Department, Rozzano, MI (Italy); Giammarile, Francesco [University of Lyon, Nuclear Medicine, Lyon (France)

    2017-08-15

    Neuroendocrine neoplasms are a heterogenous group of tumours, for which nuclear medicine plays an important role in the diagnostic work-up as well as in the targeted therapeutic options. This guideline is aimed to assist nuclear medicine physicians in recommending, performing, reporting and interpreting the results of somatostatin receptor (SSTR) PET/CT imaging using {sup 68}Ga-DOTA-conjugated peptides, as well as {sup 18}F-DOPA imaging for various neuroendocrine neoplasms. The previous procedural guideline by EANM regarding the use PET/CT tumour imaging with {sup 68}Ga-conjugated peptides has been revised and updated with the relevant and recent literature in the field with contribution of distinguished experts. (orig.)

  8. Test-retest measurements of dopamine D{sub 1}-type receptors using simultaneous PET/MRI imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kaller, Simon; Patt, Marianne; Becker, Georg-Alexander; Luthardt, Julia; Meyer, Philipp M.; Werner, Peter; Barthel, Henryk; Bresch, Anke; Sabri, Osama [University of Leipzig, Department of Nuclear Medicine, Leipzig (Germany); Rullmann, Michael [University of Leipzig, Department of Nuclear Medicine, Leipzig (Germany); Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig (Germany); Girbardt, Johanna [Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig (Germany); Fritz, Thomas H. [Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig (Germany); University of Gent, Institute for Psychoacoustics and Electronic Music (IPEM), Ghent (Belgium); Hesse, Swen [University of Leipzig, Department of Nuclear Medicine, Leipzig (Germany); Leipzig University Medical Centre, Integrated Research and Treatment Centre (IFB) Adiposity Diseases, Leipzig (Germany)

    2017-06-15

    The role of dopamine D{sub 1}-type receptor (D{sub 1}R)-expressing neurons in the regulation of motivated behavior and reward prediction has not yet been fully established. As a prerequisite for future research assessing D{sub 1}-mediated neuronal network regulation using simultaneous PET/MRI and D{sub 1}R-selective [{sup 11}C]SCH23390, this study investigated the stability of central D{sub 1}R measurements between two independent PET/MRI sessions under baseline conditions. Thirteen healthy volunteers (7 female, age 33 ± 13 yrs) underwent 90-min emission scans, each after 90-s bolus injection of 486 ± 16 MBq [{sup 11}C]SCH23390, on two separate days within 2-4 weeks using a PET/MRI system. Parametric images of D{sub 1}R distribution volume ratio (DVR) and binding potential (BP{sub ND}) were generated by a multi-linear reference tissue model with two parameters and the cerebellar cortex as receptor-free reference region. Volume-of-interest (VOI) analysis was performed with manual VOIs drawn on consecutive transverse MRI slices for brain regions with high and low D{sub 1}R density. The DVR varied from 2.5 ± 0.3 to 2.9 ± 0.5 in regions with high D{sub 1}R density (e.g. the head of the caudate) and from 1.2 ± 0.1 to 1.6 ± 0.2 in regions with low D{sub 1}R density (e.g. the prefrontal cortex). The absolute variability of the DVR ranged from 2.4% ± 1.3% to 5.1% ± 5.3%, while Bland-Altman analyses revealed very low differences in mean DVR (e.g. 0.013 ± 0.17 for the nucleus accumbens). Intraclass correlation (one-way, random) indicated very high agreement (0.93 in average) for both DVR and BP{sub ND} values. Accordingly, the absolute variability of BP{sub ND} ranged from 7.0% ± 4.7% to 12.5% ± 10.6%; however, there were regions with very low D{sub 1}R content, such as the occipital cortex, with higher mean variability. The test-retest reliability of D{sub 1}R measurements in this study was very high. This was the case not only for D{sub 1}R-rich brain areas, but

  9. Antagonism of presynaptic dopamine receptors by phenothiazine drug metabolites

    International Nuclear Information System (INIS)

    Nowak, J.Z.; Arbilla, S.; Langer, S.Z.; Dahl, S.G.

    1990-01-01

    Electrically evoked release of dopamine from the caudate nucleus is reduced by the dopamine receptor agonists, apomorphine and bromocriptine, and facilitated by neuroleptic drugs, which act as dopamine autoreceptor antagonists. The potencies of chlorpromazine, fluphenazine, levomepromazine and their hydroxy-metabolites in modulating electrically evoked release of dopamine were examined by superfusion of rabbit caudate nucleus slices pre-incubated with 3 H-dopamine. O-Desmethyl levomepromazine, 3-hydroxy- and 7-hydroxy metabolites of chlorpromazine and levomepromazine facilitated electrically evoked release of 3 H-dopamine, having potencies similar to that of the parent compounds. 7-Hydroxy fluphenazine was less active than fluphenazine in this system. These results indicate that phenolic metabolites of chlorpromazine and levomepromazine, but not of fluphenazine, may contribute to effects of the drugs mediated by presynaptic dopamine receptors

  10. Microscopic visualization of metabotropic glutamate receptors on the surface of living cells using bifunctional magnetic resonance imaging probes.

    Science.gov (United States)

    Mishra, Anurag; Mishra, Ritu; Gottschalk, Sven; Pal, Robert; Sim, Neil; Engelmann, Joern; Goldberg, Martin; Parker, David

    2014-02-19

    A series of bimodal metabotropic glutamate-receptor targeted MRI contrast agents has been developed and evaluated, based on established competitive metabotropic Glu receptor subtype 5 (mGluR5) antagonists. In order to directly visualize mGluR5 binding of these agents on the surface of live astrocytes, variations in the core structure were made. A set of gadolinium conjugates containing either a cyanine dye or a fluorescein moiety was accordingly prepared, to allow visualization by optical microscopy in cellulo. In each case, surface receptor binding was compromised and cell internalization observed. Another approach, examining the location of a terbium analogue via sensitized emission, also exhibited nonspecific cell uptake in neuronal cell line models. Finally, biotin derivatives of two lead compounds were prepared, and the specificity of binding to the mGluR5 cell surface receptors was demonstrated with the aid of their fluorescently labeled avidin conjugates, using both total internal reflection fluorescence (TIRF) and confocal microscopy.

  11. Gastrin-releasing peptide receptor-targeted gadolinium oxide-based multifunctional nanoparticles for dual magnetic resonance/fluorescent molecular imaging of prostate cancer

    Directory of Open Access Journals (Sweden)

    Cui DT

    2017-09-01

    Full Text Available Danting Cui,1 Xiaodan Lu,1 Chenggong Yan,1 Xiang Liu,1 Meirong Hou,1 Qi Xia,2 Yikai Xu,1 Ruiyuan Liu2,3 1Department of Medical Imaging Center, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, People’s Republic of China; 3School of Biomedical Engineering, Southern Medical University, Guangzhou, People’s Republic of China Abstract: Bombesin (BBN, an analog of gastrin-releasing peptide (GRP, specifically binds to GRP receptors, which are overexpressed in human prostate cancer (PC. Here, we synthesized a BBN-modified gadolinium oxide (Gd2O3 nanoprobe containing fluorescein (Gd2O3-5(6-carboxyfluorescein [FI]-polyethylene glycol [PEG]-BBN for targeted magnetic resonance (MR/optical dual-modality imaging of PC. The Gd2O3-FI-PEG-BBN nanoparticles exhibited a relatively uniform particle size with an average diameter of 52.3 nm and spherical morphology as depicted by transmission electron microscopy. The longitudinal relaxivity (r1 of Gd2O3-FI-PEG-BBN (r1 =4.23 mM–1s–1 is comparable to that of clinically used Magnevist (Gd-DTPA. Fluorescence microscopy and in vitro cellular MRI demonstrated GRP receptor-specific and enhanced cellular uptake of the Gd2O3-FI-PEG-BBN in PC-3 tumor cells. Moreover, Gd2O3-FI-PEG-BBN showed more remarkable contrast enhancement than the corresponding nontargeted Gd2O3-FI-PEG according to in vivo MRI and fluorescent imaging. Tumor immunohistochemical analysis further demonstrated improved accumulation of the targeted nanoprobe in tumors. BBN-conjugated Gd2O3 may be a promising nanoplatform for simultaneous GRP receptor-targeted molecular cancer diagnosis and antitumor drug delivery in future clinical applications. Keywords: magnetic resonance imaging, gadolinium oxide, bombesin, gastrin-releasing peptide receptor, molecular imaging

  12. Radioligands for brain 5-HT{sub 2} receptor imaging in vivo: why do we need them?

    Energy Technology Data Exchange (ETDEWEB)

    Busatto, G.F. [Section of Clinical Neuropharmacology, Dept. of Psychological Medicine, Inst. of Psychiatry, London (United Kingdom)

    1996-08-01

    Recently, PET and SPET radiotracers with high specificity for 5-HT{sub 2} receptors have been developed. These have been studied in baboons and humans with promising results, displaying a binding profile compatible with the brain distribution of 5-HT{sub 2} receptors. It is predicted that studies with the newly developed 5-HT radioligands will substantially increase knowledge about the pharmacology of brain disorders. (orig./MG)

  13. Hepatectomy simulation discrepancy between radionuclide receptor imaging and CT volumetry. Influence of decreased unilateral portal venous flow

    International Nuclear Information System (INIS)

    Akaki, Shiro; Okumura, Yoshihiro; Sasai, Nobuya; Sato, Shuhei; Tsunoda, Masatoshi; Kuroda, Masahiro; Kanazawa, Susumu; Hiraki, Yoshio

    2003-01-01

    discrepancy between hepatectomy simulations with radionuclide receptor imaging and CT volumetry. (author)

  14. Molecular imaging with {sup 68}Ga-SSTR PET/CT and correlation to immunohistochemistry of somatostatin receptors in neuroendocrine tumours

    Energy Technology Data Exchange (ETDEWEB)

    Kaemmerer, Daniel; Haugvik, Sven-Petter; Hommann, Merten [Zentralklinik Bad Berka GmbH, Department of General and Visceral Surgery, Bad Berka (Germany); Peter, Luisa; Lupp, Amelie; Schulz, Stefan [University of Jena, Department of Pharmacology and Toxicology, Jena (Germany); Saenger, Joerg [Laboratory of Pathology and Cytology, Bad Berka (Germany); Prasad, Vikas; Kulkarni, Harshad; Baum, Richard Paul [Zentralklinik Bad Berka, Department of Nuclear Medicine and Center for PET, Bad Berka (Germany)

    2011-09-15

    Somatostatin receptors (SSTR) are known for an overexpression in gastroenteropancreatic neuroendocrine tumours (GEP-NET). The aim of the present study was to find out if the receptor density predicted by the semi-quantitative parameters generated from the static positron emission tomography (PET/CT) correlated with the in vitro immunohistochemistry using a novel rabbit monoclonal anti-SSTR2A antibody (clone UMB-1) for specific SSTR2A immunohistochemistry and polyclonal antibodies for SSTR1 and 3-5. Overall 14 surgical specimens generated from 34 histologically documented GEP-NET patients were correlated with the preoperative {sup 68}Ga-DOTA-NOC PET/CT. Quantitative assessment of the receptor density was done using the immunoreactive score (IRS) of Remmele and Stegner; the additional 4-point IRS classification for immunohistochemistry and standardized uptake values (SUV{sub max} and SUV{sub mean}) were used for PET/CT. The IRS for SSTR2A and SSTR5 correlated highly significant with the SUV{sub max} on the PET/CT (p < 0.001; p < 0.05) and the IRS for SSTR2A with the SUV{sub mean} (p < 0.013). The level of SSTR2A score correlated significantly with chromogranin A staining and indirectly to the tumour grading. The highly significant correlation between SSTR2A and SSTR5 and the SUV{sub max} on the {sup 68}Ga-DOTA-NOC PET/CT scans is concordant with the affinity profile of {sup 68}Ga-DOTA-NOC to the SSTR subtypes and demonstrates the excellent qualification of somatostatin analogues in the diagnostics of NET. This study correlating somatostatin receptor imaging using {sup 68}Ga-DOTA-NOC PET/CT with immunohistochemically analysed SSTR also underlines the approval of therapy using somatostatin analogues, follow-up imaging as well as radionuclide therapy. (orig.)

  15. Imaging opiate receptors by positron tomography (PET): Evaluation by displacement of 3-Acetyl-6-Deoxy-6-Beta-/sup 18/F-flouronaltrexone with active and inactive naloxone

    International Nuclear Information System (INIS)

    Larson, S.M.; Channing, M.A.; Rice, K.R.; Pert, C.B.; Eckelman, W.C.; Burke, T.R.; Bennett, J.M.; Carson, R.E.; Di Chiro, G.

    1985-01-01

    We recently reported the development of a new radiopharmaceutical for in vivo PET imaging of opiate receptors, 3-acetyl-6-deoxy-6-Beta-/sup 18/F-fluoronaltrexone: 3-acetylcyclofoxy, or /sup 18/F-ACF. These studies involved displacement of /sup 18/F-ACF from sites of uptake in the baboon sub-cortical gray matter, and provided strong proof of the opiate receptor specificity of the tracer. We now report on the anatomic localization of /sup 18/F-ACF in the sub-cortical grapy matter of baboon, and the kinetics of uptake and displacement of the tracer. /sup 18/F-ACF was prepared from the known 3-acetyl-6-alpha-naltrexol via the triflate, using /sup 18/F produced by neutron bombardment of /sup 6/Li/sub 2/CO/sub 3/. Anesthetized baboons were imaged after injection of /sup 18/F-ACF (sp.ac.=20Ci/mmol), using the NIH NEUROPET, a high resolution PET scanner. After bolus injection, the initial distribution to brain was rapid with peak uptake at 6 minutes post-injection. Clearance from opiate receptor rich regions of thalamus and basal ganglia was gradual, but after injection of active (but not after inactive), naloxone, clearance from these regions more than doubled. In non-opiate rich regions, (e.g. cerebellum), the predominant component of clearance was equally rapid with or without the active naloxone. Displacement studies of positron labelled ligands provide a powerful tool for non-invasive study of opiate receptor in living primates

  16. Clinical Validation of a Pixon-Based Reconstruction Method Allowing a Twofold Reduction in Planar Images Time of 111In-Pentetreotide Somatostatin Receptor Scintigraphy

    Directory of Open Access Journals (Sweden)

    Philippe Thuillier

    2017-08-01

    Full Text Available ObjectiveThe objective of this study was to e