DOCSLIB.ORG

Decreased 5-Ht2a Receptor Binding in Patients with Anorexia Nervosa

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Decreased 5-Ht2a Receptor Binding in Patients with Anorexia Nervosa Decreased 5-HT2a Receptor Binding in Patients with Anorexia Nervosa Kurt Audenaert, MD, PhD1,2; Koen Van Laere, MD, PhD, DrSc2; Filip Dumont, PhD3; Miriam Vervaet, PhD1; Ingeborg Goethals, MD2; Guido Slegers, PhD3; John Mertens, PhD4; Cees van Heeringen, MD, PhD1; and Rudi A. Dierckx, MD, PhD2 1Department of Psychiatry and Medical Psychology, Ghent University Hospital, Ghent, Belgium; 2Division of Nuclear Medicine, Ghent University Hospital, Ghent, Belgium; 3Department of Radiopharmacy, Ghent University, Ghent, Belgium; and 4VUB-Cyclotron, Brussels, Belgium intake, sometimes accompanied by purging behavior (i.e., Indirect estimations of brain neurotransmitters in patients with self-induced vomiting or the misuse of laxatives or diuret- anorexia nervosa (AN) and low weight have demonstrated a ics). In addition, a disturbance in the perception of body reduction in brain serotonin (5-HT) turnover in general and led to shape and weight is an essential neuropsychologic feature of hypotheses about dysfunction in the 5-HT2a receptor system. It AN (1). was our aim to investigate the central 5-HT receptor binding 2a Psychologic and biologic mechanisms appear to play key index using SPECT brain imaging. Methods: The 5-HT2a recep- tors of low-weight patients with AN were studied by means of roles in the pathogenesis of AN. Neuropsychologic inves- the highly specific radioiodinated 5-HT2a receptor antagonist tigations have indicated cognitive deficits in the frontal and 4-amino-N-[1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl]- parietal cortices (2,3). Perceived distortion of body image 5-iodo-2-methoxybenzamide or 123I-5-I-R91150. Fifteen pa- has been associated specifically with parietal dysfunction tients with clinical diagnoses of AN and 11 age-matched healthy (4). Functional brain imaging with PET and SPECT has volunteers received intravenous injections of 185 MBq 123I-5-I- R91150 and were scanned with high-resolution brain SPECT. shown reduced parietal and frontal cortex metabolism (5) Results: Compared with healthy volunteers, patients with AN and cerebral perfusion (6). had a significantly reduced 5-HT2a binding index in the left In past decades, the involvement of serotonin as a neu- frontal cortex, the left and right parietal cortex, and the left and rotransmitter in AN was largely indicated through indirect right occipital cortex. A significant left–right asymmetry was estimations of brain serotonergic function. Impaired seroto- Ͻ noted in the frontal cortex (left right). Conclusion: These nin turnover and function were demonstrated through results are in accordance with diminished metabolic and perfu- sion of frontal and parietal cortices reported in recent neuroim- plasma measurements of tryptophan, the precursor of 5-hy- aging studies and imply localized disturbed serotonergic func- droxytryptamine (5-HT) (7) or 5-hydroxyindole acetic acid tion. The data are discussed in the light of possible confounding (5-HIAA, the metabolite of 5-HT), in cerebrospinal fluid factors related to the low-weight AN status. A regional cortical (CSF) of low-weight AN patients (8). Elevated CSF reduction in 5-HT2a binding index is not likely to be caused by a 5-HIAA concentrations have been reported in long-time general reduction in serotonergic function due to the possible weight-restored AN patients (8). Another indication of re- confounding factors. Suggestions for further research are given. duced serotonergic function in low-weight AN patients was Key Words: anorexia nervosa; serotonin; serotonin-2A recep- blunted physiologic response to the administration of selec- tor; SPECT tive pharmacologic agonists (9–11). Again, these findings J Nucl Med 2003; 44:163–169 normalized after weight restoration (10). The involvement of the 5-HT2a receptor in the pathophys- iology of AN was demonstrated indirectly via blood platelet studies, both through an enhanced mobilization of intracel- The essential features of anorexia nervosa (AN) are that lular platelet calcium content, mediated by 5-HT receptors 2 the individual refuses to maintain a minimally normal body (12), and through enhanced platelet serotonin 5-HT2a bind- weight and is intensely afraid of gaining weight. Weight ing, measured in vitro with 3H-lysergic acid diethylamide loss can be accomplished primarily through excessive phys- (13). Recently, studies with PET and 18F-altanserin as a ical exercise and through voluntary reduction in total food tracer showed reduced 5-HT2a binding in the orbitofrontal cortex in recovered bulimic patients (14). Some recent mo- lecular genetic studies in patients with eating disorders have Received Feb. 11, 2002; revision accepted Jul. 25, 2002. For correspondence or reprints contact: Dr. Kurt Audenaert, Department of demonstrated an increased frequency of one of the alleles on Psychiatry and Medical Psychology, 1K13 Ghent University Hospital, De Pintelaan 185, Ghent, Belgium. the promotor region of the 5-HT2a gene (15). Also, twin and E-mail: [email protected] family studies suggest a genetic vulnerability to AN, and the 5-HT2A RECEPTORS IN ANOREXIA NERVOSA • Audenaert et al. 163 hypothesis has been put forward that this vulnerability may Thyroid blockade was achieved by administration of a single be expressed in the central serotonergic system (16). oral dose of 100 mg potassium iodine before injection. All subjects Functional imaging techniques, such as PET and SPECT received an intravenous injection of 185 MBq 123I-5-I-R91150 in using specific 5-HT receptor ligands, make it possible to normal sitting conditions. SPECT scanning was performed using a 2 triple-head high-resolution gamma camera GCA-9300 (Toshiba evaluate in vivo receptor binding in patients with AN. Medical Systems, Oetwil am See, Switzerland) with fanbeam Preliminary research in healthy subjects has indicated that collimation. For 123I, the resulting transaxial image resolution is 4-amino-N-[1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-pi- 9.5 mm in full width at half maximum. 123 peridinyl]-5-iodo-2-methoxybenzamide ( I-5-I-R91150) is Because sequential dynamic SPECT brain scans have shown a suitable ligand for imaging 5-HT2a receptors in vivo. It that the corticocerebellar ratio reaches a plateau between 90 and binds reversibly and with high affinity in vitro to 5-HT2a 110 min, reflecting pseudoequilibrium, and remains stable there- receptors (17). On average, 2% of a bolus dose of 123I-5-I- after for up to8h(18), acquisition was started between 110 and R91150 is taken up by the brain (18). Effective blockade of 140 min after tracer injection, according to previous protocols (20). A transmission scan was acquired before the emission scan, 5-HT2a receptors in vivo was demonstrated in a study of 153 patients with schizophrenia who were treated with risperi- using 3 Gd rod sources. This scan was used for subsequent done or clozapine (19). image coregistration to stereotactic coordinates. Emission images were acquired during a 40-min period. The whole-brain volume The aim of this study was to evaluate the 5-HT2a binding was acquired within the single scanning session. Images were index (BI) in patients with AN. reconstructed using filtered backprojection and corrected for scat- ter and nonuniform attenuation (21). MATERIALS AND METHODS Analysis of the scans was performed without knowledge of patient status after automatic image coregistration to stereotactic Patients space using the transmission image (BRASS; Nuclear Diagnostics Fifteen patients were included in the study. All were right Ltd., Stockholm, Sweden) (22). handed, 16–30 y old, and diagnosed as having AN according to the The method for coregistration of SPECT receptor data using criteria of the fourth edition of the Diagnostic and Statistical transmission images has been published previously (22). In short, Manual of Mental Disorders (DSM-IV) (1). Patients were re- the sequential acquisition of transmission and emission images can cruited from an inpatient eating-disorder unit in a university psy- be used to anatomically standardize the emission image using the chiatric hospital. Patients were selected by a senior psychiatrist and same linear parameters as those used for the transmission image. a senior psychologist after DSM-IV–based structured clinical in- The latter is first reoriented to a template in Talairach space, and terviews. To create a group of patients with consistent disease the same transformation is then given to the emission images. On status, only symptom-fixed patients who stayed in the hospital as the Talairach templates, a predefined volume-of-interest (VOI) set a result of resistance of the disease to treatment were included. can be constructed (originally performed on perfusion SPECT Exclusion criteria were a comorbid psychiatric, major medical, or images), which allows a user-independent sampling of the whole- neurological disorder; antidepressant, neuroleptic, or electrocon- brain volume of different patients without previously available vulsive therapy in the preceding year; substance abuse; pregnancy structural information. or lactation; and a Mini-Mental State Examination score Ͻ 28. A diagram of the VOI map (22,23) is shown in Figure 1 and a Menstrual status was noted in female patients. description of VOIs is provided in Table 1. Radioactivity estimates The patients were compared with 11 age-matched healthy vol- in the cortex were assumed to represent total ligand binding unteers (7 women, 4 men) who were recruited from hospital staff. (specific plus nonspecific binding plus free ligand) (18). Because These
Load more

Recommended publications
  • Exaggerated 5-HT1A but Normal 5-HT2A Receptor Activity in Individuals Ill with Anorexia Nervosa Ursula F
    Exaggerated 5-HT1A but Normal 5-HT2A Receptor Activity in Individuals Ill with Anorexia Nervosa Ursula F. Bailer, Guido K. Frank, Shannan E. Henry, Julie C. Price, Carolyn C. Meltzer, Chester A. Mathis, Angela Wagner, Laura Thornton, Jessica Hoge, Scott K. Ziolko, Carl R. Becker, Claire W. McConaha, and Walter H. Kaye Background: Many studies have found disturbances of serotonin (5-HT) activity in anorexia nervosa (AN). Because little is known about 5-HT receptor function in AN, positron emission tomography (PET) imaging with 5-HT receptor-specific radioligands was used to character- ize 5-HT1A and 5-HT2A receptors. Methods: Fifteen women ill with AN (ILL AN) were compared with 29 healthy control women (CW); PET and [11C]WAY100635 were used to assess binding potential (BP) of the 5-HT1A receptor, and [18F]altanserin was used to assess postsynaptic 5-HT2A receptor BP. [15O] water and PET were used to assess cerebral blood flow. Results: The ILL AN women had a highly significant (30%–70%) increase in [11C]WAY100635 BP in prefrontal and lateral orbital frontal regions, mesial and lateral temporal lobes, parietal cortex, and dorsal raphe nuclei compared with CW. The [18F]altanserin BP was normal in ILL AN but was positively and significantly related to harm avoidance in suprapragenual cingulate, frontal, and parietal regions. Cerebral blood flow was normal in ILL AN women. Conclusions: Increased activity of 5-HT1A receptor activity may help explain poor response to 5-HT medication in ILL AN. This study extends data suggesting that 5-HT function, and, specifically, the 5-HT2A receptor, is related to anxiety in AN.
    [Show full text]
  • Test–Retest Variability of Serotonin 5-HT2A Receptor Binding Measured with Positron Emission Tomography and [18F]Altanserin in the Human Brain
    SYNAPSE 30:380–392 (1998) Test–Retest Variability of Serotonin 5-HT2A Receptor Binding Measured With Positron Emission Tomography and [18F]Altanserin in the Human Brain GWENN S. SMITH,1,2* JULIE C. PRICE,2 BRIAN J. LOPRESTI,2 YIYUN HUANG,2 NORMAN SIMPSON,2 DANIEL HOLT,2 N. SCOTT MASON,2 CAROLYN CIDIS MELTZER,1,2 ROBERT A. SWEET,1 THOMAS NICHOLS,2 DONALD SASHIN,2 AND CHESTER A. MATHIS2 1Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 2Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania KEY WORDS positron emission tomography (PET); serotonin receptor; 5-HT2A; imaging ABSTRACT The role of serotonin in CNS function and in many neuropsychiatric diseases (e.g., schizophrenia, affective disorders, degenerative dementias) support the development of a reliable measure of serotonin receptor binding in vivo in human subjects. To this end, the regional distribution and intrasubject test–retest variability of the binding of [18F]altanserin were measured as important steps in the further development of [18F]altanserin as a radiotracer for positron emission tomography (PET) 18 studies of the serotonin 5-HT2A receptor. Two high specific activity [ F]altanserin PET studies were performed in normal control subjects (n ϭ 8) on two separate days (2–16 days apart). Regional specific binding was assessed by distribution volume (DV), estimates that were derived using a conventional four compartment (4C) model, and the Logan graphical analysis method. For both analysis methods, levels of [18F]altanserin binding were highest in cortical areas, lower in the striatum and thalamus, and lowest in the cerebellum.
    [Show full text]
  • A Nonlinear Relationship Between Cerebral Serotonin Transporter And
    The Journal of Neuroscience, March 3, 2010 • 30(9):3391–3397 • 3391 Cellular/Molecular A Nonlinear Relationship between Cerebral Serotonin Transporter and 5-HT2A Receptor Binding: An In Vivo Molecular Imaging Study in Humans David Erritzoe,1,3 Klaus Holst,3,4 Vibe G. Frokjaer,1,3 Cecilie L. Licht,1,3 Jan Kalbitzer,1,3 Finn Å. Nielsen,3,5 Claus Svarer,1,3 Jacob Madsen,2 and Gitte M. Knudsen1,3 1Neurobiology Research Unit and 2PET and Cyclotron Unit, University Hospital Rigshospitalet, DK-2100 Copenhagen, Denmark, 3Center for Integrated Molecular Brain Imaging, DK-2100 Copenhagen, Denmark, 4Department of Biostatistics, University of Copenhagen, DK-2200 Copenhagen, Denmark, and 5DTU Informatics, Technical University of Denmark, DK-2800 Lyngby, Denmark Serotonergic neurotransmission is involved in the regulation of physiological functions such as mood, sleep, memory, and appetite. Withintheserotonintransmittersystem,boththepostsynapticallylocatedserotonin2A(5-HT2A )receptorandthepresynapticserotonin transporter (SERT) are sensitive to chronic changes in cerebral 5-HT levels. Additionally, experimental studies suggest that alterations in either the 5-HT2A receptor or SERT level can affect the protein level of the counterpart. The aim of this study was to explore the covariation betweencerebral5-HT2A receptorandSERT invivointhesamehealthyhumansubjects.Fifty-sixhealthyhumansubjectswithameanage of 36 Ϯ 19 years were investigated. The SERT binding was imaged with [ 11C]3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)- 18 benzonitrile (DASB) and 5-HT2A receptor binding with [ F]altanserin using positron emission tomography. Within each individual, a regionalintercorrelationforthevariousbrainregionswasseenwithbothmarkers,mostnotablyfor5-HT2A receptorbinding.Aninverted U-shaped relationship between the 5-HT2A receptor and the SERT binding was identified. The observed regional intercorrelation for both the 5-HT2A receptor and the SERT cerebral binding suggests that, within the single individual, each marker has a set point adjusted through a common regulator.
    [Show full text]
  • [18F] Altanserin Bolus Injection in the Canine Brain Using PET Imaging
    Pauwelyn et al. BMC Veterinary Research (2019) 15:415 https://doi.org/10.1186/s12917-019-2165-5 RESEARCH ARTICLE Open Access Kinetic analysis of [18F] altanserin bolus injection in the canine brain using PET imaging Glenn Pauwelyn1*† , Lise Vlerick2†, Robrecht Dockx2,3, Jeroen Verhoeven1, Andre Dobbeleir2,5, Tim Bosmans2, Kathelijne Peremans2, Christian Vanhove4, Ingeborgh Polis2 and Filip De Vos1 Abstract 18 Background: Currently, [ F] altanserin is the most frequently used PET-radioligand for serotonin2A (5-HT2A) receptor imaging in the human brain but has never been validated in dogs. In vivo imaging of this receptor in the canine brain could improve diagnosis and therapy of several behavioural disorders in dogs. Furthermore, since dogs are considered as a valuable animal model for human psychiatric disorders, the ability to image this receptor in dogs could help to increase our understanding of the pathophysiology of these diseases. Therefore, five healthy laboratory beagles underwent a 90-min dynamic PET scan with arterial blood sampling after [18F] altanserin bolus injection. Compartmental modelling using metabolite corrected arterial input functions was compared with reference tissue modelling with the cerebellum as reference region. 18 Results: The distribution of [ F] altanserin in the canine brain corresponded well to the distribution of 5-HT2A receptors in human and rodent studies. The kinetics could be best described by a 2-Tissue compartment (2-TC) model. All reference tissue models were highly correlated with the 2-TC model, indicating compartmental modelling can be replaced by reference tissue models to avoid arterial blood sampling. Conclusions: This study demonstrates that [18F] altanserin PET is a reliable tool to visualize and quantify the 5- HT2A receptor in the canine brain.
    [Show full text]
  • Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans
    molecules Review Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans Paul Cumming 1,2,* , Milan Scheidegger 3 , Dario Dornbierer 3, Mikael Palner 4,5,6 , Boris B. Quednow 3,7 and Chantal Martin-Soelch 8 1 Department of Nuclear Medicine, Bern University Hospital, CH-3010 Bern, Switzerland 2 School of Psychology and Counselling, Queensland University of Technology, Brisbane 4059, Australia 3 Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital of the University of Zurich, CH-8032 Zurich, Switzerland; [email protected] (M.S.); [email protected] (D.D.); [email protected] (B.B.Q.) 4 Odense Department of Clinical Research, University of Southern Denmark, DK-5000 Odense, Denmark; [email protected] 5 Department of Nuclear Medicine, Odense University Hospital, DK-5000 Odense, Denmark 6 Neurobiology Research Unit, Copenhagen University Hospital, DK-2100 Copenhagen, Denmark 7 Neuroscience Center Zurich, University of Zurich and Swiss Federal Institute of Technology Zurich, CH-8058 Zurich, Switzerland 8 Department of Psychology, University of Fribourg, CH-1700 Fribourg, Switzerland; [email protected] * Correspondence: [email protected] or [email protected] Abstract: Hallucinogens are a loosely defined group of compounds including LSD, N,N- dimethyltryptamines, mescaline, psilocybin/psilocin, and 2,5-dimethoxy-4-methamphetamine (DOM), Citation: Cumming, P.; Scheidegger, which can evoke intense visual and emotional experiences. We are witnessing a renaissance of re- M.; Dornbierer, D.; Palner, M.; search interest in hallucinogens, driven by increasing awareness of their psychotherapeutic potential. Quednow, B.B.; Martin-Soelch, C. As such, we now present a narrative review of the literature on hallucinogen binding in vitro and Molecular and Functional Imaging ex vivo, and the various molecular imaging studies with positron emission tomography (PET) or Studies of Psychedelic Drug Action in single photon emission computer tomography (SPECT).
    [Show full text]
  • Parametric Mapping of 5HT1A Receptor Sites in the Human Brain with the Hypotime Method: Theory and Normal Values
    Journal of Nuclear Medicine, published on July 17, 2009 as doi:10.2967/jnumed.108.053322 Parametric Mapping of 5HT1A Receptor Sites in the Human Brain with the Hypotime Method: Theory and Normal Values Mette Møller, Anders Rodell, and Albert Gjedde Center of Functionally Integrative Neuroscience, Aarhus University, and Pathophysiology and Experimental Tomography Center, Aarhus University Hospitals, Aarhus, Denmark The radioligand [carbonyl-11C]WAY-100635 (11C-WAY) is a PET tracer of the serotonin 5HT1A receptors in the human brain. It is The radioligand [carbonyl-11C]WAY-100635 (11C-WAY) metabolized so rapidly in the circulation that it behaves more binds to the serotonin 5HT receptor as an antagonist. as a chemical microsphere than as a tracer subject to continuous 1A exchange between the circulation and brain tissue. Although ref- The ligand has been used to map the neuroreceptors in erence tissue methods are useful as analyses of uptake of some healthy subjects and in patients with diseases as diverse as radioligands with indeterminate arterial input functions, their use major depression (1), bulimia nervosa (2), amyotrophic to analyze 11C-WAY uptake and binding is challenged by the lateral sclerosis (3), schizophrenia (4), Parkinson disease (5), rapid plasma metabolism, which violates the assumption that re- and temporal lobe epilepsy (6). In general, intrasubject gions of interest and reference regions continue to exchange ra- variability of the binding is low, but intersubjective variabil- dioligand with the circulation during the entire uptake period. ity is high (7,8). Although the receptor binding potentials Here, we proposed a method of calculation (Hypotime) that spe- cifically uses the washout rather than the accumulation of 11C- (BPND) globally decline in depression, other diseases reveal only subtle changes, and demographic, physiologic, and WAY to determine binding potentials (BPND), without the use of regression analysis.
    [Show full text]
  • Altanserin and [18F]Deuteroaltanserin for PET
    Nuclear Medicine and Biology 28 (2001) 271–279 Comparison of [18F]altanserin and [18F]deuteroaltanserin for PET imaging of serotonin2A receptors in baboon brain: pharmacological studies Julie K. Staleya,*, Christopher H. Van Dycka, Ping-Zhong Tana, Mohammed Al Tikritia, Quinn Ramsbya, Heide Klumpa, Chin Ngb, Pradeep Gargb, Robert Souferb, Ronald M. Baldwina, Robert B. Innisa,c aDepartment of Psychiatry, Yale University School of Medicine and VA Connecticut Healthcare System, West Haven, CT 06516, USA bDepartment of Radiology, Yale University School of Medicine and VA Connecticut Healthcare System, West Haven, CT 06516, USA cDepartment of Pharmacology, Yale University School of Medicine and VA Connecticut Healthcare System, West Haven, CT 06516, USA Received 2 September 2000; received in revised form 30 September 2000; accepted 18 November 2000 Abstract The regional distribution in brain, distribution volumes, and pharmacological specificity of the PET 5-HT2A receptor radiotracer [18F]deuteroaltanserin were evaluated and compared to those of its non-deuterated derivative [18F]altanserin. Both radiotracers were administered to baboons by bolus plus constant infusion and PET images were acquired up to 8 h. The time-activity curves for both tracers stabilized between 4 and 6 h. The ratio of total and free parent to metabolites was not significantly different between radiotracers; nevertheless, total cortical RT (equilibrium ratio of specific to nondisplaceable brain uptake) was significantly higher (34–78%) for 18 18 18 [ F]deuteroaltanserin than for [ F]altanserin. In contrast, the binding potential (Bmax/KD) was similar between radiotracers. [ F]Deu- teroaltanserin cortical activity was displaced by the 5-HT2A receptor antagonist SR 46349B but was not altered by changes in endogenous 18 18 5-HT induced by fenfluramine.
    [Show full text]
  • Serotonergic Modulation of Striatal Dopamine Measured with Positron Emission Tomography (PET) and in Viva Microdialysis
    The Journal of Neuroscience, January 1995, 75(l): 921-929 Serotonergic Modulation of Striatal Dopamine Measured with Positron Emission Tomography (PET) and in viva Microdialysis Stephen L. Dewey,’ Gwenn S. Smith,* Jean Logan,’ David Alexoff,’ Yu-Shin Ding,’ Payton King,3 Naomi Pappas,3 Jonathan D. Brodie,* and Charles Ft. Ashby, Jr.3 ‘Department of Chemistry, Brookhaven National Laboratory, Upton, New York 11973, *Department of Psychiatry, New York University School of Medicine, New York, New York 10016, and 3Medical Department, Brookhaven National Laboratory, Upton, New York 11973 Positron emission tomography and in vivo microdialysis were Neurotransmitters interact in the CNS and PNS through an used to study serotonin’s role in modulating striatal dopa- intricate network of efferent and afferent projections. Through mine. Serial PET studies were performed in adult female these interactions, the CNS biochemically mediates the transfer baboons at baseline and following drug treatment, using the of information from one specific neuroanatomic focus to an- dopamine (D,) selective radiotracer, “C-raclopride. The se- other. By taking advantage of our fundamental knowledge of rotonergic system was manipulated by administration of the many of these pathways and their neurochemical interactions, selective 5HT reuptake inhibitor, citalopram, or by seroto- we have been able to direct our neuroimaging positron emission nergic (5HT,) receptor blockade (using altanserin, a 5-HT, tomography (PET) studies at the development ofa methodology antagonist). llC-Raclopride time-activity data from striatum that can effectively be applied to an examination of these in- and cerebellum were combined with plasma arterial input teractions in the living human brain (Dewey et al., 1988, 1993d).
    [Show full text]
  • In Vivo Imaging of Neurotransmitter Systems Using Radio Labeled Receptor Ligands Lawrence S
    ELSEVIER In Vivo Imaging of Neurotransmitter Systems Using Radio labeled Receptor Ligands Lawrence S. Kegeles, M.D., Ph.D., and J. John Mann, M.D. In vivo functional brain imaging, including global blood overview of the methodology of development and selection of flow, regional cerebral blood flow (rCBF), measured with radioligands for PET and SPECT is presented. Studies positron emission tomography (PET) and single photon involving PET and SPECT ligand methods are reviewed emission computed tomography (SPECT), and regional and their findings summarized, including recent work cerebral metabolic rate (rCMR) measured with demonstrating successive mutual modulation of deoxyglucose PET, have been widely used in studies of neurotransmitter systems. Kinetic and equilibrium analysis psychiatric disorders. These studies have found modest modeling are reviewed. The emerging methodology of differences and required large numbers of patients. measuring neurotransmitter release on activation, both Activation studies using rCBF or rCMR as indices of pharmacologically and by task performance, using ligand neuronal activity are more sensitive because patients act as methods is reviewed and proposed as a promising new their own control; however, findings localize regions of approach for studying psychiatric disorders. change but provide no data about specific neurotransmitter [Neuropsychopharmacology 17:293-307, 1997] systems. After a general discussion of the role of © 1997 American College of Neuropsychopharmacology. neurotransmitter systems in neuropsychiatric
    [Show full text]
  • Automatic Synthesis of [ F]Altanserin, a Radiopharmaceuticalfor
    Published in: Clinical positron imaging (1998), vol. 1, iss. 2, pp. 111-116 Status: Postprint (Author‘s version) Automatic Synthesis of [18F]Altanserin, a Radiopharmaceutical for Positron Emission Tomographic Studies of the Serotonergic Type-2 Receptors Michel Monclus, BS, John Van Naemen, Ir, Eric Mulleneers, Philippe Damhaut, PhD, Andre Luxen, PhD, Serge Goldman, MD PET/Biomedical Cyclotron Unit, ULB Hôpital Erasme, Brussels, Belgium Abstract 18 [ F]Altanserin is routinely used in several centers to study the serotonergic type-2 receptors (5HT2) with positron emission tomography (PET). An automatic production system allowing the preparation of multimillicurie amounts [>1.5 GBq (40 mCi) EOS, mean radiochemical yield 20 ± 6% EOB, specific activity >1 Ci/fimol (mean = 2.8 Ci/ =mol), n = 50] of this radiopharmaceutical within a synthesis time of 90 minutes (quality controls included) is described in this paper. The apparatus includes the recovery of the activity from the target, the preparation of the dried [18F]KF/kryptofix 2.2.2 complex, the labeling reaction using a microwave cavity, the Sep Pak and HPLC purification. A sterile, pyrogen-free and single use unit was also developed for the formulation of the injectable solution. This last part could be used for the formulation of many other radiopharmaceuticals. 18 Key W ords: [ F]altanserin; automatic synthesis; positron emission tomography; 5HT2 receptors. Introduction Serotonergic mechanisms are implicated in behaviors and psychiatric disorders such as affective disorders, suicide, or obsessive-compulsive disorder. [1] The distribution of the serotonergic type-2 receptors (5HT2) in the human brain has already been studied in vivo using several positron emission tomography (PET) radiopharmaceuticals.
    [Show full text]
  • Federal Register / Vol. 60, No. 80 / Wednesday, April 26, 1995 / Notices DIX to the HTSUS—Continued
    20558 Federal Register / Vol. 60, No. 80 / Wednesday, April 26, 1995 / Notices DEPARMENT OF THE TREASURY Services, U.S. Customs Service, 1301 TABLE 1.ÐPHARMACEUTICAL APPEN- Constitution Avenue NW, Washington, DIX TO THE HTSUSÐContinued Customs Service D.C. 20229 at (202) 927±1060. CAS No. Pharmaceutical [T.D. 95±33] Dated: April 14, 1995. 52±78±8 ..................... NORETHANDROLONE. A. W. Tennant, 52±86±8 ..................... HALOPERIDOL. Pharmaceutical Tables 1 and 3 of the Director, Office of Laboratories and Scientific 52±88±0 ..................... ATROPINE METHONITRATE. HTSUS 52±90±4 ..................... CYSTEINE. Services. 53±03±2 ..................... PREDNISONE. 53±06±5 ..................... CORTISONE. AGENCY: Customs Service, Department TABLE 1.ÐPHARMACEUTICAL 53±10±1 ..................... HYDROXYDIONE SODIUM SUCCI- of the Treasury. NATE. APPENDIX TO THE HTSUS 53±16±7 ..................... ESTRONE. ACTION: Listing of the products found in 53±18±9 ..................... BIETASERPINE. Table 1 and Table 3 of the CAS No. Pharmaceutical 53±19±0 ..................... MITOTANE. 53±31±6 ..................... MEDIBAZINE. Pharmaceutical Appendix to the N/A ............................. ACTAGARDIN. 53±33±8 ..................... PARAMETHASONE. Harmonized Tariff Schedule of the N/A ............................. ARDACIN. 53±34±9 ..................... FLUPREDNISOLONE. N/A ............................. BICIROMAB. 53±39±4 ..................... OXANDROLONE. United States of America in Chemical N/A ............................. CELUCLORAL. 53±43±0
    [Show full text]
  • 5-HT2A Receptors in the Central Nervous System the Receptors
    The Receptors Bruno P. Guiard Giuseppe Di Giovanni Editors 5-HT2A Receptors in the Central Nervous System The Receptors Volume 32 Series Editor Giuseppe Di Giovanni Department of Physiology & Biochemistry Faculty of Medicine and Surgery University of Malta Msida, Malta The Receptors book Series, founded in the 1980’s, is a broad-based and well- respected series on all aspects of receptor neurophysiology. The series presents published volumes that comprehensively review neural receptors for a specific hormone or neurotransmitter by invited leading specialists. Particular attention is paid to in-depth studies of receptors’ role in health and neuropathological processes. Recent volumes in the series cover chemical, physical, modeling, biological, pharmacological, anatomical aspects and drug discovery regarding different receptors. All books in this series have, with a rigorous editing, a strong reference value and provide essential up-to-date resources for neuroscience researchers, lecturers, students and pharmaceutical research. More information about this series at http://www.springer.com/series/7668 Bruno P. Guiard • Giuseppe Di Giovanni Editors 5-HT2A Receptors in the Central Nervous System Editors Bruno P. Guiard Giuseppe Di Giovanni Faculté de Pharmacie Department of Physiology Université Paris Sud and Biochemistry Université Paris-Saclay University of Malta Chatenay-Malabry, France Msida MSD, Malta Centre de Recherches sur la Cognition Animale (CRCA) Centre de Biologie Intégrative (CBI) Université de Toulouse; CNRS, UPS Toulouse, France The Receptors ISBN 978-3-319-70472-2 ISBN 978-3-319-70474-6 (eBook) https://doi.org/10.1007/978-3-319-70474-6 Library of Congress Control Number: 2017964095 © Springer International Publishing AG 2018 This work is subject to copyright.
    [Show full text]