DOCSLIB.ORG

[18F] Altanserin Bolus Injection in the Canine Brain Using PET Imaging

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read 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. Keywords: Canine brain, Kinetic modelling, 5HT2a receptor, Mood-disorders Background the pathophysiology of several neurological and psychi- The G-protein coupled 5-HT2A receptor is the main exci- atric disorders including depression, anxiety disorders, tatory serotonergic receptor in the brain [1, 2]. Studies in personality disorders, obsessive-compulsive disorder, bi- humans and rodents found the highest densities of 5- polar disorder, Alzheimer’s disease and schizophrenia [2, HT2A receptors in the cortex, mainly in frontal regions. 5–13]. Positron emission tomography (PET) is an inter- The hippocampus and striatum exhibit lower densities of esting tool in brain imaging research, permitting the the receptor, while the cerebellum is virtually devoid of 5- visualization of the 5-HT2A receptor in the living brain HT2A receptors [1, 3, 4]. The receptor is also widely dis- by using receptor specific radioligands [14–16]. In vivo tributed in peripheral tissues, where it mediates platelet study of this receptor is an important field of research as aggregation, capillary permeability and smooth muscle it improves our understanding of the various diseases in contraction [2, 5]. which the receptor is implicated. Although several PET Besides its influence on numerous physiological func- radioligands for the 5-HT2A receptor have been evalu- tions, the 5-HT2A receptor is believed to be involved in ated, the clinical use of the majority of these radioligands is limited due to low selectivity or high nonspecific bind- * Correspondence: [email protected] ing [17, 18]. Currently, the selective antagonist [18F] †Glenn Pauwelyn and Lise Vlerick contributed equally to this work. 1 altanserin is the most frequently used PET radioligand Laboratory of Radiopharmacy, Ghent University, Ottergemsesteenweg 460, 18 9000 Ghent, Belgium for 5-HT2A receptor imaging. [ F] altanserin is Full list of author information is available at the end of the article © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Pauwelyn et al. BMC Veterinary Research (2019) 15:415 Page 2 of 11 characterised by a high brain uptake, high affinity (kd:0.3 (n = 5). High chemical and radiochemical purities of > nM) and high selectivity towards the 5-HT2A receptor 99% were achieved with a minimal specific activity of [19–22]. In human neuroimaging, the in vivo formation of 100 GBq/μmol at EOS. lipophilic radiolabeled metabolites that cross the blood brain barrier complicates kinetic modeling with this radio- Blood input function and metabolites tracer [15, 17, 20, 21]. However, correction for these radi- The parent compound fraction in plasma over time olabeled metabolites can be achieved by the application of (mean for five dogs) is visualised in Fig. 1a and illustrates a bolus-infusion protocol with equilibrium imaging [23] a slow metabolization of [18F] altanserin during the PET or by using a dual-input functional approach [24]butis scan. After 10 min, 86 ± 5.9% of total activity in the not feasible in clinical routine. Besides in human clinical blood plasma was intact [18F] altanserin and further de- PET studies, [18F] Altanserin has been used in studies with creased to 55 ± 4.9% at 90 min. Using HPLC one major baboons and rodents. Unlike in humans or baboons, only unknown polar metabolite (TR =t0) could be identified polar radiometabolites have been identified in rodents [1, which increased up to 41 ± 3.9% at 90 min. Furthermore, 3, 21]. To the authors’ knowledge, PET imaging with [18F] two lipophilic metabolites could be separated from [18F] Altanserin in dogs has never been demonstrated. How- altanserin (TR: 10 min) during HPLC analysis: an un- ever, since they show naturally occurring behavioral disor- known metabolite (TR: 6 min) and a metabolite identi- 18 ders which are related and possibly homologues to fied as [ F] Altanserinol (TR: 8 min). These lipophilic particular human psychiatric disorders, the dogs might metabolites together never transcended 2% of total present a valuable animal model for them [25–29]. In radioactivity in plasma. Thereafter, a Watabe function addition, dogs have a relatively large frontal cortex in was fitted to the intact fraction of [18F] altanserin in the comparison with rodents, which makes imaging studies of plasma for every individual dog and a metabolite- this region more feasible [30]. Previously performed corrected plasma input curve was calculated using SPECT and psychopharmacological studies with dogs PMOD (Fig. 1b). have already reported a potential involvement of the 5- HT2A receptor in impulsive aggression, pathological anx- Brain analysis iety and other affective behavioral disorders [27, 28, 31, A bolus injection of 352 ± 27.7 MBq [18F] altanserin 32]. For example, a decreased binding potential of the 5- showed a fast uptake in all of the regions followed by a HT2A receptor in brain regions assumed to play an im- relative fast wash-out. High radioactive uptake was portant role in the pathophysiology of anxiety disorders found in the following cortical regions: frontal cortex, was reported in dogs with pathological anxiety [28]. On parietal cortex, anterior cingulate cortex and subgenual the contrary, increased binding potential of the 5-HT2A cortex. Moderate uptake was seen in the temporal cortex receptor was found in dogs suffering from impulsive ag- and occipital cortex. The cerebellum represented the gression [31]. These findings emphasize the role of the 5- lowest radioactive uptake (i.e. the reference region). Fig- HT2A receptor in canine behavioral disorders. Using the ure 2 represents a summed PET image (frames 1 to 40) advantages of PET imaging over other imaging techniques co-registered with the MR image. Figure 3 represents to study the 5-HT2A receptor in the dogs, its involvement the corresponding time-activity curves for the different in several behavioral disorders can be further investigated VOI’s and display a fast equilibrium was achieved after which could help to gain insight in the pathophysiology of bolus injection of [18F]altanserin. certain canine behavioural disorders and would help to guide the treatment of these disorders. Kinetic modelling 18 The first objective of this study was to quantify [ F] VT-, BPND- and AIC-values (mean ± SD) for the six differ- altanserin binding in the canine brain using compart- ent modelling methods (n = 5) are added in Additional mental modelling and a metabolite corrected arterial in- data (Additional file 1). Small standard errors (SE) were put function. A second objective was to investigate seen for the 1-TC and 2-TC model with a maximum of whether compartmental modelling can be replaced by 6.56 and 4.47% in the cerebellum, respectively. The 2-TC reference tissue modelling in future experiments, since model showed excellent fits for the target ROI TACs in this would avoid invasive arterial blood sampling and contrast to the 1-TC model confirmed by the remarkable therefore facilitate application of the radiotracer in fu- lower AIC-values observed in all of the brain regions using ture studies. the 2-TC model compared to the 1-TC model. When plotting the BPND-values of the 1-TC model and 2-TC Results model in a Bland-Altman plot (Fig. 5) a large overesti- Radiosynthesis mation (38.8 ± 3.57%) of the BPND-values was found using [18F] altanserin was obtained after 70 min of synthesis the 1-TC model, which is clearly illustrated in Fig. 4. with end of synthesis (EOS) activities of 3.14 ± 1.16 GBq Moreover, a significant difference between de BPND-values Pauwelyn et al. BMC Veterinary Research (2019) 15:415 Page 3 of 11 Fig. 1 a: A Watabe function fitted to the mean fraction of intact [18F] altanserin (mean ± SD) in plasma over time for five dogs.
Load more

Recommended publications
  • Effects of Stress-Induced Depression on Parkinson's Disease
    Effects of stress-induced depression on Parkinson’s disease symptomatology A dissertation submitted to the Division of Research and Advanced Studies of the University of Cincinnati in partial fulfillment of the requirements for the degree of Doctor of Philosophy (Ph.D.) in the Graduate Program in Neuroscience of the College of Medicine 2011 By Ann Marie Hemmerle B.S., University of Dayton Advisor: Kim B. Seroogy, Ph.D. Committee Chair: Neil Richtand, M.D., Ph.D. James P. Herman, Ph.D. Kathy Steece-Collier, Ph.D. Aaron Johnson, Ph.D. Abstract Parkinson’s disease (PD) is a chronic neurodegenerative disorder that primarily affects dopaminergic neurons of the nigrostriatal pathway resulting in debilitating motor symptoms. Parkinson’s patients also have a high risk of comorbid depression, though this aspect of the disorder is less well studied. Understanding the underlying pathology of the comorbidity is important in improving clinical treatments and the quality of life for PD patients. To address this issue, we have developed a new model combining the unilateral striatal 6-hydroxydopamine lesion model of PD with the chronic variable stress model (CVS) of depression. Dysfunction of the hypothalamic-pituitary-adrenal axis and its relationship to depression symptomatology is well established. Stress dysfunction may also have a role in the etiology of preclinical PD non- motor symptoms, and later in the course of the disease, may worsen motor symptoms. The combined model allows us to test the hypothesis that experimental depression exacerbates PD symptoms and to ascertain the mechanisms behind the increased neuronal loss. In the first study, we examined several temporal paradigms of the combined model.
    [Show full text]
  • 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]
  • Brain Imaging
    Publications · Brochures Brain Imaging A Technologist’s Guide Produced with the kind Support of Editors Fragoso Costa, Pedro (Oldenburg) Santos, Andrea (Lisbon) Vidovič, Borut (Munich) Contributors Arbizu Lostao, Javier Pagani, Marco Barthel, Henryk Payoux, Pierre Boehm, Torsten Pepe, Giovanna Calapaquí-Terán, Adriana Peștean, Claudiu Delgado-Bolton, Roberto Sabri, Osama Garibotto, Valentina Sočan, Aljaž Grmek, Marko Sousa, Eva Hackett, Elizabeth Testanera, Giorgio Hoffmann, Karl Titus Tiepolt, Solveig Law, Ian van de Giessen, Elsmarieke Lucena, Filipa Vaz, Tânia Morbelli, Silvia Werner, Peter Contents Foreword 4 Introduction 5 Andrea Santos, Pedro Fragoso Costa Chapter 1 Anatomy, Physiology and Pathology 6 Elsmarieke van de Giessen, Silvia Morbelli and Pierre Payoux Chapter 2 Tracers for Brain Imaging 12 Aljaz Socan Chapter 3 SPECT and SPECT/CT in Oncological Brain Imaging (*) 26 Elizabeth C. Hackett Chapter 4 Imaging in Oncological Brain Diseases: PET/CT 33 EANM Giorgio Testanera and Giovanna Pepe Chapter 5 Imaging in Neurological and Vascular Brain Diseases (SPECT and SPECT/CT) 54 Filipa Lucena, Eva Sousa and Tânia F. Vaz Chapter 6 Imaging in Neurological and Vascular Brain Diseases (PET/CT) 72 Ian Law, Valentina Garibotto and Marco Pagani Chapter 7 PET/CT in Radiotherapy Planning of Brain Tumours 92 Roberto Delgado-Bolton, Adriana K. Calapaquí-Terán and Javier Arbizu Chapter 8 PET/MRI for Brain Imaging 100 Peter Werner, Torsten Boehm, Solveig Tiepolt, Henryk Barthel, Karl T. Hoffmann and Osama Sabri Chapter 9 Brain Death 110 Marko Grmek Chapter 10 Health Care in Patients with Neurological Disorders 116 Claudiu Peștean Imprint 126 n accordance with the Austrian Eco-Label for printed matters.
    [Show full text]
  • Personalized Treatment of Alcohol Dependence
    Curr Psychiatry Rep DOI 10.1007/s11920-012-0296-5 SUBSTANCE USE AND RELATED DISORDERS (JR MCKAY, SECTION EDITOR) Personalized Treatment of Alcohol Dependence Henry R. Kranzler & James R. McKay # Springer Science+Business Media, LLC 2012 Abstract Pharmacogenetic and adaptive treatment approaches Ondansetron . Sertraline . Adaptive trial designs . can be used to personalize care for alcohol-dependent patients. Adaptive protocol . Stepped care . Treatment algorithm Preliminary evidence shows that variation in the gene encoding the μ-opioid receptor moderates the response to naltrexone when used to treat alcohol dependence. Studies have also shown moderating effects of variation in the gene encoding Introduction the serotonin transporter on response to serotonergic treatment of alcohol dependence. Adaptive algorithms that modify alco- Traditionally, diagnostic tests and medical treatments have hol treatment based on patients’ progress have also shown been developed and evaluated using group data, a “one-size promise. Initial response to outpatient treatment appears to be fits all” approach that leaves little room for individual variation a particularly important in the selection of optimal continuing [1]. Personalized medicine, which uses individual features to care interventions. In addition, stepped-care algorithms can diagnose and treat disease, is of growing interest, having reduce the cost and burden of treatment while maintaining good produced notable successes in oncology and cardiology [2•, outcomes. Finally, matching treatment to specific problems 3]. To date, there have been fewer advances in the personalized present at intake or that emerge during treatment can also diagnosis and treatment of addictive disorders. However, on- improve outcomes. Although all of these effects require repli- going developments in genetics and pharmacogenetics and in cation and further refinement, the future of personalized care for the use of adaptive trial designs offer great potential to extend alcohol dependence appears bright.
    [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]
  • Current Status and Growth of Nuclear Theranostics in Singapore
    Nuclear Medicine and Molecular Imaging (2019) 53:96–101 https://doi.org/10.1007/s13139-019-00580-3 PERSPECTIVE ISSN (print) 1869-3482 ISSN (online) 1869-3474 Current Status and Growth of Nuclear Theranostics in Singapore Hian Liang Huang1,2 & Aaron Kian Ti Tong1,2 & Sue Ping Thang1,2 & Sean Xuexian Yan1,2 & Winnie Wing Chuen Lam1,2 & Kelvin Siu Hoong Loke1,2 & Charlene Yu Lin Tang1 & Lenith Tai Jit Cheng1 & Gideon Su Kai Ooi1 & Han Chung Low1 & Butch Maulion Magsombol1 & Wei Ying Tham1,2 & Charles Xian Yang Goh 1,2 & Colin Jingxian Tan 1 & Yiu Ming Khor1,2 & Sumbul Zaheer1,2 & Pushan Bharadwaj1,2 & Wanying Xie1,2 & David Chee Eng Ng1,2 Received: 3 January 2019 /Revised: 13 January 2019 /Accepted: 14 January 2019 /Published online: 25 January 2019 # Korean Society of Nuclear Medicine 2019 Abstract The concept of theranostics, where individual patient-level biological information is used to choose the optimal therapy for that individual, has become more popular in the modern era of ‘personalised’ medicine. With the growth of theranostics, nuclear medicine as a specialty is uniquely poised to grow along with the ever-increasing number of concepts combining imaging and therapy. This special report summarises the status and growth of Theranostic Nuclear Medicine in Singapore. We will cover our experience with the use of radioiodine, radioiodinated metaiodobenzylguanidine, peptide receptor radionuclide therapy, prostate specific membrane antigen radioligand therapy, radium-223 and yttrium-90 selective internal radiation therapy. We also include a section on our radiopharmacy laboratory, crucial to our implementation of theranostic principles. Radionuclide theranostics has seen tremendous growth and we hope to be able to grow alongside to continue to serve the patients in Singapore and in the region.
    [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]
  • In Vivo Molecular Imaging: Ligand Development and Research Applications
    31 IN VIVO MOLECULAR IMAGING: LIGAND DEVELOPMENT AND RESEARCH APPLICATIONS MASAHIRO FUMITA AND ROBERT B. INNIS In positron emission tomography (PET) and single-photon ders must be addressed. Physical barriers include limited emission computed tomography (SPECT), tracers labeled anatomic resolution and the need for even higher sensitivity. with radioactive isotopes are used to measure protein mole- However, recent developments with improved detector cules (e.g., receptors, transporters, and enzymes). A major crystals (e.g., lutetium oxyorthosilicate) and three-dimen- advantage of these two radiotracer techniques is extraordi- sional image acquisition have markedly enhanced both sen- -M), many orders sitivity and resolution. (5). Commercially available PET de 12מto 10 9מnarily high sensitivity (ϳ 10 of magnitude greater than the sensitivities available with vices provide resolution of 2 to 2.5 mm (6,7). Furthermore, -M) or mag- the relatively high cost of imaging with SPECT, and espe 4מmagnetic resonance imaging (MRI) (ϳ 10 M). cially PET, can be partially subsidized by clinical use of the 5מto 10 3מnetic resonance spectroscopy (MRS) (ϳ 10 For example, MRI detection of gadolinium occurs at con- devices. Recent approval of U.S. government (i.e., Medi- מ centrations of approximately 10 4 M (1), and MRS mea- care) reimbursement of selected PET studies for patients sures brain levels of ␥-aminobutyric acid (GABA) and gluta- with tumors, epilepsy, and cardiac disease has significantly מ mine at concentrations of approximately 10 3 M (2,3). enhanced the sales of PET cameras and their availability for In contrast, PET studies with [11C]NNC 756 in which a partial use in research studies.
    [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]