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Radiolabelled Molecules for Brain Imaging with PET and SPECT • Peter Brust Radiolabelled Molecules for Brain Imaging with PET and SPECT

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Radiolabelled Molecules for Brain Imaging with PET and SPECT • Peter Brust Radiolabelled Molecules for Brain Imaging with PET and SPECT Radiolabelled Molecules for Brain Imaging with PET and SPECT Radiolabelled • Peter Brust Molecules for Brain Imaging with PET and SPECT Edited by Peter Brust Printed Edition of the Special Issue Published in Molecules www.mdpi.com/journal/molecules Radiolabelled Molecules for Brain Imaging with PET and SPECT Radiolabelled Molecules for Brain Imaging with PET and SPECT Editor Peter Brust MDPI • Basel • Beijing • Wuhan • Barcelona • Belgrade • Manchester • Tokyo • Cluj • Tianjin Editor Peter Brust Department of Neuroradiopharmaceuticals, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf Germany Editorial Office MDPI St. Alban-Anlage 66 4052 Basel, Switzerland This is a reprint of articles from the Special Issue published online in the open access journal Molecules (ISSN 1420-3049) (available at: https://www.mdpi.com/journal/molecules/special issues/PET SPECT). For citation purposes, cite each article independently as indicated on the article page online and as indicated below: LastName, A.A.; LastName, B.B.; LastName, C.C. Article Title. Journal Name Year, Article Number, Page Range. ISBN 978-3-03936-720-7 (Hbk) ISBN 978-3-03936-721-4 (PDF) c 2020 by the authors. Articles in this book are Open Access and distributed under the Creative Commons Attribution (CC BY) license, which allows users to download, copy and build upon published articles, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. The book as a whole is distributed by MDPI under the terms and conditions of the Creative Commons license CC BY-NC-ND. Contents About the Editor .............................................. vii Preface to ”Radiolabelled Molecules for Brain Imaging with PET and SPECT” ......... ix Bright Chukwunwike Uzuegbunam, Damiano Librizzi and Behrooz Hooshyar Yousefi PET Radiopharmaceuticals for Alzheimer’s Disease and Parkinson’s Disease Diagnosis, the Current and Future Landscape Reprinted from: Molecules 2020, 25, 977, doi:10.3390/molecules25040977 .............. 1 Liqun Kuang, Deyu Zhao, Jiacheng Xing, Zhongyu Chen, Fengguang Xiong and Xie Han Metabolic Brain Network Analysis of FDG-PET in Alzheimer’s Disease Using Kernel-Based Persistent Features Reprinted from: Molecules 2019, 24, 2301, doi:10.3390/molecules24122301 ............. 37 Maria Elisa Serrano, Guillaume Becker, Mohamed Ali Bahri, Alain Seret, Nathalie Mestdagh, Jo¨el Mercier, Fr´ed´eric Mievis, Fabrice Giacomelli, Christian Lemaire, Eric Salmon, Andre´ Luxen and Alain Plenevaux Evaluating the In Vivo Specificity of [18F]UCB-H for the SV2A Protein, Compared with SV2B and SV2C in Rats Using microPET Reprinted from: Molecules 2019, 24, 1705, doi:10.3390/molecules24091705 .............. 51 Cornelius K. Donat, Henrik H. Hansen, Hanne D. Hansen, Ronnie C. Mease, Andrew G. Horti, Martin G. Pomper, Elina T. L’Estrade, Matthias M. Herth, Dan Peters, Gitte M. Knudsen and Jens D. Mikkelsen In Vitro and In Vivo Characterization of Dibenzothiophene Derivatives [125I]Iodo-ASEM and [18F]ASEM as Radiotracers of Homo- and Heteromeric α7 Nicotinic Acetylcholine Receptors Reprinted from: Molecules 2020, 25, 1425, doi:10.3390/molecules25061425 ............. 63 Ping Bai, Sha Bai, Michael S. Placzek, Xiaoxia Lu, Stephanie A. Fiedler, Brenda Ntaganda, Hsiao-Ying Wey and Changning Wang A New Positron Emission Tomography Probe for Orexin Receptors Neuroimaging Reprinted from: Molecules 2020, 25, 1018, doi:10.3390/molecules25051018 .............. 83 Susann Schroder,¨ Thu Hang Lai, Magali Toussaint, Mathias Kranz, Alexandra Chovsepian, Qi Shang, Sladjana Duki´c-Stefanovi´c, Winnie Deuther-Conrad, Rodrigo Teodoro, Barbara Wenzel, Rare¸s-Petru Moldovan, Francisco Pan-Montojo and Peter Brust PET Imaging of the Adenosine A2A Receptor in the Rotenone-Based Mouse Model of Parkinson’s Disease with [18F]FESCH Synthesized by a Simplified Two-Step One-Pot Radiolabeling Strategy Reprinted from: Molecules 2020, 25, 1633, doi:10.3390/molecules25071633 .............. 93 Rien Ritawidya, Friedrich-Alexander Ludwig, Detlef Briel, Peter Brust and Matthias Scheunemann Synthesis and In Vitro Evaluation of 8-Pyridinyl-Substituted Benzo[e]imidazo[2,1-c][1,2,4]triazines as Phosphodiesterase 2A Inhibitors Reprinted from: Molecules 2019, 24, 2791, doi:10.3390/molecules24152791 .............109 v Rien Ritawidya, Barbara Wenzel, Rodrigo Teodoro, Magali Toussaint, Mathias Kranz, Winnie Deuther-Conrad, Sladjana Dukic-Stefanovic, Friedrich-Alexander Ludwig, Matthias Scheunemann and Peter Brust Radiosynthesis and Biological Investigation of a Novel Fluorine-18 Labeled Benzoimidazotriazine-Based Radioligand for the Imaging of Phosphodiesterase 2A with Positron Emission Tomography Reprinted from: Molecules 2019, 24, 4149, doi:10.3390/molecules24224149 ..............131 Paul Cumming, J´anosMarton, Tuomas O. Lilius, Dag Erlend Olberg and Axel Rominger A Survey of Molecular Imaging of Opioid Receptors Reprinted from: Molecules 2019, 24, 4190, doi:10.3390/molecules24224190 ..............149 Jan-Michael Werner, Philipp Lohmann, Gereon R. Fink, Karl-Josef Langen and Norbert Galldiks Current Landscape and Emerging Fields of PET Imaging in Patients with Brain Tumors Reprinted from: Molecules 2020, 25, 1471, doi:10.3390/molecules25061471 .............185 Lindsey R. Drake, Ansel T. Hillmer and Zhengxin Cai Approaches to PET Imaging of Glioblastoma Reprinted from: Molecules 2020, 25, 568, doi:10.3390/molecules25030568 ..............211 vi About the Editor Peter Brust Prof., Dr., is a biologist. He received his M.S. in Immunology in 1981 and his Ph.D. in Neuroscience from Leipzig University in 1986. He worked as a postdoctoral fellow at Montreal Neurological Institute and Johns Hopkins University, Baltimore, from 1990 to 1991. He joined the Research Center Rossendorf (now known as Helmholtz-Zentrum Dresden-Rossendorf, HZDR) in 1992 and headed the Department of Biochemistry. Since 2002, he has been working in Leipzig, first at the Institute of Interdisciplinary Isotope Research and, after an operational transfer in 2010, again at the HZDR, where he leads the Department of Neuroradiopharmaceuticals. His main research interest is in radiotracer development for brain imaging with positron emission tomography, including brain tumor imaging (glioblastoma, brain metastases), imaging of blood–brain barrier transport of radiopharmaceuticals, and neuroimaging of the cholinergic system, second-messenger systems, and neuromodulatory processes. He has authored around 300 peer-reviewed publications and is the owner of numerous patents. vii Preface to ”Radiolabelled Molecules for Brain Imaging with PET and SPECT” Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) are in vivo molecular imaging methods which are widely used in nuclear medicine for diagnosis and treatment follow-up of many major diseases. These methods use target-specific molecules as probes, which are labeled with radionuclides of short half-lives that are synthesized prior to the imaging studies. These probes are called radiopharmaceuticals. Their design and development is a rather interdisciplinary process covering many different disciplines of natural sciences and medicine. In addition to their diagnostic and therapeutic applications in the field of nuclear medicine, radiopharmaceuticals are powerful tools for in vivo pharmacology during the process of preclinical drug development to identify new drug targets, investigate pathophysiology, discover potential drug candidates, and evaluate the in vivo pharmacokinetics and pharmacodynamics of drugs. The use of PET and SPECT for brain imaging is of special significance since the brain controls all the body’s functions by processing information from the whole body and the outside world. It is the source of thoughts, intelligence, memory, speech, creativity, emotion, sensory functions, motion control and other important body functions. Protected by the skull and the blood–brain barrier, the brain is somehow a privileged organ with regard to nutrient supply, immune response, and accessibility for diagnostic and therapeutic measures. Invasive procedures are rather limited for the latter purposes. Therefore, noninvasive imaging with PET and SPECT has gained high importance for a great variety of brain diseases, including neurodegenerative diseases, motor dysfunctions, stroke, epilepsy, psychiatric diseases, and brain tumors. This Special Issue focuses on radiolabeled molecules that are used for these purposes, with special emphasis on neurodegenerative diseases and brain tumors. Molecular imaging of neurodegeneration has become a useful noninvasive clinical tool to early detect pathophysiological changes in the brain and is regarded to be of special importance for prognostic purposes, therapeutic decision making, and therapy follow-up. Alzheimer’s disease (AD) and Parkinson’s disease (PD) are regarded as the most common and known neurodegenerative disorders, with a growing impact especially in countries with rapidly increased life expectancies during the last decades. Misfolded proteins such as β-amyloid, τ-protein, α-synuclein together with neuronal dystrophy characterize the main pathology of these diseases. Furthermore, multiple neurotransmitter systems are affected and involved in the cellular pathology. The initial review written by Uzuegbunam, Librizzi, and Yousefi provides an overview of the currently available PET radiopharmaceuticals, examining the timeline and important moments that led to the development
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