Professor Christer Halldin
Principal Investigator, Translational Neuroimaging Platform Laboratory
- Dr Yang Changtong, PhD, Senior Research Fellow
- Dr Krishna Kanta Ghosh, PhD, Research Fellow
Professor Christer Halldin is Visiting Professor in Lee Kong Chian School of Medicine, Nanyang Technological University, Full Professor in Karolinska Institute (KI) and Director of the Karolinska Institutet PET Centre. Prof Halldin has received many Awards such as the Bengt Lundqvist’s Memorial 1984, Sederholms Stipendium 1985, Marie Curie Award 1992, Radioactivity “100 Years” 1998, Best scientific paper “Springer Verlag 1998” 1999, Marie Curie Award 2001, Marie Curie Award 2005, Marie Curie Award 2009 and Heikki Wendelin Award 2011. Prof Halldin served as the Chairman of the Committee for Drug Development, European Association of Nuclear Medicine (EANM), since 2005, KI PI for a new Innovative Medicine Initiative (IMI), 2009-2014, NEWMEDS on schizophrenia and depression, Swedish coordinator and Vice Chair for three COST (European Cooperation in Science and Technology) Action B3 (1993-1998), B12 (2000-2005) and TD1007 (2011-2115), Swedish PI for a Human Frontier Science Program Organization Grant (2000-2004), PI for a large number of industrial research contracts and Swedish PI for INMIND (Imaging of Neuroinflammation in Neurodegenerative Diseases) (2012-2016).
Prof Halldin specialised since 1977 on the development of novel PET radioligands for the central nervous system (CNS) and their applied use in translational imaging from animal to clinical use in patients. He is focused on important parameters as criteria for optimal PET radioligands such as lipophilicity, metabolism, brain penetration and etc. Prof Halldin’s expertise is in the development of receptor, transporter and enzyme PET radioligands such as for the different dopamine subtypes and transporter as well as for the serotonin receptor subtypes and for other receptors and enzyme targets as well. Besides in vivo PET, in vitro autoradiographic studies in post-mortem human brain sections have also been applied for the new radioligands developed in his lab. In view of the medical challenge Prof Halldin mainly focuses on neuropsychiatric, neurodegenerative and neuroinflammatory diseases imaging biomarkers for diseases such as Schizophrenia, Depression, Alzheimer’s disease (AD), Parkinson’s disease (PD) and a number of other psychiatric and neurological disorders. In addition he has recently been working on the development of tracers for measuring neurotransmitter release. Prof Halldin has an H-index: 66, number of publications in the Web of Science: >766, original articles 424, citation >16.434, average citation per item: 21.45.
Prof Halldin is responsible for setting up a strategic program in translational neuroimaging (TNIP) of the school. Our TNIP is a cutting edge platform from the field of radiology due to the need for better understanding of essential molecular pathways inside living beings in a non-invasive way of approach. Among all organs, mainly brain function provides a vehicle for communicating important developments in obtaining, analysing, and the study of structure-function & brain-behaviour relationships. Furthermore, the increasing variety of novel radioligands provides the technique with a wide use to label and measure biological process in vivo.
In recent years there is a renewed interest in the field of neuroimaging. We, TNIP particularly interested in developing different radioligands and imaging protocols using nuclear imaging/medicine technology to study brain function which may be translated to human beings.
Brain Imaging and PET Radioliglands
Molecular Brain imaging procedures like PET and MRI are becoming necessary to researchers studying various biochemical and biological processes. In the field of brain imaging, PET is applied to map:
- The basic biochemical features of the living brain, with an emphasis on the neurotransmitter system (the “neuroreceptor fingerprint” of the brain)
- Test and validate novel CNS drug candidate target molecules (drug development)
- Develop novel molecular imaging biomarkers in order (i) to understand the pathophysiological-pathobiochemical changes behind diseases and to test “disease models”, (ii) to visualise disease biomarkers (i.e. to have suitable molecular imaging diagnostic agents), (iii) to support the development of CNS drugs, and (iv) to provide physicians with a tool of follow disease progress and/or treatment efficacy.
So far several neuroreceptor systems have been identified as targets for the neurodegeneration and only few radioligands are in practice to identify such disease progression. Now, there is a high need to develop novel PET radioligands for all the new target proteins recently developed but also with higher sensitivity and specificity for identified neuroreceptor systems, neuroinflammation and neurodegeneration targets, and other CNS targets (autophagy proteins, metabolic enzymes, tumour markers) in order to have adequate molecular imaging biomarkers for basic neuroscience research, applied pharmacological research as well as clinical applications.
Expertise and experience
The established joint program between Karolinska and LKCMedicine at NTU made perfect a state-of-the-art neuroimaging translational PET platform. The Karolinska PET group, one of the first research PET laboratory in Europe with continuous activities since 1974, has pioneered the development of novel PET radioligands in the past and established several basic principles of the process as well as fundamental criteria to be fulfilled by useful radioligands, including high binding affinity, selectivity, suitable lipophilicity, not a substrate for PGP, favourable metabolism, reversible binding and etc.
Design and development of radiopharmaceutical targets/probes for PET need vast experience. Regarding the development of novel PET radioligands, the KI PET center has a world leading position in which approximately one third of the routinely used CNS PET radioligands worldwide have been developed by this group during the past 25 years. The group has developed and tested in non-human primates (NHP) over 200 different PET radioligands of which about 40 were considered to be that good to be injected in to human. Of these 20 have been fully validated and are routinely applied in patients around the world.
Translational Neuroimaging Platform (TNIP)
Prof Halldin is responsible for setting up a strategic program in translational neuroimaging (TNIP) of the school. Our TNIP is mainly interested in developing brain imaging protocols using nuclear medicine technology to authenticate differences in tissue metabolism, function and circulation can be discovered in patients.
In view of Singapore immediate need, we plan to develop the following in neuroimaging: (i) health care applications, in order to improve the diagnostic and therapeutic repertoire of local health care systems and to improve the life quality of an increasing number of patients; (ii) industrial applications, related to the newly presence of major pharmaceutical companies in Singapore with an eye on develop novel drugs using PET imaging and test and validate them in the uniquely multi ethnicity population of Singapore; (iii) basic research application, with special regard to the neuroscience research programs with other RIs, health care providers and Universities.
Main Objective of TNIP
Translational Neuroimaging Platform (TNIP) is to develop, set up, test and validate novel PET radioligands as early molecular imaging biomarkers primarily for early diagnosis of neurological and psychiatric diseases, with special regard to neurodegeneration and neuroinflammation (including Alzheimer’s disease), traumatic brain injury and stroke, but also for inflammatory, metabolic (diabetes) diseases and cancer diagnostic
The main objective of our platform is threefold:
- Radioligand Development
- Preclinical Molecular Imaging
- Clinical Molecular Imaging
To deliver the TNIP objectives we intend to have fully-fledged dedicated instrumentation in our facility as well as animal as human disease models along with appropriate methodological background at various “species levels” (rodents, NHPs, humans). The TNIP Laboratory has a 3 years contract with Singapore Radiopharmaceuticals (SRP) in which cyclotron and hotcells and etc. are available.
- Nag, S., G. Kettschau, T. Heinrich, A. Varrone, L. Lehmann, B. Gulyas, A. Thiele, E. Keller, and C. Halldin, Synthesis and biological evaluation of novel propargyl amines as potential fluorine-18 labeled radioligands for detection of MAO-B activity. Bioorg. Med. Chem., 2013. 21: p. 186-195.
- Schain, M., M. Toth, Z. Cselenyi, R. Arakawa, C. Halldin, L. Farde, and A. Varrone, Improved mapping and quantification of serotonin transporter availability in the human brainstem with the HRRT. Eur J Nucl Med Mol Imaging, 2013. 40: p. 228-237.
- Amini, N., R. Nakao, M. Schou, and C. Halldin, Identification of PET radiometabolites by cytochrome P450, UHPLC/Q-ToF-MS and fast radio-LC: applied to the PET radioligands [(11)C]flumazenil, and [(11)C]PBR28. Anal Bioanal Chem., 2013. 405: p. 1303-1310.
- Ikoma, Y., A. Takano, A. Varrone, and C. Halldin, Graphic plot analysis for estimating binding potential of translator protein (TSPO) in positron emission tomography studies with [(18)F]FEDAA1106. Neuroimage, 2013. 69: p. 78-86.
- Mathe, D., I. Horvath, K. Szigeti, S. Donohue, V. Pike, Z. Jia, C. Ledent, M. Palkovits, T. Freund, C. Halldin, and B. Gulyas, In vivo SPECT and ex vivo autoradiographic brain imaging of the novel selective CB(1) receptor antagonist radioligand [(125)I]SD7015 in CB(1) knock-out and wildtype mouse. Brain Res. Bull, 2013. 91: p. 46-51.
- Takano, A., C. Halldin, and L. Farde, SERT and NET occupancy by venlafaxine and milnacipran in non-human primates: a PET study. Psychopharmacology, 2013. 226: p. 147-153.
- Nakao, R. and C. Halldin, "Mixed" anionic and non-ionic micellar liquid chromotography for high-speed radiometabolite analysis of positron emission tomography radioligands. J Chromatography A, 2013. 1281: p. 54-59.
- Dahl, K., M. Schou, N. Amini, and C. Halldin, Palladium-Mediated [11C]Carbonylation at Atmospheric Pressure: A General Method Using Xantphos as Supporting Ligand. Eur J Org Chem, 2013: p. 1228-1231.
- Schou, M., K. Varnäs, A. Jucaite, B. Gulyas, C. Halldin, and L. Farde, Radiolabeling of the cannabinoid receptor agonist AZD1940 with carbon-11 and PET microdosing in non-human primate. Nucl. Med. Biol., 2013. 40: p. 410-414.
- Forsberg, A., A. Jureus, Z. Cselenyi, M. Eriksdotter, Y. Freund-Levi, F. Jeppsson, B.-M. Swahn, J. Sandell, P. Julin, M. Schou, J. Andersson, P. Johnström, K. Varnäs, C. Halldin, L. Farde, and S. Svensson, Low background and high contrast PET imaging of amyloid-b with [(11)C]AZD2995 and [(11)C]AZD2184 in Alzheimer's disease patients. Eur J Nucl Med Mol Imaging, 2013. 40: p. 580-593.