Simple and rapid preparation of [11C]DASB with high quality and reliability for routine applications.

[(11)C]DASB combines all major prerequisites for a successful SERT-ligand, providing excellent biological properties and in-vivo behaviour. Thus, we aimed to establish a fully automated procedure for the synthesis and purification of [(11)C]DASB with a high degree of reliability reducing the overall synthesis time while conserving high yields and purity. The optimized [(11)C]DASB synthesis was applied in more than 60 applications with a very low failure rate (3.2%). We obtained yields up to 8.9 GBq (average 5.3+/-1.6 GBq). Radiochemical yields based on [(11)C]CH(3)I, (corrected for decay) were 66.3+/-6.9% with a specific radioactivity (A(s)) of 86.8+/-24.3 GBq/micromol (both at the end of synthesis, EOS). Time consumption was kept to a minimum, resulting in 43 min from end of bombardment to release of the product after quality control. From our data, it is evident that the presented method can be implemented for routine preparations of [(11)C]DASB with high reliability.

[1]  Jeffrey H Meyer,et al.  Imaging the serotonin transporter during major depressive disorder and antidepressant treatment. , 2007, Journal of psychiatry & neuroscience : JPN.

[2]  Christer Halldin,et al.  A PET study on regional coexpression of 5-HT1A receptors and 5-HTT in the human brain , 2007, Psychopharmacology.

[3]  Alan A. Wilson,et al.  Imaging the serotonin transporter with positron emission tomography: initial human studies with [11C]DAPP and [11C]DASB , 2000, European Journal of Nuclear Medicine.

[4]  Sylvain Houle,et al.  Serotonin transporter occupancy of five selective serotonin reuptake inhibitors at different doses: an [11C]DASB positron emission tomography study. , 2004, The American journal of psychiatry.

[5]  Marie-José Bélanger,et al.  Biodistribution and radiation dosimetry of [11C]DASB in baboons. , 2004, Nuclear medicine and biology.

[6]  C. Nemeroff,et al.  Role of serotonin in the pathophysiology of depression: focus on the serotonin transporter. , 1994, Clinical chemistry.

[7]  Jeffrey H. Meyer,et al.  Applying Neuroimaging Ligands to Study Major Depressive Disorder Neuroimaging Contributions to Monoamine Regulation in Mdd , 2022 .

[8]  Marc Laruelle,et al.  A new positron emission tomography imaging agent for the serotonin transporter: synthesis, pharmacological characterization, and kinetic analysis of [11C]2-[2-(dimethylaminomethyl)phenylthio]-5-fluoromethylphenylamine ([11C]AFM). , 2004, Nuclear medicine and biology.

[9]  Denis Guilloteau,et al.  Carbon-11 labelling of MADAM in two different positions: a highly selective PET radioligand for the serotonin transporter , 2001 .

[10]  J. Sandell,et al.  Precursor synthesis and radiolabelling of [11C]ADAM: a potential radioligand for the serotonin transporter exploration by PET , 2001 .

[11]  F. Yasuno,et al.  Serotonin transporter binding in patients with mood disorders: a PET study with [11C](+)McN5652 , 2002, Biological Psychiatry.

[12]  R. V. Van Heertum,et al.  Metabolite considerations in the in vivo quantification of serotonin transporters using 11C-DASB and PET in humans. , 2006, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[13]  Christer Halldin,et al.  Measurement of serotonin transporter binding with PET and [11C]MADAM: A test–retest reproducibility study , 2006, Synapse.

[14]  H. Kung,et al.  New PET imaging agent for the serotonin transporter: [(18)F]ACF (2-[(2-amino-4-chloro-5-fluorophenyl)thio]-N,N-dimethyl-benzenmethanamine). , 2002, Journal of medicinal chemistry.

[15]  Sylvain Houle,et al.  Seasonal variation in human brain serotonin transporter binding. , 2008, Archives of general psychiatry.

[16]  Denis Guilloteau,et al.  Pharmacological Characterization ofN,N-Dimethyl-2-(2-amino-4-methylphenyl thio)benzylamine as a Ligand of the Serotonin Transporter with High Affinity and Selectivity , 2003, Journal of Pharmacology and Experimental Therapeutics.

[17]  Joel S Karp,et al.  N,N-dimethyl-2-(2-amino-4-(18)F-fluorophenylthio)-benzylamine (4-(18)F-ADAM): an improved PET radioligand for serotonin transporters. , 2003, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[18]  P. Larsen,et al.  Synthesis of [11C]iodomethane by iodination of [11C]methane , 1997 .

[19]  C. Halldin,et al.  Quantification of 11C-MADAM binding to the serotonin transporter in the human brain. , 2005, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[20]  H N Wagner,et al.  A PET radiotracer for studying serotonin uptake sites: carbon-11-McN-5652Z. , 1993, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[21]  Yiyun Huang,et al.  Synthesis and pharmacological characterization of a new PET ligand for the serotonin transporter: [11C]5-bromo-2-[2-(dimethylaminomethylphenylsulfanyl)]phenylamine ([11C]DAPA). , 2002, Nuclear medicine and biology.

[22]  Alan A. Wilson,et al.  Occupancy of serotonin transporters by paroxetine and citalopram during treatment of depression: a [(11)C]DASB PET imaging study. , 2001, The American journal of psychiatry.

[23]  C. Solbach,et al.  Determination of reaction parameters for the synthesis of the serotonin transporter ligand [11C]DASB: Application to a remotely controlled high yield synthesis , 2004 .

[24]  Zsolt Szabo,et al.  Positron emission tomography imaging of serotonin transporters in the human brain using [11C](+)McN5652 , 1995, Synapse.

[25]  Mark Slifstein,et al.  Comparative evaluation of serotonin transporter radioligands 11C-DASB and 11C-McN 5652 in healthy humans. , 2004, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[26]  U. Müller,et al.  Advances in in vivo imaging of serotonergic neurons in neuropsychiatric disorders , 2004, Neuroscience & Biobehavioral Reviews.

[27]  S Kasper,et al.  Influence of escitalopram treatment on 5-HT1A receptor binding in limbic regions in patients with anxiety disorders , 2009, Molecular Psychiatry.

[28]  Sylvain Houle,et al.  Brain serotonin transporter binding potential measured with carbon 11-labeled DASB positron emission tomography: effects of major depressive episodes and severity of dysfunctional attitudes. , 2004, Archives of general psychiatry.

[29]  Yiyun Huang,et al.  A PET imaging agent with fast kinetics: synthesis and in vivo evaluation of the serotonin transporter ligand [11C]2-[2-dimethylaminomethylphenylthio)]-5-fluorophenylamine ([11C]AFA). , 2004, Nuclear medicine and biology.

[30]  Alan A. Wilson,et al.  Positron Emission Tomography Quantification of [11C]-DASB Binding to the Human Serotonin Transporter: Modeling Strategies , 2001, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[31]  M. Heitkemper,et al.  Relationship of SERT Polymorphisms to Depressive and Anxiety Symptoms in Irritable Bowel Syndrome , 2007, Biological research for nursing.

[32]  C. Halldin,et al.  PET measurement of serotonin transporter occupancy: a comparison of escitalopram and citalopram. , 2007, The international journal of neuropsychopharmacology.

[33]  Zsolt Szabo,et al.  Quantitative PET Studies of the Serotonin Transporter in MDMA Users and Controls Using [11C]McN5652 and [11C]DASB , 2005, Neuropsychopharmacology.

[34]  J. Amsterdam,et al.  PET brain imaging with [11C](+)McN5652 shows increased serotonin transporter availability in major depression. , 2004, Journal of affective disorders.

[35]  Yiyun Huang,et al.  The new PET imaging agent [11C]AFE is a selective serotonin transporter ligand with fast brain uptake kinetics. , 2004, Nuclear medicine and biology.

[36]  J. Kleinman,et al.  Serotonin Uptake Sites and Serotonin Receptors Are Altered in the Limbic System of Schizophrenics , 1993, Neuropsychopharmacology.

[37]  R Todd Ogden,et al.  Lower serotonin transporter binding potential in the human brain during major depressive episodes. , 2006, The American journal of psychiatry.

[38]  Chyng-Yann Shiue,et al.  Synthesis of N,N-dimethyl-2-(2-amino-4-[18F]fluorophenylthio)benzylamine as a serotonin transporter imaging agent. , 2003, Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine.

[39]  Christer Halldin,et al.  Sex differences in the serotonin 1A receptor and serotonin transporter binding in the human brain measured by PET , 2008, NeuroImage.

[40]  Alan A. Wilson,et al.  Radiotracer synthesis from [(11)C]-iodomethane: a remarkably simple captive solvent method. , 2000, Nuclear medicine and biology.

[41]  M Slifstein,et al.  In vivo quantification of brain serotonin transporters in humans using [11C]McN 5652. , 2000, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[42]  S. Houle,et al.  Novel Radiotracers for Imaging the Serotonin Transporter by Positron Emission Tomography: Synthesis, Radiosynthesis, and in Vitro and ex Vivo Evaluation of (11)C-Labeled 2-(Phenylthio)araalkylamines. , 2000, Journal of medicinal chemistry.