Molecular Imaging of the CNS: Drug Actions

  • Thomas Mueggler
  • Markus Rudin


Molecular imaging approaches play an important role in experimental and clinical neuroscience. Target-specific receptor ligands for positron emission tomography (PET) have been developed for the various neurotransmitter systems and a large number of CNS receptors. The PET readouts on ligand/drug biodistribution are complemented by functional/metabolic readouts provided by PET measurements of glucose utilization and blood flow or functional MRI assessment of the hemodynamic response. The tools are extensively used to characterize brain disorders such as psychiatric disorders or neurodegenerative processes and to evaluate therapeutic interventions.


Positron Emission Tomography Single Photon Emission Compute Tomography Positron Emission Tomography Study Bipolar Affective Disorder Major Depression Disorder 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Agren H, Reibring L, Hartvig P, Tedroff J, Bjurling P, Hornfeldt K, Andersson Y, Lundqvist H, Langstrom B (1991) Low brain uptake of l-[11C]5-hydroxytryptophan in major depression: a positron emission tomography study on patients and healthy volunteers. Acta Psychiat Scand 83(6):449–455PubMedGoogle Scholar
  2. Alexoff DL, Vaska P, Marsteller D, Gerasimov T, Li J, Logan J, Fowler JS, Taintor NB, Thanos PK, Volkow ND (2003) Reproducibility of 11C-raclopride binding in the rat brain measured with the microPET R4: effects of scatter correction and tracer specific activity. J Nucl Med 44(5):815–822PubMedGoogle Scholar
  3. Attar-Lévy D, Martinot JL, Blin J, Dao-Castellana MH, Crouzel C, Mazoyer B, Poirier MF, Bourdel MC, Aymard N, Syrota A, Féline A (1999) The cortical serotonin2 receptors studied with positron-emission tomography and [18F]-setoperone during depressive illness and antidepressant treatment with clomipramine. Biol Psychiatry 45(2):180–186PubMedGoogle Scholar
  4. Baron JC, Samson Y, Comar, D, Crouzel C, Deniker P, Agid Y (1985) In vivo study of central serotoninergic receptors in man using positron tomography. Rev Neurol (Paris) 141:537–545Google Scholar
  5. Bhagwagar Z et al (2004) Persistent reduction in brain serotonin1A receptor binding in recovered depressed men measured by positron emission tomography with [11C]WAY-100635. Mol Psychiatry 9(4):386–392PubMedGoogle Scholar
  6. Blier P, de Montigny C (1999) Serotonin and drug-induced therapeutic responses in major depression, obsessive-compulsive and panic disorders. Neuropsychopharmacology 21 (2 Suppl):91S–98SPubMedGoogle Scholar
  7. Blin J, Pappata S, Kiyosawa M, Crouzel C, Baron JC (1988) [18F]setoperone: a new high-affinity ligand for positron emission tomography study of the serotonin-2 receptors in baboon brain in vivo. Eur J Pharmacol 147:73–82PubMedGoogle Scholar
  8. Bockaert J, Claeysen S, Becamel C, Dumuis A, Marin P (2006) Neuronal 5-HT metabotropic receptors: fine-tuning of their structure, signaling, and roles in synaptic modulation. Cell Tissue Res. 326:553–572PubMedGoogle Scholar
  9. Bowden C, Cheetham SC, Lowther S, Katona CL, Crompton MR, Horton RW (1997) Dopamine uptake sites, labelled with [3H]GBR12935, in brain samples from depressed suicides and controls. Eur Neuropsychopharmacol 7(4):247–252PubMedGoogle Scholar
  10. Catafau AM, Perez V, Penengo MM, Bullich S, Danús M, Puigdemont D, Pascual JC, Corripio I, Llop J, Perich J, Alvarez E (2005) SPECT of serotonin transporters using 123I-ADAM: optimal imaging time after bolus injection and long-term test-retest in healthy volunteers. J Nucl Med 46:1301–1309PubMedGoogle Scholar
  11. Chen YC, Galpern WR, Brownell AL, Matthews RT, Bogdanov M, Isacson O, Keltner JR, Beal MF, Rosen BR, Jenkins BG (1999) Detection of dopaminergic neurotransmitter activity using pharmacologic MRI: correlation with PET, microdialysis, and behavioral data. Magn Reson Med 38(3):389–398Google Scholar
  12. Cliffe IA (2000) A retrospect on the discovery of WAY-100635 and the prospect for improved 5-HT(1A) receptor PET radioligands. Nucl Med Biol 27:441–447PubMedGoogle Scholar
  13. Coenen HH, Wienhard K, Stocklin G, Laufer P, Hebold I, Pawlik G, Heiss WD (1988) PET measurement of D2 and S2 receptor binding of 3-N-[(2'-18F]fluoroethyl)spiperone in baboon brain. Eur J Nucl Med 14:80–87PubMedGoogle Scholar
  14. Davies P, Maloney A (1976) Selective loss of central cholinergic neurons in Alzheimer’s disease. Lancet 2:1403PubMedGoogle Scholar
  15. Dewey SL, MacGregor RR, Brodie JD, Bendriem B, King PT, Volkow ND, Schlyer DJ, Fowler JS, Wolf AP, Gatley SJ (1990) Mapping muscarinic receptors in human and baboon brain using [N-11C-methyl]-benztropine. Synapse 5(3):213–223PubMedGoogle Scholar
  16. Ding Y-S, Lin K-S, Logan J, Benveniste H, Carter PJ (2005) Neurochem 94:337Google Scholar
  17. Drevets WC, Frank E, Price JC, Kupfer DJ, Holt D, Greer PJ, Huang Y, Gautier C, Mathis C (1999) PET imaging of serotonin 1A receptor binding in depression. Biol Psychiatry 46(10):1375–1387PubMedGoogle Scholar
  18. Duman RS, Heninger GR, Nestler EJ (1997) A molecular and cellular theory of depression. Arch Gen Psychiatry 54:597–606PubMedGoogle Scholar
  19. Eckelman WC (2001) Radiolabeled muscarinic radioligands for in vivo studies. Nucl Med Biol 28(5):485–491PubMedGoogle Scholar
  20. Firnau G, Sood S, Chirakal R, Nahmias C, Garnett ES (1987) Cerebral metabolism of 6-[18F]fluoro-L-3,4-dihydroxyphenylalanine in the primate. J Neurochem 48(4):1077–1082PubMedGoogle Scholar
  21. Frankle WG, Slifstein M, Gunn RN, Huang Y, Hwang DR, Darr EA, Narendran R, Abi-Dargham A, Laruelle M (2006) Estimation of serotonin transporter parameters with 11C-DASB in healthy humans: reproducibility and comparison of methods. J Nucl Med 47:815–826PubMedGoogle Scholar
  22. Eckelman WC, Reba RC, Rzeszotarski WJ, Gibson RE, Hill T, Holman BL, Budinger T, Conklin JJ, Eng R, Grissom MP (1984) External imaging of cerebral muscarinic acetylcholine receptors. Science 223(4633):291–293PubMedGoogle Scholar
  23. Frey KA, Koeppe RA, Mulholland GK, Jewett D, Hichwa R, Ehrenkaufer RLE, Carey JE, Wieland DM, Kuhl DE, Agranoff BW (1992) In vivo muscarinic cholinergic receptor imaging in human brain with [11C]scopolamine and positron emission tomography. J Cereb Blood Flow Metab 12:147–154PubMedGoogle Scholar
  24. Fuller RW, Wong DT (1990) Serotonin uptake and serotonin uptake inhibition. Ann N Y Acad Sci 600:68–78; discussion 9–80Google Scholar
  25. Furumoto S, Okamura N, Iwata R Yanai K, Arai H, Kudo Y (2007) Recent advances in the development of amyloid imaging agents. Curr Top Med Chem 7:1773–1789Google Scholar
  26. Gershon AA, Vishne T, Grunhaus L (2007) Dopamine D2-like receptors and the antidepressant response. Biol Psychiatry 61(2):145–153PubMedGoogle Scholar
  27. Glenner GG and Wong CW (1984) Alzheimer’s disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun 120:885PubMedGoogle Scholar
  28. Goetz CG (2006) What’s new? Clinical progression and staging of Parkinson’s disease. J Neural Transm Suppl 70:305–308PubMedGoogle Scholar
  29. Goswami R, Ponde DE, Kung MP, Hou C, Kilbourn MR, Kung HF (2006) Fluoroalkyl derivatives of dihydrotetrabenazine as positron emission tomography imaging agents targeting vesicular monoamine transporters. Nucl Med Biol 33(6):685–694PubMedGoogle Scholar
  30. Gupta S, Nihalani N, Masand P (2007) Duloxetine: review of its pharmacology, and therapeutic use in depression and other psychiatric disorders. Ann Clin Psychiatry 19(2):125–132PubMedGoogle Scholar
  31. Hall H, Lundkvist C, Halldin C, Farde L, Pike VW, McCarron JA, Fletcher A, Cliffe IA, Barf T, Wikström H, Sedvall G (1997) Autoradiographic localization of 5-HT1A receptors in the post-mortem human brain using [3H]WAY-100635 and [11C]way-100635. Brain Res 745:96–108PubMedGoogle Scholar
  32. Halldin C, Foged C, Chou YH, Karlsson P, Swahn CG, Sandell J, Sedvall G, Farde L (1998) Carbon-11-NNC 112: a radioligand for PET examination of striatal and neocortical D1-dopamine receptors. J Nucl Med 39:2061–2068PubMedGoogle Scholar
  33. Halldin C, Lundberg J, Sovago J, Gulyás B, Guilloteau D, Vercouillie J, Emond P, Chalon S, Tarkiainen J, Hiltunen J, Farde L (2005) [(11)C]MADAM, a new serotonin transporter radioligand characterized in the monkey brain by PET. Synapse 58:173–183PubMedGoogle Scholar
  34. Hardy J, Selkoe DJ (2002) The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science 297:353PubMedGoogle Scholar
  35. Hirvonen J, Aalto S, Lumme V, Någren K, Kajander J, Vilkman H, Hagelberg N, Oikonen V, Hietala J (2003) Measurement of striatal and thalamic dopamine D2 receptor binding with 11C-raclopride. Nucl Med Commun 24(12):1207–1214PubMedGoogle Scholar
  36. Hirvonen J, Karlsson H, Kajander J, Markkula J, Rasi-Hakala H, Någren K, Salminen JK, Hietala J (2008) Striatal dopamine D2 receptors in medication-naive patients with major depressive disorder as assessed with [11C]raclopride PET. Psychopharmacology (Berl) 197(4):581–590Google Scholar
  37. Horti AG, Chefer SI, Mukhin AG, Koren AO, Gundisch D, Links JM, Kurian V, Dannals RF, London ED (2000) 6-[18F]fluoro-A-85380, a novel radioligand for in vivo imaging of central nicotinic acetylcholine receptors. Life Sci 67(4):463–469PubMedGoogle Scholar
  38. Houle S, Ginovart N, Hussey D, Eyer JH, Wilson AA (2000) Imaging the serotonin transporter with positron emission tomography: initial human studies with [11C]DAPP and [11C]DASB. Eur J Nucl Med 27:1719–1722PubMedGoogle Scholar
  39. Hume SP, Opacka-Juffry J, Myers R et al (1995) Effect of l-dopa and 6-hydroxydopamine lesioning on [11C]raclopride binding in rat striatum, quantified using PET. Synapse 21:45–53PubMedGoogle Scholar
  40. Jenkins BG, Chen YI, Mandeville JB (2003) Pharmacologic magnetic resonance imaging (phmri). Biomedical imaging in experimental neuroscience. Van Bruggen N, Roberts TR, Boca Raton FL, CRC press 155–210Google Scholar
  41. Jones HM, Pilowsky LS (2002) Dopamine and antipsychotic drug action revisited. Br J Psychiatry 181:271–275PubMedGoogle Scholar
  42. Kalia M (2005) Neurobiological basis of depression: an update. Metabolism 54 (5 Suppl 1):24–27PubMedGoogle Scholar
  43. Kanegawa N, Kiyono Y, Kimura H, Sugita T, Kajiyama S, Kawashima H, Ueda M, Kuge Y, Saji H (2006) Synthesis and evaluation of radioiodinated (S,S)-2-(alpha-(2-iodophenoxy)benzyl)morpholine for imaging brain norepinephrine transporter. Eur J Nucl Med Mol Imaging 33:639PubMedGoogle Scholar
  44. Kauppinen TA, Bergström KA, Heikman P, Hiltunen J, Ahonen AK (2003) Biodistribution and radiation dosimetry of [123I]ADAM in healthy human subjects: preliminary results. Eur J Nucl Med Mol Imaging 30(1):132–136PubMedGoogle Scholar
  45. Kent JM, Mathew SJ, Gorman JM (2002) Molecular targets in the treatment of anxiety. Biol Psychiatry 52(10):1008–1030PubMedGoogle Scholar
  46. Kiesewetter DO, Lee J, Lang L, Park SG, Paik CH, Eckelman WC (1995) Preparation of 18F-labeled muscarinic agonist with M2 selectivity. J Med Chem 38:5–8PubMedGoogle Scholar
  47. Kim JS, Ichise M, Sangare J, Innis RB (2006) PET imaging of serotonin transporters with [11C]DASB: test-retest reproducibility using a multilinear reference tissue parametric imaging method. J Nucl Med 47:208–214PubMedGoogle Scholar
  48. Klunk WE, Engler H, Nordberg A et al. (2004) Imaging brain amyroid in the Alzheimer’s discase with pittsburgh compound-B. Ann Neurol 55:306–319PubMedGoogle Scholar
  49. Koeppe RA, Frey KA, Snyder SE, Meyer P, Kilbourn MR, Kuhl DE (1999) Kinetic modeling of N-[11C]methylpiperidin-4-yl propionate: alternatives for analysis of an irreversible positron emission tomography trace for measurement of acetylcholinesterase activity in human brain. J Cereb Blood Flow Metab 19(10):1150–1163PubMedGoogle Scholar
  50. Konradi C, Heckers S (2003) Molecular aspects of glutamate dysregulation: implications for schizophrenia and its treatment. Pharmacol Therapeut 97(2):153–179Google Scholar
  51. Kudo Y (2006) Development of amyloid imaging PET probes for an early diagnosis of Alzheimer’s disease. Minim Invasive Ther Allied Technol 15(4):209–213PubMedGoogle Scholar
  52. Kuhl DE, Koeppe RA, Fessler JA, Minoshima S, Ackermann RJ, Carey JE, Gildersleeve DL, Frey KA, Wieland DM (1994) In vivo mapping of cholinergic neurons in the human brain using SPECT and IBVM. J Nucl Med 35(3):405–410PubMedGoogle Scholar
  53. Kung M-P, Choi S-R, Hou C, Zhuang Z-P, Foulon C, Kung HF (2004) Selective binding of 2-[125I]iodo-nisoxetine to norepinephrine transporters in the brain. Nucl Med Biol 31:533–541PubMedGoogle Scholar
  54. Kumar JS, Prabhakaran J, Majo VJ, Milak MS, Hsiung SC, Tamir H, Simpson NR, Van Heertum RL, Mann JJ, Parsey RV (2007) Synthesis and in vivo evaluation of a novel 5-HT1A receptor agonist radioligand [O-methyl-11C]2-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl)-4-methyl-1,2,4-triazine-3,5(2H,4H)dione in nonhuman primates. Eur J Nucl Med Mol Imaging 34:1050–1060PubMedGoogle Scholar
  55. Kuroda Y, Motohashi N, Ito H, Ito S, Takano A, Nishikawa T, Suhara T (2006) Effects of repetitive transcranial magnetic stimulation on [11C]raclopride binding and cognitive function in patients with depression. J Affect Disord 95(1–3):35–42PubMedGoogle Scholar
  56. Lahti AC, Weiler MA, Tamara Michaelidis BA, Parwani A, Tamminga CA (2001) Effects of ketamine in normal and schizophrenic volunteers. Neuropsychopharmacology 25(4):455–467PubMedGoogle Scholar
  57. Lang L, Jagoda E, Ma Y, Sassaman MB, Eckelman WC (2006) Synthesis and in vivo biodistribution of F-18 labeled 3-cis-, 3-trans-, 4-cis-, and 4-trans-fluorocyclohexane derivatives of WAY 100635. Bioorg Med Chem 14(11):3737–3748PubMedGoogle Scholar
  58. Larsen AK, Brennum LT, Egebjerg J, Sánchez C, Halldin C, Andersen PH (2004) Selectivity of (3)H-MADAM binding to 5-hydroxytryptamine transporters in vitro and in vivo in mice; correlation with behavioural effects. Br J Pharmacol 141:1015–1023PubMedGoogle Scholar
  59. Laruelle M (2000) Imaging synaptic neurotransmission with in vivo binding competition techniques: a critical review. J Cereb Blood Flow Metab 20(3):423–451PubMedGoogle Scholar
  60. Lemaire C, Cantineau R, Guillaume M, Plenevaux A, Christiaens L (1991) Fluorine-18-altanserin: a radioligand for the study of serotonin receptors with PET: radiolabeling and in vivo biologic behavior in rats. J Nucl Med 32:2266–2272PubMedGoogle Scholar
  61. Liang Q, Satyamurthy N, Barrio JR, Toyokuni T, Phelps MP, Gambhir SS, Herschman HR (2001) Noninvasive, quantitative imaging in living animals of a mutant dopamine D2 receptor reporter gene in which ligand binding is uncoupled from signal transduction. Gene Ther 8(19):1490–1498PubMedGoogle Scholar
  62. Lundberg J, Halldin C, Farde L (2006) Measurement of serotonin transporter binding with PET and [11C]MADAM: a test-retest reproducibility study. Synapse 60:256–263PubMedGoogle Scholar
  63. Lundkvist C, Halldin C, Ginovart N, Nyberg S, Swahn CG, Carr AA, Brunner F, Farde L (1996) [11C]MDL 100907, a radioligland for selective imaging of 5-HT(2A) receptors with positron emission tomography. Life Sci. 58:PL 187–192Google Scholar
  64. Maelicke A, Albuquerque EX (2000) Allosteric modulation of nicotinic acetylcholine receptors as a treatment strategy for Alzheimer’s disease. Eur J Pharmacol 393(1-3):165–170PubMedGoogle Scholar
  65. Maletic V, Robinson M, Oakes T, Iyengar S, Ball SG, Russell J (2007) Neurobiology of depression: an integrated view of key findings. Int J Clin Pract 61(12):2030–2040PubMedGoogle Scholar
  66. Mattson MP (2004) Pathways towards and away from Alzheimer’s disease. Nature 430:631–639PubMedGoogle Scholar
  67. Mayberg HS (1997) Limbic-cortical dysregulation: a proposed model of depression. J Neuropsychiatry Clin Neurosci 9(3):471–481PubMedGoogle Scholar
  68. Mazière B, Coenen HH, Halldin C, Någren K, Pike VW (1992) PET radioligands for dopamine receptors and re-uptake sites: chemistry and biochemistry. Int J Rad Appl Instrum B 19(4):497–512PubMedGoogle Scholar
  69. Meltzer CC et al (2004) Serotonin 1A receptor binding and treatment response in late-life depression. Neuropsychopharmacology 29(12):2258–2265PubMedGoogle Scholar
  70. Meyer JH (2007) Imaging the serotonin transporter during major depressive disorder and antidepressant treatment. J Psychiatry Neurosci 32(2):86–102PubMedGoogle Scholar
  71. Meyer JH, McNeely HE, Sagrati S, Boovariwala A, Martin K, Verhoeff NP, Wilson AA, Houle S (2006) Elevated putamen D(2) receptor binding potential in major depression with motor retardation: an [11C]raclopride positron emission tomography study. Am J Psychiatry 163(9):1594–1602PubMedGoogle Scholar
  72. Meyer JH, Wilson AA, Ginovart N, Goulding V, Hussey D, Hood K, Houle S (2001) Occupancy of serotonin transporters by paroxetine and citalopram during treatment of depression: a [(11)C]DASB PET imaging study. Am J Psychiatry 158(11):1843–1849PubMedGoogle Scholar
  73. Minoshima S, Giordani B, Berent S, Frey KA, Foster NL, Kuhl DE (1997) Metabolic reduction in the posterior cingulate cortex in very early Alzheimer’s disease. Ann Neurol 42(1):85–94PubMedGoogle Scholar
  74. Mischoulon D, Dougherty DD, Bottonari KA Gresham RL, Sonawalla SB, Fischman AJ, Fava M (2002) An open pilot study of nefazodone in depression with anger attacks: relationship between clinical response and receptor binding. Psychiatry Res 116:151–161PubMedGoogle Scholar
  75. Moeller O, Norra C, Grunder G (2006) Monoaminergic function in major depression. A possibly helpful tool for choosing treatment strategy. Nervenarzt 77:800–808Google Scholar
  76. Montgomery AJ, Stokes P, Kitamura Y, Grasby PM (2007) Extrastriatal D2 and striatal D2 receptors in depressive illness: pilot PET studies using [11C]FLB 457 and [11C]raclopride. J Affect Disord. 101(1–3):113–122PubMedGoogle Scholar
  77. Moresco RM, Matarrese M, Fazio F (2006) PET and SPET molecular imaging: focus on serotonin system. Curr Top Med Chem 6:2027–2034PubMedGoogle Scholar
  78. Moses-Kolko EL, Price JC, Thase ME, Meltzer CC, Kupfer DJ, Mathis CA et al (2007) Measurement of 5-HT(1A) receptor binding in depressed adults before and after antidepressant drug treatment using positron emission tomography and [11C]WAY-100635. Synapse 61(7):523–530PubMedGoogle Scholar
  79. Muller-Gartner HW, Wilson AA, Dannals RF, Wagner HN Jr, Frost JJ (1992) Imaging muscarinic cholinergic receptors in human brain in vivo with Spect, [123I]4-iododexetimide, and [123I]4-iodolevetimide. J Cereb Blood Flow Metab 12(4):562–570PubMedGoogle Scholar
  80. Näslund J, Haroutunian V, Mohs R, Davis KL, Davies P, Greengard P, Buxbaum JD (2000) Correlation between levels of amyloid beta-peptide in the brain and cognitive decline. J Am Med Assoc 283:1571–1577Google Scholar
  81. Nestler EJ and Carlezon WA (2006) The mesolimbic dopamine reward circuit in depression. Biol Psychiatry 5 (12):1151–1159Google Scholar
  82. Nordberg A, Appel SH, Gottfries CG, Mesulam MM (1990) Future prospects of research on central cholinergic mechanisms. Prog Brain Res 84:415–418PubMedGoogle Scholar
  83. Nordberg A, Lundqvist H, Hartvig P, Lilja A, Langstrom B (1995) Kinetic analysis of regional (S)(-)[11]C-nicotine binding in normal and Alzheimer brains–in vivo assessment using positron emission tomography. Alzheimer Dis Assoc Disord 9(1):21–27PubMedGoogle Scholar
  84. Nordberg A, Lundqvist H, Hartvig P, Andersson J, Johansson M, Hellström-Lindahi E, Långström B (1997) Imaging of nicotinic and muscarinic receptors in Alzheimer’s disease: effect of tacrine treatment. Dement Geriatr Cogn Disord 8(2):78–84PubMedGoogle Scholar
  85. Nordberg A (2004) PET imaging of amyloid in Alzheimer’s disease. Lancet Neurol 3:19–27Google Scholar
  86. Nutt DJ (2008) Relationship of neurotransmitters to the symptoms of major depressive disorder. J Clin Psychiatry 69(Suppl E1):4–7Google Scholar
  87. Ogawa S, Tank DW, Menon R, Ellermann JM, Kim SG, Merkle H, Ugurbil K (1992) Intrinsic signal changes accompanying sensory stimulation: functional brain mapping with magnetic resonance imaging. Proc Natl Acad Sci USA 89:5 951–5955Google Scholar
  88. Ogawa O, Umegaki H, Ishiwata K, Asai Y, Ikari H, Oda K, Toyama H, Ingram DK, Roth GS, Iguchi A, Senda M (2000) In vivo imaging of adenovirus-mediated over-expression of dopamine D2 receptors in rat striatum by positron emission tomography. Neuroreport 11(4):743–748PubMedGoogle Scholar
  89. Opacka-Juffry J, Ashworth S, Ahier RG, Hume SP (1998) Modulatory effects of L-DOPA on D2 dopamine receptors in rat striatum, measured using in vivo microdialysis and PET. J Neural Transm 105:349–364PubMedGoogle Scholar
  90. Parsey RV, Oquendo MA, Zea-Ponce Y, Rodenhiser J, Kegeles LS, Pratap M, Cooper TB, Van Heertum R, Mann JJ, Laruelle M (2001) Dopamine D(2) receptor availability and amphetamine-induced dopamine release in unipolar depression. Biol Psychiatry 50(5):313–322PubMedGoogle Scholar
  91. Peremans K, Audenaert K, Coopman F, Jacobs F, Dumont F, Slegers G, Verschooten F, van Bree H, Mertens J, Dierckx R (2003) Regional binding index of the radiolabeled selective 5-HT2A antagonist 123I-5-I-R91150 in the normal canine brain imaged with single photon emission computed tomography. Vet Radiol Ultrasound 44:344–351PubMedGoogle Scholar
  92. Pettibone DJ, Pflueger AB, Totaro JA (1984) Tetrabenazine-induced depletion of brain monoamines: mechanism by which desmethylimipramine protects cortical norepinephrine. Eur J Pharmacol 102(3-4):431–436PubMedGoogle Scholar
  93. Phelps ME, Huang SC, Hoffman EJ, Selin C, Sokoloff L, Kuhl DE (1979) Tomographic measurement of local cerebral glucose metabolic rate in humans with (F-18)2-fluoro-2-deoxy-D-glucose: validation of method. Ann Neurol. 6:371–388PubMedGoogle Scholar
  94. Pike VW, Halldin C, McCarron JA, Lundkvist C, Hirani E, Olsson H, Hume SP, Karlsson P, Osman S, Swahn CG, Hall H, Wikström H, Mensonidas M, Poole KG, Farde L (1998) [carbonyl-11C]Desmethyl-WAY-100635 (DWAY) is a potent and selective radioligand for central 5-HT1A receptors in vitro and in vivo. Eur J Nucl Med. 25(4):338–346PubMedGoogle Scholar
  95. Pike VW, Halldin C, Wikstrom H et al (2000) Radioligands for the study of brain 5-HT(1A) receptors in vivo-development of some new analogues of way. Nucl Med Biol 27:449–455PubMedGoogle Scholar
  96. Pappata S, Tavitian B, Traykov L, Jobert A, Dalger A, Mangin JF, Crouzel C, DiGiamberardino L (1996) In vivo imaging of human cerebral acetylcholinesterase. J Neurochem 67(2):876–879PubMedGoogle Scholar
  97. Podruchny TA, Connolly C, Bokde A, Herscovitch P, Eckelman WC, Kiesewetter DO, Sunderland T, Carson RE, Cohen RM (2003) In vivo muscarinic 2 receptor imaging in cognitively normal young and older volunteers. Synapse 48(1):39–44PubMedGoogle Scholar
  98. Ressler KJ, Nemeroff CB (2000) Role of serotonergic and noradrenergic systems in the pathophysiology of depression and anxiety disorders. Dep Anx 12(Suppl 1):2–19Google Scholar
  99. Sandell J, Halldin C, Chou Y-H, Swahn C-G, Thorberg S-O, Farde L (2002) PET-examination and metabolite evaluation in monkey of [(11)C]NAD-299, a radioligand for visualisation of the 5-HT(1A) receptor. Nucl Med Biol 29:39–45PubMedGoogle Scholar
  100. Sargent PA, Kjaer KH, Bench CJ, Rabiner EA, Messa C, Meyer J, Gunn RN, Grasby PM, Cowen PJ (2000) Brain serotonin 1A receptor binding measured by positron emission tomography with [11C] way-100635. Effects of depression and antidepressant treatment. Arch Gen Psychiatry 57:174–180PubMedGoogle Scholar
  101. Schoenheit B, Zarski R, Ohm T (2004) Spatial and temporal relationship between plaques and tanges in Alzheimer-pathology. Neurobiol Aging 25:697–711Google Scholar
  102. Schou M, Halldin C, Sovago J, Pike VW, Gulyas B, Mozley PD, Johnson DP, Hall H, Innis RB, Farde L (2003) Specific in vivo binding to the norepinephrine transporter demonstrated with the PET radioligand, (S,S)-[11C]MeNER. Nucl Med Biol 30:707–714PubMedGoogle Scholar
  103. Shiue CY, Shiue GG, Mozley PD, Kung MP, Zhuang ZP, Kim HJ, Kung HF (1997) P-[18F]-MPPF: a potential radioligand for PET studies of 5-HT1A receptors in humans. Synapse 25:147–154PubMedGoogle Scholar
  104. Shoghi-Jadid K, Small GW, Agdeppa ED, Kepe V, Ercoli LM, Siddarth P, Read S, Satyamurthy N, Petric A, Huang SC, Barrio JR (2002) Localization of neurofibrillary tangles and beta-amyloid plaques in the brains of living patients with Alzheimer disease. Am J Geriatr Psychiatry 10:24–35PubMedGoogle Scholar
  105. Selkoe DJ (2002) Alzheimer’s disease is a synaptic failure. Science 298:789–791PubMedGoogle Scholar
  106. Seneca N, Gulyas B, Varrone A, Schou M, Airaksinen A, Tauscher J et al (2006) Atomoxetine occupies the norepinephrine transporter in a dose-dependent fashion: a PET study in nonhuman primate brain using (S,S)-[18F]FMeNER-D2. Psychopharmacol (Berl) 188:119–127Google Scholar
  107. Soloff PH, Price JC, Meltzer CC, Fabio A, Frank GK, Kaye WH (2007) 5HT2A receptor binding is increased in borderline personality disorder. Biol Psychiatry 62:580–587PubMedGoogle Scholar
  108. Suhara T, Inoue O, Kobayashi K, Suzuki K, Tateno Y (1993) Age-related changes in human muscarinic acetylcholine receptors measured by positron emission tomography. Neurosci Lett 149(2):225–228PubMedGoogle Scholar
  109. Suhara T, Takano A, Sudo Y, Ichimiya T, Inoue M, Yasuno F, Ikoma Y, Okubo Y (2003) High levels of serotonin transporter occupancy with low-dose clomipramine in comparative occupancy study with fluvoxamine using positron emission tomography. Arch Gen Psychiatry 60(4):386–391PubMedGoogle Scholar
  110. Talvik M, Nordström AL, Okubo Y, Olsson H, Borg J, Halldin C, Farde L (2006) Dopamine D2 receptor binding in drug-naïve patients with schizophrenia examined with raclopride-C11 and positron emission tomography. Psychiatry Res 148(2–3):165–173PubMedGoogle Scholar
  111. Tamagnan GD, Brenner E, Alagille D, Staley JK, Haile C, Koren A, Early M, Baldwin RM, Tarazi FI, Baldessarini RJ, Jarkas N, Goodman MM, Seibyl JP (2007) Development of SPECT imaging agents for the norepinephrine transporters: [123I]INER. Bioorg Med Chem Lett 17:533–537PubMedGoogle Scholar
  112. Tauscher J, Bagby RM, Javanmard M, Christensen BK, Kasper S, Kapur S (2001) Inverse relationship between serotonin 5-HT(1A) receptor binding and anxiety: a [(11)C]WAY-100635 PET investigation in healthy volunteers. Am J Psychiatry 158(8):1326–1328PubMedGoogle Scholar
  113. Thanos PK, Taintor NB, Alexoff DL et al (2002) In vivo comparative imaging of dopamine D2 knockout and wild-type mice with 11C-raclopride and microPET. J Nucl Med 43:1570–1577PubMedGoogle Scholar
  114. Verhoeff NP (1999) Radiotracer imaging of dopaminergic transmission in neuropsychiatric disorders. Psychopharmacology 147:217–249PubMedGoogle Scholar
  115. Verhoeff NP, Wilson AA, Takeshita S, Trop L, Hussey D, Singh K, Kung HF, Kung MP, Houle S (2004) In-vivo imaging of Alzheimer disease beta-amyloid with [11C]SB-13 PET. Am J Geriatr Psychiatry 12:584–595PubMedGoogle Scholar
  116. Vermetten E, Bremner JD (2002a) Circuits and systems in stress. I. Preclinical studies. Dep Anx 15(3):126–147Google Scholar
  117. Vermetten E, Bremner JD (2002b) Circuits and systems in stress. II. Applications to neurobiology and treatment in posttraumatic stress disorder. Dep Anx 16(1):14–38Google Scholar
  118. Voineskos AN, Wilson AA, Boovariwala A, Sagrati S, Houle S, Rusjan P, Sokolov S, Spencer EP, Ginovart N, Meyer JH (2007) Serotonin transporter occupancy of high-dose selective serotonin reuptake inhibitors during major depressive disorder measured with [11C]DASB positron emission tomography. Psychopharmacology (Berl) 193(4):539–545Google Scholar
  119. Whitehouse P, Price D, Clark A et al (1981) Alzheimer disease: evidence for selective loss of cholinergic neurons in the nucleus basalis. Ann Neurol 10:122–126PubMedGoogle Scholar
  120. Willeit M, Ginovart N, Kapur S, Houle S, Hussey D, Seeman P, Wilson AA (2006) High-affinity states of human brain dopamine D2/3 receptors imaged by the agonist [11C]-(+)-PHNO. Biol Psychiatry 59(5):389–394PubMedGoogle Scholar
  121. Wilson AA, Ginovart N, Hussey D, Meyer J, Houle S (2002) In vitro and in vivo characterisation of [11C]-DASB: a probe for in vivo measurements of the serotonin transporter by positron emission tomography. Nucl Med Biol 29:509–515PubMedGoogle Scholar
  122. Zeng F, Jarkas N, Stehouwer JS, Voll RJ, Owens MJ, Kilts CD, Nemeroff CB, Goodman MM (2008) Synthesis, in vitro characterization, and radiolabeling of reboxetine analogs as potential PET radioligands for imaging the norepinephrine transporter. Bioorg Med Chem 16(2):783–793PubMedGoogle Scholar
  123. Zhang Z, Andersen A, Grondin R, Barber T, Avison R, Gerhardt G, Gash D (2001) Pharmacological MRI mapping of age-associated changes in basal ganglia circuitry of awake rhesus monkeys. Neuroimage 14(5):1159–1167PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Institute for Biomedical EngineeringUniversity and ETH ZürichZürichSwitzerland

Personalised recommendations