Measuring serotonin synthesis: From conventional methods to PET tracers and their (pre)clinical implications

European Journal of Nuclear Medicine and Molecular Imaging

Volumn 38, Issue 3, 2011, Pages 576-591

  Visser, Anniek K D ^a   Van Waarde, Aren ^a   Willemsen, Antoon T M ^a   Bosker, Fokko J ^a   Luiten, Paul G M ^b   Den Boer, Johan A ^a   Kema, Ido P ^a   Dierckx, Rudi A J O ^a,c  

^a UNIVERSITY MEDICAL CENTER GRONINGEN   (Netherlands)

^b UNIVERSITY OF GRONINGEN   (Netherlands)

^c GHENT UNIVERSITY HOSPITAL   (Belgium)

Author keywords

11C AMT; 11C 5 HTP; Depression; Positron Emission Tomography; Serotonin

Indexed keywords

1 (3 TRIFLUOROMETHYLPHENYL)PIPERAZINE; 3 (1,2,5,6 TETRAHYDRO 4 PYRIDYL)PYRROLO[3,2 B]PYRIDIN 5 ONE; 3 (3 DIMETHYLAMINOPROPYL) 3 (3 METHOXYPHENYL) 4,4 DIMETHYL 2,6 PIPERIDINEDIONE; 3 HYDROXYBENZYLHYDRAZINE; 4 (4 METHYL 1 PIPERAZINYL) 7 TRIFLUOROMETHYLPYRROLO[1,2 A]QUINOXALINE; 5 HYDROXYTRYPTOPHAN C 11; ALPHA METHYLTRYPTOPHAN C 11; ANTIDEPRESSANT AGENT; BUSPIRONE; CITALOPRAM; FENCLONINE; KYNURENINE; RADIOPHARMACEUTICAL AGENT; SEROTONIN; TRACER; UNCLASSIFIED DRUG;

BLOOD BRAIN BARRIER; CEREBROSPINAL FLUID; DEPRESSION; DRUG MECHANISM; HUMAN; ISOTOPE LABELING; NEUROTRANSMISSION; NONHUMAN; POSITRON EMISSION TOMOGRAPHY; REVIEW; SEROTONINERGIC SYSTEM; THROMBOCYTE;

ANIMALS; BLOOD PLATELETS; HUMANS; POSITRON-EMISSION TOMOGRAPHY; RADIOACTIVE TRACERS; RADIOPHARMACEUTICALS; SEROTONIN;

EID: 79953744705     PISSN: 16197070     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00259-010-1663-2     Document Type: Review

References (112)

1. Barnes NM, Sharp T. A review of central 5-HT receptors and their function. Neuropharmacology 1999;38(8):1083-152. (Pubitemid 29292403)
2. Fink KB, Göthert M. 5-HT receptor regulation of neurotransmitter release. Pharmacol Rev 2007;59(4):360-417.
3. Richardson-Jones JW, Craige CP, Guiard BP, Stephen A, Metzger KL, Kung HF, et al. 5-HT1A autoreceptor levels determine vulnerability to stress and response to antidepressants. Neuron 2010;65(1):40-52.
4. Dantzer R, O'Connor JC, Freund GG, Johnson RW, Kelley KW. From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci 2008;9 (1):46-56. (Pubitemid 350295688)
5. Bjurling P, Watanabe Y, Tokushige M, Oda T, Långström B. Syntheses of β-11C-labelled L-tryptophan and 5-hydroxy-Ltryptophan using a multi-enzymatic reaction route. J Chem Soc Perkin Trans 1989;1(7):1331-4.
6. Blin J, Pappata S, Kiyosawa M, Crouzel C, Baron JC. [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 1988;147(1):73-82. (Pubitemid 18058727)
7. Diksic M, Nagahiro S, Sourkes TL, Yamamoto YL. A new method to measure brain serotonin synthesis in vivo. I. Theory and basic data for a biological model. J Cereb Blood Flow Metab 1990;10(1):1-12. (Pubitemid 20035849)
8. Gallezot JD, Nabulsi N, Neumeister A, Planeta-Wilson B, Williams WA, Singhal T, et al. Kinetic modeling of the serotonin 5-HT(1B) receptor radioligand [(11)C]P943 in humans. J Cereb Blood Flow Metab 2010;30(1):196-210.
9. Halldin C, Lundberg J, Sóvágó J, Gulyás B, Guilloteau D, Vercouillie J, et al. [(11)C]MADAM, a new serotonin transporter radioligand characterized in the monkey brain by PET. Synapse 2005;58(3):173-83. (Pubitemid 41443737)
10. Herth MM, Piel M, Debus F, Schmitt U, Lüddens H, Rösch F. Preliminary in vivo and ex vivo evaluation of the 5-HT2A imaging probe [(18)F]MH.MZ. Nucl Med Biol 2009;36(4):447-54.
11. Houle S, Ginovart N, Hussey D, Meyer JH, Wilson AA. Imaging the serotonin transporter with positron emission tomography: initial human studies with [11C]DAPP and [11C]DASB. Eur J Nucl Med 2000;27(11):1719-22.
12. Kumar JS, Prabhakaran J, Majo VJ, Milak MS, Hsiung SC, Tamir H, et al. 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 2007;34(7):1050-60. (Pubitemid 46919551)
13. Lang L, Jagoda E, Schmall B, Vuong BK, Adams HR, Nelson DL, et al. Development of fluorine-18-labeled 5-HT1A antagonists. J Med Chem 1999;42(9):1576-86.
14. Lemaire C, Cantineau R, Guillaume M, Plenevaux A, Christiaens L. Fluorine-18-altanserin: a radioligand for the study of serotonin receptors with PET: radiolabeling and in vivo biologic behavior in rats. J Nucl Med 1991;32(12):2266-72.
15. Lundkvist C, Halldin C, Ginovart N, Nyberg S, Swahn CG, Carr AA, et al. [11C]MDL 100907, a radioligland for selective imaging of 5-HT(2A) receptors with positron emission tomography. Life Sci 1996;58(10):PL 187-92.
16. Ma KH, Huang WS, Kuo YY, Peng CJ, Liou NH, Liu RS, et al. Validation of 4-[18F]-ADAM as a SERT imaging agent using micro-PET and autoradiography. Neuroimage 2009;45(3):687-93.
17. Marner L, Gillings N, Comley RA, Baaré WF, Rabiner EA, Wilson AA, et al. Kinetic modeling of 11C-SB207145 binding to 5-HT4 receptors in the human brain in vivo. J Nucl Med 2009;50 (6):900-8.
18. Pierson ME, Andersson J, Nyberg S, McCarthy DJ, Finnema SJ, Varnäs K, et al. [11C]AZ10419369: a selective 5-HT1B receptor radioligand suitable for positron emission tomography (PET). Characterization in the primate brain. Neuroimage 2008;41 (3):1075-85.
19. Pike VW, McCarron JA, Lammertsma AA, Osman S, Hume SP, Sargent PA, et al. Exquisite delineation of 5-HT1A receptors in human brain with PET and [carbonyl-11 C]WAY-100635. Eur J Pharmacol 1996;301(1-3):R5-7.
20. Pike VW, Halldin C, McCarron JA, Lundkvist C, Hirani E, Olsson H, et al. [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 1998;25 (4):338-46. (Pubitemid 28211596)
21. Sakai Y, Nishikawa M, Leyton M, Benkelfat C, Young SN, Diksic M. Cortical trapping of alpha-[(11)C]methyl-l-tryptophan, an index of serotonin synthesis, is lower in females than males. Neuroimage 2006;33(3):815-24. (Pubitemid 44584762)
22. Sandell J, Halldin C, Hall H, Thorberg SO, Werner T, Sohn D, et al. Radiosynthesis and autoradiographic evaluation of [11C] NAD-299, a radioligand for visualization of the 5-HT1A receptor. Nucl Med Biol 1999;26(2):159-64. (Pubitemid 29125332)
23. Shiue CY, Shiue GG, Mozley PD, Kung MP, Zhuang ZP, Kim HJ, et al. P-[18F]-MPPF: a potential radioligand for PET studies of 5-HT1A receptors in humans. Synapse 1997;25(2):147-54. (Pubitemid 27121225)
24. Suehiro M, Scheffel U, Ravert HT, Dannals RF, Wagner Jr HN. [11C](+)McN5652 as a radiotracer for imaging serotonin uptake sites with PET. Life Sci 1993;53(11):883-92.
25. Yasuno F, Zoghbi SS, McCarron JA, Hong J, Ichise M, Brown AK, et al.Quantification of serotonin 5-HT1A receptors inmonkey brain with [11C](R)-(-)-RWAY. Synapse 2006;60(7):510-20. (Pubitemid 44537084)
26. Meltzer CC, Smith G, DeKosky ST, Pollock BG, Mathis CA, Moore RY, et al. Serotonin in aging, late-life depression, and Alzheimer's disease: the emerging role of functional imaging. Neuropsychopharmacology 1998;18(6):407-30. (Pubitemid 28202350)
27. Moresco RM, Matarrese M, Fazio F. PET and SPET molecular imaging: focus on serotonin system. Curr Top Med Chem 2006;6 (18):2027-34. (Pubitemid 44524475)
28. Kim C, Speisky MB, Kharouba SN. Rapid and sensitive method for measuring norepinephrine, dopamine, 5-hydroxytryptamine and their major metabolites in rat brain by high-performance liquid chromatography. Differential effect of probenecid, haloperidol and yohimbine on the concentrations of biogenic amines and metabolites in various regions of rat brain. J Chromatogr 1987;386:25-35. (Pubitemid 17005185)
29. Mignot E, Serrano A, Laude D, Elghozi JL, Dedek J, Scatton B. Measurement of 5-HIAA levels in ventricular CSF (by LCEC) and in striatum (by in vivo voltammetry) during pharmacological modifications of serotonin metabolism in the rat. J Neural Transm 1985;62(1-2):117-24. (Pubitemid 15072769)
30. Stenfors C, Ross SB. Changes in extracellular 5-HIAA concentrations as measured by in vivo microdialysis technique in relation to changes in 5-HT release. Psychopharmacology (Berl) 2004;172(2):119-28. (Pubitemid 38388760)
31. Diksic M, Young SN. Study of the brain serotonergic system with labeled alpha-methyl-L-tryptophan. J Neurochem 2001;78 (6):1185-200. (Pubitemid 32899751)
32. Sneddon JM. Blood platelets as a model for monoaminecontaining neurones. Prog Neurobiol 1973;1(2):151-98.
33. Stahl SM. The human platelet. A diagnostic and research tool for the study of biogenic amines in psychiatric and neurologic disorders. Arch Gen Psychiatry 1977;34(5):509-16. (Pubitemid 8108950)
34. Bianchi M, Moser C, Lazzarini C, Vecchiato E, Crespi F. Forced swimming test and fluoxetine treatment: in vivo evidence that peripheral 5-HT in rat platelet-rich plasma mirrors cerebral extracellular 5-HT levels, whilst 5-HT in isolated platelets mirrors neuronal 5-HT changes. Exp Brain Res 2002;143 (2):191-7. (Pubitemid 34212255)
35. Janusonis S, Anderson GM, Shifrovich I, Rakic P. Ontogeny of brain and blood serotonin levels in 5-HT receptor knockout mice: potential relevance to the neurobiology of autism. J Neurochem 2006;99(3):1019-31. (Pubitemid 44583458)
36. Anderson GM, Mefford IN, Tolliver TJ, Riddle MA, Ocame DM, Leckman JF, et al. Serotonin in human lumbar cerebrospinal fluid: a reassessment. Life Sci 1990;46(4):247-55. (Pubitemid 20038356)
37. van Praag HM, Korf J. Serotonin metabolism in depression: clinical application of the probenecid test. Int Pharmacopsychiatry 1974;9(1):35-51.
38. van Praag HM, de Haan S. Central serotonin metabolism and frequency of depression. Psychiatry Res 1979;1(3):219-24. (Pubitemid 10123382)
39. van Praag HM. Depression, suicide and the metabolism of serotonin in the brain. J Affect Disord 1982;4(4):275-90. (Pubitemid 13196491)
40. Barton DA, Esler MD, Dawood T, Lambert EA, Haikerwal D, Brenchley C, et al. Elevated brain serotonin turnover in patients with depression: effect of genotype and therapy. Arch Gen Psychiatry 2008;65(1):38-46.
41. van Praag HM, Kahn RS, Asnis GM, Wetzler S, Brown SL, Bleich A, et al. Denosologization of biological psychiatry or the specificity of 5-HT disturbances in psychiatric disorders. J Affect Disord 1987;13(1):1-8. (Pubitemid 17138082)
42. Peremans K, Audenaert K, Hoybergs Y, Otte A, Goethals I, Gielen I, et al. The effect of citalopram hydrobromide on 5-HT2A receptors in the impulsive-aggressive dog, as measured with 123I-5-I-R91150 SPECT. Eur J Nucl Med Mol Imaging 2005;32(6):708-16. (Pubitemid 40897495)
43. Goethals I, Vervaet M, Audenaert K, Van de Wiele C, Ham H, Vandecapelle M, et al. Comparison of cortical 5-HT2A receptor binding in bulimia nervosa patients and healthy volunteers. Am J Psychiatry 2004;161(10):1916-8. (Pubitemid 39314690)
44. van Heeringen C, Audenaert K, Van Laere K, Dumont F, Slegers G, Mertens J, et al. Prefrontal 5-HT2a receptor binding index, hopelessness and personality characteristics in attempted suicide. J Affect Disord 2003;74(2):149-58. (Pubitemid 36428696)
45. Audenaert K, Van Laere K, Dumont F, Vervaet M, Goethals I, Siegers G, et al. Decreased 5-HT2a receptor binding in patients with anorexia nervosa. J Nucl Med 2003;44(2):163-9.
46. Fernstrom JD, Wurtman RJ. Brain serotonin content: physiological dependence on plasma tryptophan levels. Science 1971;173 (992):149-52.
47. Fernstrom JD. Effects on the diet on brain neurotransmitters. Metabolism 1977;26(2):207-23.
48. Muzik O, Chugani DC, Chakraborty P, Mangner T, Chugani HT. Analysis of [C-11]alpha-methyl-tryptophan kinetics for the estimation of serotonin synthesis rate in vivo. J Cereb Blood Flow Metab 1997;17(6):659-69. (Pubitemid 27306690)
49. Tracqui P, Morot-Gaudry Y, Staub JF, Brézillon P, Perault-Staub AM, Bourgoin S, et al. Model of brain serotonin metabolism. II. Physiological interpretation. Am J Physiol 1983;244(2):R206-15. (Pubitemid 13147242)
50. Roberge AG, Missala K, Sourkes TL. Alpha-methyltryptophan: effects on synthesis and degradation of serotonin in the brain. Neuropharmacology 1972;11(2):197-209.
51. Nagahiro S, Takada A, Diksic M, Sourkes TL, Missala K, Yamamoto YL. A new method to measure brain serotonin synthesis in vivo. II. A practical autoradiographic method tested in normal and lithium-treated rats. J Cereb Blood Flow Metab 1990;10(1):13-21. (Pubitemid 20035850)
52. Diksic M. alpha-Methyl tryptophan as a tracer for in vivo studies of brain serotonin system, from autoradiography to positron emission tomography. J Chem Neuroanat 1992;5 (4):349-54.
53. Vanier M, Tsuiki K, Grdisa M, Worsley K, DiksicM. Determination of the lumped constant for the alpha-methyltryptophan method of estimating the rate of serotonin synthesis. J Neurochem 1995;64 (2):624-35.
54. Diksic M. Labelled alpha-methyl-L-tryptophan as a tracer for the study of the brain serotonergic system. J Psychiatry Neurosci 2001;26(4):293-303. (Pubitemid 32912423)
55. Patlak CS, Blasberg RG, Fenstermacher JD. Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data. J Cereb Blood Flow Metab 1983;3(1):1-7. (Pubitemid 13129630)
56. Gharib A, Balende C, Sarda N, Weissmann D, Plenevaux A, Luxen A, et al. Biochemical and autoradiographic measurements of brain serotonin synthesis rate in the freely moving rat: a reexamination of the alpha-methyl-L-tryptophan method. J Neurochem 1999;72(6):2593-600. (Pubitemid 29242212)
57. Shoaf SE, Carson RE, Hommer D, Williams WA, Higley JD, Schmall B, et al. The suitability of [11C]-alpha-methyl-Ltryptophan as a tracer for serotonin synthesis: studies with dual administration of [11C] and [14C] labeled tracer. J Cereb Blood Flow Metab 2000;20(2):244-52. (Pubitemid 30108441)
58. Diksic M. Does labeled alpha-methyl-L-tryptophan image ONLY blood-brain barrier transport of tryptophan? J Cereb Blood Flow Metab 2000;20(10):1508-11.
59. Chugani DC, Muzik O. Alpha[C-11]methyl-L-tryptophan PET maps brain serotonin synthesis and kynurenine pathway metabolism. J Cereb Blood Flow Metab 2000;20(1):2-9. (Pubitemid 30019823)
60. Cohen Z, Tsuiki K, Takada A, Beaudet A, Diksic M, Hamel E. In vivo-synthesized radioactively labelled alpha-methyl serotonin as a selective tracer for visualization of brain serotonin neurons. Synapse 1995;21(1):21-8.
61. Mück-Seler D, Jevric-Causevic A, Diksic M. Influence of fluoxetine on regional serotonin synthesis in the rat brain. J Neurochem 1996;67(6):2434-42. (Pubitemid 26392514)
62. Tsuiki K, Yamamoto YL, Diksic M. Effect of acute fluoxetine treatment on the brain serotonin synthesis as measured by the alpha-methyl-L-tryptophan autoradiographic method. J Neurochem 1995;65(1):250-6.
63. Hasegawa S, Watanabe A, Nguyen KQ, Debonnel G, Diksic M. Chronic administration of citalopram in olfactory bulbectomy rats restores brain 5-HT synthesis rates: an autoradiographic study. Psychopharmacology (Berl) 2005;179(4): 781-90. (Pubitemid 40767898)
64. Okazawa H, Yamane F, Blier P, Diksic M. Effects of acute and chronic administration of the serotonin1A agonist buspirone on serotonin synthesis in the rat brain. J Neurochem 1999;72 (5):2022-31. (Pubitemid 29186006)
65. Sharp T, Bramwell SR, Grahame-Smith DG. 5-HT1 agonists reduce 5-hydroxytryptamine release in rat hippocampus in vivo as determined by brain microdialysis. Br J Pharmacol 1989;96 (2):283-90. (Pubitemid 19045101)
66. VanderMaelen CP, Matheson GK, Wilderman RC, Patterson LA. Inhibition of serotonergic dorsal raphe neurons by systemic and iontophoretic administration of buspirone, a non-benzodiazepine anxiolytic drug. Eur J Pharmacol 1986;129(1-2):123-30. (Pubitemid 16033014)
67. Tohyama Y, Yamane F, Fikre Merid M, Blier P, Diksic M. Effects of serotine receptors agonists, TFMPP and CGS12066B, on regional serotonin synthesis in the rat brain: an autoradiographic study. J Neurochem 2002;80(5):788-98. (Pubitemid 34809231)
68. Vergé D, Daval G, Marcinkiewicz M, Patey A, el Mestikawy S, Gozlan H, et al. Quantitative autoradiography of multiple 5-HT1 receptor subtypes in the brain of control or 5, 7-dihydroxytryptamine- treated rats. J Neurosci 1986;6(12):3474-82. (Pubitemid 17208532)
69. Hasegawa S, Watanabe A, Nishi K, Nguyen KQ, Diksic M. Selective 5-HT1B receptor agonist reduces serotonin synthesis following acute, and not chronic, drug administration: results of an autoradiographic study. Neurochem Int 2005;46(3):261-72.
70. Hasegawa S, Kanemaru K, Gittos M, Diksic M. The tryptophan hydroxylase activation inhibitor, AGN-2979, decreases regional 5-HT synthesis in the rat brain measured with alpha-[14C] methyl-L-tryptophan: an autoradiographic study. Brain Res Bull 2005;67(3):248-55. (Pubitemid 41242931)
71. Tohyama Y, Takahashi S, Merid MF, Watanabe A, Diksic M. The inhibition of tryptophan hydroxylase, not protein synthesis, reduces the brain trapping of alpha-methyl-L-tryptophan: an autoradiographic study. Neurochem Int 2002;40(7):603-10. (Pubitemid 34246238)
72. Mück-Seler D, Diksic M. The acute effects of reserpine and NSD-1015 on the brain serotonin synthesis rate measured by an autoradiographic method. Neuropsychopharmacology 1995;12 (3):251-62.
73. Treseder SA, Rose S, Summo L, Jenner P. Commonly used L-amino acid decarboxylase inhibitors block monoamine oxidase activity in the rat. J Neural Transm 2003;110 (3):229-38. (Pubitemid 36359688)
74. Diksic M, Nagahiro S, Chaly T, Sourkes TL, Yamamoto YL, Feindel W. Serotonin synthesis rate measured in living dog brain by positron emission tomography. J Neurochem 1991;56(1):153-62. (Pubitemid 21901943)
75. Nishisawa S, Mzengeza S, Diksic M. Acute effects of 3, 4- methylenedioxymethamphetamine on brain serotonin synthesis in the dog studied by positron emission tomography. Neurochem Int 1999;34(1):33-40. (Pubitemid 29104865)
76. Molliver ME, Berger UV, Mamounas LA, Molliver DC, O'Hearn E, Wilson MA. Neurotoxicity of MDMA and related compounds: anatomic studies. Ann N Y Acad Sci 1990;600:649-61.
77. Shoaf SE, Carson R, Hommer D, Williams W, Higley JD, Schmall B, et al. Brain serotonin synthesis rates in rhesus monkeys determined by [11C]alpha-methyl-L-tryptophan and positron emission tomography compared to CSF 5-hydroxyindole-3-acetic acid concentrations. Neuropsychopharmacology 1998;19(5):345-53. (Pubitemid 28451591)
78. Nishizawa S, Benkelfat C, Young SN, Leyton M, Mzengeza S, de Montigny C, et al. Differences between males and females in rates of serotonin synthesis in human brain. Proc Natl Acad Sci U S A 1997;94(10):5308-13. (Pubitemid 27214779)
79. Leyton M, Diksic M, Benkelfat C. Brain regional alpha-[11C] methyl-L-tryptophan trapping correlates with post-mortem tissue serotonin content and [11C]5-hydroxytryptophan accumulation. Int J Neuropsychopharmacol 2005;8(4):633-4. (Pubitemid 41400895)
80. Nishizawa S, Leyton M, Okazawa H, Benkelfat C, Mzengeza S, Diksic M. Validation of a less-invasive method for measurement of serotonin synthesis rate with alpha-[11C]methyl-tryptophan. J Cereb Blood Flow Metab 1998;18(10):1121-9. (Pubitemid 28465360)
81. Tanke MA, Alserda E, Doornbos B, van der Most PJ, Goeman K, Postema F, et al. Low tryptophan diet increases stresssensitivity, but does not affect habituation in rats. Neurochem Int 2008;52(1-2):272-81. (Pubitemid 350235702)
82. Van der Does AJ. The effects of tryptophan depletion on mood and psychiatric symptoms. J Affect Disord 2001;64(2-3):107-19.
83. Jans LA, Riedel WJ, Markus CR, Blokland A. Serotonergic vulnerability and depression: assumptions, experimental evidence and implications. Mol Psychiatry 2007;12(6):522-43. (Pubitemid 46816766)
84. Chugani DC, Muzik O, Chakraborty P, Mangner T, Chugani HT. Human brain serotonin synthesis capacity measured in vivo with alpha-[C-11]methyl-L- tryptophan. Synapse 1998;28 (1):33-43. (Pubitemid 128770601)
85. Davis JN, Carlsson A, MacMillan V, Siesjo BK. Brain tryptophan hydroxylation: dependence on arterial oxygen tension. Science 1973;182(107):72-4.
86. Nishikawa M, Kumakura Y, Young SN, Fiset P, Vogelzangs N, Leyton M, et al. Increasing blood oxygen increases an index of 5-HT synthesis in human brain as measured using alpha-[(11)C] methyl-L-tryptophan and positron emission tomography. Neurochem Int 2005;47(8):556-64. (Pubitemid 41437900)
87. Rosa-Neto P, Diksic M, Okazawa H, Leyton M, Ghadirian N, Mzengeza S, et al. Measurement of brain regional alpha-[11C] methyl-L-tryptophan trapping as a measure of serotonin synthesis in medication-free patients with major depression. Arch Gen Psychiatry 2004;61(6):556-63. (Pubitemid 38747310)
88. Drevets WC. Neuroimaging and neuropathological studies of depression: implications for the cognitive-emotional features of mood disorders. Curr Opin Neurobiol 2001;11(2):240-9. (Pubitemid 32289413)
89. Berney A, Nishikawa M, Benkelfat C, Debonnel G, Gobbi G, Diksic M. An index of 5-HT synthesis changes during early antidepressant treatment: alpha-[11C]methyl-L-tryptophan PET study. Neurochem Int 2008;52(4-5):701-8.
90. Artigas F, Perez V, Alvarez E. Pindolol induces a rapid improvement of depressed patients treated with serotonin reuptake inhibitors. Arch Gen Psychiatry 1994;51(3):248-51. (Pubitemid 24081512)
91. Lejeune F, Millan MJ. Pindolol excites dopaminergic and adrenergic neurons, and inhibits serotonergic neurons, by activation of 5-HT1A receptors. Eur J Neurosci 2000;12 (9):3265-75.
92. Cremers TI, Wiersma LJ, Bosker FJ, Den Boer JA, Westerink BH, Wikström HV. Is the beneficial antidepressant effect of coadministration of pindolol really due to somatodendritic autoreceptor antagonism? Biol Psychiatry 2001;50 (1):13-21. (Pubitemid 32701989)
93. Frey BN, Rosa-Neto P, Lubarsky S, Diksic M. Correlation between serotonin synthesis and 5-HT1A receptor binding in the living human brain: a combined alpha-[11C]MT and [18F]MPPF positron emission tomography study. Neuroimage 2008;42 (2):850-7.
94. Batista CE, Juhász C, Muzik O, Kupsky WJ, Barger G, Chugani HT, et al. Imaging correlates of differential expression of indoleamine 2, 3-dioxygenase in human brain tumors. Mol Imaging Biol 2009;11(6):460-6.
95. Hartvig P, Bergström M, Antoni G, Langstrom B. Positron emission tomography and brain monoamine neurotransmission - entries for study of drug interactions. Curr Pharm Des 2002;8 (16):1417-34. (Pubitemid 34693061)
96. Koopmans KP, Neels OC, Kema IP, Elsinga PH, Sluiter WJ, Vanghillewe K, et al. Improved staging of patients with carcinoid and islet cell tumors with 18F-dihydroxy-phenyl-alanine and 11C-5-hydroxy-tryptophan positron emission tomography. J Clin Oncol 2008;26(9):1489-95.
97. Orlefors H, Sundin A, Lu L, Oberg K, Långström B, Eriksson B, et al. Carbidopa pretreatment improves image interpretation and visualisation of carcinoid tumours with 11C-5-hydroxytryptophan positron emission tomography. Eur J Nucl Med Mol Imaging 2006;33(1):60-5. (Pubitemid 41785310)
98. Bombardieri E, Maccauro M, De Deckere E, Savelli G, Chiti A. Nuclear medicine imaging of neuroendocrine tumours. Ann Oncol 2001;12 Suppl 2:S51-61. (Pubitemid 33069688)
99. Neels OC, Koopmans KP, Jager PL, Vercauteren L, van Waarde A, Doorduin J, et al. Manipulation of [11C]-5-hydroxytryptophan and 6-[18F]fluoro-3, 4-dihydroxy-L-phenylalanine accumulation in neuroendocrine tumor cells. Cancer Res 2008;68 (17):7183-90.
100. Hartvig P, Lindner KJ, Tedroff J, Andersson Y, Bjurling P, Långström B. Brain kinetics of 11 C-labelled L-tryptophan and 5-hydroxy-L-tryptophan in the rhesus monkey. A study using positron emission tomography. J Neural Transm Gen Sect 1992;88(1):1-10.
101. Lindner KJ, Hartvig P, Bjurling P, Fasth KJ, Westerberg G, Långström B. Determination of 5-hydroxy-L-[beta-11C]tryptophan and its in vivo-formed radiolabeled metabolites in brain tissue using high performance liquid chromatography: a study supporting radiotracer kinetics obtained with positron emission tomography. Nucl Med Biol 1997;24(8):733-8. (Pubitemid 27486484)
102. Hartvig P, Lindner KJ, Bjurling P, Laengstrom B, Tedroff J. Pyridoxine effect on synthesis rate of serotonin in the monkey brain measured with positron emission tomography. J Neural Transm Gen Sect 1995;102(2):91-7.
103. Hartvig P, Tedroff J, Lindner KJ, Bjurling P, Chang CW, Tsukada H, et al. Positron emission tomographic studies on aromatic Lamino acid decarboxylase activity in vivo for L-dopa and 5-hydroxy-L-tryptophan in the monkey brain. J Neural Transm Gen Sect 1993;94(2):127-35. (Pubitemid 23345521)
104. Arai R, Karasawa N, Nagatsu T, Nagatsu I. Exogenous L-5- hydroxytryptophan is decarboxylated in neurons of the substantia nigra pars compacta and locus coeruleus of the rat. Brain Res 1995;669(1):145-9.
105. Lundquist P, Blomquist G, Hartvig P, Hagberg GE, Torstenson R, Hammarlund-Udenaes M, et al. Validation studies on the 5-hydroxy-L-[beta-11C]- tryptophan/PET method for probing the decarboxylase step in serotonin synthesis. Synapse 2006;59 (8):521-31.
106. Lundquist P, Hartvig P, Blomquist G, Hammarlund-Udenaes M, Långström B. 5-Hydroxy-L-[beta-(11)C]tryptophan versus alpha-[(11)C]methyl-L-tryptophan for positron emission tomography imaging of serotonin synthesis capacity in the rhesus monkey brain. J Cereb Blood Flow Metab 2007;27 (4):821-30. (Pubitemid 46474613)
107. Agren H, Reibring L, Hartvig P, Tedroff J, Bjurling P, Hömfeldt K, et al. Low brain uptake of L-[11C]5-hydroxytryptophan in major depression: a positron emission tomography study on patients and healthy volunteers. Acta Psychiatr Scand 1991;83(6):449-55.
108. Eriksson O, Wall A, Marteinsdottir I, Agren H, Hartvig P, Blomqvist G, et al. Mood changes correlate to changes in brain serotonin precursor trapping in women with premenstrual dysphoria. Psychiatry Res 2006;146(2):107-16.
109. Hagberg GE, Torstenson R, Marteinsdottir I, Fredrikson M, Långström B, Blomqvist G. Kinetic compartment modeling of [11C]-5-hydroxy-L-tryptophan for positron emission tomography assessment of serotonin synthesis in human brain. J Cereb Blood Flow Metab 2002;22(11):1352-66. (Pubitemid 35285093)
110. Neels OC, Jager PL, Koopmans KP, Eriks E, de Vries EGE, Kema IP, et al. Development of a reliable remote-controlled synthesis of beta-[C-11]-5-hydroxy- L-tryptophan on a Zymark robotic system. J Labelled Comp Radiopharm 2006;49(10):889-95. (Pubitemid 44519293)
111. Agren H, Reibring L. PET studies of presynaptic monoamine metabolism in depressed patients and healthy volunteers. Pharmacopsychiatry 1994;27(1):2-6. (Pubitemid 24078981)
112. Lynn-Bullock CP, Welshhans K, Pallas SL, Katz PS. The effect of oral 5-HTP administration on 5-HTP and 5-HT immunoreactivity in monoaminergic brain regions of rats. J Chem Neuroanat 2004;27(2):129-38. (Pubitemid 38581108)