Development of radioligands for imaging of brain norepinephrine transporters in vivo with positron emission tomography

Current Topics in Medicinal Chemistry

Volumn 7, Issue 18, 2007, Pages 1806-1816

  Schou, Magnus ^a,c   Pike, Victor K ^b   Halldin, Christer ^a  

^a KAROLINSKA INSTITUTE   (Sweden)

^b NATIONAL INSTITUTE OF MENTAL HEALTH   (United States)

^c ASTRAZENECA R AND D   (Sweden)

Author keywords

Carbon 11; Fluorine 18; NET; PET; Radioligand

Indexed keywords

5 (7 BENZOFURANYL) 8 CHLORO 2,3,4,5 TETRAHYDRO 7 HYDROXY 3 METHYL 1H 3 BENZAZEPINE; 8 CHLORO 2,3,4,5 TETRAHYDRO 3 METHYL 5 PHENYL 1H 3 BENZAZEPIN 7 OL HYDROGEN MALEATE; CARBON 11; CITALOPRAM; COCAINE; DOPAMINE; FLUMAZENIL; FLUORINE 18; FLUOXETINE; IMIPRAMINE; ISOREMOXIPRIDE; MONOAMINE; MONOAMINE OXIDASE INHIBITOR; N [2 [4 (2 METHOXYPHENYL) 1 PIPERAZINYL]ETHYL] N (2 PYRIDYL)CYCLOHEXANECARBOXAMIDE; N SEC BUTYL 1 (2 CHLOROPHENYL) N METHYL 3 ISOQUINOLINECARBOXAMIDE; NAXAGOLIDE; NEUROTRANSMITTER; NISOXETINE; NORADRENALIN; NORADRENALIN TRANSPORTER; NORADRENALIN UPTAKE INHIBITOR; RACLOPRIDE; RADIOISOTOPE; RADIOLIGAND; REBOXETINE; SEROTONIN; SEROTONIN UPTAKE INHIBITOR; SERTRALINE; TRICYCLIC ANTIDEPRESSANT AGENT; UNINDEXED DRUG;

ATTENTION DEFICIT DISORDER; BINDING SITE; CENTRAL NERVOUS SYSTEM; CLINICAL RESEARCH; CLINICAL TRIAL; DEGENERATIVE DISEASE; DEPRESSION; DRUG DESIGN; DRUG TARGETING; HUMAN; IMAGE QUALITY; IMAGING; IN VIVO STUDY; ISOTOPE LABELING; MENTAL DISEASE; NEUROLOGIC DISEASE; NONHUMAN; POSITRON EMISSION TOMOGRAPHY; PROTEIN EXPRESSION; RECEPTOR DENSITY; REVIEW; SINGLE PHOTON EMISSION COMPUTER TOMOGRAPHY; SYNAPSE;

BRAIN; HUMANS; LIGANDS; NOREPINEPHRINE PLASMA MEMBRANE TRANSPORT PROTEINS; POSITRON-EMISSION TOMOGRAPHY; RADIOPHARMACEUTICALS;

EID: 36349008186     PISSN: 15680266     EISSN: None     Source Type: Journal    
DOI: 10.2174/156802607782507411     Document Type: Review

References (98)

1. Tellioglu, T.; Robertson, R. Genetic or aquired deficits in the norepinephrine tranporter: Current understanding of clinical implications. Exp. Rev. Mol. Med. 2001, http://www-ermm.cbcu.cam.ac.uk/01003878h.htm.
2. Blakely, R.; De Felice, R.; Hartzell, H. Mollecular physiology of norepinephrine and serotonin transporters. J. Exp. Biol. 1994, 196, 263-81.
3. Sullivan, G. M.; Coplan, J. D.; Kent, J. M.; Gorman, J. M. The noradrenergic system in pathological anxiety: A focus on panic with relevance to generalized anxiety and phobias. Biol. Psychiatry 1999, 46, 1205-18.
4. Spencer, T.; Heilieenstein, J.; Biederman, J.; Faries, D.; Kratochvil, C.; Conners, C.; Potter, W. Results from 2 proof-of-concept, placebo-controlled studies of atomoxetine in children with attention-deficit/hyperactivity disorder. J. Clin. Psychiatry 2002, 63, 1140-7.
5. Klimek, V.; Stockmeier, C.; Overholser, J.; Meltzer, H. Y.; Kalka, S.; Dilley, G.; Ordway, G. A. Reduced levels of norepinephrine transporters in the locus coeruleus in major depression. J. Neurosci. 1997, 17, 8451-8.
6. Brunello, N.; Mendlewicz, J.; Kasper, S.; Leonard, B.; Montgomery, S.; Nelson, J.; Paykel, E.; Versiani, M.; Racagni, G. The role of noradrenaline and selective noradrenaline reuptake inhibition in depression. Eur. Neuropsychopharmacol. 2002, 12, 461-75.
7. Macey, D. J.; Smith, H. R.; Nader, M. A.; Porrino, L. J. Chronic cocaine self-administration upregulates the norepinephrine transporter and alters functional activity in the bed nucleus of the stria terminalis of the rhesus monkey. J. Neurosci. 2003, 23, 12-6
8. Tejani-Butt, S.; Yang, J.; Zaffar, H. Norepinephrine transporter sites are decreased in the locus coeruleus in Alzheimer's disease. Brain Res. 1993, 631, 147-50.
9. Kuhn, R. Treatment of depressive states with an iminodibenzyl derivative (G 22355) Schweiz Med. Wochenschr. 1957, 87, 1135-40.
10. Loomer, H. P.; Saunders, I. C.; Kline, N. S. A clinical and pharmacodynamic evaluation of iproniazid as a psychic energizer. Psychiatr. Res. Rep. Am. Psychiatr. Assoc. 1957, 135, 129-41.
11. Bymaster, F. P.; Beedle, E. E.; Findlay, J.; Gallagher, P. T.; Krushinski, J. H.; Mitchell, S.; Robertson, D. W.; Thompson, D. C.; Wallace, L.; Wong, D. T. Duloxetine (Cymbalta), a dual inhibitor of serotonin and norepinephrine reuptake. Bioorg. Med. Chem. Lett. 2003, 13, 4477-80.
12. Bymaster, F. P.; Katner, J. S.; Nelson, D. L.; Hemrick-Luecke, S. K.; Threlkeld, P. G.; Heiligenstein, J. H.; Morin, S. M.; Gehlert, D. R.; Perry, K. W. Atomoxetine increases extracellular levels of norepinephrine and dopamine in prefrontal cortex of rat: A potential mechanism for efficacy in attention deficit/hyperactivity disorder. Neuropsychopharmacology 2002, 27, 699-711.
13. Sesack, S. R.; Hawrylak, V. A., Matus, U.; Guido, M. A.; Levey, A. I. Dopamine axon varicosities in the prelimbic division of the rat prefrontal cortex exhibit sparse immunoreactivity for the dopamine transporter. J. Neurosci. 1998, 18, 2697-708.
14. Paczkowski, F. A.; Bryan-Lluka, L. J.; Porzgen, P.; Bruss, M.; Bonisch, H. Comparison of the pharmacological properties of cloned rat, human, and bovine norepinephrine transporters. J. Pharmacol. Exp. Ther. 1999, 290, 761-7.
15. Phelps, M. E. PET: The mergmg of biology and imaging into molecular imaging. J. Nucl. Med. 2000, 41, 661-81.
16. Farde, L.; Hall, H.; Ehrin, E.; Sedvall, G. Quantitative analysis of D2 dopamine receptor binding in the living human brain by PET. Science 1986, 231, 258-61.
17. Farde, L.; Nordstrom, A. L.; Wiesel, F. A.; Pauli, S.; Halldin, C.; Sedvall, G. Positron emission tomographic analysis of central D1 and D2 dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine. Relation to extrapyramidal side effects. Arch. Gen. Psychiatry 1992, 49, 538-44.
18. 11C]flumazenil PET to demonstrate that pagoclone is a partial agonist. Psychopharmacology (Berl) 2005, 180, 789-91.
19. Bergstrom, M.; Grahnen, A.; Langstrom, B. Positron emission tomography microdosing: A new concept with application in tracer and early clinical drug development. Eur. J. Clin. Pharmacol. 2003, 59, 357-66.
20. Holford, N. Concepts and usefulness of pharmacokinetic-pharmacodynamic modelling. Fundam. Clin. Pharmacol. 1990, 4, 93s-101s.
21. Halldin, C.; Gulyas, B.; Farde, L. PET studies with carbon-11 radioligands in neuropsychopharmacological drug development. Curr. Pharm. Des. 2002, 7, 1907-29.
22. Mash, D. C.; Ouyang, Q.; Qin, Y.; Pablo, J. Norepinephrine transporter immunoblotting and radioligand binding in cocaine abusers. J. Neurosci. Methods 2005, 143, 79-85.
23. 3H]mazindol autoradiography. J. Comp. Neurol. 1991, 304, 419-34.
24. Smith, H. R.; Beveridge, T. J.; Porrino, L. J. Distribution of norepinephrine transporters in the non-human primate brain. Neuroscience 2006, 138, 703-14.
25. 3H]Nisoxetine: A radioligand for quantitation of norepinephrine uptake sites by autoradiography or by homogenate binding. J. Pharm. Exp. Ther. 1992, 260, 427-36.
26. Halldin, C.; Farde, L.; Hogberg, T.; Mohell, N., Hall, H.; Suhara, T.; Karlsson, P.; Nakashima, Y.; Swahn, C. G. Carbon-11-FLB 457: A radioligand for extrastriatal D2 dopamine receptors. J. Nucl. Med. 1995, 36, 1275-81.
27. Fowler, J. S.; Volkow, N. D.; Wang, G. J.; Galley, S. J.; Logan, J. [(11)]Cocaine: PET studies of cocaine pharmacokinetics, dopamine transporter availability and dopamine transporter occupancy. Nucl. Med. Biol. 2001, 28, 561-72.
28. 3H]GBR 12;935 binding. Mol. Pharmacol. 1994, 45, 125-33.
29. Bock, N.; Quentin, D. J.; Huther, G.; Moll, G. H.; Banaschewski, T.; Rothenberger, A. Very early treatment with fluoxetine and reboxetine causing long-lasting change of the serotonin but not the noradrenaline transporter in the frontal cortex of rats. World J. Biol. Psychiatry 2005, 6, 107-12.
30. 18F]fluoromethyl)-(+)-McN5652. Eur. Neuropsychopharmacol. 2003 13, 387-97.
31. Halldin, C.; Swahn, C. -G.; Farde, L.; Sedvall, G.; Radioligand disposition and metabolism. PET for drug development and evaluation, ed. D. Comar. 1995: Kluwer Academic Publishers. pp. 55-65.
32. 11C]RS-15385-197 as a positron emission tomography radioligand for central alpha2-adrenoceptors. Eur. J. Nucl. Med. 2000, 27, 475-84.
33. 11C]WAY-100635-explanation of high signal contrast in PET and an aid to biomathematical modelling. Nucl. Med. Biol. 1998, 25, 215-23.
34. Balle, T.; Halldin, C.; Andersen, L., Hjorth Alifranglis, L.; Badolo, L.; Gjervig Jensen, K.; Chou, Y. W.; Andersen, K.; Perregaard, J.; Farde, L. New alpha(1)-adrenoceptor antagonists derived from the antipsychotic sertindole - carbon-11 labelling and pet examination of brain uptake in the cynomolgus monkey. Nucl. Med. Biol. 2004, 31, 327-36.
35. Lipinski, C. A.; Lombardo, F.; Dominy, B. W.; Feeney, P. J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev. 2001, 46, 3-26.
36. 3H]citalopram as markers of the human brain 5-HT uptake site: A comparison study. J. Neural. Transm. Gen. Sect. 1994, 97, 27-40.
37. Waterhouse, R. N. Determination of lipophilicity and its use as a predictor of blood-brain barrier penetration of molecular imaging agents. Mol. Immaging Biol. 2003, 5, 376-89.
38. Welch, M. J.; Chi, D. Y.; Mathias, C.J.; Kilbourn, M. R.; Brodack, J. W.; Katzenellenbogen, J. A. Biodistribution of N-alkyl and N-fluoroalkyl derivatives of spiroperidol; radiopharmaceuticals for PET studies of dopamine receptors. Int. J. Rod. Appl. Instrum.'B' 1986, 13, 523-6.
39. Zoghbi, S. S.; Shetty, H. U.; Ichise, M.; Fujita, M.; Imaizumi, M.; Liow, J. S.; Shah, J.; Musachio, J. L.; Pike, V. W.; Innis, R. B. PET imaging of the dopamine transporter with 18F-FECNT: A polar radiometabolite confounds brain radioligand measurements. J. Nucl. Med. 2006, 47, 520-7.
40. Wathey, B.; Tierney, J.; Lidstrom, P.; Westman, J. The impact of microwave-assisted organic chemistry on drug discovery. Drug Discov. Today 2002, 7, 373-80.
41. 11C-methyl-L-methionine. Int. J. Appl. Radiat. Isot. 1976, 27, 357-63.
42. 11C]carbon monoxide. J. Org. Chem. 1999, 64, 9201-5.
43. 1> 11 C-labeled octanal and benzaldehyde. J. Label. Compds. Radiopharm. 1979, 16, 435-40.
44. 18F]fluoroethyl bromide as a synthetic precursor. Appl. Radiat. Isot. 2002, 57, 335-42.
45. Coenen, H. H.; Colosimo, M.; Schuller, M.; Stocklin, G. Preparation of Nca F-18 Ch2brf via aminopolyether supported nucleophilic-substitution. J. Label. Compds. Radiopharm. 1986, 23, 587-95.
46. Javaid, J. L; Perel, J. M.; Davis, J. M. Inhibition of biogenic amines uptake by imipramine, destpramine, 2 OH-imipramine and 2 OH-desipramine in rat brain. Life Sci. 1979, 24, 21-8.
47. Waldmeier, P. C.; Baumann, P. A.; Hauser, K.; Maitre, L.; Storni, A. Oxaprotiline, a noradrenaline uptake inhibitor with an active and an inactive enaritiomer. Biochem. Pharmacol. 1982, 31, 2169-76.
48. Gehlert, D. R.; Hemrick-Luecke, S. K.; Schober, D. A.; Krushinski, J.; Howbert, J. J.; Robertson, D. W.; Wong, D, T.; Fuller, R. W. (R)-thionisoxetine, a potent and selective inhibitor of central and peripheral norepinephrine uptake. Life Sci. 1995, 56, 1915-20.
49. Melloni, P.; Carniel, U.; Della Torre, Bonsignori, A.; Buonamici, M.; Pozzi, O.; Ricciardi, S.; Rossi, A. Potential antidepressant agents. a-Aryloxy-benzyl derivatives of ethanolamine and morpholine. Eur. J. Med. Chem. Chim. Ther. 1984, 19, 235-42.
50. Chumpradit, S.; Kung, M.; Panyachotipun, C.; Prapansiri, V.; Foulun, C.; Brooks, B.; Szabo, S.; Tejani-Butt, S.; Frazer, A.; Kung, H. Iodinated tomoxetine derivatives as selective ligands for serotonin and norepinephrine uptake sites. J. Med. Chem. 1992, 35, 4492-7.
51. Wong, D. T.; Threlkeld, P. G.; Best, K. L; Bymaster, F. P. A new inhibitor of norepinephrine uptake devoid of affinity for receptors in rat brain. J. Pharmacol. Exp. Ther. 1982, 61.
52. Bogeso, K.; Christiansen, A.; Hyttel, J.; Liljefors, T. 3-Phenyl-1-Indanamines. Potential antidepressant activity and potent inhibitors of dopamine, norepinephrine and serotonin uptake. J. Med. Chem. 1985, 28, 1817-28.
53. Blough, B. E.; Holmquist, C. R.; Abraham, P.; Kuhar, M. J.; Carroll, F. I. 3alpha-(4-Substituted phenyl)nortropane-2beta-carboxylic acid methyl esters show selective binding at the norepinephrine transporter. Bloorg. Med. Chem. Lett. 2000, 10, 2445-7.
54. Hoepping, A.; Johnson, K. M.; George, C.; Flippen-Anderson, J.; Kozikowski, A. P. Novel conformationally constrained tropane analogues by 6-endo-trig radical cyclization and stille coupling - switch of activity toward the serotonin and/or norepinephrine transporter. J. Med. Chem. 2000, 43, 2064-71.
55. Maryanoff, B.; McComsey, D.; Gardocki, J.; Shank, R.; Costanzo, M.; Nortey, S.; Schneider, C.; Seder, P. Pyrroloisoquinoline antidepressants 2. In-depth expolration of structure-activity relationships. J. Med. Chem. 1987, 30, 1433-54.
56. Hyttel, J. Citalopram - pharmacological profile of a specific serotonin uptake inhibitor with antidepressant activity. Prog. Neuro-Psychopharmacol. Biol. Psychiat. 1982, 6, 277-95
57. Gehlert, D.; Schober, D.; Hemrick-Luecke, S.; Krushinski, J.; Howbert, J.; Robertson, D.; Fuller, R.; Wong D. Novel halogenated analogs of tomoxetine that are potent and selective inhibitors of norepinephrine uptake in brain. Neurachem. Int. 1995, 26, 47-52
58. Wong, D. T,; Horng, J. S.; Bymaster, F. P. dl-N-methyl-3-(o-methoxy-phenoxy)-3-phenylpropylamine hydrochloride, Lilly 94939, a potent inhibitor for uptake of norepinephrine into rat brain synaptosomes and heart. Life Sci. 1975, 17, 755-60.
59. 125I]iodo-nisoxetine to norepinephrine transporters in the brain. Nucl. Med. Biol. 2004, 31, 533-41.
60. Kiyono, Y.; Kanegawa, N.; Kawashima, H.; Kitamura, Y.; Iida, Y.; Saji, H. Evaluation of radioiodinated -(R)-N-methy1-3-(2-iodophenoxy)-3-phenylpropanamine as a ligand for brain norepinephrine transporter imaging. Nucl. Med. Biol. 2004, 31, 147-53.
61. Schou, M.; Halldin, C.; Sovago, J.; Pike, V. W.; Hall, H.; Gulyas, B.; Mozley, P. D.; Dobson, D.; Shchukin, E.; Innis, R. B.; Farde, L. PET evaluation of novel radiofluorinated reboxetine analogs as norepinephrine transporter probes in the monkey brain. Synapse 2004, 53, 57-67.
62. 11C]lortalamine. J. Neurochem. 2005, 94, 337-51.
63. 11C-labelled (R)-OHDMI and CFMME and their evaluation as candidate radioligands for imaging central-norepinephrine transporters with PET. Bioorg. Med. Chem. 2007, 15, 616-25.
64. Musachiro, J. L.; Hong, J.; Ichise, M.; Seneca, N.; Brown, A. K; Liow, J. -S.; Halldin, C.; Innis, R. B.; Pike, V. W.; He, R.; Zhou, J.; Kozikowski, A. P. Development of new, brain imaging agents based upon nocaine-modafinil hybrid monoamine transporter inhibitors. Bioorg. Med. Chem. Lett. 2006, in press.
65. 11C]talsupram: candidate PET ligands for the norepinephrine transporter. Nucl. Med. Biol. 2004, 31, 705-18.
66. McConathy, J.; Owens, M. J.; Kilts, C. D.; Malveaux, E. J.; Votaw, J. R.; Nemeroff, C. B.; Goodman, M. M. Synthesis and biological evaluation of trans-3-phenyl-1-indanamines as potential norepinephrine transporter imaging agents. Nucl. Med. Biol. 2005, 32, 593-605.
67. Tatsumi, M.; Groshan, K.; Blakely, R. D.; Richelson, E. Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur. J. Pharmacol. 1997, 340, 249-58.
68. Houlihan, W. J.; Kelly, L.; Pankuch, J.; Koletar, J.; Brand, L.; Janowsky, A.; Kopajtic, T. A. Mazindol analogues as potential inhibitors of the cocaine binding site at the dopamine trunsporter. J. Med. Chem. 2002, 45, 4097-109.
69. 11C]nisoxetine, a norepinephrine transporter inhibitor. Nucl. Med. Biol. 1989, 16, 771-4.
70. Wilson, A.; Johnson, D.; Mozley, P.; Hussey, D.; Ginovart, N.; Nobrega, J.; Garcia, A.; MeyerJ,Houle, S. Synthesis and in vivo evaluation of novel radiotracers for the in vivo imaging of the norepinephrine transporter. Nucl. Med. Biol. 2003, 30, 85-92.
71. 3H]MeNER to riorepinepirpne transporters. Synapse 2005, 56, 100-4.
72. 11C]MeNER. Nucl. Med. Biol. 2003, 30, 707-14.
73. Ding, Y. S.; Lin, K. S.; Garza, V.; Carter, P.; Alexoff, D.; Logan, J.; Shea, C.; Xu, Y.; King, P. Evaluation Z new norepinephrine transporter PET ligand in baboons, both in brain and peripheral organs. Synapse 2003, 50, 435-52.
74. Minuzzi, L.; Olsen, A. K.; Bender, D.; Arnfred, S.; Grant R.; Danielren, E. H.; Cumming, P. Quantitative autoradiography of ligands for dopamine receptors and transporters in brain of Gottingen minipig: Comparison with results in vivo. Synapse 2006, 59, 211-9.
75. 11C]MeNER binding to the norepinephrine transporter in healthy subjects using PET. manuscript 2006.
76. 18F]fluoroputrescine: Preparation, biodistribution, and mechanism of defluorination. Int. J. Rad. Appl. Instrum [A] 1986, 37, 607-12.
77. Hamill, T.; Burns, H.; Eng, W.; Ryan, C.; Krause, S.; Gibson, R.; Hargreaves, R. An Improved Fluorine-18 Labeled Neurokinin-1 Receptor Ligand. Mol. Imagnig Biol. 2002, 4, S34.
78. Lin, K. S.; Ding, Y. S.; Kim, S. W.; Kil, K. E. Synthesis, enantiomeric resolution, F-18 labeling and biodistribution of reboxetine analogs: promising radioligands for imaging the norepinephrine transporter with positron emission tomography. Nucl. Med. Biol. 2005, 32, 415-22.
79. Kanegawa, N.; Kiyono, Y.; Kimura, H.; Sugita, T.; Kajiyama, S.; Kawashima, H.; Ueda, M.; Kuge, Y.; Saji, H. Synthesis and evaluation of radioiodinated (S,S)-2-(alpha-(2-iodophenoxy) benzyl)morpholine for imaging brain norepinephrine transporter. Eur. J. Nucl. Med. Mol. Imaging 2006.
80. Schou, M.; Pike, V.; Varrone, A.; Gulyás, B.; Farde, L.; Halldin, C. Synthesis and PET evaluation of (R)-S-methyl-11C]thionisoxetine, a candidate radioligand for imaging brain norepinephrine transporters. J. Label. Compd. Radiopharm. 2006, 49, 1007-19.
81. Zavidovskaia, G. I. The use of LU-3-010 in the treatment of depressive states. Zh Nevropatol. Psikhiatr. Im. S S Korsakova 1969, 69, 594-8.
82. Stromgren, L. S.; Friderichsen, T. Lu 5-003 in antidepressive therapy. Nord. Psykiatr. Tidsskr. 1971, 25, 119-28.
83. Schou, M.; Sovago, J.; Pike, V. W.; Gulyas, B.; Bogeso, K. P.; Farde, L.; Halldin, C. Synthesis and positron emission tomography evaluation of three norepinephrine transporter radioligands: [C-11]desipramine, [C-11]talopram and [C-11]talsupram. Mol. Imaging Biol. 2006, 8, 1-8.
84. Cusack, B.; Nelson, A.; Richelson, E. Binding of antidepressants to human brain receptors: Focus on newer generation compounds. Psychopharmacology (Berl) 1994, 114, 559-65.
85. 3H] desipramine-binding sites in human postmortem brain tissue. Neuropyschobiology 1990, 23, 68-73.
86. 3H]desmethylimipramine binding in the human brain postmortem. Brain Res. 1988, 456, 120-6.
87. Lin, K. -S.; Ding, Y. -S.; Betzel, T.; Quandt, G. Synthesis and in vivo evaluation of C-11 labeled mazindol analogs for imaging the norepinephrine transporter with PET. J. Label. Compd. Radiopharm. 2005, 48, S152.
88. Logan, J.; Ding, Y. S.; Lin, K. S.; Fareto, D.; Fowler, J.; Biegon, A. Modeling and analysis of PET studies with norepinephrine transporter ligands: The search for a reference region. Nucl. Med. Biol. 2005, 32, 531-42.
89. Biegon, A.; Rainbow, T. C. Localization and characterization of [3H]desmethylimipramine binding sites in rat brain by quantitative autoradiography. J.Neurosci. 1983, 3, 1069-76.
90. Lee, C. M.; Javitch, J. A.; Snyder, S. H. Characterization of [3H]desipramine binding associated with neuronal norepinephrine uptake sites in rat brain membranes. J. Neurosci. 1982, 2, 1515-25.
91. 11C]MeNER PET. Brain and Brain PET 2005 2005, BP-12.
92. 18F]FMeNER-D2. Eur. Neuropsychopharmacol. 2005, 15, 517-20.
93. 18F]FMeNER-D2. Psychopharmacology (Berl) 2006, 188, 119-27.
94. Madras, B. K,; Gracz,; L. M.; Fahey, M. A.; Elthaleh, D.; Meltzer, P. C.; Liang, A. Y.; Stopa, E. G.; Babich, J.; Fischman, A. J. Altropane, a SPECT or PET imaging probe for dopamine neurons: III. Human dopamine transporter in postmortem normal and Parkinson's diseased brain. Synapse 1998, 29, 116-27.
95. Du, L.; Faludi,. G.; Palkovits, M.; Demeter, E.; Bakish, D.; Lapierre, Y. D.; Sotonyi, P.; Hrdina, P. D. Frequency of long allele in scrotonin transporter gene is increased in depressed suicide victims. Biol. Psychiatry 1999, 46, 196-201.
96. 11)C]PEN2I: A highly selective radioligand for PET examination of the dopamine transporter in monkey and human brain. Eur. J. Nucl. Med. Mol. Imaging 2003, 30, 1220-30
97. 11C]-DASB: a probe for in vivo measurement of the serotonin transporter by positron emission tomography. Nucl. Med. Biol. 2002, 29, 509-15.
98. Bracha, H. S.; Garcia-Rill, E.; Mrak, R. E.; Skinner, R. Postmortem locus coeruleus neuron count in three American veterans with probable or possible war related PTSD. J. Neuropsychiatry Clin. Neurosci. 2005, 17, 503-9.