[en] The status of the radiochemical development and biological evaluation of radioligands and tracers for PET studies of the serotonergic system is reviewed, indicating those agents with present value and those with future potential. Practical recommendations are given for the preparation of two useful radioligands for PET studies of central 5-HT2 receptors, namely [18F]setoperone and [18F]altanserin. Though, it has not proved possible to recommend tracers or radioligands for the study of other aspects of serotonergic system, prospects for future radiochemical development are indicated, especially for developing radioligands for the 5-HT re-uptake site, and for the 5-HT1 and 5-HT3 receptors.
Disciplines :
Chemistry
Author, co-author :
Crouzel, C.
Guillaume, Marcel ; Université de Liège - ULiège > Département de physique > Spectroscopie atomique et Physique des atomes froids
Barre, L.
Lemaire, Christian ; Université de Liège - ULiège > Centre de recherches du cyclotron
Pike, V. W.
Language :
English
Title :
Ligands and tracers for PET studies of the 5-HT system--current status.
Publication date :
1992
Journal title :
International Journal of Radiation Applications and Instrumentation. Part B, Nuclear Medicine and Biology
Ågren, Reibring, Hartvig, Tedroff, Bjurling, Hornfeldt, Andersson, Lundqvist, Långström (1991) Low brain uptake of l-[11C]5-hydroxytryptophan in major depression—a positron emission tomography study on patients and healthy volunteers. Acta Psychiatrica Scandinavica 83:449.
Angelini, Speranza, Wolf, Shiue (1990) Synthesis of N-(α1, α1, α1-tri[18F]fluoro-m-tolyl)-piperazine. A potent serotonin agonist. Journal of Labelled Compounds and Radiopharmaceuticals 28:1441.
Atkins, Christman, Fowler, Hauser, Hoyte, Klopper, Lin, Wolf (1972) Organic radiopharmaceuticals labeled with isotopes of short half-life. 18F-Labeled 5- and 6-fluorotryptophan. J Nucl Med 13:713.
Barré, Lasne, Camsonne, Baron (1991) Synthesis of [11C]MDL 72222 as a potential radiopharmaceutical for the study of the 5-hydroxytryptamine 3 (5HT3) receptor. J. Labelled Cmpd. Radiopharm. 30:346.
Barnes, Costall, Naylor (1988) [3H]Zacopride identifies 5-HT3, binding sites in rat entorhinal cortex. Br. J. Pharmacol. , (Suppl.); 94:391P.
Barnes, Barnes, Champaneria, Costall, Naylor (1990) Characterization and autoradiographic localization of 5-HT3 receptor recognition sites identified with [3H]-(S)-zacopride in the forebrain of the rat. Neuropharmacology 29:1037.
Baron, Samson, Crouzel, Berridge, Chretien, Deniker, Comar, Agid (1985) Pharmacologic studies in man with PET: an investigation using 11C-labelled ketanserin, a 5HT2 receptor antagonist. J. Cereb. Bld Flow Metab. 471.
Baron, Samson, Comar, Crouzel, Deniker, Agid (1985) Etude in vivo des récepteurs sérotoninergiques centraux chez l'homme par tomographie à positons. Rev. Neurol. (Paris) 141:537.
Bénavidès, Savaki, Malgouris, Laplace, Margelidon, Daniel, Courteix, Uzan, Guérémy, Le Fur (1985) Quantitative autoradiography of [3H]indalpine binding sites in the rat brain: I. Pharmacological characterization. Journal of Neurochemistry 45:514.
Berger, Maziére, Marazano, Comar (1978) Carbon-11 labelling of the psychoactive drug O-methyl-bufotenine and its distribution in the animal organism. European Journal of Nuclear Medicine 3:101.
Berger, Maziére, Sastre, Comar (1980) Carrier-free 11C formaldehyde: an approach. Journal of Labelled Compounds and Radiopharmaceuticals 17:59.
Berger, Mazière, Knipper, Prenant, Comar (1979) Automated synthesis of 11C-labelled radiopharmaceuticals: imipramine, nicotine and methionine. The International Journal of Applied Radiation and Isotopes 30:393.
Berridge, Comar, Crouzel, Baron (1983) 11C-Labelled ketanserin: a selective serotonin S2 antagonist. Journal of Labelled Compounds and Radiopharmaceuticals 20:73.
Bjurling, Långström (1989) Synthesis of some 11C-labelled fluoro- and methyl-analogues of l-tyrosine and l-tryptophan. Doctoral dissertation at Uppsala University.
Bjurling, Antoni, Watanabe, Långström (1990) Enzymatic synthesis of carboxy-11C-labelled l-tyrosine, l-DOPA, l-tryptophan and 5-hydroxy-l-tryptophan. Acta Chemica Scandinavica 44:178.
Bjurling, Watanabe, Tokushige, Oda, Långström (1989) Synthesis of β-11C-labelled l-tryptophan and 5-hydroxy-l-tryptophan using a multi-enzymatic reaction route. Journal of the Chemical Society, Perkin Transactions 1 1331.
Bjurling, Watanabe, Malmborg, Långström (1989) Multi-enzymatic syntheses of some 11C-labelled neurotransmitter precursors: tyrosine, DOPA, tryptophan and 5-hydroxytryptophan. Journal of Labelled Compounds and Radiopharmaceuticals 26:243.
Blin, Pappata, Kiyosawa, Crouzel, Baron (1988) [18F]Setoperone: a new high affinity ligand for positron emission tomography study of the serotonin-2 receptors in baboon brain in vivo. European Journal of Pharmacology 147:73.
Blin, Sette, Fiorelli, Bletry, Elghozi, Crouzel, Baron (1990) A method for the in vivo investigation of the serotonergic 5-HT2 receptors in the human cerebral cortex using positron emission tomography and 18F-labelled setoperone. Journal of Neurochemistry 54:1744.
Boegesoe Preparation and isolation of antidepressant drug, Eur. Patent Appl., EP 347, 066; 1990.
Bradley, Engel, Feniuk, Fozard, Humphrey, Middlemiss, Mylecharane, Richardson, Saxena (1986) Proposals for the classification and nomenclature of functional receptors for 5-hydroxytryptamine. Neuropharmacology 25:563.
Chaly, Diksic (1988) Synthesis of “no-carrieradded” α-[11C]methyl-l-tryptophan. J Nucl Med 29:370.
Chirakal, Sayer, Firnau, Garnett (1988) Synthesis of F-18 labelled fluoromelatonins and 5-hydroxy-fluoro-tryptophans. Journal of Labelled Compounds and Radiopharmaceuticals 25:63.
Clark, Goulding, Roman, Palmer (1973) The preparation of fluorine-18 labelled compounds using a recirculatory neon target. Radiochem. Radioanalyt. Lett. 14:101.
Coenen, Wienhard, Stöcklin, Laufer, Hebold, Pawlik (1988) PET measurement of D2 and S2 receptor binding of 3-N-(2′-18F]fluoroethyl)spiperone in baboon brain. European Journal of Nuclear Medicine 14:80.
Crouzel, Långström, Pike, Coenen (1987) Recommendations for a practical production of [11C]methyl iodide. International Journal of Radiation Applications and Instrumentation. Part A. Applied Radiation and Isotopes 38:601.
Crouzel, Venet, Irie, Sanz, Boullais (1988) Labelling of a serotonergic ligand with 18F: [18F]setoperone. Journal of Labelled Compounds and Radiopharmaceuticals 25:403.
Crouzel, Venet, Sanz, Denis (1988) Labelling of a new serotoninergic ligand with 18F: [18F]ritanserin. Journal of Labelled Compounds and Radiopharmaceuticals 25:827.
Dannals, Ravert, Wilson, Wagner (1990) Synthesis of a selective serotonin uptake inhibitor: [11C]citalopram. International Journal of Radiation Applications and Instrumentation. Part A. Applied Radiation and Isotopes 41:541.
Dannals, Ravert, Wilson, Frost, Mayberg, Kuhar, Wagner (1989) Synthesis of a radiotracer for studying serotonin-2 receptors carbon-11 labeled N-methylketanserin. Journal of Labelled Compounds and Radiopharmaceuticals 26:195.
Dannals, Ravert, Wilson, Scheffel, Frost, Wagner (1989) Synthesiś of a radiotracer for studying serotonin uptake sites carbon-11 labelled N-methylparoxetine. Journal of Labelled Compounds and Radiopharmaceuticals 26:205.
Dennis, Dubois, Benavides, Scatton (1988) Distribution of central ω1 (benzodiazepine1) and ω2 (benzodiazepine2) receptor subtypes in the monkey and human brain. An autoradiographic study with 3H-flunitrazepam and the ω1 selective ligand 3H-zolpidem. J Pharmacol Exp Ther 247:309.
Denutte, Goethals, Cattoir, Bogaert, Vandewalle, Vandecasteele, Jonckheere, De Leenheer (1983) The production in high yield of N′-(4-[11C]methyl)-imipramine. J Nucl Med 24:1185.
Dumius, Bouhelal, Sebben, Cory, Bockaert (1988) A non-classical 5-hydroxytryptamine receptor positively coupled with adenylate cyclase in the central nervous system. Molec. Pharmacol. 34:880.
Fowler, Gallagher, MacGregor, Wolf, Ansari, Som (1977) 11C-Serotonin: a tracer for the pulmonary endothelial extraction of serotonin. J. Labelled Cmpd. Radiopharm. 13:194.
Fozard (1984) MDL 72222; a potent and highly selective antagonist at neuronal 5-hydroxytryptamine receptors. Naunyn-Schmiedeberg's Archives of Pharmacology 326:36.
Fozard (1987) 5-HT the enigma variations. Trends in Pharmacological Sciences 8:501.
Frazer, Maayani, Wolfe (1990) Subtypes of receptors for serotonin. Annual Review of Pharmacology and Toxicology 30:307.
Frost (1986) Imaging neuronal biochemistry by emission computed tomography focus on neuroreceptors. Trends in Pharmacological Sciences 7:490.
Gaddum, Picarelli (1957) Two kinds of tryptamine receptor. Br. J. Pharmacol. 12:323.
Glennon (1986) Central serotonin receptors as targets for drug research. Journal of Medicinal Chemistry 30:1.
Guillaume, Luxen, Nebeling, Argentini, Clark, Pike (1991) Recommendations for fluorine-18 production. International Journal of Radiation Applications and Instrumentation. Part A. Applied Radiation and Isotopes 42:749.
Hansch, Leo (1979) The FRAGMENT method of calculating partition coefficients. Substituent Constants for Correlation Analysis in Chemistry and Biology, Wiley, New York; .
Hartvig, Tedroff, Lundquist, Bjurling, Långström (1992) Brain kinetics of 11C-labelled tryptophan and 5-hydroxytryptophan in the brain of the Rhesus monkey measured with positron emission tomography. J. Neural Transm., Submitted to; .
Hartvig, Lindner, Tedroff, Bjurling, Chang, Tsukada, Watanabe, Långström (1992) Positron emission tomographic studies on the selectivity and saturation of 5-hydroxy-L-tryptophan de-carboxylase in the monkey brain. J. Neural. Transm., Submitted to; .
Hashimoto, Goromaru (1990) Evaluation of [3H]paroxetine as a radioligand for in vivo study of 5-hydroxytryptamine uptake sites in mouse brain. RADIOISOTOPES 39:335.
Hashimoto, Goromaru (1990) Reduction of in vivo binding of [3H]paroxetine in mouse brain by 3,4-methylenedioxymethamphetamine. Neuropharmacology 29:633.
Hashimoto, Goromaru (1990) In vivo labelling of 5-hydroxytryptamine uptake sites in mouse brain with [3H]-6-nitroquipazine. J Pharmacol Exp Ther 255:146.
Hashimoto, Inoue, Suzuki, Yamasaki, Kojima (1987) Synthesis and evaluation of [11C]cyanimipramine. Nucl. Med. Biol. 14:587.
Hayes, Washburn, Wieland, Sun, Anon, Butler, Callahan (1978) Synthesis and purification of 11C-carboxyl-labeled amino acids. The International Journal of Applied Radiation and Isotopes 29:186.
Hoyer, Middlemiss (1989) Species difference in the pharmacology of terminal 5-HT autoreceptors in mammalian brain. Trends in Pharmacological Sciences 10:130.
Hoyer, Pazos, Probst, Palacios (1986) Serotonin receptors in the human brain. I. Characterization and autoradiographic localization of 5-HT1A recognition sites. Apparent absence of 5-HT1B recognition sites. Brain Research 376:85.
Hoyer, Waeber, Neijt, Palacios (1989) 5-HT3, recognition sites in the central and peripheral nervous system: autoradiographic and radioligand binding studies. Br. J. Pharmacol. , (Suppl.); 96:7.
Hrdina (1984) Differentiation of two components of specific [3H]imipramine binding in rat brain. European Journal of Pharmacology 102:481.
Hume, Myers, Manjil, Dolan (1989) Sertraline and paroxetine fail tests in vivo as 5-HT reuptake site ligands for PET. Journal of Cerebral Blood Flow & Metabolism 9:S117.
Hume, Pascali, Pike, Turton, Ahier, Myers, Bateman, Cremer, Manjil, Dolan (1991) Citalopram: labelling with carbon-11 and evaluation in rat as a potential radioligand for in vivo PET studies of 5-HT re-uptake sites. Nucl. Med. Biol. 18:339.
Hume, Lammertsma, Bench, Pike, Pascali, Luthra, Turton, Ahier, Cremer, Dolan, Frackowiak Investigation of (+)-[N-methyl-11C]citalopram as a tracer for 5-hydroxytryptamine uptake site in vivo, Submitted; 1992.
Hyttel (1982) Citalopram-pharmacological profile of a specific serotonin uptake inhibitor with antidepressant activity. Progress in Neuro-Psychopharmacology and Biological Psychiatry 6:277.
Kilbourn, Haka, Mulholland, Jewett, Kuhl (1989) Synthesis of radiolabeled inhibitors of pre-synaptic monoamine uptake systems: [18F]GBR 13119 (DA) [11C]nisoxetine (NE), and [11C]fluoxetine (5-HT). Journal of Labelled Compounds and Radiopharmaceuticals 26:412.
Kilpatrick, Jones, Tyers (1987) Identification and distribution of 5-HT3 receptors in rat brain using radioligand binding. Nature 330:746.
Kloster, Hanus, Voges, Stöcklin (1984) 11C-Mesulergin, a potential agent for mapping the serotonin receptor: synthesis and animal experiments. J. Labelled Cmpd. Radiopharm. 21:1155.
Lasne, Pike, Turton (1989) The radiosynthesis of [N-methyl-11C]-sertraline. International Journal of Radiation Applications and Instrumentation. Part A. Applied Radiation and Isotopes 40:147.
Lemaire, Cantineau, Christiaens, Guillaume (1989) NCA Radiofluorination of altanserine a potential serotonin receptor-binding radiopharmaceutical for positron emission tomography. Journal of Labelled Compounds and Radiopharmaceuticals 26:336.
Lemaire, Cantineau, Guillaume, Plenevaux, Christiaens (1992) [18F]Altanserine, a potential radioligand for the study of serotonin receptors: radiolabeling and in vivo biological behaviour in rats. J. Nucl. Med., In press; .
Leonhardt, Titeler (1989) Serotonin 5-HT2 receptors: two states versus two subtypes. Journal of Neurochemistry 53:316.
Leonhardt, Herrick-Davis, Titeler (1989) Detection of a novel serotonin receptor sub-type (5-HT1E) in human brain: interaction with a GTP-binding protein. Journal of Neurochemistry 53:465.
Lever, Dannals, Wilson, Ravert, Scheffel, Hoffman, Hartig, Wong, Wagner (1989) Synthesis and in vivo characterization of d-(+)-(N-[11C]methyl)-2-Br-LSD: a radioligand for positron emission tomographic studies of serotonin 5-HT2 receptors. Nucl. Med. Biol. 16:697.
Leysen, Gommeren (1986) The drug-receptor dissociation time: new tool for drug research. Receptor binding affinity and drug-receptor dissociation profiles of serotonin-S2, dopamine-D2, histamine-H1 antagonists and opiates. Drug Development Research 8:119.
Liau, Sleight, Pitha, Peroutka (1991) Characterization of a novel and potent 5-hydroxytryptamine1A receptor antagonist. Pharmacology Biochemistry and Behavior 38:555.
Matzke, Meyer, Osterholz, Coates, Fimau (1991) Synthesis of 11C-labelled 5-hydroxytryptamine for the measurement of pulmonary endothelial cell function. International Journal of Radiation Applications and Instrumentation. Part A. Applied Radiation and Isotopes 42:401.
Maziére, Berger, Comar (1978) 11C-Clomipramine: synthesis and analysis. Journal of Radioanalytical Chemistry 45:453.
Mazière, Coenen, Halldin, Någren, Pike (1992) PET radioligands for dopamine receptors and re-uptake sites: chemistry and biochemistry. Nucl. Med. Biol. 19:497.
Mazière, Crouzel, Venet, Stulzaft, Sanz, Ottaviani, Sejourné, Pascal, Bisserbe (1988) Synthesis, affinity and specificity of 18F-setoperone a potential ligand for in-vivo imaging of cortical serotonin receptors. Nucl. Med. Biol. 15:463.
Middlemiss, Hibert, Fozart (1986) Drugs acting at central 5-hydroxy tryptamine a receptors. Annual Report in Medicinal Chemistry , D.M. Barley, Academic Press, San Diego, Calif; 21:41-50.
Nakamura, Edo, Hishinuma, Takahashi, Ido, Mizugaki (1989) Synthesis of 11C-labelled imipramine and its biodistribution in mice: a potential tracer for positron emission tomography. CHEMICAL & PHARMACEUTICAL BULLETIN 37:3376.
Pascali, Pike, Turton (1990) The radiosynthesis of NCA [O-methyl-11C]viqualine through an N-trityl-protected intermediate, as a potential PET radioligand for 5HT re-uptake sites. Journal of Labelled Compounds and Radiopharmaceuticals 28:1341.
Pazos, Hoyer, Palacios (1987) Mesulergine a selective serotonin-2 ligand in the rat cortex does not label these receptors in porcine and human cortex evidence for species differences in brain serotonin-2 receptors. European Journal of Pharmacology 106:531.
Pazos, Probst, Palacios (1986) Serotonin receptors in the human brain Autoradiographic mapping of serotonin-2 receptors. Neuroscience 21:123.
Peroutka, Hamik (1988) [3H]Quipazine labels 5-HT3 recognition sites in rat cortical membranes. European Journal of Pharmacology 148:297.
Perry (1990) Autoradiography of [3H]quipazine in rodent brain. European Journal of Pharmacology 187:75.
Pierce, Peroutka (1989) Evidence for distinct 5-hydroxytryptamine2 binding subtypes in cortical membrane preparations. Journal of Neurochemistry 52:656.
Pinkus, Gorbon, Sarbin, Barefoot (1989) Characterization of [3H]zacopride binding: inhibition by its (R+) enantiomer (AHR-4964), (S−) enantiomer (AHR-4965), and 5HT3 antagonists. Lorenzini Foundation, Symposium 179 on Serotonin from Cell Biology to Pharmacology and Therapeutics , Florence, Italy; 72.
Pinkus, Sarbin, Barefoot, Gordon (1989) Association of [3H]zacopride with 5-HT3 binding sites. European Journal of Pharmacology 168:355.
Plenge, Mellerup (1991) [3H]Citalopram binding to brain and platelet membranes of human and rat. Journal of Neurochemistry 56:248.
Ram (1989) Synthesis of 11C-labelled citalopram, a selective Serotonin uptake inhibitor. International Journal of Radiation Applications and Instrumentation. Part A. Applied Radiation and Isotopes 41:645.
Ram, Ehrenhaufer, Jewett (1986) Rapid reductive-carboxylation of secondary amines, one pot synthesis of N′-(4-11C-methyl)imipramine. International Journal of Radiation Applications and Instrumentation. Part A. Applied Radiation and Isotopes 37:391.
Rapport, Green, Page (1947) Purification of the substance which is responsible for vasoconstrictor activity of serum. Fedn Proc. 6:184.
Reynolds, Leslie, Grahame-Smith, Harvey (1989) Localization of 5-HT3 receptor binding sites in human dorsal vagal complex. European Journal of Pharmacology 174:127.
Sadzot, Lemaire, Cantineau, Salmon, Plenevaux, Maquet, Hermanne, Franck, Guillaume (1990) Imaging 5HT2 receptors in the human brain with PET and [18F]altanserin. Preliminary results. J. Nucl. Med. 31:1584.
Scheffel, Ricaurte (1990) Paroxetine as an in vivo indicator of 3 4-methylenedioxmethamphetamine neurotoxicity a presynaptic serotonergic positron emission tomography ligand?. Brain Research 527:89.
Schmidt, Peroutka (1989) Three dimensional steric modelling of the 5-hydroxytryptamine3 receptor pharmacophore. Three dimensional steric modelling of the 5-hydroxytryptamine3 receptor pharmacophore 36:505.
Sedvall, Farde, Persson, Wiesel (1986) Imaging of neurotransmitter receptors in the living human brain. Archives of General Psychiatry 43:995.
Suehiro, Wilson, Scheffel, Dannals, Ravert, Wagner (1991) Radiosynthesis and evaluation of N-(3-[18F]fluoropropyl)paroxetine as a radiotracer for in vivo labeling of serotonin re-uptake sites by PET. Nucl. Med. Biol. 18:791.
Takahashi, Takahashi, Ido, Yanai, Iwato, Ishiwata, Nozoe (1985) 11C-Labelling of indolealkylamine alkaloids and the comparative study of their tissue distributions. The International Journal of Applied Radiation and Isotopes 36:965.
Tedroff, Hartvig, Ågren, Bjurling, Långström (1991) Monoamine precursors in PET research—biochemical issues and functional significance. Brain Dopaminergic Systems: Imaging with Positron Emission Tomography , J.C. Baron, D. Comar, L. Farde, J.L. Martinot, B. Mazoyer, Developments in Nuclear Medicine, Kluwer, The Netherlands; 20:39.
Twarog, Page (1953) Serotonin content of some mammalian tissues and urine and a method for its determination. Am J Physiol 175:157.
Vialli, Erpsamer (1933) Cellule enterocromaffini e cellule basigranulose acidofile nei vertebrata. Zeitschrift für Zellforschung und Mikroskopische Anatomie 19:743.
Waeber, Hoyer, Palacios (1989) 5HT3 receptors in the human brain: autoradiographic visualisation using 3H-ICS 205930. Neuroscience 31:393.
Wagner (1986) Quantitative imaging of neuroreceptors in the living human brain. Seminars in Nuclear Medicine 16:51.
Washburn, Sun, Byrd, Hayes, Butler (1979) dl-[Carboxyl-11C]tryptophan, a potential agent for pancreatic imaging; production and preclinical investigations. J Nucl Med 20:857.
Watling (1989) 5HT3 receptor agonists and antagonists. Neurotransmissions 5:1.
Wong, Lever, Hartig, Dannals, Villemagne, Hoffmann, Wilson, Ravert, Links, Scheffel, Wagner (1987) Localization of serotonin 5-HT2 receptors in living human brain by positron emission tomography using N-([11C]--methyl)-2-Br LSD. Synapse 1:393.
Xiong, Nelson (1989) Characterization of a [3H]-5-hydroxytryptamine binding site in rabbit caudate nucleus that differs from the 5-HT1A, 5-HT1B, 5-HT1C and 5-HT1D subtypes. Life Sciences 45:1433.
Yanai, Takahashi, Ishiwata, Takahashi, Kawashima, Iwata, Ido (1984) 11C-Labelled indolealkylamines as potential serotonin1 receptor mapping agents: synthesis and biodistribution. J. Labelled Cmpd. Radiopharm. 21:1152.