An alternative for PET imaging the 5-HT2A receptor is the [11C]volinanserin (MDL-100,907) radioligand.18F-altanserin and3H-volinanserin have shown very comparable binding.[3]Both altanserin and MDL 100,907 are 5-HT2A receptorantagonists.[3][18F]-setoperone can also be used in PET.
An alternativeSPECT radioligand is the [123I]-5-I-R91150 receptor antagonist.[4]
A rapid chemical synthesis of fluorine-18 andH-2 dual-labeled altanserin has been described.[5]
Other ligands for other parts of the serotonin system used in PET studies are, e.g.,DASB,ketanserin, andWAY-100635.
APET scanner. Human experiments with fluorine-18 altanserin are performed in these types of brain scanners.
As of 2007[update] altanserin is probably not used in clinical routine.However, there have been performed several research-basedneuroimaging studies with the compound in humans since the 1990s.[6][7] Some of these studies have considered methodogical issues such as thereproducibility of the method[8][9]or whether to use constant infusion[10] or bolus-infusion[11] delivery of altanserin.Other studies have compared altanserinbinding to subject variables such asage,personality trait andneuropsychiatric disorder.
The altanserin PET scan shows high binding inneocortex.Thecerebellum is often regarded as a region with no specific 5-HT2A binding and the brain region is used as a reference in some studies, even though anautoradiography study has found nonnegligible levels of 5-HT2A binding in the human cerebellum,[12]and another type of study have observed strongimmunoreaction against 5-HT2A receptor protein in ratPurkinje cells.[13]
In the table below is an overview of the results of altanserin binding seen in human PET-studies.A consistent finding across altanserin studies has been that the binding decreases withage.This is in line within vitro studies of the 5-HT2A receptor,[14] as well as PET studies with other radioligands that binds to the receptor.[15]
The result for recoveredbulimia-typeanorexia nervosa[16]is in line with a SPECT study of anorexia nervosa patients, that found a decrease in frontal, occipital and parietal cortices.[4]The results of PET studies of the 5-HT2A indepression has been mixed.[17]
Altanserin binding has also been examine intwins, where one study showed higher correlation between monozygotic twin pairs than between dizygotic twin pairs, giving evidence that the binding is "strongly genetically determined".[18]
The reaction of 4-(4-fluorobenzoyl)piperidine [56346-57-7] (1) with 2-bromoethylamine [107-09-5] gives [1-(2-aminoethyl)piperidin-4-yl]-(4-fluorophenyl)methanone [83763-22-8] (2). The reaction of the terminal amino group with thiophosgene [463-71-8] leads to the corresponding isothiocyanate derivative, 4-fluorophenyl 1-(2-isothiocyanatoethyl)piperidin-4-yl ketone [84946-22-5] (3). Upon reaction of this reactive intermediate with ethyl anthranilate [87-25-2] (4), the transient addition product might be expected to be initially formed (5'). An intramolecular lactamization to the heterocyclic ring then occurs giving altanserin (6).
^Lemaire C, Cantineau R, Guillaume M, Plenevaux A, Christiaens L (December 1991). "Fluorine-18-altanserin: a radioligand for the study of serotonin receptors with PET: radiolabeling and in vivo biologic behavior in rats".Journal of Nuclear Medicine.32 (12):2266–2272.PMID1744713.
^Biver F, Lotstra F, Monclus M, Dethy S, Damhaut P, Wikler D, et al. (May 1997). "In vivo binding of [18F]altanserin to rat brain 5HT2 receptors: a film and electronic autoradiographic study".Nuclear Medicine and Biology.24 (4):357–360.doi:10.1016/s0969-8051(97)00054-1.hdl:2268/144404.PMID9257335.
^abKristiansen H, Elfving B, Plenge P, Pinborg LH, Gillings N, Knudsen GM (December 2005). "Binding characteristics of the 5-HT2A receptor antagonists altanserin and MDL 100907".Synapse.58 (4):249–257.doi:10.1002/syn.20205.PMID16206185.S2CID19110277.
^abAudenaert K, Van Laere K, Dumont F, Vervaet M, Goethals I, Slegers G, et al. (February 2003). "Decreased 5-HT2a receptor binding in patients with anorexia nervosa".Journal of Nuclear Medicine.44 (2):163–169.PMID12571204.
^abTan PZ, Baldwin RM, Fu T, Charney DS, Innis RB (1999). "Rapid synthesis of F-18 and H-2 dual-labeled altanserin, a metabolically resistant PET ligand for 5-HT2a receptors".Journal of Labelled Compounds and Radiopharmaceuticals.42 (5):457–467.doi:10.1002/(SICI)1099-1344(199905)42:5<457::AID-JLCR206>3.0.CO;2-0.ISSN0362-4803.
^Biver F, Goldman S, Luxen A, Monclus M, Forestini M, Mendlewicz J, Lotstra F (September 1994). "Multicompartmental study of fluorine-18 altanserin binding to brain 5HT2 receptors in humans using positron emission tomography".European Journal of Nuclear Medicine.21 (9):937–946.doi:10.1007/BF00238117.PMID7995287.S2CID20200751.
^Haugbøl S, Pinborg LH, Arfan HM, Frøkjaer VM, Madsen J, Dyrby TB, et al. (June 2007). "Reproducibility of 5-HT2A receptor measurements and sample size estimations with [18F]altanserin PET using a bolus/infusion approach".European Journal of Nuclear Medicine and Molecular Imaging.34 (6):910–915.doi:10.1007/s00259-006-0296-y.PMID17195073.S2CID1828118.
^Eastwood SL, Burnet PW, Gittins R, Baker K, Harrison PJ (November 2001). "Expression of serotonin 5-HT(2A) receptors in the human cerebellum and alterations in schizophrenia".Synapse.42 (2):104–114.doi:10.1002/syn.1106.PMID11574947.S2CID40304220.
^Marcusson JO, Morgan DG, Winblad B, Finch CE (October 1984). "Serotonin-2 binding sites in human frontal cortex and hippocampus. Selective loss of S-2A sites with age".Brain Research.311 (1):51–56.doi:10.1016/0006-8993(84)91397-0.PMID6488044.S2CID1203974.
^Wong DF, Wagner HN, Dannals RF, Links JM, Frost JJ, Ravert HT, et al. (December 1984). "Effects of age on dopamine and serotonin receptors measured by positron tomography in the living human brain".Science.226 (4681):1393–1396.Bibcode:1984Sci...226.1393W.doi:10.1126/science.6334363.PMID6334363.S2CID24278577.
^Biver F, Lotstra F, Monclus M, Wikler D, Damhaut P, Mendlewicz J, Goldman S (February 1996). "Sex difference in 5HT2 receptor in the living human brain".Neuroscience Letters.204 (1–2):25–28.doi:10.1016/0304-3940(96)12307-7.PMID8929969.S2CID43416706.
^Erritzoe D, Frokjaer VG, Haugbol S, Marner L, Svarer C, Holst K, et al. (May 2009). "Brain serotonin 2A receptor binding: relations to body mass index, tobacco and alcohol use".NeuroImage.46 (1):23–30.doi:10.1016/j.neuroimage.2009.01.050.PMID19457377.S2CID26525667.
^Frokjaer VG, Mortensen EL, Nielsen FA, Haugbol S, Pinborg LH, Adams KH, et al. (March 2008). "Frontolimbic serotonin 2A receptor binding in healthy subjects is associated with personality risk factors for affective disorder".Biological Psychiatry.63 (6):569–576.doi:10.1016/j.biopsych.2007.07.009.PMID17884017.S2CID25979780.
^Biver F, Wikler D, Lotstra F, Damhaut P, Goldman S, Mendlewicz J (November 1997). "Serotonin 5-HT2 receptor imaging in major depression: focal changes in orbito-insular cortex".The British Journal of Psychiatry.171 (5):444–448.doi:10.1192/bjp.171.5.444.PMID9463603.S2CID38577128.
^Mintun MA, Sheline YI, Moerlein SM, Vlassenko AG,Huang Y, Snyder AZ (February 2004). "Decreased hippocampal 5-HT2A receptor binding in major depressive disorder: in vivo measurement with [18F]altanserin positron emission tomography".Biological Psychiatry.55 (3):217–224.doi:10.1016/j.biopsych.2003.08.015.PMID14744461.S2CID24849671.
^Hurlemann R, Matusch A, Kuhn KU, Berning J, Elmenhorst D, Winz O, et al. (January 2008). "5-HT2A receptor density is decreased in the at-risk mental state".Psychopharmacology.195 (4):579–590.doi:10.1007/s00213-007-0921-x.PMID17899021.S2CID7784253.
^Hurlemann R, Boy C, Meyer PT, Scherk H, Wagner M, Herzog H, et al. (December 2005). "Decreased prefrontal 5-HT2A receptor binding in subjects at enhanced risk for schizophrenia".Anatomy and Embryology.210 (5–6):519–523.doi:10.1007/s00429-005-0036-2.PMID16187138.S2CID4113675.
^Rosier A, Dupont P, Peuskens J, Bormans G, Vandenberghe R, Maes M, et al. (November 1996). "Visualisation of loss of 5-HT2A receptors with age in healthy volunteers using [18F]altanserin and positron emission tomographic imaging".Psychiatry Research.68 (1):11–22.doi:10.1016/S0925-4927(96)02806-5.PMID9027929.S2CID32317795.
^Meltzer CC, Smith G, Price JC, Reynolds CF, Mathis CA, Greer P, et al. (November 1998). "Reduced binding of [18F]altanserin to serotonin type 2A receptors in aging: persistence of effect after partial volume correction".Brain Research.813 (1):167–171.doi:10.1016/S0006-8993(98)00909-3.PMID9824691.S2CID21884218.
^Adams KH, Pinborg LH, Svarer C, Hasselbalch SG, Holm S, Haugbøl S, et al. (March 2004). "A database of [(18)F]-altanserin binding to 5-HT(2A) receptors in normal volunteers: normative data and relationship to physiological and demographic variables".NeuroImage.21 (3):1105–1113.doi:10.1016/j.neuroimage.2003.10.046.PMID15006678.S2CID24403109.
^Hasselbalch SG, Madsen K, Svarer C, Pinborg LH, Holm S, Paulson OB, et al. (December 2008). "Reduced 5-HT2A receptor binding in patients with mild cognitive impairment".Neurobiology of Aging.29 (12):1830–1838.doi:10.1016/j.neurobiolaging.2007.04.011.PMID17544547.S2CID23665678.
^Meltzer CC, Price JC, Mathis CA, Greer PJ, Cantwell MN, Houck PR, et al. (December 1999). "PET imaging of serotonin type 2A receptors in late-life neuropsychiatric disorders".The American Journal of Psychiatry.156 (12):1871–1878.doi:10.1176/ajp.156.12.1871.PMID10588399.S2CID7678215.
^EP0013612 idem Jan Vandenberk, Ludo Kennis, Marcel Van der Aa, Albert Van Heertum,U.S. patent 4,522,945 (1985 to Janssen Pharmaceutica N.V.).
^Massarweh G, Kovacevic M, Rosa-Neto P, Evans AC, Diksic M, Schirrmacher R (November 2009). "Time-efficient and convenient synthesis of [(18)F]altanserin for human PET imaging by a new work-up procedure".Applied Radiation and Isotopes.67 (11):2040–2043.doi:10.1016/j.apradiso.2009.07.020.PMID19692252.
^Monclus M, Van Naemen J, Mulleneers E, Damhaut P, Luxen A, Goldman S (March 1998). "Automatic Synthesis of [(18)F]Altanserin, a Radiopharmaceutical for Positron Emission Tomographic Studies of the Serotonergic Type-2 Receptors".Clinical Positron Imaging.1 (2):111–116.doi:10.1016/s1095-0397(98)00005-3.hdl:2268/144402.PMID14516599.
