Subscribe to RSS
DOI: 10.1055/s-0038-1623896
Distribution of 5HT2A receptors in the human brain: comparison of data in vivo and post mortem
Verteilung der 5HT2A-Rezeptoren im menschlichen Gehirn: Datenvergleich in vivo und post mortemPublication History
Received:
29 November 2001
04 April 2002
Publication Date:
11 January 2018 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00034924/200204/lookinside/thumbnails/10-1055-s-0038-1623896_de-1.jpg)
Summary
Aim: The study presented here firstly compars the distribution of the binding potential of the serotonin-5HT2A receptor as measured in vivo with data of receptor density taken from literature. Secondly, the sensitivity of the method to detect gradual differences in receptor densities is evaluated. Methods: Positron emission tomography (PET) studies were carried out in 6 healthy volunteers using the selective serotonin-5HT2A ligand 18F-altanserin. The binding potential was quantified in 12 regions using Logan’s graphical method and the equilibrium method. These data were compared to the distribution of receptor density as taken from literature. Results: The binding data in vivo correlated to autoradiography data (post mortem) with r = 0.83 (Pearson regression coefficient; p <0.0001). A difference in the receptor density between two regions could be detected with p <0.05 when it amounted at least to 18%. Conclusion: This study demonstrates a good agreement between in vivo data obtained with 18F-altanserin and PET in healthy volunteers and the true autoradiographically determined distribution of 5HT2A receptors in human brains. The in vivo method seems to be sensitive enough to detect changes in receptor density of more than 18%.
Zusammenfassung
Ziel: Vergleich der Verteilung der in vivo gemessenen Bindungspotentiale der Serotonin-5HT2A-Rezeptoren im menschlichen Gehirn mit der aus der Literatur bekannten Verteilung und Bestimmung der Sensitivität der Methode für den Nachweis kleiner Veränderungen in der Rezeptordichte. Methoden: Sechs gesunde Probanden wurden mit dem selektiven 5HT2A-Rezeptorliganden 18F-Altanserin und Positronenemissionstomographie (PET) untersucht. Die Quantifizierung des Bindungspotentials dieses Tracers erfolgte in 12 Hirnregionen sowohl nach Logans graphischer Methode als auch nach der Equilibrium-methode. Ergebnisse: Die in vivo gemessenen Bindungspotentiale und die autoradiographisch ermittelten Literaturdaten korrelierten in den 12 Regionen mit r = 0,83 (Pearson-Korrelationskoeffizient; p <0,0001). Unterschiede in der Rezeptordichte zweier Regionen wurden signifikant (p <0,05), wenn sie mehr als ca. 18% betrugen. Schlussfolgerung: Diese Studie demonstriert die Übereinstimmung von in vivo mit 18F-Altanserin und PET gemessenen Daten von gesunden Personen mit der autoradiographisch bestimmten Verteilung zerebraler 5HT2A-Rezeptoren. Unterschiede der Rezeptordichte von mehr als 18% können mit der In-vivo-Methode detektiert werden.
-
References
- 1 Blin J, Pappata S, Kiyosawa M. et al. [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: 73-82.
- 2 Biver F, Goldman S, Luxen A. et al. Multicompartmental study of fluorine-18 altanserin binding to brain 5HT2 receptors in humans using positron emission tomography. Eur J Nucl Med 1994; 21: 937-46.
- 3 Burns HD, Dannals RF, Langstrom B. et al. (3-N-[11C]methyl)spiperone, a ligand binding to dopamine receptors: radiochemical synthesis and biodistribution studies in mice. J Nucl Med 1984; 25: 1222-7.
- 4 Bush G, Luu P, Posner MI. Cognitive and emotional influences in anterior cingulate cortex. Trends Cogn Sci 2000; 4: 215-22.
- 5 Eckelman WC. Sensitivity of new radiopharmaceuticals. Nucl Med Biol 1998; 25: 169-73.
- 6 Larisch R, Klimke A, Mayoral F. et al. Disturbance of serotonin 5HT2 receptors in remitted patients suffering from hereditary depressive disorder. Nucl Med 2001; 40: 129-34.
- 7 Lemaire C, Cantineau R, Guillaume M. et al. Fluorine-18-altanserin: a radioligand for the study of serotonin receptors with PET: radio-labeling and in vivo biologic behavior in rats. J Nucl Med 1991; 32: 2266-72.
- 8 Leonard BE. Serotonin receptors and their function in sleep, anxiety disorders and depression. Psychother Psychosom 1996; 65: 66-75.
- 9 Logan J, Fowler JS, Volkow ND. et al. Graphical analysis of reversible radioligand binding from time-activity measurements applied to [N-11Cmethyl]-cocaine PET studies in human subjects. J Cereb Blood Flow Metab 1990; 10: 740-7.
- 10 Maesden CA. The neuropharmacology of serotonin in the central nervous system. In: Feighner JP, Boyer WF. (eds). Selective serotonin re-uptake inhibitors. Chichester, New York, Brisbane, Toronto, Singapore: John Wiley & Sons; 1996: 1-34.
- 11 Pazos A, Probst A, Palacios JM. Serotonin receptors in the human brain-IV. Autoradio-graphic mapping of serotonin-2 receptors. Neuroscience 1987; 21: 123-39.
- 12 Sadzot B, Lemaire C, Maquet P. et al. Serotonin 5HT2 receptor imaging in the human brain using positron emission tomography and a new radioligand, [18F]altanserin: results in young normal controls. J Cereb Blood Flow Metab 1995; 15: 787-97.
- 13 Smith GS, Price JC, Lopresti BJ. et al. Test-retest variability of serotonin 5-HT2A receptor binding measured with positron emission tomography and [18F]altanserin in the human brain. Synapse 1998; 30: 380-92.
- 14 van Dyck CH, Tan PZ, Baldwin RM. et al. PET quantification of 5-HT2A receptors in the human brain: a constant infusion paradigm with [18F]altanserin. J Nucl Med 2000; 41: 234-41.
- 15 Economo v. CF Koskinas GN. Die Cytoarchitektonik der Hirnrinde des erwachsenen Menschen. Wien, Berlin: Springer; 1925
- 16 Wienhard K, Coenen HH, Pawlik G. et al. PET studies of dopamine receptor distribution using [18F]fluoroethylspiperone: findings in disorders related to the dopaminergic system. J Neural Transm Gen Sect 1990; 81: 195-213.