Distribution of 5HT_2A receptors in the human brain: comparison of data in vivo and post mortem

Summary

Aim: The study presented here firstly compars the distribution of the binding potential of the serotonin-5HT_2A 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-5HT_2A 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 5HT_2A 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-5HT_2A-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 5HT_2A-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 5HT_2A-Rezeptoren. Unterschiede der Rezeptordichte von mehr als 18% können mit der In-vivo-Methode detektiert werden.

Keywords

Serotonin receptor - 5-HT_2A - PET - autoradiography

Schlüsselwörter

Serotoninrezeptor - 5HT_2A - PET - Autoradiographie

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