No change in [¹¹C]CUMI-101 binding to 5-HT(1A) receptors after intravenous citalopram in human

TY - JOUR

T1 - No change in [¹¹C]CUMI-101 binding to 5-HT(1A) receptors after intravenous citalopram in human

AU - Pinborg, Lars H

AU - Feng, Ling

AU - Haahr, Mette E

AU - Gillings, Nic

AU - Dyssegaard, Agnete

AU - Madsen, Jacob

AU - Svarer, Claus

AU - Yndgaard, Stig

AU - Kjaer, Troels W

AU - Parsey, Ramin V

AU - Hansen, Hanne D

AU - Ettrup, Anders

AU - Paulson, Olaf B

AU - Knudsen, Gitte M

N1 - Copyright © 2012 Wiley Periodicals, Inc.

PY - 2012/10

Y1 - 2012/10

N2 - The main objective of this study was to determine the sensitivity of [ 11C]CUMI-101 to citalopram challenge aiming at increasing extracellular 5-HT. CUMI-101 has agonistic properties in human embryonic kidney 293 cells transfected with human recombinant 5-HT 1A receptors (Hendry et al. [2011] Nucl Med Biol 38:273-277; Kumar et al. [2006] J Med Chem 49:125-134) and has previously been demonstrated to be sensitive to bolus citalopram in monkeys (Milak et al. [2011] J Cereb Blood Flow Metab 31:243-249). We studied six healthy individuals. Two PET-scans were performed on the same day in each individual before and after constant infusion of citalopram (0.15 mg/kg). The imaging data were analyzed using two tissue compartment kinetic modeling with metabolite corrected arterial input and Simplified Reference Tissue Modeling using cerebellum as a reference region. There was no significant difference in regional distribution volume or non-displaceable binding potential values before and after citalopram infusion. The mean receptor occupancy was 0.03 (range -0.14 to 0.17). Our data imply that [ 11C]CUMI-101 binding is not sensitive to citalopram infusion in humans. Synapse, 2012.

AB - The main objective of this study was to determine the sensitivity of [ 11C]CUMI-101 to citalopram challenge aiming at increasing extracellular 5-HT. CUMI-101 has agonistic properties in human embryonic kidney 293 cells transfected with human recombinant 5-HT 1A receptors (Hendry et al. [2011] Nucl Med Biol 38:273-277; Kumar et al. [2006] J Med Chem 49:125-134) and has previously been demonstrated to be sensitive to bolus citalopram in monkeys (Milak et al. [2011] J Cereb Blood Flow Metab 31:243-249). We studied six healthy individuals. Two PET-scans were performed on the same day in each individual before and after constant infusion of citalopram (0.15 mg/kg). The imaging data were analyzed using two tissue compartment kinetic modeling with metabolite corrected arterial input and Simplified Reference Tissue Modeling using cerebellum as a reference region. There was no significant difference in regional distribution volume or non-displaceable binding potential values before and after citalopram infusion. The mean receptor occupancy was 0.03 (range -0.14 to 0.17). Our data imply that [ 11C]CUMI-101 binding is not sensitive to citalopram infusion in humans. Synapse, 2012.

U2 - 10.1002/syn.21579

DO - 10.1002/syn.21579

M3 - Journal article

SN - 0887-4476

VL - 66

SP - 880

EP - 884

JO - Synapse

JF - Synapse

IS - 10

ER -