Brain imaging of serotonin 4 receptors in humans with [11C]SB207145-PET
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Brain imaging of serotonin 4 receptors in humans with [11C]SB207145-PET. / Marner, Lisbeth; Gillings, Nic; Madsen, Karine; Erritzoe, David; Baaré, William F C; Svarer, Claus; Hasselbalch, Steen G; Knudsen, Gitte M.
In: NeuroImage, Vol. 50, No. 3, 15.04.2010, p. 855-61.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Brain imaging of serotonin 4 receptors in humans with [11C]SB207145-PET
AU - Marner, Lisbeth
AU - Gillings, Nic
AU - Madsen, Karine
AU - Erritzoe, David
AU - Baaré, William F C
AU - Svarer, Claus
AU - Hasselbalch, Steen G
AU - Knudsen, Gitte M
N1 - Copyright 2010 Elsevier Inc. All rights reserved.
PY - 2010/4/15
Y1 - 2010/4/15
N2 - Pharmacological stimulation of the serotonin 4 (5-HT(4)) receptor has shown promise for treatment of Alzheimer's disease and major depression. A new selective radioligand, [(11)C]SB207145, for positron emission tomography (PET) was used to quantify brain 5-HT(4) receptors in sixteen healthy subjects (20-45 years, 8 males) using the simplified reference tissue model. We tested within our population the effect of age and other demographic factors on the endpoint. In seven subjects, we tested the vulnerability of radioligand binding to a pharmacolological challenge with citalopram, which is expected to increase competition from endogenous serotonin. Given radiotracer administration at a range of specific activities, we were able to use the individual BP(ND) measurements for population-based estimation of the saturation binding parameters; B(max) ranged from 0.3 to 1.6 nM. B(max) was in accordance with post-mortem brain studies (Spearman's r=0.83, p=0.04), and the regional binding potentials, BP(ND), were on average 2.6 in striatum, 0.42 in prefrontal cortex, and 0.91 in hippocampus. We found no effect of sex but a decreased binding with age (p=0.046). A power analysis showed that, given the low inter-and intrasubject variation, use of the present method will enable detection of a 15% difference in striatum with only 7-13 subjects in a 2-sample test and with only 4-5 subjects in a paired test. The citalopram challenge did not discernibly alter [(11)C]SB207145 binding. In conclusion, the 5-HT(4) receptor binding in human brain can be reliably assessed with [(11)C]SB207145, which is encouraging for future PET studies of drug occupancy or patients with neuropsychiatric disorders.
AB - Pharmacological stimulation of the serotonin 4 (5-HT(4)) receptor has shown promise for treatment of Alzheimer's disease and major depression. A new selective radioligand, [(11)C]SB207145, for positron emission tomography (PET) was used to quantify brain 5-HT(4) receptors in sixteen healthy subjects (20-45 years, 8 males) using the simplified reference tissue model. We tested within our population the effect of age and other demographic factors on the endpoint. In seven subjects, we tested the vulnerability of radioligand binding to a pharmacolological challenge with citalopram, which is expected to increase competition from endogenous serotonin. Given radiotracer administration at a range of specific activities, we were able to use the individual BP(ND) measurements for population-based estimation of the saturation binding parameters; B(max) ranged from 0.3 to 1.6 nM. B(max) was in accordance with post-mortem brain studies (Spearman's r=0.83, p=0.04), and the regional binding potentials, BP(ND), were on average 2.6 in striatum, 0.42 in prefrontal cortex, and 0.91 in hippocampus. We found no effect of sex but a decreased binding with age (p=0.046). A power analysis showed that, given the low inter-and intrasubject variation, use of the present method will enable detection of a 15% difference in striatum with only 7-13 subjects in a 2-sample test and with only 4-5 subjects in a paired test. The citalopram challenge did not discernibly alter [(11)C]SB207145 binding. In conclusion, the 5-HT(4) receptor binding in human brain can be reliably assessed with [(11)C]SB207145, which is encouraging for future PET studies of drug occupancy or patients with neuropsychiatric disorders.
KW - Adult
KW - Aging
KW - Brain
KW - Brain Mapping
KW - Citalopram
KW - Corpus Striatum
KW - Female
KW - Hippocampus
KW - Humans
KW - Male
KW - Middle Aged
KW - Piperidines
KW - Positron-Emission Tomography
KW - Prefrontal Cortex
KW - Receptors, Serotonin, 5-HT4
KW - Serotonin Uptake Inhibitors
KW - Sex Characteristics
KW - Young Adult
U2 - 10.1016/j.neuroimage.2010.01.054
DO - 10.1016/j.neuroimage.2010.01.054
M3 - Journal article
C2 - 20096787
VL - 50
SP - 855
EP - 861
JO - NeuroImage
JF - NeuroImage
SN - 1053-8119
IS - 3
ER -
ID: 34091310