Brain imaging of serotonin 4 receptors in humans with [11C]SB207145-PET.
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.
Marner
Lisbeth
L
The Neuroscience Centre, Copenhagen University Hospital Rigshospitalet, Copenhagen O, Denmark. lisbeth.marner@nru.dk
Gillings
Nic
N
Madsen
Karine
K
Erritzoe
David
D
Baaré
William F C
WF
Svarer
Claus
C
Hasselbalch
Steen G
SG
Knudsen
Gitte M
GM
D000328:Adult; D000375:Aging; D001921:Brain / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism*; D001931:Brain Mapping / Q000379:methods*; D015283:Citalopram / Q000494:pharmacology; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D010880:Piperidines; D049268:Positron-Emission Tomography / Q000379:methods*; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D044422:Receptors, Serotonin, 5-HT4 / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D012727:Sex Characteristics; D055815:Young Adult
D015283:Citalopram; D010880:Piperidines; D044422:Receptors, Serotonin, 5-HT4; D017367:Selective Serotonin Reuptake Inhibitors; C534709:SB 207145