Imaging the serotonin transporter with positron emission tomography: initial human studies with [11C]DAPP and [11C]DASB.
Two novel radioligands, N,N-dimethyl-2-(2-amino-4-methoxyphenylthio) b enzylamine (DAPP) and (N,N-dimethyl-2-(2-amino-4-cyanophenylthio) benzylamine (D ASB), were radiolabeled with carbon-11 and evaluated as in vivo probes of the serotonin transporter (SERT) using positron emission tomography (PET). Both compounds are highly selective, with nanomolar affinity for the serotonin transporter and micromolar affinity for the dopamine and norepinephrine transporters. Six volunteers were imaged twice, once with each of the two radioligands. Both ligands displayed very good brain penetration and selective retention in regions rich in serotonin reuptake sites. Both had similar brain uptake and kinetics, but the cyano analogue, [11C]DASB, had a slightly higher brain penetration in all subjects. Plasma analysis revealed that both radiotracers were rapidly metabolized to give mainly hydrophilic species as determined by reverse-phase high-performance liquid chromatography. Inhibition of specific binding to the SERT was demonstrated in three additional subjects imaged with [11C]DASB following an oral dose of the selective serotonin reuptake blocker citalopram. These preliminary studies indicate that both these substituted phenylthiobenzylamines have highly suitable characteristics for probing the serotonin reuptake system with PET in humans.
Houle
S
S
Vivian Rakoff PET Centre, University of Toronto, ON, Canada.
Ginovart
N
N
Hussey
D
D
Meyer
J H
JH
Wilson
A A
AA
D000328:Adult; D001596:Benzylamines / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002352:Carrier Proteins / Q000032:analysis*; D005260:Female; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis*; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; D014055:Tomography, Emission-Computed
D001596:Benzylamines; D002250:Carbon Radioisotopes; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; C420885:N,N-dimethyl-2-(2-amino-4-cyanophenylthio)benzylamine; C420884:N,N-dimethyl-2-(2-amino-4-methoxyphenylthio)benzylamine; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins