In vitro and in vivo characterisation of [11C]-DASB:: a probe for in vivo measurements of the serotonin transporter by positron emission tomography

3-Amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile, labeled with carbon-11 ([Cl-11-DASB), is a recently introduced radiotracer for imaging the serotonin transporter (SERT) by positron emission tomography (PET). A series of in vitro and in vivo experiments were performed to further characterise the properties of [C-11]-DASB as an in vivo imaging agent for SERT. In vitro binding assays confirmed that DASB binds specifically to SERT,kith nanomolar affinity and high selectivity over a large number of other receptors, ion-channels and enzymes in the central nervous system. Ex vivo, [C-11]-DASB binding in rat brain was shown to be saturable (ED50 of 56 nmoles/kg). and sensitive to both the number of available SERT binding sites and the number of viable serotonin neurons. Estimates of the radiation dose in man were extrapolated from rat biodistribution data effective dose 5.5 E-03 mSv/MBq; critical organ-urinary bladder wall). Together with previous studies, the present findings indicate that [C-11]-DASB is a very useful radiopharmaceutical for probing changes in SERT densities using PET imaging in the living human brain, (C) 2002 Elsevier Science Inc. All rights reserved.