A new single-photon emission computed tomography (SPECT) imaging agent for serotonin transporters: [125I]Flip-IDAM, (2-((2-((dimethylamino)methyl)-4-iodophenyl)thio)phenyl)methanol

New ligands for in vivo brain imaging of serotonin transporter (SERT) with single photon emission tomography (SPECT) were prepared and evaluated. An efficient synthesis and radiolabeling of a biphenylthiol, FLIP-IDAM, 4, was accomplished. The affinity of FLIP-IDAM was evaluated by an in vitro inhibitory binding assay using [125I]-IDAM as radioligand in rat brain tissue homogenates (Ki=0.03nM). New [125I]Flip-IDAM exhibited excellent binding affinity to SERT binding sites with a high hypothalamus to cerebellum ratio of 4 at 30min post iv injection. The faster in vivo kinetics for brain uptake and a rapid washout from non-specific regions provide excellent signal to noise ratio. This new agent, when labeled with 123I, may be a useful imaging agent for mapping SERT binding sites in the human brain.