title: A new single-photon emission computed tomography (SPECT) imaging agent for serotonin transporters: [(125)I]Flip-IDAM, (2-((2-((dimethylamino)methyl)-4-iodophenyl)thio)phenyl)methanol.
abstract: 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 [(125)I]-IDAM as radioligand in rat brain tissue homogenates (K(i) = 0.03 nM). New [(125)I]Flip-IDAM exhibited excellent binding affinity to SERT binding sites with a high hypothalamus to cerebellum ratio of 4 at 30 min 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 (123)I, may be a useful imaging agent for mapping SERT binding sites in the human brain.
authors.affiliation: Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Pinguan
authors.initials: P
authors.lastname: Zheng
authors.forename: Brian P
authors.initials: BP
authors.lastname: Lieberman
authors.forename: Karl
authors.initials: K
authors.lastname: Ploessl
authors.forename: Laetitia
authors.initials: L
authors.lastname: Lemoine
authors.forename: Sara
authors.initials: S
authors.lastname: Miller
authors.forename: Hank F
authors.initials: HF
authors.lastname: Kung
mesh_terms: D000818:Animals; D001596:Benzylamines / Q000138:chemical synthesis / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D007457:Iodine Radioisotopes / Q000737:chemistry*; D015394:Molecular Structure; D011485:Protein Binding; D019275:Radiopharmaceuticals / Q000737:chemistry*; D051381:Rats; D050486:Serotonin Plasma Membrane Transport Proteins / Q000737:chemistry*; D013440:Sulfides / Q000138:chemical synthesis / Q000737:chemistry*; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: C581853:(2-((2-((dimethylamino)methyl)-4-iodophenyl)thio)phenyl)methanol; D001596:Benzylamines; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D050486:Serotonin Plasma Membrane Transport Proteins; D013440:Sulfides