Abstract
Imaging serotonin transporters (SERT) is an emerging research tool potentially useful to cast light on the mechanisms of drug action as well as to monitor the treatment of depressed patients. We have prepared two new derivatives of 3, 2-(2-(dimethylaminomethyl)phenoxy)-5-iodophenylamine (4) and 2-(2-(dimethylaminomethyl)benzyl)-5-iodophenylamine (5) (K(i) for SERT = 0.37 and 48.6 nM, respectively). Both [(125)I]4 and [(125)I]5 displayed excellent brain uptakes in rats, and they showed a highest uptake in hypothalamus (between 60 and 240 min), a region populated with the highest density of SERT. The specific uptake of [(125)I]4 in the hypothalamus resulted in a target to nontarget ratio ([hypothalamus-cerebellum]/cerebellum) of 4.3 at 2 h. Autoradiography of rat brain sections (ex vivo at 2 h) of [(125)I]4 showed an excellent regional distribution pattern consistent with known SERT localization. These data suggest that [(123)I]4 may be useful for imaging SERT binding sites in the brain by single photon emission computed tomography (SPECT).
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Aniline Compounds / chemical synthesis*
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Aniline Compounds / chemistry
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Aniline Compounds / pharmacokinetics
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Animals
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Autoradiography
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Benzylamines / chemical synthesis*
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Benzylamines / chemistry
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Benzylamines / pharmacokinetics
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Brain / metabolism
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Carrier Proteins / metabolism*
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Cell Line
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In Vitro Techniques
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Iodine Radioisotopes
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Isotope Labeling
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Membrane Glycoproteins / metabolism*
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Membrane Transport Proteins*
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Nerve Tissue Proteins / metabolism*
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Radioligand Assay
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Radiopharmaceuticals / chemical synthesis*
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Radiopharmaceuticals / chemistry
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Radiopharmaceuticals / pharmacokinetics
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Rats
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Serotonin / metabolism*
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Serotonin Plasma Membrane Transport Proteins
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Structure-Activity Relationship
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Tissue Distribution
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Tomography, Emission-Computed, Single-Photon
Substances
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2-(2-(dimethylaminomethyl)benzyl)-5-iodophenylamine
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Aniline Compounds
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Benzylamines
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Carrier Proteins
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Iodine Radioisotopes
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Membrane Glycoproteins
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Membrane Transport Proteins
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Nerve Tissue Proteins
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Radiopharmaceuticals
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Serotonin Plasma Membrane Transport Proteins
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Slc6a4 protein, rat
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Serotonin