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Selective in vitro and in vivo binding of [ 125 I]ADAM to serotonin transporters in rat brain
Author(s) -
Choi SeokRye,
Hou Catherine,
Oya Shunichi,
Mu Mu,
Kung MeiPing,
Siciliano Michael,
Acton Paul D.,
Kung Hank F.
Publication year - 2000
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/1098-2396(20001215)38:4<403::aid-syn5>3.0.co;2-z
Subject(s) - ketanserin , globus pallidus , interpeduncular nucleus , striatum , serotonin , chemistry , medicine , endocrinology , cerebellum , in vivo , hypothalamus , raphe nuclei , raclopride , basal ganglia , 5 ht receptor , biology , serotonergic , dopamine , central nervous system , receptor , biochemistry , midbrain , microbiology and biotechnology
An improved iodinated tracer, ADAM (2‐((2‐((dimethylamino)methyl)‐ phenyl)thio)‐5‐iodophenylamine) for imaging serotonin transporters (SERT) with single photon emission computerized tomography (SPECT), was prepared and characterized. Scatchard analysis of saturation binding of [ 125 I]ADAM to rat frontal cortical membrane homogenates gave a K d value of 0.15 ± 0.03 nM and a B max value of 194 ± 65 fmol/mg protein. Biodistribution of [ 125 I]ADAM in rat brain after an iv injection showed a high specific binding in the regions of hypothalamus, cortex, striatum, and hippocampus, where SERT are concentrated and the specific binding peaked at 120–240 min postinjection [(hypothalamus‐cerebellum)/cerebellum = 4.3 at 120 min post‐iv injection]. Moreover, the specific hypothalamic uptake was blocked by pretreatment with SERT selective competing drugs, such as paroxetine and (+)McN5652, while other noncompeting drugs, such as ketanserin, raclopride, and methylphenidate, showed no effect. The radioactive material recovered from rat brain homogenates at 120 min after [ 125 I]ADAM injection showed primarily the original compound (>90%), a good indication of in vivo stability in the brain tissues. Both male and female rats showed similar and comparable organ distribution pattern and regional brain uptakes. Ex vivo autoradiograms of rat brain sections (120 min after iv injection of [ 125 I]ADAM) showed intense labeling in several regions (olfactory tubercle, lateral septal nucleus, hypothalamic and thalamic nuclei, globus pallidus, central gray, superior colliculus, substantia nigra, interpeduncular nucleus, dorsal and median raphes, and locus coerulus), which parallel known SERT density. These results strongly suggest that the novel tracer ADAM is superior to the congers (i.e., IDAM) reported previously. When labeled with I‐123, ADAM will be an improved and useful SPECT imaging agent for SERT in the brain. Synapse 38:403–412, 2000. © 2000 Wiley‐Liss, Inc.