Abstract
Two novel radioligands for the serotonin transporter (SERT), [^125^I]{3‐[5‐iodo‐1‐[4‐fluorophenyl)‐1,3‐dihydroisobenzofuran‐1‐yl]‐propyl}‐dimethylamine ([^125^I]‐2) and S‐[^125^I]{3‐[5‐iodo‐1‐(4‐fluorophenyl)‐1,3‐dihydroisobenzofuran‐1‐yl]‐propyl}‐dimethylamine ([^125^I]‐(S)‐2) were synthesized in a Br/^125^I exchange reaction. Binding experiments in rats yielded K~d~ values of 0.7 ± 0.06 and 0.52 ± 0.02 nM for [^125^I]‐2 and [^125^I]‐(S)‐2, respectively. One hour after intravenous injection of [^125^I]‐2, 0.34% of the injected dose had accumulated in the brain. The highest hypothalamus‐to‐cerebellum ratio was reached 2 h after injection of [^125^I]‐(S)‐2 and amounted to 2.4. Pre‐treatment experiments with paroxetine resulted in effective reduction of the target‐to‐cerebellum ratios.
The corresponding iodine‐123 labelled compound S‐[^123^I]{3‐[5‐Iodo‐1‐(4‐fluorophenyl)‐1,3‐dihydroisobenzofuran‐1‐yl]‐propyl}‐dimethylamine [^123^I]‐S‐2 was investigated in a pig single photon emission computed tomography (SPECT) study. Between 60 and 110 min after IV injection, the midbrain‐to‐cerebellum ratio was 1.2. However, the uptake did not differ between high‐density and medium‐density regions questioning the feasibility of the radioligand in imaging cortical SERT distribution in vivo.
These data suggest that the iodine‐labelled derivatives of citalopram and escitalopram are not superior to another SPECT tracer for the SERT, namely [^123^I]ADAM. Copyright © 2010 John Wiley & Sons, Ltd.