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Synthesis, Radiosynthesis, and Biological Evaluation of Carbon-11 Labeled 2β-Carbomethoxy-3β-(3‘-((Z)-2-haloethenyl)phenyl)nortropanes: Candidate Radioligands for in Vivo Imaging of the Serotonin Transporter with Positron Emission Tomography
journal contribution
posted on 2006-11-16, 00:00 authored by Jeffrey S. Stehouwer, Nachwa Jarkas, Fanxing Zeng, Ronald J. Voll, Larry Williams, Michael J. Owens, John R. Votaw, Mark M. Goodman2β-Carbomethoxy-3β-(3‘-((Z)-2-iodoethenyl)phenyl)nortropane (mZIENT, 1) and 2β-carbomethoxy-3β-(3‘-((Z)-2-bromoethenyl)phenyl)nortropane (mZBrENT, 2) were synthesized and evaluated for binding to the
human serotonin, dopamine, and norepinephrine transporters (SERT, DAT, and NET, respectively) using
transfected cells. Both 1 and 2 have a high affinity for the SERT (Ki = 0.2 nM) and are ∼160 times more
selective for the SERT than the DAT. Compound 2 has a significantly higher affinity for the NET than 1,
and this may be a result of the different size and electronegativity of the halogen atoms. MicroPET imaging
in nonhuman primates with [11C]1 and [11C]2 demonstrated that both tracers behave similarly in vivo with
high uptake being observed in the SERT-rich brain regions and peak uptake being achieved in about 55 min
postinjection. Chase studies with citalopram and methylphenidate demonstrated that this uptake is the result
of preferential binding to the SERT.