Synthesis, Radiosynthesis, and Biological Evaluation of Carbon-11 Labeled 2β-Carbomethoxy-3β-(3‘-((<i>Z</i>)-2-haloethenyl)phenyl)nortropanes:  Candidate Radioligands for in Vivo Imaging of the Serotonin Transporter with Positron Emission Tomography

2β-Carbomethoxy-3β-(3‘-((<i>Z</i>)-2-iodoethenyl)phenyl)nortropane (<i>m</i>ZIENT, <b>1</b>) and 2β-carbomethoxy-3β-(3‘-((<i>Z</i>)-2-bromoethenyl)phenyl)nortropane (<i>m</i>ZBrENT, <b>2</b>) were synthesized and evaluated for binding to the human serotonin, dopamine, and norepinephrine transporters (SERT, DAT, and NET, respectively) using transfected cells. Both <b>1</b> and <b>2</b> have a high affinity for the SERT (<i>K</i><sub>i</sub> = 0.2 nM) and are ∼160 times more selective for the SERT than the DAT. Compound <b>2</b> has a significantly higher affinity for the NET than <b>1</b>, and this may be a result of the different size and electronegativity of the halogen atoms. MicroPET imaging in nonhuman primates with [<sup>11</sup>C]<b>1</b> and [<sup>11</sup>C]<b>2</b> 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.