Synthesis and radiolabelling of 2β-carbomethoxy-3β-(3′-iodo-4′-isopropylphenyl) nortropane as a radioligand for the exploration of the serotonin transporter by SPET.

In order to develop a potential tool for SPET examination of the serotonin transporter (5-HTT) in the human brain, we report the synthesis and radiolabelling of 2 beta-carbomethoxy-3 beta-(3'-iodo-4'-isopropylphenyl) nortropane (LBT-44). We also report ex vivo autoradiography performed in the rat brain. The radiosynthesis of [I-125]LBT-44 was accomplished by iododestannylation of a trimethyltin precursor using [I-125]sodium iodide and peracetic acid or choramine-T as oxidant. After purification by reverse phase HPLC, [I-125]LBT-44 was obtained in a radiochemical yield higher than 75% and a radiochemical purity greater than 95%. Ex vivo autoradiographic studies revealed a marked accumulation of [[I-125]LBT-44 in brain areas rich in 5-HTT whereas no accumulation was observed in the striatum, which is rich in dopamine transporters. These results are in favour of specific binding of [I-125]LBT-44 to 5-HTT that is required for SPET exploration in human.