SYNTHESIS OF 3-F-18!FLUOROMETHYL BTCP AND EVALUATION AS A POTENTIAL PET RADIOLIGAND FOR THE DOPAMINE TRANSPORTER IN BABOONS

In an attempt to visualize in vivo the dopamine transporter and evalua te its potential as an imaging tool for monitoring dopamine fiber dege neration by positron emission tomography, the F-18-positron-emitting a nalogue of thyl-1-1-(2-benzothienyl)-cyclohexyl!-piperidine, F-18!BT CP, was synthetized and tested in a primate model of hemiparkinsonism. F-18!BTCP was obtained from cyclotron-produced n.c.a. F-18!fluoride (110 min half-life) and by nucleophilic substitution from 3-bromometh yl-BTCP with a radiochemical yield of 6% (decay-corrected). After intr avenous injection, the cerebral distribution of the radioactivity was observed mainly in cortical areas and cerebral structures enriched in catecholamine reuptake sites such as the caudate-putamen complex and t he thalamus. The binding ratio, defined with respect to the cerebellum (taken as a region of non-specific binding), was highest in the thala mus (1.42), intermediate in the putamen (1.36) and lowest in the cauda te nucleus (1.17), suggesting that some specific binding occurs in the se regions. After saturation of dopamine and norepinephrine transporte rs by nomifensine, the binding ratio in the thalamus, putamen and caud ate nucleus striatum remained essentially unchanged in the non-lesione d hemisphere. When comparing binding ratios between the intact and the dopamine-denervated striatum, there was a modest loss of binding in t he denervated striatum, suggesting that degeneration of dopaminergic f ibers could be detected using 3-F-18!fluoromethyl-BTCP. However due t o a high non-specific binding in vivo, the interest of 3-F-18!fluorom ethyl-BTCP to image the dopamine reuptake system in vivo appears rathe r limited.