Synthesis and C-11-radiolabelling of a tropane derivative lacking the 2 beta ester group: A potential pet-tracer for the dopamine transporter

The synthesis and C-11-radiolabelling of a new tropane analogue, 3 beta-(4' -chlorophenyl)-2 beta-(3'-phenylisoxazol-5'-yl)tropane (beta-CPPIT), an inh ibitor of the dopamine transporter, is reported. The desmethyl compound, 3 beta-(4'-chlorophenyl)-2 beta-(3'-phenylisoxazol-5'-yl)nortropane (5) was p repared via a six-step reaction sequence starting from cocaine. [C-11]-beta -CPPIT was labelled by N-methylation using [C-11]-methyl iodide obtained fr om the gas phase reaction of [C-11]-methane with iodine in 60 +/- 10 % radi ochemical yield (decay corrected from [C-11]-methyl iodide). The overall sy nthesis time was on average 60 minutes at EOB (end of bombardment). The fin al product had a specific activity of 2000 - 2700 Ci/mmol (74 - 100 TBq/mmo l) at EOS (end of synthesis) and the radiochemical purity was greater than 99%. [C-11]-beta-CPPIT showed a logP value of 2.1 indicating that a free di ffusion through the blood-brain-barrier should be possible.