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

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