SYNTHESIS OF [C-11] TETRABENAZINE, A VESICULAR MONOAMINE UPTAKE INHIBITOR, FOR PET IMAGING STUDIES

Tetrabenazine (TBZ), a high affinity and specific inhibitor of the vesicular monoamine transporter, has been labeled with carbon-11 as a potential probe for in vivo positron emission tomographic imaging of monoaminergic neuronal losses in neurodegenerative diseases. [C-11]TBZ was synthesized by O-[C-11]methylation of the 9-O-desmethylTBZ using [C-11]methyl iodide in the presence of tetrabutylammonium hydroxide. The radiochemical yields were 35-55% (decay corrected) and the synthesis time 32-37 min from EOB. [C-11]TBZ was obtained with specific activities of 2000-2500 Ci/mmol (EOS) and radiochemical and chemical purities were >95%. [C-11]Tetrabenazine is a promising new radioligand for the in vivo study of monoaminergic neurons using PET.