8-(()-4-Fluoro-but-2-enyl)-3β-p-tolyl-8-aza-bicyclo[3.2.1]octane-2β-carboxylic acid [C]methyl ester

Dopamine, a neurotransmitter, plays an important role in the mediation of movement, cognition, and emotion. Parkinson’s disease (PD) is associated with a loss of dopamine-containing neurons in the striatum, resulting in a loss of dopamine transporters (DAT) in the presynaptic nerve terminals (1, 2). Reduction of DAT density is inversely correlated with the severity of motor dysfunction in PD patients. Several cocaine analogs were developed for the evaluation of DAT density in neurons of PD patients. Radiolabeled 2β-carboxymethoxy-3β-(4-iodophenyl)tropane (β-CIT) and -(3-fluoropropyl)-2β-carbomethoxy-3β-(4-iodophenyl)nortropane (FP-CIT) have been used for brain imaging (3-6). Because of the short physical half-life of C-labeled analogs, equilibrium conditions are difficult to achieve in positron emission tomography (PET) measurements. [I]β-CIT was studied in single-photon emission computed tomography (SPECT), which showed slow tracer uptake kinetics (7, 8). A new tropane derivative, [C]-()--(4-fluorobut-2-enyl)-2β-carbomethoxy-3β-(4'-tolyl)nortropane ([C]LBT-999), was evaluated as a radioligand for studies of the DAT with PET imaging (9-11).