2β-Carbomethoxy-3β-(4-chlorophenyl)-8-(2-[F]fluoroethyl)nortropane

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 transporter (DAT) protein in the presynaptic nerve terminals (1, 2). DAT is important to the regulation of synaptic concentration of dopamine. However, reduction of DAT density is not necessarily a measure of the clinical severity of motor dysfunction in PD patients (3). Several cocaine analogs were developed for the evaluation of DAT density in striatal neurons of PD patients (4). 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 (5-8). [I]β-CIT was studied in humans in single photon emission computed tomography (SPECT), which showed slow tracer uptake kinetics (9, 10). I tracer allows delayed scanning. [F]FP-CIT has been evaluated in humans (6). A switch was made to F to gain better resolution and quantitation. However, the radiochemical yields were reported to be 1-4% (6, 8). This led to the development of 2β-carbomethoxy-3β-(4-chlorophenyl)-8-(2-[F]fluoroethyl)nortropane ([F]FECNT) for positron emission tomography (PET) brain imaging in PD patients.