[2[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3,2,1]-oct-2-yl]-methyl](2-mercaptoethyl)amino]ethyl]amino]ethanethiolato(3-)- N2,N2’,S2,S2]oxo-[1R-exo-exo)])- [99mTc]-technetium

Excerpt

Dopamine is a neurotransmitter that modulates a variety of human functions such as motion, cognition, emotions, and the peristaltic reflexes in the gastrointestinal tract. The transport of this molecule at the neuron pre- and postsynaptic junctions is mediated by an axonal membrane dopamine transporter (DAT) that regulates dopamine levels within the synaptic cleft (1). The process of dopamine release and reuptake within the synaptic cleft facilitates nerve transmission. The striatum region of the brain has a high density of DAT and is rich in dopamine. Psychotic drugs such as cocaine, amphetamines, and methylphenidate (MPH) target DAT, which suggests that the dopamine system modulates the mood of an individual (1-3). Also, changes in DAT are of particular interest in individuals with Parkinson’s disease (PD), which is caused by the loss of neurons bearing these transporters in the basal ganglia and substantia nigra regions of the striatum (4). Development of various imaging ligands that specifically bind to DAT has been of interest to understand the functioning of these transporters and also to diagnose and monitor the treatment of PD. Dopamine receptors and transporters have also been suggested to play a role in the development of the heritable and disruptive attention deficit hyperactivity disorder (ADHD) that is sometimes observed in children (5). Although several ligands are available that can be used for DAT imaging, they have a limited availability and require cyclotron-produced radionuclides that have short half-lives (6). In addition, these ligands require from a few hours to >18 hours to reach a suitable concentration at the imaging target area (4).

In an effort to alleviate the limitations observed with the cyclotron-produced radionuclides, DAT ligands labeled with ^99mTc were developed for research and possibly for clinical use. These ligands are neutral lipophilic complexes that contain N-(alkylthiolate)tropane, aminobis(ethylthiolate), and a center core of ^99mTc (4). The cocaine derivative [2[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3,2,1]-oct-2-yl]-methyl](2-mercaptoethyl)amino]ethyl]amino]ethanethiolato(3-)-N2,N2’,S2,S2]oxo-[1R-exo-exo)])- [^99mTc]-technetium (^99mTc-TRODAT-1) is a ligand that belongs to this group. Hu et al. suggested the possible benefit of ^99mTc-TRODAT-1 for an early and differential diagnosis of PD (7).

The application of ^99mTc-TRODAT-1 for the imaging of DAT is reviewed in this chapter.