Dopamine, a neurotransmitter, is transported across the presynaptic neuron membranes (1, 2) by the dopamine transporter (DAT) and results in termination of the signaling action of the molecule (3). High densities of this transporter are present in certain regions of the brain, such as the putamen, caudate, nucleus accumbens, and the olfactory tubercle, whereas the substantia nigra, amygdala, and hypothalamus show comparatively low amounts of the DAT (4, 5). Negligible amounts of DATs are found in the cerebellum. The DAT has been implicated in several neuropsychiatric disorders including Parkinson’s disease (6-8), attention-deficit hyperactivity disorder (9), supranuclear palsy (10), Tourette’s syndrome (11), and cocaine addiction (12, 13). Because of the involvement of DAT in a variety of neurological disorders, positron emission tomography (PET) is often used for the non-invasive imaging to determine the density of DAT in different regions (12) and to visualize the localization of therapeutic drugs (14) and cocaine (15) in the brain. Therefore, the use of PET tracers is considered useful for the detection of neuropsychiatric diseases (including cocaine addiction) and to monitor the efficacy of drugs used to treat these conditions (16). To this end, several C-labeled 3β-phenyl tropane compounds were prepared and used for the imaging of the DAT; however, due to the short half-life of C (half-life ~20 min), the DAT imaging sessions with these PET tracers are limited to ~2 h (17). In addition, C produces high-energy positrons (maximum energy, 0.97 MeV) that have a long linear range and consequently generates low-resolution images. In an attempt to increase the resolution of PET images, investigators labeled some tropane-based DAT ligands with F (maximum energy, 0.64 MeV; half-life ~110 min) and evaluated the use of these radiolabeled compounds for the imaging of the DAT (17). However, these F-labeled tracers were determined to be unsuitable for the imaging of the DAT because they were either defluorinated or generated polar metabolites that crossed the blood–brain barrier and produced low signal/noise ratios, or they exhibited a higher affinity for the serotonin transporter (SERT) compared to the DAT, or they had a prolonged period for washout from the brain. In a continuing effort to produce F-labeled DAT-binding PET tracers, Stehouwer et al. synthesized a nortropane derivative, -(()-4-[F]fluorobut-2-en-1-yl)-2β-carbomethoxy-3β-(4’-fluorophenyl)nortropane ([F]FBFNT), and evaluated the radiolabel for the imaging of the DAT in an anesthetized cynomolgus monkey and in a conscious rhesus monkey (17).
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