Introduction of [(18) F]fluoride ion into the aromatic core of phenylazocarboxylic esters was achieved in only 30 seconds, with radiochemical yields of up to 95 % (85(±10) %). For labeling purposes, the resulting (18) F-substituted azoester can be further converted in radical-arylation reactions to give biaryls, or in substitutions at its carbonyl unit to produce azocarboxamides.

To date there is no validated, 18 F-labeled dopamine transporter (DAT) radiotracer with a rapid kinetic profile suitable for preclinical small-animal positron emission tomography (PET) studies in rodent models of human basal ganglia disease. Herein we report radiosynthesis and validation of the phenyltropane 18 F-FP-CMT. Dynamic PET recordings were obtained for 18 F-FP-CMT in six untreated rats, and six rats pretreated with the high-affinity DAT ligand GBR 12909; mean parametric maps of binding potential (BP ND ) relative to the cerebellum reference region, and maps of total distribution volume (V T ) relative to the metabolite-corrected arterial input were produced. 18 F-FP-CMT BP ND maps showed peak values of B4 in the striatum, versus B0.4 in the vicinity of the substantia nigra. Successive truncation of the PET recordings indicated that stable BP ND estimates could be obtained with recordings lasting only 45 minutes, reflecting rapid kinetics of 18 F-FP-CMT. Pretreatment with GBR 12909 reduced the striatal binding by 72% to 76%. High-performance liquid chromatography analysis revealed rapid metabolism of 18 F-FP-CMT to a single, non-brain penetrant hydrophilic metabolite. Total distribution of volume calculated relative to the metabolite-corrected arterial input was 4.4 mL/g in the cerebellum. The pharmacological selectivity of 18 F-FP-CMT, rapid kinetic profile, and lack of problematic metabolites constitute optimal properties for quantitation of DAT in rat, and may also predict applicability in human PET studies. INTRODUCTIONThe plasma membrane dopamine transporter (DAT) is abundantly expressed in the terminals of the nigrostriatal pathway and throughout the extended striatum, where it mediates the re-uptake of dopamine; the activity of DAT determines the spatial and temporal dynamics of dopamine signaling in the basal ganglia, and its expression is a sensitive indicator of the integrity of the nigrostriatal dopamine innervation. As such, DAT presents an important target for molecular imaging by positron emission tomography (PET) and single-photon computer tomography, in both research and clinical settings. We were interested in a DAT radiotracer to investigate the impact of nutrition and diabetes on dopaminergic signaling in rat models. However, because of constraints imposed by radionuclides other than 18 F in combination with the kinetic profiles of the available radiotracers in the required imaging protocols, there remains a need for a tracer with optimal properties for quantitative imaging of multiple animals from a single radiosynthesis. Although, a plethora of agents have been developed for imaging of DAT, 1-3 all may suffer in varying degrees from lack of selectivity, unfavorable kinetics, and adverse metabolism. A particular issue is the pharmacological selectivity of tracers for DAT versus serotonin transporters (SERT), and to a

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