Visualization of dopamine nerve terminals in monkey by positron emission tomography using 4-[18F]fluoro-L-m-tyrosine.

Abstract

4-[18F]Fluoro-L-m-tyrosine (FMT) is an L-Dopa analog that essentially follows the L-Dopa metabolic pathway, but without 3-O-methylation or extensive peripheral metabolism. As such, FMT may serve as a useful probe of striatal dopaminergic function with positron emission tomography (PET). FMT was synthesized, as previously described by Perlmutter et al. [Appl Radiat Isot 1990;41:801-807]. Scanning was undertaken with the SHR2000 positron tomograph (image spatial resolution, 3.5 x 4.5 x 6.5 mm). Two Macaca monkeys were anesthetized with ketamine (10 mg/kg) and pentobarbital (20 mg/kg). FMT was administered intravenously (5-6 mCi; specific activity 1-2 Ci/mmol) following carbidopa pretreatment (5 mg/kg i.v., 60 min before FMT administration). Dynamic image acquisition was done for 2 h immediately after tracer injection. This emission acquisition involved twelve 2-min frames followed by nine 4-min frames, and six 10-min images. Arterial blood samples were collected according to a schedule for assay of plasma [18F] radioactivity. Specific uptake of FMT in aromatic L-amino-acid-decarboxylase-rich areas of the monkey striatum was observed with PET imaging. The striatum-to-cerebellum ratio of the accumulation increased over time to 3.0 at 2 h. These results show the promise of FMT as a PET tracer in evaluating the CNS dopaminergic system.