Abstract
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Objectives: The assessment of striatal dopaminergic function using 18F-DOPA (18F-fluoro-3,4-dihydroxy-L-phenylalanine) of high specific activity was evaluated for the test-retest reliability in five rhesus monkeys, which received two 18F-DOPA PET scans, 10 to 18 days apart.
Methods: 18F-DOPA was synthesized by nucleophilic 18F- substitution and acidic hydrolysis from a precursor possessing a p-methoxyphenyl iodonium salt (ALPDOPA, Ground Fluor Pharmaceuticals, Inc.) by a modification of a published method1. The animal study was approved by the IACUC of Emory University. (S)-(-)-Carbidopa (a peripheral aromatic L-amino acid decarboxylase inhibitor, 3 mg/kg) was injected 1 hour before a scan, and 74 - 111 MBq of an 18F-DOPA dose solution was injected. An emission scan was performed for two hours using a Siemens MicroPET Focus 220 scanner (1.7 mm of reconstructed image resolution). 18F-DOPA utilization (ki, 18F-DOPA influx constant) at quasi-equilibrium in the left and right caudate nucleus and putamen were determined relative to the cerebellar reference region, using Patlak graphical analysis. The test-retest reliability was determined by the within-subject and between-subject coefficient of variation (%COV). Results: The specific activity of 18F-DOPA at injection was greater than 37 GBq/µmol, the radiochemical purity was greater than 99%, the enantiometric purity was greater than 99%, and 8 - 79 µg/kg of 6-hydroxy-L-DOPA in a dose solution was injected. The 18F-DOPA influx constant (ki, min-1) at quasi-equilibrium ranged from 0.0073 to 0.013 (exclusion of one outliner), 0.0087 to 0.012, 0.011 to 0.016, and 0.010 to 0.015 in the left and right caudate nucleus and putamen respectively. The within-subject and between-subject coefficient of variation ranged from 3.1% to 4.7% and 7.4% to 15% respectively. Conclusions: The test-retest reliability of 18F-DOPA of high specific activity in five rhesus monkeys indicated no significant differences within and between subjects in dopamine synthesis capability in caudate nucleus and putamen. 18F-DOPA of high specific activity could be used to assess striatal dopaminergic function for disease diagnosis and drug treatment efficacy monitoring.