Progression of Parkinson’s disease symptoms is imperfectly correlated with positron emission tomography biomarkers for dopamine biosynthetic pathways. The radiopharmaceutical 6-[¹⁸F]fluoro-m-tyrosine is not a substrate for catechol-O-methyltransferase and therefore has a more favorable uptake-to-background ratio than 6-[¹⁸F]fluoro-l-dopa. The objective of this study was to evaluate 6-[¹⁸F]fluoro-m-tyrosine relative to 6-[¹⁸F]fluoro-l-dopa with partial catechol-O-methyltransferase inhibition as a biomarker for clinical status in Parkinson’s disease. Twelve patients with early-stage Parkinson’s disease, off medication, underwent Unified Parkinson Disease Rating Scale scoring, brain magnetic resonance imaging, and 3-dimensional dynamic positron emission tomography using equivalent doses of 6-[¹⁸F]fluoro-m-tyrosine and 6-[¹⁸F]fluoro-l-dopa with tolcapone, a catechol-O-methyltransferase inhibitor. Images were realigned within subject, after which the tissue-derived uptake rate constant was generated for volumes of interest encompassing the caudate nucleus, putamen, and subregions of the putamen. We computed both bivariate (Pearson) and partial (covariate of age) correlations between clinical subscores and tissue-derived uptake rate constant. Tissue-derived uptake rate constant values were correlated between the radiopharmaceuticals (r = 0.8). Motor subscores were inversely correlated with the contralateral putamen 6-[¹⁸F]fluoro-m-tyrosine tissue-derived uptake rate constant (|r| > 0.72, P < .005) but not significantly with the 6-[¹⁸F]fluoro-l-dopa tissue- derived uptake rate constant. The uptake rate constants for both radiopharmaceuticals were also inversely correlated with activities of daily living subscores, but the magnitude of correlation coefficients was greater for 6-[¹⁸F]fluoro-m-tyrosine. In this design, 6-[¹⁸F]fluoro-m-tyrosine uptake better reflected clinical status than did 6-[¹⁸F]fluoro-l-dopa uptake. We attribute this finding to 6-[¹⁸F]fluoro-m-tyrosine’s higher affinity for the target, l-aromatic amino acid decarboxylase, and the absence of other major determinants of the uptake rate constant. These results also imply that l-aromatic amino acid decarboxylase activity is a major determinant of clinical status.