Cerebral uptake and utilization of therapeutic [β-11C]-L-DOPA in Parkinson's disease measured by positron emission tomography. Relations to motor response

Abstract

Cerebral uptake and utilization of levodopa was measured in eight patients with idiopathic Parkinson's disease (PD) by [β‐¹¹C]‐L‐DOPA and positron emission tomography (PET). By adding pharmacological doses of unlabelled levodopa to the radioactive solution it was possible to evaluate the clinical effect simultaneously with the cerebral kinetics of the drug. Additionally, in two of the patients with advanced PD, investigations with the dopamine re‐uptake blocker [¹¹C]‐(+)‐nomifensine and PET were carried out to get a measure of the density of striatal dopaminergic nerve‐terminals. The brain uptake of [β‐¹¹C]‐L‐DOPA was inversely correlated to the sum of large neutral amino acids in plasma. In the eight PD patients studied with [β‐11C]‐L‐DOPA striatal k₃, which reflects the ability for striatal tissue to decarboxylate the tracer by the action of aromatic L‐amino acid decarboxylase (AADC), was decreased 35% compared to healthy subjects. It was demonstrated that, in the patients with advanced PD and motor fluctuations on oral L‐DOPA medication, reversal of parkinsonian symptoms occurred at very low striatal tissue dopamine concentrations. In the two very advanced patients studied with [¹¹C]‐(+)‐nomifensine the striatal binding of the tracer was 50% reduced.