Quantitative PET analyses of regional [11C]PE2I binding to the dopamine transporter - Application to juvenile myoclonic epilepsy

The dopamine transporter (DAT) is of central interest in research on the pathophysiology and treatment of neuro-psychiatric disorders. [11C]PE2I is an established radioligand that provides high-contrast delineation of brain regions that are rich in DAT. The aim of the present PET study in eight patients with juvenile myoclonic epilepsy (JME) was to evaluate the kinetics of [11C]PE2I in the brain and to compare binding parameters with those of age-matched control subjects (n = 6). Each patient participated in 90-minute PET measurements with [11C]PE2I. Data were analyzed using kinetic compartment analyses with metabolite-corrected arterial plasma input and reference tissue models using the cerebellum as a reference region. The time-activity curves were well described by the two-tissue compartment model (2TCM) for the DAT-rich regions. The 2TCM with fixed K1/k2 ratio derived from the cerebellum provided robust and reliable estimates of binding potential (BPND) and total distribution volume (VT). The reference tissue models also provided robust estimates of BPND, although they gave lower BPND values than the kinetic analysis. Compared with those of control subjects, we found that BPND values obtained by all approaches were reduced in the midbrain of the patients with JME. The finding indicates impaired dopamine uptake in the midbrain of JME patients. The three-tissue compartment model could best describe uptake in the cerebellum, indicating that two kinetically distinguishable compartments exist in cerebellar tissue, which may correspond to nonspecific binding and the blood-brain barrier passing metabolite. The reference tissue models should be applied with better understanding of the biochemical nature of the radioligand and the reliability of these approaches.

► We examine the dopamine transporters binding using [11C]PE2I and PET. ► Binding potential is reduced in the midbrain of juvenile myoclonic epilepsy. ► The two-tissue compartment model provides reliable estimates of binding parameters. ► The three-tissue compartment best describes uptake in the cerebellum. ► A metabolite that passes the blood-brain barrier exists in the cerebellum.