A new quantitative approach for dopamine transporter binding using [11C]PE2I and PET allowing BBB-penetrating radiolabeled metabolite

Objectives [11C]PE2I is an established PET radioligand for the dopamine transporter (DAT) providing high-contrast images in human subjects. An unresolved issue that an unknown radiolabeled metabolite may penetrate the blood-brain barrier (BBB) thereby reduces reliable quantification. The purpose of the present analysis is to evaluate a new approach for quantification of [11C]PE2I binding using the conventional compartment model. The mixed-arterial plasma input function is used, and composed of unchanged parent radioligand and BBB-penetrating metabolite. The two compounds are individually estimated from a standardized time-activity curve (TAC) of metabolized radioligand by a calibration.

Methods [11C]PE2I PET studies were performed on normal control subjects (n=7) and patients with juvenile myoclonic epilepsy (JME) (n=8). Sequential arterial blood samples were obtained and both unchanged parent radioligand and metabolized radioligand were analyzed. A standardized TAC for the radiolabeled metabolite was first prepared for the control subjects. The standardized TAC was then calibrated for each patient with JME using plasma data obtained at 10 min after radioligand injection. The binding potential (BP), k3/k4, and total distribution volume (DV) for the putamen, caudate and midbrain were obtained and compared.

Results Both regional BP and DV of the patients with JME obtained by the mixed-arterial plasma input were 7 - 18 % less than those obtained by the unchanged parent input. The percent COV for calculation was also 8 - 22 % less for the mixed-arterial plasma input.

Conclusions The proposed approach may provide more accurate binding parameters in quantitative analysis of [11C]PE2I binding to the DAT