Abstract
1600
Objectives: Measuring density changes in the serotonin transporter has gained considerable attention because of its involvement in the pathophysiology of neuropsychiatric disorders. Carbon-11 labeled 2β-carbomethoxy-3β-[4’-((Z)-2-iodoethenyl)phenyl]nortropane ([11C]ZIENT) is a novel PET radioligand that has desirable binding site kinetics and high uptake in the thalamus, striatum, and midbrain of monkeys. The objective of this study was to investigate kinetic modeling approaches that describe [11C]ZIENT binding to SERT in humans.
Methods: Five volunteers fitted with arterial catheters received dynamic PET scans collected on a high resolution research tomography (HRRT) following a slow bolus (4min) injection of 15mCi of [11C]ZIENT. The binding of [11C]ZIENT was evaluated in 16 SERT-rich and cortical brain regions including raphe nuclei, striatum, thalamus and select cortical areas. Data was fit to a two and four parameter metabolite-corrected arterial input kinetic model and a three and five parameter reference (cerebellum) tissue model.
Results: HRRT imaging was able to separate nuclei of the brainstem raphe with activity peaking between 80-100 min in all regions. A two-parameter arterial input compartment model was statistically superior (AIC 2 params < AIC 4 params) and fit all brain regions well. A three-parameter (R,k2,k2’) reference tissue model was also optimal in describing regional activity curves.
Conclusions: The reference tissue method agreed well with the arterial input model and provided a reliable estimate of kinetic parameters.
- Society of Nuclear Medicine, Inc.