Modeling Considerations for In Vivo Quantification of the Dopamine Transporter using [11C]PE2I and Positron Emission Tomography

The dopamine transporter (DAT) is an important imaging target as changes in DAT have been implicated in a variety of neurologic and psychiatric disorders and can result from certain classes of medications. [11C]N-(3-iodoprop-2E-enyl)-2β-carbomethoxy-3β-(4-methylphenyl)nortropane ([11C]PE2I), a radioligand with high specificity for DAT, has been shown to exhibit favorable kinetics and to produce high contrast positron emission tomography (PET) images. To better characterize this ligand and to assess its measurement reliability, PET images of seven subjects were acquired in a test–retest paradigm. For optimal model performance, each subject was scanned for 120 mins, ensuring that high binding regions could reach equilibrium, a validated coregistration method was performed for accurate anatomic delineations and an exhaustive search for a reference region having one-tissue compartment kinetics was undertaken. Eleven modeling methods were tested and six metrics were used for method evaluation. A noniterative two-tissue compartment method with 100 mins of scanning time was found to be optimal for characterizing [11C]PE2I.