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

• Published in: Journal of cerebral blood flow and metabolism Vol. 29; no. 7; pp. 1332 - 1345
• Main Authors: DeLorenzo, Christine, Kumar, JS Dileep, Zanderigo, Francesca, Mann, J John, Parsey, Ramin V
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01-07-2009; Nature Publishing Group; Sage Publications Ltd
• Subjects: Adult; Biological and medical sciences; Carbon Radioisotopes; Dopamine Plasma Membrane Transport Proteins - analysis; Dopamine Plasma Membrane Transport Proteins - metabolism; Female; Humans; Investigative techniques, diagnostic techniques (general aspects); Ligands; Male; Medical sciences; Middle Aged; Models, Theoretical; Nervous system; Neurology; Nortropanes; Positron-Emission Tomography - methods; Radionuclide investigations; Vascular diseases and vascular malformations of the nervous system; compartment models; dopamine transporter; positron emission tomography; [11C]PE2I; graphical models; Nervous system diseases; Dopamine; Catecholamine; Modeling; Cerebral disorder; Central nervous system disease; Neurotransmitter; [; Positron emission tomography; Cerebrovascular disease; C]PE2I; Emission tomography
• ISSN: 0271-678X; 1559-7016
• DOI: 10.1038/jcbfm.2009.49

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.