Compartmental Modeling of 11C-HOMADAM Binding to the Serotonin Transporter in the Healthy Human Brain

• Type of Material: Article
• Authors: Jonathon A Nye, Emory University; John R Votaw, Emory University; Nashwa Jarkas, Emory University; David C Purselle, Emory University; Vernon Camp, Emory University; J. Douglas Bremner, Emory University; Clinton D. Kilts, Emory University; Charles B. Nemeroff, Emory University; Mark Goodman, Emory University
• Language: English
• Date: 2008-12
• Publisher: OMICS International
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2008 by the Society of Nuclear Medicine, Inc.
• Final Published Version (URL): http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=19038997
• Title of Journal or Parent Work: Journal of Nuclear Medicine and Radiation Therapy
• ISSN: 2155-9619
• Volume: 49
• Issue: 12
• Start Page: 2018
• End Page: 2025
• Grant/Funding Information: This work was supported by National Institute of mental Health grant 1-R21-MH-66622-01.
• Keywords: kinetic modeling; PET; serotonin transporter
• Research Categories: Chemistry, Nuclear

Abstract

The novel PET radioligand 11C-N,N-dimethyl-2-(2′-amino-4′-hydroxymethylphenylthio)benzylamine (11C-HOMADAM) binds with high affinity and selectively to the serotonin transporter (SERT). The purpose of this study was to develop a reliable kinetic model to describe the uptake of 11C-HOMADAM in the healthy human brain.Methods Eight volunteers participated in the study; 5 of them were fitted with arterial catheters for blood sampling and all were scanned on a high-resolution research tomograph after the injection of 11C-HOMADAM. Regional distribution volumes and binding potentials were calculated with 2- and 4-parameter arterial-input compartment models, a 3-parameter reference tissue compartment model, and the Logan graphic approach. Results The 2-parameter arterial-input compartment model was statistically superior to the 4-parameter model and described all brain regions. Calculated binding potentials agreed well between the arterial-input model and the reference tissue model when the cerebellum was used as the reference tissue. The Logan graphic approach was not able to estimate the higher concentration of SERT in the dorsal raphe than in the midbrain. Conclusion 11C-HOMADAM is a highly promising radioligand with high ratios of specific binding to nonspecific binding in known SERT-rich structures, such as the raphe nuclei. The 3-parameter reference tissue model approach permits a simplified quantitatively accurate method for estimating SERT binding potentials.