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

¹ Department of Radiology, Emory University, Atlanta, Georgia; ² Emory University Center for Positron Emission Tomography, Emory University, Atlanta, Georgia; and ³ Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, Georgia

Correspondence: For correspondence or reprints contact: Jonathon A. Nye, Department of Radiology, 1365 Clifton Rd. NE, Atlanta, GA 30322. E-mail: jnye{at}emory.edu

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.

Key Words: PET • serotonin transporter • kinetic modeling

COPYRIGHT © 2008 by the Society of Nuclear Medicine, Inc.

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