Compartmental modeling of 11C-HOMADAM binding to the serotonin transporter in the healthy human brain.
The novel PET radioligand (11)C-N,N-dimethyl-2-(2'-amino-4'-hydroxymethylphenylthio)benzylamine ((11)C-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 (11)C-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 (11)C-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.


CONCLUSIONS
(11)C-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.
Nye
Jonathon A
JA
Department of Radiology, Emory University, Atlanta, Georgia, USA. jnye@emory.edu
Votaw
John R
JR
Jarkas
Nachwa
N
Purselle
David
D
Camp
Vernon
V
Bremner
James D
JD
Kilts
Clinton D
CD
Nemeroff
Charles B
CB
Goodman
Mark M
MM
D001596:Benzylamines / Q000493:pharmacokinetics*; D001665:Binding Sites; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D003198:Computer Simulation; D005260:Female; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008959:Models, Neurological; D049268:Positron-Emission Tomography / Q000379:methods; D011485:Protein Binding; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D014018:Tissue Distribution; D055815:Young Adult
D001596:Benzylamines; C504057:N,N-dimethyl-2-(2'-amino-4'-hydroxymethylphenylthio)benzylamine; D019275:Radiopharmaceuticals; D050486:Serotonin Plasma Membrane Transport Proteins