UNLABELLED: 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. CONCLUSION: (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.
UNLABELLED: 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. CONCLUSION:(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.
Authors: John R Votaw; Leonard L Howell; Laurent Martarello; John M Hoffman; Clinton D Kilts; Kimberly P Lindsey; Mark M Goodman Journal: Synapse Date: 2002-06-15 Impact factor: 2.562
Authors: R V Parsey; L S Kegeles; D R Hwang; N Simpson; A Abi-Dargham; O Mawlawi; M Slifstein; R L Van Heertum; J J Mann; M Laruelle Journal: J Nucl Med Date: 2000-09 Impact factor: 10.057
Authors: W Gordon Frankle; Yiyun Huang; Dah-Ren Hwang; Peter S Talbot; Mark Slifstein; Ronald Van Heertum; Anissa Abi-Dargham; Marc Laruelle Journal: J Nucl Med Date: 2004-04 Impact factor: 10.057
Authors: Vikram Adhikarla; Boadie W Dunlop; Nashwa Jarkas; Mark M Goodman; Helen Mayberg; Michael J Owens; Jonathon A Nye Journal: J Nucl Med Date: 2017-09-21 Impact factor: 10.057
Authors: Yanguang Lin; Justin P Haldar; Quanzheng Li; Peter S Conti; Richard M Leahy Journal: IEEE Trans Med Imaging Date: 2013-11-07 Impact factor: 10.048