Positron Emission Tomography Quantification of [ C]-DASB Binding to the Human Serotonin Transporter: Modeling Strategies

• Published in: Journal of cerebral blood flow and metabolism Vol. 21; no. 11; pp. 1342 - 1353
• Main Authors: Ginovart, Nathalie, Wilson, Alan A., Meyer, Jeffrey H., Hussey, Doug, Houle, Sylvain
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.11.2001; Lippincott Williams & Wilkins; Sage Publications Ltd
• Subjects: Adult; Aniline Compounds - blood; Biological and medical sciences; Brain Chemistry; Carbon Radioisotopes; Carrier Proteins - metabolism; Chromatography, High Pressure Liquid; Computer Simulation; Female; Humans; Investigative techniques, diagnostic techniques (general aspects); Kinetics; Male; Medical sciences; Membrane Glycoproteins - metabolism; Membrane Transport Proteins; Middle Aged; Models, Biological; Nerve Tissue Proteins; Nervous system; Radiodiagnosis. Nmr imagery. Nmr spectrometry; Radiopharmaceuticals - blood; Serotonin Plasma Membrane Transport Proteins; Sulfides - blood; Tomography, Emission-Computed - methods; Human; [11C]-DASB; Serotonin transporter; Modeling; PET; Radionuclide study; Ligand binding; Serotoninergic transmission; Central nervous system; Benzonitrile derivatives; Exploration; Brain (vertebrata); Positron; Emission tomography
• ISSN: 0271-678X; 1559-7016
• DOI: 10.1097/00004647-200111000-00010

[11C]-DASB, namely [11C]-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile, is a new highly selective radioligand for the in vivo visualization of the serotonin transporter (SERT) using positron emission tomography (PET). The current study evaluates different kinetic modeling strategies for quantification of [11C]-DASB binding in five healthy humans. Kinetic analyses of tissue data were performed with a one-tissue (1CM) and a two-tissue (2CM) compartment model. Time-activity curves were well described by a 1CM for all regions. A 2CM model with four parameters failed to converge reliably. Reliable fits of the data were obtained only if no more than three parameters were allowed to vary. However, even then, the rate constants k3 and k4 were estimated with poor precision. Only the ratio k3/k4 was stable. Goodness of fit was not improved by using a 2CM as compared with a 1CM. The minimal study duration required to obtain stable k3/k4 estimates was 80 minutes. For routine use of [11C]-DASB, several simplified methods using the cerebellum as a reference region to estimate nonspecific binding were also evaluated. The transient equilibrium, the linear graphical analysis, the ratio of target to reference region, and the simplified reference tissue methods all gave binding potential values consistent with those obtained with the 2CM. The suitability of [11C]-DASB for research on the SERT using PET is thus supported by the observations that tissue data can be described using a kinetic analysis and that simplified quantitative methods, using the cerebellum as reference, provide reliable estimates of SERT binding parameters.