Positron Emission Tomography Quantification of [ 11 C]-DASB Binding to the Human Serotonin Transporter: Modeling Strategies
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[ 11 C]-DASB, namely [ 11 C]-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 [ 11 C]-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 k 3 and k 4 were estimated with poor precision. Only the ratio k 3 /k 4 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 k 3 /k 4 estimates was 80 minutes. For routine use of [ 11 C]-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 [ 11 C]-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.
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The included ligands have all been extensively validated via kinetic modeling of arterial input sampling.
“In addition, these ligands have all been extensively validated via kinetic modeling of arterial input sampling [23–26].”
From The relationship between dose and serotonin transporter occupancy of antidepressants—a systematic review (2022) · cites this paper as [23]
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- Authors
- Ginovart, N., Wilson, A. A., Meyer, J. H., Hussey, D., & Houle, S.
- Affiliations
- Centre for Addiction and Mental Health (CA)
- Venue
- Journal of Cerebral Blood Flow & Metabolism
- Publisher
- SAGE Publications
- Published
- 2001-11
- Volume
- 21
- Issue
- 11
- Pages
- 1342-1353
- ISSN
- 0271-678X (ISSN-L)
- 1559-7016
- OpenAlex
- W1540089293
- Cited by
- 209
- References
- 50
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 3 · 2023: 2 · 2022: 6 · 2021: 4 · 2020: 8 · 2019: 5 · 2018: 5 · 2017: 6 · 2016: 7 · 2015: 9 · 2014: 7 · 2013: 10 · 2012: 12
- FWCI
- 11.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Cerebral Blood Flow & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Eli Lilly and Company
- Medical Research Council Canada
- Medical Research Council
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Radiopharmaceutical Chemistry and Applications
- Keywords
- [11C]DASB, serotonin transporter, PET radiotracer, kinetic modeling, binding potential, cerebellum reference region, two-tissue compartment model, time-activity curves
- MeSH terms
- Adult, Aniline Compounds, Brain Chemistry, Carbon Radioisotopes, Carrier Proteins, Chromatography, High Pressure Liquid, Computer Simulation, Female, Humans, Kinetics, Male, Membrane Glycoproteins, Middle Aged, Models, Biological, Nerve Tissue Proteins, Sulfides, Tomography, Emission-Computed, Radiopharmaceuticals, Membrane Transport Proteins, Serotonin Plasma Membrane Transport Proteins
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