In vivo imaging of serotonin transporters with [ 99m Tc]TRODAT-1 in nonhuman primates
Abstract
[99mTc]TRODAT-1 was the first 99mTc-labeled imaging agent to show specific binding to dopamine transporters (DAT) in the striatum (STR) of human brain. Additionally, in vitro binding and autoradiographic experiments demonstrated that this tracer also binds to serotonin transporters (SERT) in the midbrain/hypothalamus (MB) area. In this study, [99mTc]TRODAT-1 was investigated as a potentially useful ligand to image SERT in the MB of living brain. A total of eight single-photon emission tomography (SPET) scans were performed in two baboons (Papio anubis) after intravenous (i.v.) injection of 740 MBq (20 mCi) of [99mTc]TRODAT-1 using a triple-head gamma camera equipped with ultra-high-resolution fan-beam collimators (scan time: 0-210 min). In four blocking studies, baboons were pretreated with (+)McN5652 (1 mg/kg, i.v.) or methylphenidate (1 mg/kg, i.v.) to specifically block SERT or DAT, respectively. After co-registration with magnetic resonance images of the same baboon, a region of interest analysis was performed using predefined templates to calculate specific uptake in the midbrain area and the striatum, with the cerebellum as the background region [(MB-CB)/CB, (STR-CB)/CB]. Additionally, two PET scans of the same baboons were performed after i.v. injections of 74-111 MBq (2-3 mCi) of [11C](+)McN5652 to identify the SERT sites. In [99mTc]TRODAT-1/SPET scans, the SERT sites in the MB region were clearly visualized. Semiquantitative analysis revealed a specific uptake in MB…
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Methylphenidate directly inhibits dopamine and norepinephrine transporters, has agonist activity at the 5-HT1A receptor, and redistributes VMAT-2.
“The direct effects of MPH include inhibition of the DAT and NET (113, 114, 118, 120, 123, 128), an affinity for and agonist activity at the 5-HT1A receptor (119, 120), and redistribution of VMAT-2 (88, 125).”
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- Authors
- Dresel, S. H. J., Kung, M.-P. T., Huang, X., Plössl, K., Hou, C., Shiue, C. Y., Karp, J., & Kung, H. F.
- Affiliations
- University of Pennsylvania (US)
- Venue
- European Journal of Nuclear Medicine and Molecular Imaging
- Published
- 1999-03-25
- Volume
- 26
- Issue
- 4
- Pages
- 342-347
- ISSN
- 1619-7070 (ISSN-L)
- 1619-7089
- OpenAlex
- W2065631237
- Cited by
- 26
- References
- 26
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 1 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 1 · 2017: 2 · 2016: 1 · 2013: 1 · 2012: 1
- FWCI
- 0.24
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- European Journal of Nuclear Medicine and Molecular Imaging (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Radiopharmaceutical Chemistry and Applications
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
- Keywords
- 99mTc-TRODAT-1, serotonin transporter, dopamine transporter, striatum, midbrain, baboons, non-human primates, methylphenidate, radiotracer binding, single photon emission tomography, autoradiography
- MeSH terms
- Animals, Brain, Carrier Proteins, Female, Image Processing, Computer-Assisted, Isoquinolines, Membrane Glycoproteins, Methylphenidate, Nerve Tissue Proteins, Papio, Serotonin Antagonists, Tissue Distribution, Tomography, Emission-Computed, Tropanes, Organotechnetium Compounds, Tomography, Emission-Computed, Single-Photon, Adrenergic Uptake Inhibitors, Radiopharmaceuticals, Membrane Transport Proteins, Serotonin Plasma Membrane Transport Proteins
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