[123I]AM281 single-photon emission computed tomography imaging of central cannabinoid CB1 receptors before and after Δ9-tetrahydrocannabinol therapy and whole-body scanning for assessment of radiation dose in tourette patients
Abstract
Background The cannabinoid CB1 receptor agonist Delta9-THC has been suggested for treatment of Tourette syndrome (TS). Based on animal studies, the CB1 antagonist [123I]AM281 (N-(Morpholin-4-yl)-1-(2,4-dichlorophenyl)-5-(4-[123I]iodophenyl)-4-methyl-1H-pyrazole-3-carboxamide) has been proposed for single photon emission computed tomography (SPECT) in humans. Our aims were to 1) evaluate specific binding of [123I]AM281 to CB1 receptors in TS patients and 2) assess radiation exposure associated with the use of AM281 labeled with 123I for SPECT and 124I for positron emission tomography.Methods We employed [123I]AM281 in six TS patients before and after Delta9-THC treatment. Dynamic SPECT, plasma measurements (including metabolite analysis with thin layer chromatography), and whole-body imaging were performed. Regions of interest derived from magnetic resonance images were used to extract from SPECT uptake in an area with high CB1 density (lentiform nuclei) and reference regions. Specific over nonspecific partition coefficients V3" were calculated. Whole-body images were carried out for dosimetric analysis. Data obtained with [123I]AM281 were used to predict doses from [124I]AM281.Results Mean V3" ranged from .19 to .31 and did not change significantly after Delta9-THC treatment. Nevertheless, in the only patient with a marked clinical response, V3" clearly declined. Thin layer chromatography revealed biexponential kinetics of tracer metabolism; about 60% remained nonmetabolized after 3 hours. Effective doses of .011 mSv/MBq for [123I]AM281 and .34 for [124I]AM281 were computed.Conclusions This study suggests that specific binding of [123I]AM281 to CB1 receptors can be detected in patients using SPECT. Radiation exposure with [123I]AM281 is low; that with [124I]AM281 is higher but acceptable for single investigations.
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Increased [11C]OMAR VT values are explained to the most part by receptor up-regulation in response to low anandamide levels rather than low receptor occupancy by anandamide.
“The lack of displacement of CB1 radioligands by agonists42–44 which has been attributed to a large receptor reserve45 suggests that increased [11C]OMAR VT values are explained to the most part by receptor up-regulation in response to low anandamide levels rather than low receptor occupancy by anandamide.”
From Elevated brain cannabinoid CB1 receptor availability in post-traumatic stress disorder: A positron emission tomography study (2013) · cites this paper as [44]
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References 67 · Cited by 54
- Authors
- Berding, G., Müller-Vahl, K., Schneider, U., Gielow, P., Fitschen, J., Stuhrmann, M., Harke, H., Buchert, R., Donnerstag, F., Hofmann, M., Knoop, B. O., Brooks, D. J., Emrich, H. M., & Knapp, W. H.
- Affiliations
- Medizinische Hochschule Hannover (DE)
- University Medical Center Hamburg-Eppendorf (DE)
- Hammersmith Hospital (GB)
- Corresponding author
- Berding, Georg
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2004-05
- Volume
- 55
- Issue
- 9
- Pages
- 904-915
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W2045507315
- Cited by
- 54
- References
- 67
- Citations by year
- 2024: 1 · 2023: 2 · 2022: 6 · 2021: 1 · 2020: 4 · 2019: 2 · 2018: 2 · 2016: 3 · 2015: 2 · 2014: 4 · 2013: 4 · 2012: 1
- FWCI
- 2.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- 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
- Tourette syndrome, delta-9-tetrahydrocannabinol, radiation dose assessment, dosimetry, specific binding, tracer metabolism, lentiform nucleus, positron emission tomography, radiotracer biodistribution
- MeSH terms
- Adult, Brain, Chromatography, Thin Layer, Female, Tourette Syndrome, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Psychotropic Drugs, Radiation Dosage, Dronabinol, Time Factors, Tomography, Emission-Computed, Single-Photon, Radiopharmaceuticals, Receptor, Cannabinoid, CB1, Whole Body Imaging
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