[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
| Autor: | David J. Brooks, Bernd O. Knoop, Hinderk M. Emrich, Ralph Buchert, Kirsten R. Müller-Vahl, Michael Hofmann, Wolfram H. Knapp, Frank Donnerstag, Heinrich Harke, Peter Gielow, Georg Berding, Manfred Stuhrmann, Udo Schneider, Jürgen Fitschen |
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| Rok vydání: | 2004 |
| Předmět: |
Adult
Male Agonist Time Factors Cannabinoid receptor medicine.drug_class medicine.medical_treatment Single-photon emission computed tomography Radiation Dosage Receptor Cannabinoid CB1 medicine Humans Whole Body Imaging Dronabinol Tetrahydrocannabinol Biological Psychiatry Tomography Emission-Computed Single-Photon Psychotropic Drugs medicine.diagnostic_test Chemistry business.industry Antagonist Brain Magnetic resonance imaging Middle Aged Magnetic Resonance Imaging Positron emission tomography Female Chromatography Thin Layer Cannabinoid Radiopharmaceuticals Nuclear medicine business Tourette Syndrome medicine.drug |
| Zdroj: | Biological Psychiatry. 55:904-915 |
| ISSN: | 0006-3223 |
| DOI: | 10.1016/j.biopsych.2004.01.005 |
| Popis: | Background The cannabinoid CB 1 receptor agonist Δ 9 -THC has been suggested for treatment of Tourette syndrome (TS). Based on animal studies, the CB 1 antagonist [ 123 I]AM281 (N-(Morpholin-4-yl)-1-(2,4-dichlorophenyl)-5-(4-[ 123 I]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 [ 123 I]AM281 to CB 1 receptors in TS patients and 2) assess radiation exposure associated with the use of AM281 labeled with 123 I for SPECT and 124 I for positron emission tomography. Methods We employed [ 123 I]AM281 in six TS patients before and after Δ 9 -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 CB 1 density (lentiform nuclei) and reference regions. Specific over nonspecific partition coefficients V 3 ′′ were calculated. Whole-body images were carried out for dosimetric analysis. Data obtained with [ 123 I]AM281 were used to predict doses from [ 124 I]AM281. Results Mean V 3 ′′ ranged from .19 to .31 and did not change significantly after Δ 9 -THC treatment. Nevertheless, in the only patient with a marked clinical response, V 3 ′′ 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 [ 123 I]AM281 and .34 for [ 124 I]AM281 were computed. Conclusions This study suggests that specific binding of [ 123 I]AM281 to CB 1 receptors can be detected in patients using SPECT. Radiation exposure with [ 123 I]AM281 is low; that with [ 124 I]AM281 is higher but acceptable for single investigations. |
| Databáze: | OpenAIRE |
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