[123 I]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

Background- The cannabinoid CB, receptor agonist Delta(9)-THC has been suggested for treatment of Tourette syndrome (TS). Based on animal studies, the CB, antagonist [I-123]AM281 (N-(Morpbolin-4-yl)-1-(2,4-dicbloropbenyl)-5-(4-[I-123]iodopbenyl)-4-metbyl-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 [I-123]AM281 to CB1 receptors in TS patients and 2) assess radiation exposure associated with the use of AM281 labeled with I-123 for SPECT and I-124 for positron emission tomography. Methods. We employed [I-123]AM281 in six TS patients before and after Delta(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, 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 [I-123]AM281 were used to predict doses from [I-124]AM281. Results. Mean V-3" ranged from .19 to .31 and did not change significantly after Delta(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 [I-123]AM281 and .34 for [I-124]AM281 were computed. Conclusions. This study suggests that specific binding of [I-123]AM281 to CB, receptors can be detected in patients using SPECT. Radiation exposure with [I-123]AM281 is low; that with [I-124]AM281 is higher but acceptable for single investigations.