Quantification of cerebral cannabinoid receptors subtype 1 (CB1) in healthy subjects and schizophrenia by the novel PET radioligand [11C]OMAR.

Abstract

Several studies have examined the link between the cannabinoid CB1 receptor and several neuropsychiatric illnesses, including schizophrenia. As such, there is a need for in vivo imaging tracers so that the relationship between CB1 and schizophrenia (SZ) can be further studied. In this paper, we present our first human studies in both healthy control patients and patients with schizophrenia using the novel PET tracer, [(11)C]OMAR (JHU75528), we have shown its utility as a tracer for imaging human CB1 receptors and to investigate normal aging and the differences in the cannabinoid system of healthy controls versus patients with schizophrenia. A total of ten healthy controls and nine patients with schizophrenia were included and studied with high specific activity [(11)C]OMAR. The CB1 binding (expressed as the distribution volume; V(T)) was highest in the globus pallidus and the cortex in both controls and patients with schizophrenia. Controls showed a correlation with the known distribution of CB1 and decline of [(11)C]OMAR binding with age, most significantly in the globus pallidus. Overall, we observed elevated mean binding in patients with schizophrenia across all regions studied, and this increase was statistically significant in the pons (p<0.05), by the Students t-test. When we ran a regression of the control subjects V(T) values with age and then compared the patient data to 95% prediction limits of the linear regression, three patients fell completely outside for the globus pallidus, and in all other regions there were at least 1-3 patients outside of the prediction intervals. There was no statistically significant correlations between PET measures and the individual Brief Psychiatry Rating Score (BPRS) subscores (r=0.49), but there was a significant correlation between V(T) and the ratio of the BPRS psychosis to withdrawal score in the frontal lobe (r=0.60), and middle and posterior cingulate regions (r=0.71 and r=0.79 respectively). In conclusion, we found that [(11)C] OMAR can image human CB1 receptors in normal aging and schizophrenia. In addition, our initial data in subjects with schizophrenia seem to suggest an association of elevated binding specific brain regions and symptoms of the disease.

• Authors: Dean F Wong, Hiroto Kuwabara, Andrew G Horti, Vanessa Raymont, James Brasic, Maria Guevara, Weiguo Ye, Robert F Dannals, Hayden T Ravert, Ayon Nandi, Arman Rahmim, Jeffrey E Ming, Igor Grachev, Christine Roy, Nicola Cascella
• Journal: NeuroImage (Neuroimage) Vol. 52 Issue 4 Pg. 1505-13 (Oct 01 2010) ISSN: 1095-9572 [Electronic] United States
• PMID: 20406692 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 Elsevier Inc. All rights reserved.

Chemical References

• 4-cyano-1-(2,4-dichlorophenyl)-5-(4-methoxyphenyl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide
• Piperidines
• Pyrazoles
• Radiopharmaceuticals
• Receptor, Cannabinoid, CB1

Topics

• Adult
• Brain (metabolism)
• Female
• Humans
• Male
• Middle Aged
• Piperidines (pharmacokinetics)
• Positron-Emission Tomography (methods)
• Pyrazoles (pharmacokinetics)
• Radiopharmaceuticals (pharmacokinetics)
• Receptor, Cannabinoid, CB1 (metabolism)
• Schizophrenia (diagnostic imaging, metabolism)
• Tissue Distribution