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

Objectives As a step towards developing in vivo imaging tracers for cannabinoid receptor subtype 1 (CB1) we present here our first human studies in both healthy control patients and patients with schizophrenia using the novel PET tracer, [¹¹C]OMAR (JHU 75528). In this study [¹¹C]OMAR will be used to investigate normal aging and the differences in the cannabinoid system of healthy controls vs. patients with schizophrenia.

Methods We studied ten healthy controls and six patients with schizophrenia using high specific activity [¹¹C]OMAR. CB1 binding was expressed as the distribution volume (V_T).

Results V_T was the highest in the globus pallidus and the cortex in both controls and patients with schizophrenia. Within the controls, there was a significant negative correlation of [¹¹C]OMAR binding (i.e, CB1 distribution) and age, most significantly in the globus pallidus. Amongst patients with schizophrenia, there was no significant decline with age. In fact, patients had an overall elevated binding which fell significantly outside the 95% prediction limits of the linear regression of V_T vs. age (p = 0.003). There was also a significant correlation between V_T in patients and the ratio of the BPRS (Brief Psychiatry Rating Score) psychosis to withdrawal subscores in frontal lobe (r²=0.61), cingulate gyrus (r²=0.60), parietal cortex (r²=0.64) and putamen (r²=0.58).

Conclusions In conclusion, [¹¹C] OMAR can image human CB1 receptors in normal aging and schizophrenia. Our initial data in schizophrenia subjects seem to suggest an association of elevated binding specific brain regions and symptoms of the disease.

Research Support Sanofi-Aventis, NIH grants DA000412, MH07901