In vivo measurement of haloperidol affinity to dopamine D2/D3 receptors by[I-123]IBZM and single photon emission computed tomography

This study examines the feasibility of a steady-state bolus-integration met hod with the dopamine D2/D3 receptor single photon emission computer tomogr aphy (SPECT) tracer, [ I-123]IBZM, for determination of in vivo affinity of haloperidol. The nonspecific binding of [I-123]IBZM was examined in the ra t brain by infusion of haloperidol to plasma levels approximately 100 times the Kd level in man. In humans, Kd for haloperidol binding was measured in four healthy volunteers that were examined twice: once with partial dopami ne D2/D3 receptor blockade obtained by a scheduled infusion of unlabeled ha loperidol (0.7 mg total dosage), and once in an unblocked state. Blood samp ling and SPECT were performed intermittently during 6 hours after intraveno us [I-123]IBZM bolus injection. Plasma [I-123]IBZM was determined by octane extraction. Plasma haloperidol was determined by a radioimmunoassay, and p lasma protein binding was determined by equilibrium dialysis. In humans, th e striatal D2/D3 receptor occupancy was 0.27 +/- 0.085 and the in vivo Kd f or haloperidol was 0.25 +/- 0.1 nmol/L, which is comparable to Kd values as obtained from in vitro studies. The authors conclude that steady-state [I- 123]IBZM SPECT studies allow for determination of dopamine D2/D3 receptor o ccupancy in striatum and in vivo measurement of drug affinity to striatal d opamine D2 and D3 receptors.