Dynamic SPECT imaging of dopamine D2 receptors in human subjects with iodine-123-IBZM

We studied the uptake, distribution, metabolism and washout of the dopamine D2 receptor ligand [¹²³I]IBZM in healthy subjects (n = 12) with dynamic brain SPECT. The highest radioactivity level was detected in the striatum. Operationally-defined striatal 'specific' uptake peaked at 69 min postinjection of radioligand and showed a gradual decline of 15% per hour thereafter. 'Specific' uptake at maximal counts represented 53% of the total striatal radioactivity. Two subjects received haloperidol (20 μg/kg i.v.) 80 min postinjection of radioligand. Haloperidol caused a 2.6-fold increase in the rate of washout of specific striatal activity in comparison to that in the 10 control subjects and was consistent with drug-induced displacement of radioligand from the dopamine D2 receptor. Two classes of metabolites were detected in plasma and urine: a polar fraction, not extracted by ethyl acetate, and a nonpolar, extractable fraction consisting of parent compound and two compounds having shorter retention times on reversed-phase HPLC. Greater than half the plasma parent was metabolized within 10-15 min after administration. The volume of distribution, estimated from the peak arterial plasma concentration at 50-75 sec, was 7.7-10.21; the free (nonprotein bound) fraction of [¹²³I]IBZM after in vitro incubation with blood or plasma was 4.4% ± 0.4%. These results suggest that [¹²³I]IBZM exhibits uptake in brain regions with high D2 receptor density and shows a relatively stable washout during which drugs affecting dopaminergic transmission may be administered.