Amphetamine‐stimulated dopamine release competes in vivo for [123I]IBZM binding to the D2 receptor in nonhuman primates

We used the reversibly binding D2 dopamine receptor radioligand [123I]IBZM (iodobenzamide) to test whether the endogenous neurotransmitter dopamine competes in vivo for radiotracer binding measured with single photon emission computed tomography (SPECT). In a series of nonhuman primate experiments (n = 27), the effects of temperature, amphetamine, haloperidol, and reserpine on brain uptake of [123I]IBZM were measured. Specific brain uptake of [123I]IBZM reached a peak by 100 min postinjection of radioligand and demonstrated a gradual, apparent “steady‐state” washout over the next 2 hr. Brain uptake was temperature dependent, with rates of washout of specifically bound radioligand greater under normothermic conditions (26%/hr: core body temperature 35–37°C) than under conditions of controlled hypothermia (11%/hr; 32–34°C). Given the greater retention of radioactivity, low‐temperature conditions were used in all other experiments. Administration of haloperidol (0.02 mg/kg IV) during the period of apparent steady state resulted in a dramatic increase in washout (60%/hr; p < 0.0001), consistent with its potent D2 receptor antagonist properties. d‐Amphetamine (1.0 mg/kg IV), which has negligible affinity for the D2 receptor but mediates the release of endogenous stores of dopamine, also enhanced washout (34%/hr; p < 0.0005). Reserpine pretreatment at doses (1.0 mg/kg) sufficient to cause greater than 90% depletion of striatal dopamine levels blocked this amphetamine‐enhanced washout (10%/hr; p < 0.05). Reserpine did not block the increased washout induced by the direct‐acting D2 receptor antagonist haloperidol. These results are consistent with the hypothesis that endogenous dopamine may effectively compete for radioligand binding in vivo in neuroreceptor imaging studies using PET and SPECT.