Stability of [¹²³I]IBZM SPECT measurement of amphetamine-induced striatal dopamine release in humans

Binding competition between endogenous dopamine (DA) and the D₂ receptor radiotracer [¹²³I]IBZM allows measurement of the change in synaptic DA following amphetamine challenge with SPECT in the living human brain. Previous investigations using this technique in healthy subjects have shown that the magnitude of amphetamine effect on [¹²³I]IBZM binding potential (BP) is small (range between 5 to 15% decrease), and that a large between-subject variability in this effect is observed. Therefore, it was unclear how much of the apparent between-subject variability was due to a low signal-to-noise ratio in the measurement, vs. true between-subject differences in the magnitude of the response. The goals of this investigation were to test the within-subject reproducibility and reliability of amphetamine-induced decrease in [¹²³I]IBZM BP with a test/retest paradigm, and to establish the presence or absence of tolerance or sensitization to single administration of i.v. amphetamine. Six healthy male subjects, never previously exposed to psychostimulants, twice underwent measurement of striatal amphetamine-induced DA release (between-measurement interval 16 ± 10 days) using SPECT and the [¹²³I]IBZM constant infusion technique. Results demonstrated an excellent within-subject reproducibility of amphetamine-induced DA release: amphetamine-induced decreases in [¹²³I]IBZM BP were significant on each day, and had an intraclass correlation coefficient (ICC) of 0.89. Moreover, values from the second experiment were not significantly different from first experiment, suggesting the absence of either sensitization or tolerance to the effect of amphetamine on DA release in these experimental conditions. The subjective activation, as rated by the subjects on analog scales, was also highly reproducible. In conclusion, this scanning technique provides a reliable measurement of amphetamine-induced reduction of [¹²³I]IBZM BP and enables detection of between-subject differences that appear stable over time.