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

Abstract

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 ofi.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.

Amphetamine-Induced Dopamine Release and Neurocognitive Function in Treatment-Naive Adults with ADHD

“…However, these variables were estimated at different times and only once in each participant. Nonetheless, high test-retest reliability of our inhibition measures (Ettinger et al, 2003;Logan et al, 1984) as well as of DBP ND to d-amph (Kegeles et al, 1999) supports the interpretation that dopaminergic dysfunction is related to response inhibition deficits in ADHD. (2) Our sample size had power to detect only associations of a medium to large effect size, given the Bonferroni correction for multiple comparisons.…”

Imaging Human Mesolimbic Dopamine Transmission with Positron Emission Tomography. Part II: Amphetamine-Induced Dopamine Release in the Functional Subdivisions of the Striatum

“…This ⌬V 3 Љ value was derived from pooling four independent samples studied under identical experimental conditions (Laruelle et al, 1995(Laruelle et al, , 1996Abi-Dargham et al, 1998;Kegeles et al, 1999) and was not statistically different from ⌬V 3 Љ measured with [ 11 C]raclopride in the present study (P ‫ס‬ 0.21, unpaired t-test).…”

Within-Subject Comparison of [11C]-( + )-PHNO and [11C]raclopride Sensitivity to Acute Amphetamine Challenge in Healthy Humans

“…123 I]IBZM single photon emission computed tomography (Kegeles et al, 1999). Subjects underwent measurement of striatal dopamine release on two occasions, 16 ± 10 days apart, after administration of 0.3 mg/kg amphetamine.…”