PT - JOURNAL ARTICLE AU - Kimura, Yasuyuki AU - Ito, Hiroshi AU - Maeda, Jun AU - Yamada, Makiko AU - Fujiwara, Hironobu AU - Kodaka, Fumitoshi AU - Takahata, Keisuke AU - Takano, Harumasa AU - Higuchi, Makoto AU - Suhara, Tetsuya TI - Occupancy of dopamine transporter and the effect of dopamine reuptake inhibition by mazindol in living human brain DP - 2013 May 01 TA - Journal of Nuclear Medicine PG - 1746--1746 VI - 54 IP - supplement 2 4099 - http://jnm.snmjournals.org/content/54/supplement_2/1746.short 4100 - http://jnm.snmjournals.org/content/54/supplement_2/1746.full SO - J Nucl Med2013 May 01; 54 AB - 1746 Objectives Regional alterations in extracellular dopamine levels can be observed in the striatum during performance of neuropsychological tasks using PET. To increase detection of the alteration, dopamine reuptake inhibitor could be useful for producing a greater magnitude of change in 11C-raclopride binding. Mazindol is a non-selective catecholamine reuptake inhibitor, which blocks dopamine reuptake and thus could be used as an enhancer of dopamine release by neuropsyhological tasks. To investigate basic potency of mazindol in human, we measured occupancy of the dopamine transporter and change in 11C-raclopride binding using PET after single oral administration of mazindol. Methods Two sets of PET scans were acquired on seven healthy volunteers after oral administration of placebo and 1.5 mg of mazindol. 11C-raclopride was injected at 3 hours after the administration of placebo or mazindol, and 18F-FE-PE2I was injected at 5 hours. Binding potential of sub-regions of striatum was calculated by the simplified reference tissue model using cerebellum as reference region. Dopamine transporter occupancy was calculated by the % change of the binding potential of 18F-FE-PE2I, and change in extracellular dopamine levels was measured by the % change of that of 11C-raclopride. Results After oral administration of 1.5 mg of mazindol, the binding potential of 18F-FE-PE2I significantly reduced by 20 - 27 % (p < 0.01, paired t-test), indicating 20 - 27 % of dopamine transporters in the striatum was occupied by mazindol. Meanwhile, the binding potential of 11C-raclopride reduced by 3 - 6%, but the reduction was not significant, indicating the change in extracellular dopamine levels by mazindol without neuropsyhological tasks was small. Conclusions After oral administration of 1.5 mg of mazindol, dopamine transporters were occupied in a small proportion, and the change in extracellular dopamine levels was minimal.