Test-retest reproducibility of dopamine D2/3 receptor binding in human brain measured by PET with [11C]MNPA and [11C]raclopride

Dopamine D2/3 receptors (D2/3Rs) have two affinity states for endogenous dopamine, referred to as high-affinity state (D2/3HIGH), which has a high affinity for endogenous dopamine, and low-affinity state (D2/3LOW). The density of D2/3HIGH can be measured with (R)-2-11CH3O-N-n-propylnorapomorphine ([11C]MNPA), while total density of D2/3HIGH and D2/3LOW (D2/3Rs) can be measured with [11C]raclopride using positron emission tomography (PET). Thus, the ratio of the binding potential (BP) of [11C]MNPA to that of [11C]raclopride ([11C]MNPA/[11C]raclopride) may reflect the proportion of the density of D2/3HIGH to that of D2/3Rs. In the caudate and putamen, [11C]MNPA/[11C]raclopride reflects the proportion of the density of D2HIGH to that of D2Rs. To evaluate the reliability of the PET paradigm with [11C]MNPA and [11C]raclopride, we investigated the test-retest reproducibility of non-displaceable BP (BPND) measured with [11C]MNPA and of [11C]MNPA/[11C]raclopride in healthy humans. Eleven healthy male volunteers underwent two sets of PET studies on separate days that each included [11C]MNPA and [11C]raclopride scans. BPND values in the caudate and putamen were calculated. Test-retest reproducibility of BPND of [11C]MNPA and [11C]MNPA/[11C]raclopride was assessed by intra-subject variability (absolute variability) and test-retest reliability (intraclass correlation coefficient: ICC). The absolute variability of [11C]MNPA BPND was 5.30 ± 3.96 % and 12.3 ± 7.95 % and the ICC values of [11C]MNPA BPND were 0.72 and 0.82 in the caudate and putamen, respectively. The absolute variability of [11C]MNPA/[11C]raclopride was 6.11 ± 3.68 % and 11.60 ± 5.70 % and the ICC values of [11C]MNPA/[11C]raclopride were 0.79 and 0.80 in the caudate and putamen, respectively. In the present preliminary study, the test-retest reproducibility of BPND of [11C]MNPA and of [11C]MNPA/[11C]raclopride was reliable in the caudate and putamen. (orig.)