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

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