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Test-retest reproducibility of dopamine D2/3 receptor binding in human brain measured by PET with [11C]MNPA and [11C]raclopride
Authors:Fumitoshi Kodaka  Hiroshi Ito  Yasuyuki Kimura  Saori Fujie  Harumasa Takano  Hironobu Fujiwara  Takeshi Sasaki  Kazuhiko Nakayama  Christer Halldin  Lars Farde  Tetsuya Suhara
Affiliation:1. Molecular Neuroimaging Program, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan
3. Department of Psychiatry, Jikei University School of Medicine, Tokyo, Japan
2. Biophysics Program, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555, Japan
4. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
Abstract:

Purpose

Dopamine D2/3 receptors (D2/3Rs) have two affinity states for endogenous dopamine, referred to as high-affinity state (D2/3 HIGH), which has a high affinity for endogenous dopamine, and low-affinity state (D2/3 LOW). The density of D2/3 HIGH can be measured with (R)-2-11CH3O-N-n-propylnorapomorphine ([11C]MNPA), while total density of D2/3 HIGH and D2/3 LOW (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 D2/3 HIGH to that of D2/3Rs. In the caudate and putamen, [11C]MNPA/[11C]raclopride reflects the proportion of the density of D2 HIGH 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 (BP ND) measured with [11C]MNPA and of [11C]MNPA/[11C]raclopride in healthy humans.

Methods

Eleven healthy male volunteers underwent two sets of PET studies on separate days that each included [11C]MNPA and [11C]raclopride scans. BP ND values in the caudate and putamen were calculated. Test-retest reproducibility of BP ND of [11C]MNPA and [11C]MNPA/[11C]raclopride was assessed by intra-subject variability (absolute variability) and test-retest reliability (intraclass correlation coefficient: ICC).

Results

The absolute variability of [11C]MNPA BP ND was 5.30?±?3.96 % and 12.3?±?7.95 % and the ICC values of [11C]MNPA BP ND 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.

Conclusion

In the present preliminary study, the test-retest reproducibility of BP ND of [11C]MNPA and of [11C]MNPA/[11C]raclopride was reliable in the caudate and putamen.
Keywords:
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