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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

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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.

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Acknowledgements

We thank Mr. Katsuyuki Tanimoto and Mr. Takahiro Shiraishi for their assistance in performing the PET experiments at the National Institute of Radiological Sciences. We also thank Ms. Yoshiko Fukushima of the National Institute of Radiological Sciences for her help as clinical research coordinator. This study was supported in part by a Grant-in-Aid for the Molecular Imaging Program from the Ministry of Education, Culture, Sports, Science and Technology (MEXT).

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Correspondence to Hiroshi Ito.

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Kodaka, F., Ito, H., Kimura, Y. et al. Test-retest reproducibility of dopamine D2/3 receptor binding in human brain measured by PET with [11C]MNPA and [11C]raclopride. Eur J Nucl Med Mol Imaging 40, 574–579 (2013). https://doi.org/10.1007/s00259-012-2312-8

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  • DOI: https://doi.org/10.1007/s00259-012-2312-8

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