@misc{oai:repo.qst.go.jp:00072104,
 author = {Matsubara, Keisuke and Ito, Hiroshi and Ikoma, Yoko and Okada, Maki and Masanobu, Ibaraki and Nakamura, Kazuhiro and Yamaguchi, Hiroshi and Suhara, Tetsuya and Kinoshita, Toshibumi and 松原 佳亮 and 伊藤 浩 and 生駒 洋子 and 岡田 真希 and 茨木 正信 and 中村 和浩 and 山口 博司 and 須原 哲也},
 month = {Aug},
 note = {Objectives: Dopamine synthesis rate, one of the presynaptic functions of the central dopaminergic
system, can be measured by positron emission tomography (PET) measurement with L-[β-11C]DOPA
[1]. The radiolabeled O-methyl metabolite of L-[β-11C]DOPA in peripheral organ, L-[β-11
C]O-methyl-DOPA (L-[β-11C]OMD), suggested to penetrate the blood-brain barrier (BBB). Thus, L-[β-
11C]OMD may affect tissue radioactivity measured by PET and the endogenous dopamine synthesis rate
estimated by kinetic analyses. However, the influence of L-[β-11C]OMD in the living tissue for the
kinetic analyses has not been investigated in detail. In the present study, to evaluate the influence of
L-[β-11C]OMD on the tissue time-activity curve (TAC) with L-[β-11C]DOPA PET, the metabolite
correction was applied to tissue TACs acquired from healthy volunteers.
Methods: The metabolite correction method proposed by Kumakura et al. in [18F]FDOPA PET study
[2] was employed. In this method, component for O-methyl metabolite in the tissue TAC is estimated by
compartmental analysis with two kinds of arterial input function for L-[β-11C]DOPA and L-[β-11
C]OMD, and TAC in occipital cortex as a reference region with no irreversible binding. TAC in each
brain region for L-[β-11C]DOPA PET studies with ten healthy volunteers [1] was corrected by using the
estimated L-[β-11C]OMD TAC. This method assumes the distribution of O-methyl metabolite is
uniform around the brain [3].
The endogenous dopamine synthesis rate (Ki) was estimated by Gjedde-Patlak plot analysis with the
arterial input function and the metabolite-corrected TAC. The Ki was also estimated from the
non-corrected TAC. For comparison to conventional analysis, relative influx constant (kref) was also
estimated by Gjedde-Patlak plot analysis using TAC in occipital cortex, regarded as reference tissue
input function. Data of 29 – 64 min and 29 – 89 min were used for linear regression in Gjedde-Patlak
plot analysis.
Results: Calculated OMD component had only a marginal effect on tissue TAC (fraction of area under
curve (AUC) of L-[β-11C]OMD TAC in putaminal TAC: 9.4 ± 2.1 %). Ki with no metabolite corrected
TAC correlated significantly to Ki with the metabolite correction (p < 0.001, r = 0.99 (29 – 64 min), p <
0.001, r = 0.99 (29 – 89 min)), and Ki were overestimated in all brain regions with no metabolite
correction, see Figure A. kref also correlated to Ki with the metabolite correction, as shown in Figure B
(p < 0.001, r = 0.99 (29 – 64 min), p < 0.001, r = 0.99 (29 – 89 min)).
Conclusion: The results suggest that the influence of the O-methyl metabolite L-[β-11C]OMD to tissue
TAC and kinetic parameters in L-[β-11C]DOPA PET is marginal. This finding is accounted for by low
fraction of L-[β-11C]OMD in plasma in case of L-[β-11C]DOPA, in contrast with high fraction of
O-methyl metabolite for [18F]FDOPA. The results also suggest the net endogenous dopamine synthesis
rate can be determined without the metabolite correction in case of L-[β-11C]DOPA, not same as [18
F]FDOPA.
Reference
[1] Ito H., et al., 2006, Nucl. Med. Commun. 27, 723-731
[2] Kumakura Y., et al., 2005, J. Cereb. Blood Flow Metab. 25, 807-819
[3] Doudet D.J., et al., 1991, J. Cereb. Blood Flow Metab. 11, 726-734
Note - image will be printed in black & white, The Ninth International Symposium on Functional Neuroreceptor Mapping of the Living Brain},
 title = {Correction for Radiolabeled O-Methyl Metabolite in Human Brain},
 year = {2012}
}