2003 Fiscal Year Final Research Report Summary
Imaging of Central Dopamine Discharge using Positron Emission Tomography
| Project/Area Number |
14370268
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Radiation science
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| Research Institution | Tohoku University |
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Principal Investigator |
ITOH Masatoshi Tohoku University, Cyclotron Radioisotope Center, Division of Nuclear Medicine, Professor, サイクロトロン・ラジオアイソトープセンター, 教授 (00125501)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAGUCHI Keiichiro Tohoku University, Cyclotron Radioisotope Center, Division of Nuclear Medicine, Assistant Professor, サイクロトロン・ラジオアイソトープセンター, 助手 (40210356)
IWATA Ren Tohoku University, Cyclotron Radioisotope Center, Division of Radiopharmaceuticals, Professor, サイクロトロン・ラジオアイソトープセンター, 教授 (60143038)
ISHI Keizo Tohoku University, Postgraduate School of Engineering, Dep.of Quantum Engineering, Professor, 大学院・工学研究科, 教授 (00134065)
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| Project Period (FY) |
2002 – 2003
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| Keywords | Dopamine / PET / Raclopride / Nemonapride / Neurotransmission / Compartment Analysis |
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| Research Abstract |
The aim of this study is to establish a simplified non-invasive method to assess central dopamine release using positron emission tomography. Single bolus injection method with activations of dopamine (DA) systems was tested both in silico and in vivo. [^<11>C] labeled raclopride and nemonapride were compared in their kinetics in the striatum and in reference tissues (cerebellum/occipital cortex). The simplified reference tissue model implemented by Lammertsma and Gunn was employed for the simulation and analysis of tissue data. Simulation studies revealed that ligand binding to DA receptors could be changed after intervention that alters binding potentials of receptor sites. Continuous dual 45 minutes scans was chosen as a practical protocol of DA activations. [^<11>C]nemonapride was selected for the test ligand because of the following reasons; (1)relatively high non-specific bindings which is beneficial for continuous supply of free ligands to the receptors, (2)relatively high affinity to the D2-like receptors. Consequently, nemonapride radioactivity in the striatum reaches quasi-equilibrium in the late phase of scans, the state closely similar with continuous ligand injection method implemented by Carson et al. For human studies mild 10 Hz photo driving was used as a DA stimulus for 30 minutes. Kinetic analyses of nemonapride tissue radioactivity revealed clear discrepancies of actual tissue radioactivity from predicted tissue curves calculated from the kinetic data taken up to 50 minutes. Although this discrepancies were found in the control data without activation, the difference was significant between with activation and without activation (average fractional difference between the predicted and actual tissue data were 6.0±5.6% and 2.1±4.9%.for with activation and without activation respectively (t = 3.423, p<0.001).
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[Publications] Tanaka, Y., Meguro, K., Yamaguchi, S., Ishii, H., Wananuki, W., Funaki, Y., Yamaguchi, K., Yamadori, A., Iwata, R., Itoh, M.: "Decreased striatal D2 receptor density associated with severe behavioral abnormality in Alzheimer's disease"Ann.Nucl.Med.. 17(7). 567-573 (2003)
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[Publications] Nakajima T, Nimura T, Yamaguchi K, Ando T, Itoh M, Yoshimoto T, Shirane R., Nakajima T, Nimura T, Yamaguchi K, Ando T, Itoh M, Yoshimoto T, Shirane R.: "The impact of stereotactic pallidal surgery on the dopamine D2 receptor in Parkinson disease : a positron emission tomography study"J Neurosurg. 98(1). 57-63 (2003)
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[Publications] Okuda, J., Fujii, T., Ohtake, H., Tsukiura, T., Tanji, K., Suzuki, K., Kawashima, R., Fukuda, H., Itoh, M., Yamadori, A.: "Thinking of the future and past: the roles of the frontal pole and the medial temporal lobes"Neuroimage. 19(4). 1369-1380 (2003)
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