Molecular imaging of altered dopamine transmission in patients with schizophrenia

• Project/Area Number: 19390308
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Nippon Medical School
• Principal Investigator: OKUBO Yoshiro Nippon Medical School, 大学院・医学研究科, 教授 (20213663)
• Co-Investigator(Kenkyū-buntansha): SAITO Takuya 日本医科大学, 医学部, 准教授 (20246961) ; TATENO Amane 日本医科大学, 医学部, 講師 (50297917) ; ICHIMIYA Tetsuya 日本医科大学, 医学部, 講師 (50398864) ; KOEDA Michihiko 日本医科大学, 医学部, 助教 (60434130) ; 須原 哲也 独立行政法人放射線医学総合研究所, 分子イメージング研究センター分子神経イメージング研究グループ, グループリーダー (90216490)
• Project Period (FY): 2007 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000); Fiscal Year 2010: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2009: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2008: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2007: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
• Keywords: 統合失調症 / 分子イメージング / ドパミン / D2受容体 / PET / 神経科学 / 放射線 / 臨床 / 総合失調症

Research Abstract

Using positron emission tomography (PET) and different radioligands, we aimed to elucidate altered dopamine transmission in patients with schizophrenia. Using two different radioligands, [^<11>C]NNC112 and [^<11>C]SCH23390, we measured dopamine D1 receptor binding in patients with chronic schizophrenia and healthy controls. In patients with schizophrenia, the binding potentials of both ligands were significantly lower in the striatum and cortical regions than those of healthy controls. We measured presynaptic dopamine synthesis using PET with L-[β-^<11>C]DOPA and found that patients with schizophrenia showed higher dopamine synthesis in the left caudate nucleus, and that dopaminergic transmission in the thalamus and right temporal cortex might be implicated in the expression of symptoms in schizophrenia. Finally, we performed PET using [^<11>C]PE2I in patients with schizophrenia and healthy subjects to investigate dopamine transporter binding. Dopamine transporter binding in the thalamus of patients with schizophrenia was significantly higher than in control subjects. There were significant correlations between dopamine transporter binding and clinical symptom scores suggesting that altered dopamine transporter binding in the thalamus might be related to the pathophysiology and clinical symptoms of schizophrenia.

Research Products

• [Journal Article] Contribution of dopamine D1 and D2 receptors to amygdala activity in human. (2010)
  • Author(s): Takahashi H, Takano H, Kodaka F, Arakawa R, Yamada M, Otsuka T, Hirano Y, Kikyo H, Okubo Y, Kato M, Obata T, Ito H, Suhara T
  • Journal Title: J Neurosci. 30(8) Pages: 3043-3047
  • Peer Reviewed
• [Journal Article] Peripheral benzodiazepine receptors in patients with chronic schizophrenia : a PET study with [11C]DAA1106. (2010)
  • Author(s): Takano A, Arakawa R, Ito H, Tateno A, Takahashi H, Matsumoto R, Okubo Y, Suhara T
  • Journal Title: Int J Neuropsychopharmacol. 13(7) Pages: 943-950
  • Peer Reviewed
• [Journal Article] Decreased binding of [11C]NNC112 and [11C]SCH23390 in patients with chronic schizophrenia. (2010)
  • Author(s): Kosaka J, Takahashi H, Ito H, Takano A, Fujimura Y, Matsumoto R, Nozaki S, Yasuno F, Okubo Y, Kishimoto T, Suhara T
  • Journal Title: Life Sci. 86(21-22) Pages: 814-818
  • Peer Reviewed
• [Journal Article] Dopamine D1 receptors and nonlinear probability weighting in risky choice. (2010)
  • Author(s): Takahashi H, Matsui H, Camerer C, Takano H, Kodaka F, Ideno T, Okubo S, Takemura K, Arakawa R, Eguchi Y, Murai T, Okubo Y, Kato M, Ito H, Suhara T
  • Journal Title: J Neurosci 28 Pages: 12032-12038
  • Peer Reviewed
• [Journal Article] Electroconvulsive therapy decreases dopamine D2 receptor binding in the anterior cingulate in patients with depression : a controlled study using positron emission tomography with radioligand 11CFLB 457 (2010)
  • Author(s): Saijo T, Takano A, Suhara T, Arakawa R, Okumura M, Ichimiya T, Ito H, Okubo Y.
  • Journal Title: J Clin Psychiatry. Volume: 71 Pages: 793-799
  • Peer Reviewed
• [Journal Article] Positron emission tomography measurement of dopamine D receptor occupancy in the pituitary and cerebral cortex : relation to antipsychotic-induced hyperprolactinemia (2010)
  • Author(s): Arakawa R, Okumura M, Ito H, Takano A, Takahashi H, Takano H, Maeda J, Okubo Y, Suhara T.
  • Journal Title: J Clin Psychiatry. Volume: 71 Pages: 1131-1137
  • Peer Reviewed
• [Journal Article] Contribution of dopamine D1 and D2 receptors to amygdala activity in human. (2010)
  • Author(s): Takahashi H, Takano H, Kodaka F, Arakawa R, Yamada M, Otsuka T, Hirano Y, Kikyo H, Okubo Y, Kato M, Obata T, Ito H, Suhara T.
  • Journal Title: J Neurosci. Volume: 24 Pages: 3043-7
  • Peer Reviewed
• [Journal Article] Decreased binding of (11)CNNC112 and (11)CSCH23390 in patients with chronic schizophrenia. (2010)
  • Author(s): Kosaka J, Takahashi H, Ito H, Takano A, Fujimura Y, Matsumoto R, Nozaki S, Yasuno F, Okubo Y, Kishimoto T, Suhara T.
  • Journal Title: Life Sci. Volume: 86 Pages: 814-818
  • Peer Reviewed
• [Journal Article] Peripheral benzodiazepine receptors in patients with chronic schizophrenia : a PET study with 11CDAA1106 (2010)
  • Author(s): Takano A, Arakawa R, Ito H, Tateno A, Takahashi H, Matsumoto R, Okubo Y, Suhara T.
  • Journal Title: Int J Neuropsychopharmacol. Volume: 13 Pages: 943-950
  • Peer Reviewed
• [Journal Article] Decreased binding of [(11)C] NNC112 and [(11)C] SCH23390 in patients with chronic schizophrenia (2010)
  • Author(s): Kosaka J, Takahashi H, Ito H, Takano A, Fujimura Y, Matsumoto R, Nozaki S, Yasuno F, Okubo Y, Kishimoto T, Suhara T.
  • Journal Title: Life Sci. 30
• [Journal Article] Peripheral benzodiazepine receptors in patients with chronic schizophrenia : a PET study with [11C] DAA1106 (2010)
  • Author(s): Takano A, Arakawa R, Ito H, Tateno A, Takahashi H, Matsumoto R, Okubo Y, Suhara T.
  • Journal Title: Int J Neuropsychopharmacol 30 Pages: 1-8
• [Journal Article] Contribution of dopamine D1 and D2 receptors to amygdala activity in human (2010)
  • Author(s): Takahashi H, Takano H, Kodaka F, Arakawa R, Yamada M, Otsuka T, Hirano Y, Kikyo H, Okubo Y, Kato M, Obata T, Ito H, Suhara T.
  • Journal Title: J Neurosci. 24 ; 30 (8) Pages: 3043-7
• [Journal Article] Contribution of dopamine D1 and D2 receptors to amygdala activity in human. (2010)
  • Author(s): Takahashi H, Takano H, Kodaka F, Arakawa R, Yamada M, Otsuka T, Hirano Y, Kikyo H, Okubo Y, Kato M, Obata T, Ito H, Suhara T.
  • Journal Title: J Neurosci. 24 Pages: 3043-3047
  • Peer Reviewed
• [Journal Article] Increase in thalamic binding of [(11)C]PE2I in patients with schizophrenia: a positron emission tomography study of dopamine transporter. (2009)
  • Author(s): Arakawa R, Ichimiya T, Ito H, Takano A, Okumura M, Takahashi H, Takano H, Yasuno F, Kato M, Okubo Y, Suhara T
  • Journal Title: J Psychiatr Res. 43(15) Pages: 1219-1223
  • Peer Reviewed
• [Journal Article] Regional dopamine synthesis in patients with schizophrenia using L-[beta-11C]DOPA PET. (2009)
  • Author(s): Nozaki S, Kato M, Takano H, Ito H, Takahashi H, Arakawa R, Okumura M, Fujimura Y, Matsumoto R, Ota M, Takano A, Otsuka A, Yasuno F, Okubo Y, Kashima H, Suhara T
  • Journal Title: Schizophr Res. 108(1-3) Pages: 78-84
  • Peer Reviewed
• [Journal Article] Regional dopamine synthesis in patients with schizophrenia using L- [beta-11C] DOPA PET (2009)
  • Author(s): Nozaki S, Kato M, Takano H, Ito H, Takahashi H, Arakawa R, Okumura M, Fujimura Y, Matsumoto R, Ota M, Takano A, Otsuka A, Yasuno F, Okubo Y, Kashima H, Suhara T
  • Journal Title: Schizophr Res 108 Pages: 78-84
• [Journal Article] Increase in thalamic binding of [(11)C] PE2I in patients with schizophrenia : a positron emission tomography study of dopamine transporter (2009)
  • Author(s): Arakawa R, Ichimiya T, Ito H, Takano A, Okumura M, Takahashi H, Takano H, Yasuno F, Kato M, Okubo Y, Suhara T
  • Journal Title: J Psychiatr Res 43 Pages: 1219-1223
• [Journal Article] Regional dopamine synthesis in patients with schizophrenia using L-[beta-(11)C]DOPA PET. (2009)
  • Author(s): Nozaki S, Kato M, Takano H, Ito H, Takahashi H, Arakawa R, Okumura M, Fujimura Y, Matsumoto R, Ota M, Takano A, Otsuka A, Yasuno F, Okubo Y, Kashima H, Suhara T.
  • Journal Title: Schizophr Res. 108 Pages: 78-84
  • Peer Reviewed
• [Journal Article] Increase in thalamic binding of [(11)C]PE2I in patients with schizophrenia : a positron emission tomography study of dopamine transporter. (2009)
  • Author(s): Arakawa R, Ichimiya T, Ito H, Takano A, Okumura M, Takahashi H, Takano H, Yasuno F, Kato M, Okubo Y, Suhara T.
  • Journal Title: J Psychiatr Res 43 Pages: 1219-1223
  • Peer Reviewed
• [Journal Article] Regional dopamine synthesis in patients with schizophrenia using L- [beta-(ll)C] DOPA PET. (2009)
  • Author(s): 13. Nozaki S, Kato M, Takano H, Ito H, Takahashi H, Arakawa R, Okumura M, Fujimura Y, Matsumoto R, Ota M, Takano A, Otsuka A, Yasuno F, Okubo Y, Kashima H, Suhara T.
  • Journal Title: Schizophr Res. 108 Pages: 78-84
  • Peer Reviewed
• [Journal Article] Differential contributions of prefrontal and hippocampal dopamine D(1) and D(2) receptors in human cognitive functions. (2008)
  • Author(s): Takahashi H, Kato M, Takano H, Arakawa R, Okumura M, Otsuka T, Kodaka F, Hayashi M, Okubo Y, Ito H, Suhara T
  • Journal Title: J Neurosci. 28(46) Pages: 12032-12038
  • Peer Reviewed
• [Journal Article] GABAA/Benzodiazepine receptor binding in patients with schizophrenia using [11C]Ro15-4513, a radioligand with relatively high affinity for alpha5 subunit. (2008)
  • Author(s): Asai Y, Takano A, Ito H, Okubo Y, Matsuura M, Otsuka A, Takahashi H, Ando T, Ito S, Arakawa R, Asai K,Suhara T
  • Journal Title: Schizophr Res 99 Pages: 333-340
  • Peer Reviewed
• [Journal Article] GABAA/Benzodiazepine receptor binding in patients with schizophrenia using [11c] Ro15-4513, a radioligand with relatively high affinity for alpha5 subunit. (2008)
  • Author(s): Asai Y, Takano A, Ito H, Okubo Y, Matsuura M, Otsuka A, Takahashi H, Ando T, Ito S, Arakawa R, Asai K, Suhara T.
  • Journal Title: Schizophr Res. 99 Pages: 333-340
  • Peer Reviewed
• [Journal Article] Differential contributions of prefrontal and hippocampal dopamine D(1) and D(2) receptors in human cognitive functions. (2008)
  • Author(s): 10. Takahashi H, Kato M, Takano H, Arakawa R, Okumura M, Otsuka T, Kodaka F, Hayashi M, Okubo Y, Ito H, Suhara T.
  • Journal Title: J Neurosci. 28 Pages: 12032-8
  • Peer Reviewed
• [Journal Article] Cerebral response to cognition of human voice inflexion in schizophrenia: An fMRI study (2008)
  • Author(s): M. Koeda, H. Takahashi, N. Yahata, K. Asai, M. Matsuura, H. Tanaka and Y. Okubo
  • Journal Title: Schizophrenia Research Vol 98,S1 Pages: 118-119
  • Peer Reviewed
• [Journal Article] Normal database of dopaminergic neurotransmission system in human brain measured by positron emission tomography. (2008)
  • Author(s): H. Ito, H. Takahashi, R. Arakawa, H. Takano, T. Suhara T
  • Journal Title: Neuroimage 15 Pages: 555-65
  • Peer Reviewed
• [Journal Article] Dose-finding study of paliperidone ER based on striatal and extrastriatal dopamine D2 receptor occupancy in patients with schizophrenia. (2008)
  • Author(s): R. Arakawa, H. Ito, A. Takano, H. Takahashi, T. Morimoto, T. Sassa, K. Ohta, M. Kato, Y. Okubo, T. Suhara
  • Journal Title: Psychopharmacology(Ber1) 197 Pages: 229-35
  • Peer Reviewed
• [Journal Article] C GABA(A)/Benzodiazepine receptor binding in patients with schizophrenia using[(11)C]Ro15-4513, a radioligand with relatively high affinity for alpha5 subunit. (2008)
  • Author(s): Y. Asai, A. Takano, H. Ito, Y. Okubo, M. Matsuura, A. Otsuka, H. Takahashi, T. Ando, S. Ito, R. Arakawa, K. Asai, T. Suhara.
  • Journal Title: Schizophrenia Research 99 Pages: 333-340
  • Peer Reviewed
• [Journal Article] Memory and frontal lobe functions ; possible relations with dopamine D2 receptors in the hippocampus. (2007)
  • Author(s): Takahashi H, Kato M, Hayashi M, Okubo Y, Takano A, Ito H, Suhara T
  • Journal Title: Neuroimage 34 Pages: 1643-1649
  • Peer Reviewed
• [Journal Article] Enhanced dopamine release by nicotine in cigarette smokers: a double-blind, randomized, placebo-controlled pilot study.
  • Author(s): H. Takahashi, Y. Fujimura, M. Hayashi, H. Takano, M. kato, Y. Okubo, I. Kanno, H. Ito, T. Suhara
  • Journal Title: Int J Neuropsychopharmacol (印刷中)
  • Peer Reviewed
• [Presentation] ドパミン系の分子イメージング-精神症状の理解 (2010)
  • Author(s): 大久保善朗
  • Organizer: 東京パーキンソンニズム臨床研究会(第10回)
  • Place of Presentation: 東京
  • Year and Date: 2010-10-22
• [Presentation] 統合失調症の病態と治療～脳画像検査でわかったこと～ (2010)
  • Author(s): 大久保善朗
  • Organizer: 平成22年度精神研都民講座(第4回)
  • Place of Presentation: 東京(教育講演)
  • Year and Date: 2010-10-13
• [Presentation] 統合失調症の病態と治療-脳画像検査でわかったこと- (2010)
  • Author(s): 大久保善朗
  • Organizer: 平成22年度精神研都民講座(第4回)
  • Place of Presentation: 東京
  • Year and Date: 2010-10-13
• [Presentation] 統合失調症の病態と治療～脳機能画像研究からわかったこと～心理教育 (2010)
  • Author(s): 大久保善朗
  • Organizer: 家族教室ネットワーク第13回研究集会(福岡大会)
  • Place of Presentation: 福岡
  • Year and Date: 2010-02-20
• [Presentation] Implications of Brain Imaging for the Management of Schizophrenia. (2010)
  • Author(s): 大久保善朗
  • Organizer: The 50th Anniversary International Conference, Department of Psychiatry, the Catholic University of Korea.
  • Place of Presentation: Seoul, Koria
  • Year and Date: 2010-02-13
• [Presentation] ドパミン系の分子イメージング,～精神症状の理解～ (2010)
  • Author(s): 大久保善朗
  • Organizer: 東京パーキンソンニズム臨床研究会(第10回)
  • Place of Presentation: 東京(特別講演)
• [Presentation] Molecular imaging of psychotropic drug action using positron emission tomography (2010)
  • Author(s): 大久保善朗
  • Organizer: The World Psychiatric Association International Congress
  • Place of Presentation: Beijing, China
• [Presentation] ここまでわかったこころの病～統合失調症の新しい知識～ (2009)
  • Author(s): 大久保善朗
  • Organizer: 平成21年度江戸川区精神保健福祉講演会
  • Place of Presentation: 東京
  • Year and Date: 2009-11-25
• [Presentation] 分子イメージングによる抗精神病薬の薬効評価 (2009)
  • Author(s): 大久保善朗
  • Organizer: 第19回日本臨床精神神経薬理学会第39回日本神経精神薬理学会合同年会
  • Place of Presentation: 京都
  • Year and Date: 2009-11-14
• [Presentation] 分子イメージングによる抗精神病薬の薬効評価 (2009)
  • Author(s): 大久保善朗
  • Organizer: 第19回日本臨床精神神経薬理学会 第39回日本神経精神薬理学会 合同年会
  • Place of Presentation: 京都
  • Year and Date: 2009-11-14
• [Presentation] 脳機能画像からみた精神疾患の病態と治療 (2009)
  • Author(s): 大久保善朗
  • Organizer: 学術講演会栃木県精神衛生協会・栃木県精神医学会共催
  • Place of Presentation: 栃木
  • Year and Date: 2009-07-16
• [Presentation] 分子イメージングの最近の進歩-精神科臨床への応用- (2009)
  • Author(s): 大久保善朗
  • Organizer: 第31回日本生物学的精神医学会
  • Place of Presentation: 京都
  • Year and Date: 2009-04-24
• [Presentation] 分子イメージングの最近の進歩 (2009)
  • Author(s): 大久保善朗
  • Organizer: 第31回日本生物学的精神医学会
  • Place of Presentation: 京都
  • Year and Date: 2009-04-24
• [Presentation] 不安のニューロイメージング (2009)
  • Author(s): 大久保善朗
  • Organizer: 第8回日本トラウマティック・ストレス学会
  • Place of Presentation: 東京
  • Year and Date: 2009-03-14
• [Presentation] 分子イメージングによる抗精神病薬の薬効評価.ランチョンセミナー (2009)
  • Author(s): 大久保善朗
  • Organizer: 第4回日本統合失調症学会
  • Place of Presentation: 大阪
  • Year and Date: 2009-01-30
• [Presentation] 脳画像からみた統合失調症の病態と治療 (2008)
  • Author(s): 大久保善朗
  • Organizer: 第3回東京五大学精神医学集談会
  • Place of Presentation: 東京
  • Year and Date: 2008-02-14
• [Presentation] A functional MRI study:Cerebral Activation for Human Voice Inflexion in Schizophrenia (2008)
  • Author(s): M. Koeda, H. Takahashi, N. Yahata, K. Asai, M. Matsuura, H. Tanaka and Y. Okubo
  • Organizer: British Neuropsychiatry Assocition Annual General Meeting, 21th Meeting
  • Place of Presentation: The Institute of Child Health, Guilford St, London
  • Year and Date: 2008-02-07
• [Presentation] Cerebral response to cognition of Human Voice Inflexion in Schizophrenia:An FMRI Study (2008)
  • Author(s): M. Koeda, H. Takahashi, N. Yahata, K. Asai, M. Matsuura, H. Tanaka and Y. Okubo
  • Organizer: 14th biennial Winter Workshops on Schizophrenia and Bipolar disorders
  • Place of Presentation: スイス、モントルーMontreux Music and Convention Centre
  • Year and Date: 2008-02-05
• [Presentation] 分子イメージングによる抗精神病薬の薬効評価.ランチョンセミナー (2008)
  • Author(s): 大久保善朗
  • Organizer: 第18回日本臨床精神神経薬理学会、第38回日本神経精神薬理学会合同年会
  • Place of Presentation: 東京
• [Presentation] Quantive analysis of dopamine D2 receptor binding in humanbrain using PET with a agonist radioligand [11c] MNPA. (2008)
  • Author(s): Ohtsuka T, Ito H, Takahashi H, Takano H, Arakawa R, Okumura M, Kodaka F, Miyoshi M, Sekine M, Seki C, Suhara T, Halldin C, Farde L.
  • Organizer: Neuroreoeptor Mapping 2008
  • Place of Presentation: Pittsburg, USA
• [Presentation] Roles of hippocampal and prefrontal dopamine D1 and D2 receptors in human neurocognitive functions. (2008)
  • Author(s): 10. Takahashi H, Takano H, Suzuki K, Okubo Y, Suhara T, Halldin C.
  • Organizer: Neuroreceptor Mapping 2008
  • Place of Presentation: Pittsburg, USA
• [Presentation] 脳機能画像からみた精神疾患の病態と治療 (2007)
  • Author(s): 大久保善朗
  • Organizer: 広島精神神経学会
  • Place of Presentation: 広島
  • Year and Date: 2007-12-08
• [Presentation] 脳機能画像からみた統合失調症の薬物療法PsyMEX (2007)
  • Author(s): 大久保善朗
  • Place of Presentation: 郡山
  • Year and Date: 2007-11-10
• [Presentation] 分子イメージングを用いた向精神薬の薬効評価 (2007)
  • Author(s): 大久保善朗
  • Organizer: 第36回慶應ニューロサイエンス研究会
  • Place of Presentation: 東京
  • Year and Date: 2007-10-28
• [Presentation] 脳機能画像からみた精神科薬物療法 (2007)
  • Author(s): 大久保善朗
  • Organizer: 第17回日本臨床精神神経薬理学会
  • Place of Presentation: 大阪
  • Year and Date: 2007-09-30
• [Presentation] PETを用いた抗精神病薬の薬効評価 (2007)
  • Author(s): 大久保善朗
  • Organizer: 第10回日本薬物脳波学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2007-07-07
• [Presentation] ニューロイメージングでみた統合失調症治療 (2007)
  • Author(s): 大久保善朗
  • Organizer: 第2回米子精神科セミナー
  • Place of Presentation: 米子
  • Year and Date: 2007-06-22
• [Presentation] 声に含まれる感情の認知に関するfMRI研究 (2007)
  • Author(s): 肥田道彦、高橋英彦、松浦雅人、浅井邦彦、田中博、大久保善朗
  • Organizer: 第29回日本生物学的精神医学会
  • Place of Presentation: 札幌コンベンションセンター
• [Presentation] 抗精神病薬による下垂体ドーパミンD2受容体占有率についての検討:高プロラクチン血症との関係 (2007)
  • Author(s): 荒川亮介、伊藤浩、奥村正紀、大久保善朗、須原哲也
  • Organizer: 第29回日本生物学的精神医学会
  • Place of Presentation: 札幌コンベンションセンター
• [Presentation] 統合失調症発症後の脳の形態変化に関するMRI研究 (2007)
  • Author(s): 福田一、伊藤逸生、八幡憲明、高橋英彦、田井冶康友、浅井邦彦、鈴木秀典、大久保善朗
  • Organizer: 第29回日本生物学的精神医学会
  • Place of Presentation: 札幌コンベンションセンター
• [Presentation] 統合失調症患者における脳形態変化の性差に関するMRI研究 (2007)
  • Author(s): 伊藤逸生、八幡憲明、織田健司、高橋英彦、田井冶康友、浅井邦彦、鈴木秀典、大久保善朗
  • Organizer: 第29回日本生物学的精神医学会
  • Place of Presentation: 札幌コンベンションセンター