Acetylcholine metabolism in pancreas by C-11 Donepezil PET

• Project/Area Number: 25670533
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Radiation science
• Research Institution: Osaka University
• Principal Investigator: Hatazawa Jun 大阪大学, 医学系研究科, 教授 (70198745)
• Co-Investigator(Kenkyū-buntansha): 渡部 直史 大阪大学, 医学系研究科, 招へい教員 (90648932)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: アセチルコリンエステラーゼ / アセチルコリン / PET / ドネペジル / 膵

Outline of Final Research Achievements

Acetylcholine is a neurotransmitter contributing to control of pancreatic excretion and insulin secretion from beta cells. We tested C-11 labeled acetylcholine esterase inhibitor Donepezil (DNP) as a biomarker of pancreatic function in rats and normal humans. In rats, high accumulation of DNP was found in intestine, pancreas, and adrenal gland where acetylcholine esterase concentration was high in the autopsied tissue, indicating C-11 DNP is a marker of acetlycholinergic function. In humans, high accumulation of C-11 DNP was found in myocardium, pancreas, and intestine, but not in adrenal gland. The current study revealed a species difference in controlling myocardium and adrenal gland function by acetylcholine between rat and humans.

Research Products

• [Journal Article] (18)F-FBPA as a tumor-specific probe of L-type amino acid transporter 1 (LAT1): a comparison study with (18)F-FDG and (11)C-Methionine PET. (2017)
  • Author(s): Watabe T, Ikeda H, Nagamori S, Wiriyasermkul P, Tanaka Y, Naka S, Kanai Y, Hagiwara K, Aoki M, Shimosegawa E, Kanai Y, Hatazawa J.
  • Journal Title: Eur J Nucl Med Mol Imaging. Volume: 44 Issue: 2 Pages: 321-331
  • DOI: 10.1007/s00259-016-3487-1
  • Peer Reviewed
• [Journal Article] Whole-Body Distribution of Donepezil as an Acetylcholinesterase Inhibitor after Oral Administration in Normal Human Subjects: A 11C-donepezil PET Study. (2017)
  • Author(s): Mochida I, Shimosegawa E, Kanai Y, Naka S, Matsunaga K, Isohashi K, Horitsugi G, Watabe T, Kato H, Hatazawa J.
  • Journal Title: Asia Ocean J Nucl Med Biol. Volume: 5 Pages: 3-9
  • Peer Reviewed / Open Access
• [Journal Article] Genetic and Environmental Influences on Regional Brain Uptake of 18F-FDG: A PET Study on Monozygotic and Dizygotic Twins. (2016)
  • Author(s): Watanabe S, Kato H, Shimosegawa E, Hatazawa J.
  • Journal Title: J Nucl Med. Volume: 57 Issue: 3 Pages: 392-397
  • DOI: 10.2967/jnumed.115.164004
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Correlation between apparent diffusion coefficients on diffusion-weighted MRI and standardized uptake value on FDG-PET/CT in pancreatic adenocarcinoma. (2015)
  • Author(s): Sakane M, Tatsumi M, Kim T, Hori M, Onishi H, Nakamoto A, Eguchi H, Nagano H, Wakasa K, Hatazawa J, Tomiyama N.
  • Journal Title: Acta Radiol. Volume: 56 Issue: 9 Pages: 1034-1041
  • DOI: 10.1177/0284185114549825
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Distribution of intravenously administered acetylcholinesterase inhibitor and acetylcholinesterase activity in the adrenal gland: 11C-donepezil PET study in the normal rat. (2014)
  • Author(s): Watabe T, Naka S, Ikeda H, Horitsugi G, Kanai Y, Isohashi K, Ishibashi M, Kato H, Shimosegawa E, Watabe H, Hatazawa J.
  • Journal Title: PLoS One. Volume: 9 Issue: 9 Pages: 116-116
  • DOI: 10.1371/journal.pone.0107427
  • Peer Reviewed / Open Access
• [Journal Article] CBF/CBV maps in normal volunteers studied with 15O PET: a possible index of cerebral Perfusion pressure. (2014)
  • Author(s): Watabe T, Shimosegawa E, Kato H, Isohashi K, Ishinashi M, Hatazawa J.
  • Journal Title: Neuroscience Bulletin Volume: (in press)
  • Peer Reviewed
• [Journal Article] Paradocical reduction of cerebral blood flow after acetazolamide loading: a hemodynamic and metabolic studies with 15O-PET. (2014)
  • Author(s): Watabe T, Shimosegawa E, Kato H, Isohashi K, Ishinashi M, Kitagawa K, Fujinaka T, Hatazawa J.
  • Journal Title: Neuroscience Bulletin Volume: (in press)
  • Peer Reviewed
• [Journal Article] Development of an ultrahigh resolution Si-PM based PET system for small animals. (2014)
  • Author(s): Yamamoto S, Watabe H, Kanai Y, Watabe T, Kato K, Hatazawa J.
  • Journal Title: Phys Med Biol. Volume: 58(21) Issue: 21 Pages: 7875-88
  • DOI: 10.1088/0031-9155/58/21/7875
  • Peer Reviewed
• [Presentation] Estimation of 10B concentration in BNCT: Potential of image-guided therapy by 18FBPA-PET. (2015)
  • Author(s): Shimosegawa E, Isohashi K, Hanaoka K, Naka S, Kanai Y, Horitsugi G, Hatazawa J.
  • Organizer: The 1st Academic Meeting of Taiwan Society of Neutron capture Therapy.
  • Place of Presentation: Grear Roots Foresty SPA Resort, Taiwan
  • Year and Date: 2015-12-05
  • Int'l Joint Research
• [Presentation] Early prediction of chemotherapeutic response with volumetric FDG PET parameters in recurrent gynecological malignancies. (2015)
  • Author(s): Tatsumi M, Isohashi K, Kato H, Hori M, Tomiyama N, Hatazawa J.
  • Organizer: The 101st Scientific Assembly and Annual Meeting of the Radiological Society of North America (RSNA 2015).
  • Place of Presentation: McCormick Place, U.S.A.
  • Year and Date: 2015-11-29
  • Int'l Joint Research
• [Presentation] Study of optical isomer (D-form) analysis condition contained in L-[11C] methionine injection． (2015)
  • Author(s): 仲定宏、金井泰和、西嶋剣一、木下大輔、河端伸哉、杉田幸、礒橋佳也子、加藤弘樹、久下裕司、下瀬川恵久、畑澤順
  • Organizer: 第55回日本核医学会学術総会
  • Place of Presentation: ハイアットリージェンシー東京
  • Year and Date: 2015-11-05
• [Presentation] 膵癌におけるdual-energy CT上ヨード造影量とテクスチャ指標等の各種 FDG PETパラメータとの関連 (2015)
  • Author(s): 巽光朗、坂根誠、大西浩満、礒橋佳也子、石橋愛、畑澤順
  • Organizer: 第55回日本核医学会学術総会
  • Place of Presentation: ハイアットリージェンシー東京
  • Year and Date: 2015-11-05
• [Presentation] FBPA and FAMT dynamic PET: evaluation of usefulness in differentiating malignant tumors from inflammatory lesions (2015)
  • Author(s): 青木政尚、渡部直史、永森收志、池田勇人、仲定宏、金井泰和、花岡宏平、下瀬川恵久、金井好克、畑澤順
  • Organizer: 第55回日本核医学会学術総会
  • Place of Presentation: ハイアットリージェンシー東京
  • Year and Date: 2015-11-05
• [Presentation] Attenuation correction by CT can improve detectability of lesions by voxel based statistical analysis of brain SPECT. (2015)
  • Author(s): Kato H, Ishibashi M, Isohashi K, Tatsumi M, Shimosegawa E, Naka S, Kanai Y, Watabe H, Hatazawa J.
  • Organizer: The 28th Annual Congress of the European Association of Nuclear Medicine (EANM2015)
  • Place of Presentation: CCH-Congress Center Hamburg, Germany
  • Year and Date: 2015-10-10
  • Int'l Joint Research
• [Presentation] Evaluation of the amino acid transporter: comparison study between FBPA and BPA in vitro. (2015)
  • Author(s): Ikeda H, Watabe T, Nagamori S, Tanaka Y, Wiriyasermkul P, Kanai Y, Naka S, Shimosegawa E, Kanai Y, Hatazawa J.
  • Organizer: Society of Nuclear Medicine and Molecular Imaging's 62th Annual Meeting (SNMMI 2015)
  • Place of Presentation: Baltimore Convention Center, U.S.A.
  • Year and Date: 2015-06-06
  • Int'l Joint Research
• [Presentation] A comparative investigation of 11C labeling method swith the aim of stable clinical supply. (2015)
  • Author(s): Naka S, Kanai Y, Kato H, Isohashi K, Shimosegawa E, Hatazawa J.
  • Organizer: Society of Nuclear Medicine and Molecular Imaging's 62th Annual Meeting (SNMMI 2015)
  • Place of Presentation: Baltimore Convention Center, U.S.A.
  • Year and Date: 2015-06-06
  • Int'l Joint Research
• [Presentation] Associations of iodine content obtained from dual-energy contrast-enhanced CT and texture features or volumetric parameters on FDG PET in pancreatic cancer. (2015)
  • Author(s): Tatsumi M, Sakane M, Onishi H, Isohashi K, Ishibashi M, Hatazawa J.
  • Organizer: Society of Nuclear Medicine and Molecular Imaging's 62th Annual Meeting (SNMMI 2015)
  • Place of Presentation: Baltimore Convention Center, U.S.A.
  • Year and Date: 2015-06-06
  • Int'l Joint Research
• [Presentation] ヒトにおいて血漿中のドネペジル濃度から組織中のドネペジルの濃度は予測できない－PETを用いた検討 (2014)
  • Author(s): 持田郁子、下瀬川恵久、金井泰和、仲定宏、堀次元気、礒橋佳也子、加藤弘樹、石橋愛、渡部直史、畑澤順
  • Organizer: 第54回日本核医学会学術総会
  • Place of Presentation: 大阪市
  • Year and Date: 2014-11-06 – 2014-11-08
• [Presentation] Prediction of tissue concentration C-11 Donepezil is difficult: Using PET microdosing-wholebody dynamic study in human. (2014)
  • Author(s): Mochida I, Isohashi1 K, Kanai Y, Naka S, Horitugi G, Shimosegawa1 E, Watabe T, Ishibashi K, Kato H, Hatazawa J.
  • Organizer: The 27th Annual Congress of the European Association of Nuclear Medicine (EANM2014)
  • Place of Presentation: Gothenburg, Sweden.
  • Year and Date: 2014-10-18 – 2014-10-23
• [Presentation] PETマイクロドーズ臨床試験について (2014)
  • Author(s): 持田郁子、渡部直史、畑澤順
  • Organizer: 腫瘍分子イメージング夏期集中セミナー
  • Place of Presentation: 小樽市
  • Year and Date: 2014-08-02 – 2014-08-03
• [Presentation] Quantitative PET imaging of intratumoral oxygen metabolism by 15O-labeled gas inhalation PET. (2014)
  • Author(s): Watabe T, Horitsugi G, Knai Y, Ikeda H, Kato H, Hanaoka K, Naka S, Shimosegawa E, Hatazawa J.
  • Organizer: SNMMI2014
  • Place of Presentation: セントルイス（アメリカ合衆国）
  • Invited
• [Presentation] Quantitative evaluation of myocardial blood flow and oxygen metabolism in the normal anesthetized rat: 15O-labeled gas inhalation PET. (2013)
  • Author(s): Watabe T, Watabe H, Kanai Y, Shimosegawa E, Hanaoka K, Horitsugi G, Isohashi K, Kato H, Tatsumi M, Hatazawa J.
  • Organizer: SNMMI2013
  • Place of Presentation: バンクーバー （カナダ）
• [Presentation] O15ガス定常吸入法によるラット脳血流・酸素代謝の定量評価
  • Author(s): 渡部直史
  • Organizer: 第9回小動物インビボイメージング研究会
  • Place of Presentation: 福井
• [Remarks] 大阪大学大学院医学系研究科附属PET分子イメージングセンター
  • URL: http://www.pet.med.osaka-u.ac.jp/
• [Remarks] 大阪大学医学系研究科附属PET分子イメージングセンター
  • URL: http://www.pet.med.osaka-u.ac.jp/