Development of novel radiopharmaceuticals for diagnosis of cerebral neurodegeneration and functional recovery after intrastriatal grafts/gene therapy

2011 Fiscal Year Final Research Report

• Project/Area Number: 20249055
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Radiation science
• Research Institution: Kanazawa University
• Principal Investigator: KAWAI Keiichi 金沢大学, 保健学系, 教授 (30204663)
• Co-Investigator(Kenkyū-buntansha): ISHIDA Yasushi 宮崎大学, 医学部, 教授 (20212897) ; MAGATA Yasuhiro 浜松医科大学, メディカルフォトニクス研究センター, 教授 (20209399) ; OKAZAWA Hidehiko 福井大学, 高エネルギー医学研究センター, 教授 (50360813) ; TENMA Takashi 京都大学, 薬学研究科, 助教 (90378787) ; YOSHIMOTO Mitsuyoshi 国立がん研究センター研究所, 発がんシステム研究分野, 主任研究員 (00345638) ; KOBAYASHI Masato 金沢大学, 保健学系, 助教 (30444235)
• Project Period (FY): 2008 – 2011
• Keywords: 脳内神経変性疾患 / 再生医療 / 遺伝子治療 / 治療効果判定 / 放射性診断薬 / PET撮影 / 遺伝子発現解析

Research Abstract

As a result of analyzing by PET tracers relevant to function analysis of cerebral dopaminergic neuron using the transplant group which was transplanted the rat intrastriatal grafts of fetal ventral mesencephalon of a Parkinson's disease model rat aiming at the diagnostic application to the regeneration effect of medicine, the individual specificity in a transplant group was large, but the significant correlation was acquired between the functional recovery by the degree of methamphetamine-induced rotation test and immunity dyeing analysis. Furthermore, functional change of cerebral dopaminergic neuron in a psychiatry drug administration model rat was also evaluated, the gene expression level of the functional molecule relevant to the nervous function in the pathological part after a transplant or drug administration was analyzed comprehensively, and comparison examination was carried out with functional change of cerebral dopaminergic neuron.

Research Products

• [Journal Article] N-Isopropyl-p-iodoamphetamine Hydrochloride(IMP) is Predominantly Metabolized by CYP2C19 (2012)
  • Author(s): Fujita K., Sugiyama M., Akiyama Y., Hioki K., Kunishima M., Nishi K., Kobayashi M., Kawai K., Sasaki Y.
  • Journal Title: Drug Metab. Dispos Volume: (in press)
• [Journal Article] Cerebral Oxygen Metabolism of Rats using Injectable^<15> O-Oxygen with a Steady-state Method (2012)
  • Author(s): Kobayashi M., Mori T., Kiyono Y., Tiwari V., Maruyama R., Kawai K., Okazawa H.
  • Journal Title: J. Cereb. Blood Flow Metab Volume: 32 Pages: 33-40
• [Journal Article] Appropriate Parameters of Ordered-Subset Expectation Maximization Algorithm on Measurement of Myocardial Blood Flow and Oxygen Consumption with^<11> C-Acetate PET (2012)
  • Author(s): Kobayashi M., Mori T., Kiyono Y., Tsujikawa T., Maruyama R., Higaki Y., Shikano N., Nishii R., Kawai K., Kudo T., Okazawa H.
  • Journal Title: Nucl. Med. Commun Volume: 33 Pages: 130-138
• [Journal Article] Functional Characterization of Apical Transporters Expressed in Rat Proximal Tubular Cells(PTCs) in Primary Culture (2011)
  • Author(s): Nakanishi T., Fukushi A., Sato M., Yoshifuji M., Gose T., Shirasaka Y., Ohe K., Kobayashi M., Kawai K., Tamai I.
  • Journal Title: Mol. Pharm Volume: 8 Pages: 2142-2150
• [Journal Article] Putative Transport Mechanism and Intracellular Fate of Anti-^<18> F-FACBC(Trans1-amino-3-^<18> Ffluorocyclobutanecarboxylic Acid) in Human Prostate Cancer (2011)
  • Author(s): Okudaira H., Shikano N., Nishii R., Miyagi T., Yoshimoto M., Kobayashi M., Ohe K., Nakanishi T., Tamai I., Namiki M., Kawai K.
  • Journal Title: J. Nucl. Med. Volume: 52 Pages: 822-829
• [Journal Article] Differential Expression of Fos B, c-Fos, and Zif 268 in Forebrain Regions after Acute or Chronic L-DOPA Treatment in a Rat Model of Parkinson's Disease. Neurosci (2011)
  • Author(s): Ebihara K., Ishida Y., Takeda R., Abe H., Matsuo H., Kawai K., Magata Y., NishimoriT.
  • Journal Title: Neurosci. Lett Volume: 496 Pages: 90-94
• [Journal Article] Development of an H_2^<15> O Steady-state Method Combining a Bolus and Slow Increasing Injection with a Multiprogramming Syringe Pump (2011)
  • Author(s): Kobayashi M., Kiyono Y., Maruyama R., Mori T., Kawai K., Okazawa H.
  • Journal Title: J. Cereb. Blood Flow Metab Volume: 31 Pages: 527-534
• [Journal Article] Improvement of N-isopropyl-p-[^<123> I] iodoamphetamine Cerebral Accumulation by Competitive Displacement of Serum Protein Binding with Amino-Acid Infusion (2009)
  • Author(s): Kuga N., Shikano N., Takamura N., Nishii R., Yamasaki K., Kobayashi M., Nagamachi S., Tamura S., Kawai K.
  • Journal Title: J. Nucl. Med Volume: 50 Pages: 1378-1383
• [Journal Article] Serum Protein Binding Displacement : Theoretical Analysis using a Hypothetical Radiopharmaceutical and Experimental Analysis with^<123> I-N-isopropyl-p-iodoamphetamine (2009)
  • Author(s): Kawai K., Nishii R., Shikano N., Makino N., Kuga N., Yoshimoto M., Jinnouchi S., Nagamachi S., Tamura S., Takamura N.
  • Journal Title: Nucl. Med. Biol Volume: 36 Pages: 99-106
• [Journal Article] Differential Expression of Fos and Zif268 in the Nigrostriatal System after Methamphetamine Administration in a Rat Model of Parkinson's Disease (2008)
  • Author(s): Ishida Y., Kawai K., Magata Y., Ebihara K., Takeda R., Abe H., Yoshimoto M., Hashiguchi H., Odagiri K., Matsuo H., Nishimori T.
  • Journal Title: Synapse Volume: 62 Pages: 920-926
• [Presentation] N-Isopropyl-p-iodoamphetamine Hydrochloride(IMP) is Predominantly Metabolized by CYP2C19 (2012)
  • Author(s): Fujita K., Sugiyama M., Akiyama Y., Yamada K., Kunishima M., Kobayashi M., Kawai K., Sasaki Y.
  • Organizer: Society for Clinical Pharmacology and Therapeutics 2012 Annual Meeting
  • Place of Presentation: National Harbor, Maryland(U. S. A.)
  • Year and Date: 2012-03-14
• [Presentation] 放射性医薬品の開発・体内動態制御と個別化医療 (2011)
  • Author(s): 川井恵一
  • Organizer: バイオセミナー"未来へのバイオ技術"月例会特別講演
  • Place of Presentation: バイオインダストリー協会(東京都)
  • Year and Date: 2011-12-05
• [Presentation] Usefulness of Double Tracer PET Study using[^<18> F] FDG and Amino Acid Radiotracer,[^<11> C] MeAIB, in the Diagnosis of Mediastinal Diseases (2011)
  • Author(s): Higashi T., Nishii R., Kagawa S., Kishibe Y., Takahashi M., Kobayashi M., Kawai K.
  • Organizer: The Society of Nuclear Medicine 58th Annual Meeting
  • Place of Presentation: San Antonio Convention Center(U. S. A.)
  • Year and Date: 2011-06-04
• [Presentation] Development of a New Steady-State Method using Injectable^<15> O_2 for Measurement of Oxygen Metabolism in The Rat Brain (2011)
  • Author(s): Kobayashi M., Mori T., Kiyono Y., Tiwari V. N., Maruyama R., Kawai K., Okazawa H.
  • Organizer: The 10th International Conference on Quantification of Brain Function with PET(Brain11 & Brain PET11)
  • Place of Presentation: International Convention Centre of Barcelona(Spain)
  • Year and Date: 2011-05-26
• [Presentation] 薬物体内動態制御法と薬物療法の適正化を目指した個別化変動要因モニタリング法の開発 (2010)
  • Author(s): 川井恵一
  • Organizer: 第7回次世代医療システム産業化フォーラム2010
  • Place of Presentation: 京都商工会議所(京都府)
  • Year and Date: 2010-12-21
• [Presentation] L-DOPA慢性投与に伴う行動及び脳内転写調節因子発現の変化 (2010)
  • Author(s): 石田康,蛯原功介,武田龍一郎,安部博史,松尾寿栄,西森利数,川井恵一,間賀田泰寛
  • Organizer: 第32回日本生物学的精神医学会
  • Place of Presentation: リーガロイヤルホテル小倉(福岡県)
  • Year and Date: 2010-10-07
• [Presentation] Accumulation and Transport Mechanism of Anti-1-Amino-3-[^<18> F] fluorocyclobutane-1-carboxylic Acid in Representative Human Carcinomas (2010)
  • Author(s): Kobayashi M., Kagawa S., Nishii R., Takahashi F., Ohe K., Yoshimoto M., Shikano N., Higashi T., Nagamachi S., Kawai K.
  • Organizer: The Society of Nuclear Medicine 57th Annual Meeting
  • Place of Presentation: Salt Palace Convention Center(U. S. A.)
  • Year and Date: 2010-06-05
• [Presentation] 放射性医薬品の体内動態制御とターゲティングコンファーマティヴ個別化医療 (2010)
  • Author(s): 川井恵一
  • Organizer: 第66回日本放射線技術学会総会学術大会教育講演
  • Place of Presentation: パシフィコ横浜会議センター(神奈川県)
  • Year and Date: 2010-04-09
• [Presentation] Measurement of Cerebral Oxygen Metabolism of Rats using Injectable O-15 Oxygen and Steady-state Method (2009)
  • Author(s): Kobayashi M., Tiwari V. N., Maruyama R., Kiyono Y., Kudo T., Tsujikawa T., Kawai K., Fujibayashi Y., Okazawa H.
  • Organizer: The Society of Nuclear Medicine 56th Annual Meeting
  • Place of Presentation: Metro Toronto Convention Center(U. S. A.)
  • Year and Date: 2009-06-13
• [Presentation] Mechanism of Renal FDG Tran cellular Transport and Cellular Accumulation using LLC-PK_1 Cells (2009)
  • Author(s): Kobayashi M., Araki H., Nishi K., Shikano N., Kiyono Y., Nishii R., Fujibayashi Y., Okazawa H., Kawai K.
  • Organizer: The Society of Nuclear Medicine 56th Annual Meeting
  • Place of Presentation: Metro Toronto Convention Center(U. S. A.)
  • Year and Date: 2009-06-13
• [Presentation] Comparison of System A and System L Amino Acid Transports in Human Pancreas with C-11 MeAIB and C-11 MET PET Study (2009)
  • Author(s): Nishii R., Kagawa S., Higashi T., Kishibe Y., Iwasaki T., Uehara T., Kobayashi M., Nagamachi S., Arano Y., Kawai K.
  • Organizer: The Society of Nuclear Medicine 56th Annual Meeting
  • Place of Presentation: Metro Toronto Convention Center(U. S. A.)
  • Year and Date: 2009-06-13
• [Presentation] Alteration of Striatal[^<11> C] Raclopride and[^<18> F] FDOPA Uptake Precedes Development of Methamphetamine induced Rotation in the Unilateral 6-Hydroxydopamine Lesioned Rats (2008)
  • Author(s): Ishida Y., Kawai K., Magata Y., Abe H., Takeda R., Ebihara K., Yoshimoto M., Mukai T., Saji H.
  • Organizer: The 38th Annual Meeting of the Society for Neuroscience
  • Place of Presentation: Walter E. Washington Convention Center(U. S. A.)
  • Year and Date: 2008-11-16
• [Presentation] Assessment of Emission-based Segmented Attenuation Correction Method without Transmission Scan on Small Animal PET (2008)
  • Author(s): Kobayashi M., Higaki Y., Kudo T., Kiyono Y., Tsujikawa T., Yoshii Y., Michibata Y., Sakai K., Watanabe M., Kawai K., Fujibayashi Y., Okazawa H.
  • Organizer: World Molecular Imaging Congress 2008
  • Place of Presentation: Nice-Acropolis Palais Des Congres(France)
  • Year and Date: 2008-09-10
• [Remarks] 金沢大学研究紹介データベース
  • URL: http://kurt.kanazawa-u.ac.jp/souran_ku/info.php?teacher_id=488
• [Remarks] 金沢大学医薬保健研究域保健学系量子医療技術学講座川井研究室
  • URL: http://kawai.w3.kanazawa-u.ac.jp/index.html