2007 Fiscal Year Final Research Report Summary
DEVELOPMENT OF NOVEL RADIOPHARMACEUTICALS FOR EARLY STAGE DIAGNOSIS OF CEREBRAL NEURODEGENERATION AND FUNCTIONAL RECOVERRY AFTER INTRASTRIATAL GRAFTS
| Project/Area Number |
17390329
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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 | Kanazawa University |
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Principal Investigator |
KAWAI Keiichi Kanazawa University, Graduate School of Medicine, Professor (30204663)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIDA Yasushi Univ. of Miyazaki, Miyazaki Medical College, Professor (20212897)
MAGATA Yasuhiro Hamamatsu Univ. of Medicine, Photon Med. Res. Center, Professor (20209399)
TEMMA Takashi Kyoto Univ., Graduate School of Pharm. Sci, Assistant (90378787)
KAWASHIMA Hidekazu Kyoto Univ., Graduate School of Medicine, Assistant (70359438)
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| Project Period (FY) |
2005 – 2007
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| Keywords | Neurodegeneration / Intrastriatal grafts / Early detection / Parkinsonism model rat / Dopaminergic neuron / Amino acid transport / Dopa decarboxylase / Imaging diagnosis |
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| Research Abstract |
We studied the PET tracer distributions of ligands for dopamine D_1 receptors ([^<11>C]SCH23390) and D_2 receptors ([^<11>C]raclopride) and of the dopamine precursor analog ([^<18>F]FDOPA) after 6-hydroxydopamine (6-OHDA) lesions of the medial forebrain bundle in rats. The brains of 6-OHDA treated rats were analyzed by tissue dissection at 3 days (acute stage) or 3 weeks (chronic stage) postlesion. [^<11>C] Raclopride, but not [^<11>C]SCH23390, showed a higher accumulation in the striatum on the lesion side compared with that on the intact side both 3 days and 3 weeks postlesion. On the other hand, a lower accumulation of [^<18>F]FDOPA was found in the striatum on the lesion side 3 days postlesion, and both in the striatum and cerebral cortex on the lesion side 3 weeks postlesion. An increase in raclopride and a decrease in FDOPA uptake in the denervated striatum is evident even at 3 days following the 6-OHDA lesions when the degree of methamphetamine (MAP)-induced rotation is not esta
… More
blished. Therefore the combination of D_2 antagonist and FDOPA may provide a potentially useful method for assessing the effects of dopamine depletion in Parkinson's disease.
In addition, we examined the topological specificity of MAP-induced activation of the immediate-early gene proteins, Fos and Zif268, in the nigrostriatal system in a unilateral 6-OHDA rat model of Parkinson's disease with or without intrastriatal grafts of fetal ventral mesencephalon. The differential expression of Fos and Zif268 was observed among the three regions of the nigrostriatal system following MAP in the 6-OHDA rats. This may suggest that Fos and Zif268 therefore possess gene-specific and region-specific functions in the basal ganglia nuclei.
For SPECT application, radioiodinated derivatives of dopamine biosynthesis precursor, [^<123>I]I-IMT and [^<123>I]I-FTM, were evaluated as diagnosis agents for early detection of neurodegeneration. In the biodistribution study, I-IMT accumulation in the striatum on the lesion side 3 days postlesion increased, then decreased in 2 weeks postlesion, compared with the intact side. On the other hand, I-FTM showed a lower accumulation in the striatum on the lesion side compared with that on the intact side both 3 days and 2 weeks postlesion. I-FTM, with an affinity to the final enzyme of dopamine biosynthesis, was sensitive for detection of neurodegeneration in acute stage. Thus, both I-IMT and I-FTM may be new candidates of sensitive radiopharmaceuticals in detecting function of cerebral dopaminergic neuron. Less
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Research Products
(150 results)
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[Journal Article] Assessment of diastolic function using 16-frame ^<201>T1 gated myocardial perfusion SPECT : A comparative study of QGS2 and nFAST2.2008
Author(s)
Nagamachi S., Wakamatsu H., Fujita S., Nishii R., Kamimura K., Kiyohara S., Futami S., Onitsuka H., Nagoshi Y., Tamura S., Kawai K, Arita H.
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Journal Title
Ann. Nucl. Med. 22
Pages: 115-122
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Difference in brain distributions of carbon 11-labeled 4-hydroxy-2(lH)-quinolones as PET radioligands for the glycine-binding site of the NMDA ionchannel.2008
Author(s)
Fuchigami T., Haradahira T., Fujimoto N., Okauchi T., Maeda J., Suzuki K., Suhara T., Yamamoto F., Sasaki S., Mukai T., Yamaguchi H., Ogawa M., Magata Y., Maeda M.
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Journal Title
Nucl. Med. Biol. 35
Pages: 203-212
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Psychological prenatal stress reduced the number of BrdU immunopositive cells in the dorsal hippocampus without affecting the open field behavior of male and female rats at one month of age.2008
Author(s)
Odagiri K., Abe H., Kawagoe C, Takeda R., Ikeda T., Matsuo H., Nonaka H., Ebihara K., Nishimori T., Ishizuka Y., Hashiguchi H., Ishida Y.
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Journal Title
Neumsci. Lett. 446
Pages: 25-29
Description
「研究成果報告書概要(欧文)」より
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[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.
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Journal Title
Synapse 62
Pages: 920-926
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Usefulness of rCBF analysis in diagnosing Parkinson's disease : supplemental role with MIBG myocardial scintigraphy.2008
Author(s)
Nagamachi S., Wakamatsu H., Kiyohara S., Fujita S., Futami S., Tamura S., Nakazato M., Yamashita S., Arita H., Nishii R., Kawai K.
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Journal Title
Ann. Nucl. Med. 22
Pages: 557-564
Description
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[Journal Article] Prenatal psychological stress causes higher emotionality, depression-like behavior, and elevated activity in the hypothalamo-pituitary-adrenal axis.2007
Author(s)
Abe H., Hidaka N., Kawagoe C., Odagiri K., Watanabe Y., Ikeda T., Ishizuka Y., Hashiguchi H., Takeda R., Nishimori T., Ishida Y
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Journal Title
Neurosci. Res. 59
Pages: 145-151
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Pharmacokinetics of 3-[^<125>I]iodo-a-methyl-L-tyrosine a tumor imaging agent, after probenecid loading in mice implanted with colon cancer DLD-1 cells.2007
Author(s)
Nakajima S., Shikano N., Kotani T., Ogura M., Nishii R., Yoshimoto M., Yamaguchi N., Iwamuura Y., Kubota N., Ishikawa N., Kawai K.
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Journal Title
Nucl. Med Biol. 34
Pages: 1003-1008
Description
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[Journal Article] Fluorescent X-ray imaging with synchrotron radiation for the evaluation of probes for biomedical functions : A pilot study on 4-bromo-DL-Dhenvlalanine for cancer detection in mice.2007
Author(s)
Shikano N., Kotani T., Nakajima S., Ogura M., Hyodo K., Sugiyama H., Monma M., Kawai K., Takeda T., Kubota N., Nishimura K., Mori K., Ishikawa N.
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[Journal Article] Synthesis and evaluation of radioiodinated cyclooxygenase-2 inhibitors as potential SPECT tracers for cyclooxygenase-2 expression.2006
Author(s)
Kuge Y., Katada Y., Shimonaka S., Temma T., Kimura H., Kiyono Y., Yokota C., Minematsu K., Seki K., Tamaki N., Ohkura K., Saji H.
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Journal Title
Nucl Med. Biol. 33
Pages: 21-27
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Peripheral ghrelin transmits orexigenic signals through the noradrenergic pathway from the hindbrain to the hypothalamus.2006
Author(s)
Date Y., Shimbara T., Koda S., Toshinai K., Ida T., Murakami N., Miyazato M., Kokame K., Ishizuka Y., Ishida Y., Kageyama H., Shioda S., Kangawa K., Nakazato M.
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Journal Title
Cell Metab. 4
Pages: 323-331
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Estimation of oxygen metabolism in a rat model of permanent ischemia using positron emission tomography with injectable ^<15>O-O_2.2006
Author(s)
Temma T., Magata Y., Kuge Y., Shimonaka S., Sano K., Katada Y., Kawashima H., Mukai T., Watabe H., lida H., Saji H.
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Journal Title
J. Cereb. Blood Flow Metab. 26
Pages: 1577-1583
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Bucolome, a potent binding inhibitor for furosemide, alters the pharmacokinetics and diuretic effect of furosemide: Potential for use of bucolome to restore diuretic response in nephrotic syndrome.2005
Author(s)
Takamura N., Maruyama T., Chosa E., Kawai K., Tsutsumi Y., Uryu Y., Yamasaki K., Deguchi T., Otagiri M.
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Journal Title
Drug Metab. Dispos. 33
Pages: 596-602
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Evaluation of Quantitative Accuracy using the Transmissionless-based Emission Segmented Attenuation Correction Method in Small Animal PET.2007
Author(s)
Kobayashi M., Okazawa H., Oh M., Tsujikawa T., Mori T., Sakai K., Watanabe M., Kiyono Y., Kudo T., Kawai K., Fujibayashi Y.
Organizer
The Society for Molecular Imaging Joint Molecular Imaging 2007 Conference
Year and Date
2007-09-08
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Anticipated Effectiveness of Community Intervention Trial of Multimodal Suicide Prevention Program in Japan (NOCOMIT-J) : A Study based on the Comparison of Intervention Trials from 2002 to 2004.2007
Author(s)
Sakai A., Ono Y, Otsuka K., Motohashi Y, Hiroto I., Awata S., Kamei Y, Nakamura J., Uda H., Ishida Y. Yamada M., Takahashi K.
Organizer
XXIV International Association for Suicide Prevention World Congress
Year and Date
2007-08-28
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Evaluation of a New Imaging Agent for Central Nicotinic Acetylcholine Receptor α7 Subtype.2007
Author(s)
Ogawa M., Tsukada H., Hatano K., Yamaguchi H., Abe J., Nishiyama S., Kakiuchi T., Oba H., Harada N., Matsushima Y., Fuchigami T., Ito K., Magata Y.
Organizer
The Society of Nuclear Medicine 54th Annual Meeting
Year and Date
2007-06-02
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Renal Accumulation of 3-[^<125>I]Iodo-alpha-methyl-L-tyrosine in Experimental Fanconi Syndrome.2005
Author(s)
Shikano N., Nakajima S., Kotani T., Itoh Y., Fujimoto S., Yagi A., Nobayashi Y., Nishii R., Yoshimoto M., Kobayashi M., Ishikawa N., Saji H., Kawai K.
Organizer
16th International Symposium on Radiopharmaceutical Chemistry
Year and Date
2005-06-24
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Renal Accumulation of 3-[^<125>I]Iodo-alpha-methyl-L-tyrosine in Experimental Fanconi Syndrome.2005
Author(s)
Shikano N., Nakajima S., Kotani T., Itoh Y, Fujimoto S., Yagi A., Nobayashi Y, Nishii R., Yoshimoto M., Kobayashi M., Ishikawa N., Saji H., Kawai K.
Organizer
16th International Symposium on Radiopharmaceutical Chemistry
Year and Date
2005-06-24
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Estimation of Oxygen Metabolism with Injectable ^<15>O-O_2 in a Rat Model of Permanent Cerebral Ischemia.2005
Author(s)
Tenuna T., Magata Y., Kuge Y., Kawashima H., Mukai T., Ueda M., Ogawa M., Watabe H., Iida H., Saji H.
Organizer
The Society of Nuclear Medicine 52nd Annual Meeting, Jun.
Year and Date
2005-06-21
Description
「研究成果報告書概要(欧文)」より
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[Presentation] A Novel ^<99>Tc-labeled Annexin V using Bis(Hydroxamamide)-based Bifunctional Chelating Agent.2005
Author(s)
Ogawa K., Ohtsuki K., Nakayama M., Ono M., Ueda M., Shiba K., Onoguchi M., Kinuya S., Doue T., Azuma A., Kawai K,. Strauss H. W., Matsubara H., Saji H., Mori H.
Organizer
The Society of Nuclear Medicine 52nd Annual Meeting
Year and Date
2005-06-18
Description
「研究成果報告書概要(欧文)」より
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[Presentation] A Novel 99mTc-labeled Annexin V using Bis(Hydroxamamide)-based Bifunctional Chelating Agent.2005
Author(s)
Ogawa K., Ohtsuki K., Nakayama M., Ono M., Ueda M., Shiba K., Onoguchi M., Kinuya S., Doue T., Azuma A., Kawai K,. Strauss H. W., Matsubara H., Saji H., Mori H.
Organizer
The Society of Nuclear Medicine 52nd Annual Meeting, Jun.
Year and Date
2005-06-18
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Rapid Clearance of Daughter ^<211>Pb by DOTMP Co-administrered with ^<223>Ra.2005
Author(s)
Washiyama K., Ogawa D., Yoshimoto M., Kinuya S., Kanayama Y., Mitsugashira T., Haba H., Enomoto S., Kawai K., Amano R.
Organizer
The Society of Nuclear Medicine 52nd Annual Meeting, Jun.
Year and Date
2005-06-18
Description
「研究成果報告書概要(欧文)」より
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[Book] 放射線安全管理学2005
Author(s)
西谷源展, 富樫厚彦, 鈴木昇一, 川井恵一, 他
Total Pages
229
Publisher
オーム社
Description
「研究成果報告書概要(和文)」より
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