2004 Fiscal Year Final Research Report Summary
DEVELOPMENT OF NOVEL RADIOPHARMACEUTICALS FOR EARLY STAGE DIAGNOSIS OF CEREBRAL NEURODEGENERATION.
| Project/Area Number |
14370273
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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 Univ., Graduate School of Medicine, Professor, 医学系研究科, 教授 (30204663)
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| Co-Investigator(Kenkyū-buntansha) |
MAGATA Yasuhiro Hamamatsu Univ.of Medicine, Photon Med.Res.Center, Professor, 光量子医学研究センター, 教授 (20209399)
ISHIDA Yasushi Univ.of Miyazaki, Miyazaki Medical College, Professor, 医学部, 教授 (20212897)
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| Project Period (FY) |
2002 – 2004
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| Keywords | Neurodegeneration / Early detection / Parkinsonism model rat / Dopaminergic neuron / Dopamine receptor / 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 6-[^<18>F]fluoro-L-3,4-dihydroxyphenylalanine ([^<18>F]FDOPA) in the brain after 6-hydroxydopamine (6-OHDA) lesions of the medial forebrain bundle in rats. The number of methamphetamine-induced rotation was higher at 14 days than that at 3 days following the 6-OHDA lesions. The brains of 6-OHDA treated rats were analyzed by tissue dissection following i.v.bolus of each tracer 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 non-lesioned (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
… More
weeks postlesion. Our studies demonstrate that an increase in [^<11>C]raclopride and a decrease in [^<18>F]FDOPA uptake in the denervated striatum is evident even at 3 days following the 6-OHDA lesions when the degree of methamphetamine-induced rotation is not established. Therefore the combination of a D_2 antagonist and FDOPA may provide a potentially useful method for assessing the effects of dopamine depletion in Parkinson's disease.
For SPECT application, radioiodinated derivatives of L-tyrosine, dopamine biosynthesis precursor, were evaluated as diagnosis agents for early detection of neurodegeneration. 3-[^<123>I]iodo-α-methyl-L-tyrosine (I-IMT) and 3-[^<123>I]iodo-α-difluoromethyl-tyrosine methyl ester (I-FTM) were selected as SPECT imaging agents for cerebral amino acid transpoter and dopa decarboxylase (DDC) activity. 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. It shows that 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 radiopharmaceuticals that can be useful in assessing function of cerebral dopaminergic neuron. Less
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Research Products
(94 results)
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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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[Journal Article] A Tc-99m-labeled long chain fatty acid derivative for myocardial imaging.2004
Author(s)
Magata Y., Kawaguchi T., Ukon M., Yamamura N., Uehara T., Ogawa K., Arano Y., Temma T., Mukai T., Tadamura E., Saji H.
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Journal Title
Bioconj.Chem. 15
Pages: 389-393
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] 3-Iodo-4-hydroxyphenyl-cysteamine as a high-affinity tumor-seeking agent for melanin formation.2003
Author(s)
Nishii R., Kawai K., Kobayashi M., Yoshimoto M., Nishimura K., Kinuya S., Uehara T., Nagamachi S., Arano Y., Tonami N., Tamura S.
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Journal Title
J.Labelled Compd.Radiopharm. 46
Pages: S137
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Improvement of ^<99m>Tc-pertechnetate thyroid accumulation by means of displacement of serum protein binding.2003
Author(s)
Kawai K., Kamei S., Yoshimoto M., Kobayashi M., Kinuya S., Nishii R., Takamura N., Nagamachi S., Arimori K., Tamura S., Tonami N., Amano R., Fujibayashi Y.
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Journal Title
J.Labelled Compd.Radiopharm. 46
Pages: S343
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Quantitative FDG-uptake by myocardial positron emission tomography in rats.2002
Author(s)
Handa N., Magata Y., Tadamura E., Mukai T., Nishina T., Miwa S., Sakakibara Y., Nomoto T., Konishi J., Nishimura K., Komeda M.
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Journal Title
J.Nucl.Cardiol. 9
Pages: 616-621
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Evaluation of radioiodinated 5-iodo-3(2(S)-azetidinylmethoxy)pyridine as a ligand for SPECT investigation of brain nicotinic acetylcholine receptors.2002
Author(s)
Saji H., Ogawa M., Ueda M., Iida Y., Magata Y., Tominaga A., Kawashima H., Kitamura Y., Nakagawa M., Kiyono Y., Mukai T.
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Journal Title
Ann.Nucl.Med. 16
Pages: 189-200
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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