| 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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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥12,020,000 (Direct Cost: ¥11,300,000、Indirect Cost: ¥720,000)
Fiscal Year 2007: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2006: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2005: ¥6,200,000 (Direct Cost: ¥6,200,000)
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| Keywords | Neurodegeneration / Intrastriatal grafts / Early detection / Parkinsonism model rat / Dopaminergic neuron / Amino acid transport / Dopa decarboxylase / Imaging diagnosis / 神経変性疾患 / 早期検出 / 再生医療効果判定 / 放射性診断薬 / 神経化学的評価 |
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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
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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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