Grant-in-Aid for Scientific Research (B)
|Allocation Type||Single-year Grants|
|Research Institution||KYOTO UNIVERSITY|
KUGE Yuji KYOTO UNIVERSITY, Graduate School of Pharmaceutical Sciences, Associate Professor, 薬学研究科, 助教授 (70321958)
SAJI Hideo KYOTO UNIVERSITY, Graduate School of Pharmaceutical Sciences, Professor, 薬学研究科, 教授 (40115853)
KIYONO Yasushi KYOTO UNIVERSITY, Graduate School of Medicine, Assistant Professor, 医学研究科, 助手 (50305603)
TAMAKI Nagara Hokkaido University, Graduate School of Medicine, Professor, 医学研究科, 教授 (30171888)
SEKI Koh-ichi Hokkaido University, Central Institute of Isotope Science, Professor, アイソトープ総合センター, 教授 (60094835)
YOKOTA Chiaki National Cardiovascular Center, Research Institute, Department of Etiology and Pathogenesis, Cerebrovascular Laboratory, Research staff, 研究所・病因部・脳血管障害研究室, 室員 (80300979)
飯田 靖彦 京都大学, 薬学研究科, 助手 (60252425)
|Project Period (FY)
2002 – 2004
Completed(Fiscal Year 2004)
|Budget Amount *help
¥13,700,000 (Direct Cost : ¥13,700,000)
Fiscal Year 2004 : ¥3,400,000 (Direct Cost : ¥3,400,000)
Fiscal Year 2003 : ¥5,100,000 (Direct Cost : ¥5,100,000)
Fiscal Year 2002 : ¥5,200,000 (Direct Cost : ¥5,200,000)
|Keywords||pathophysiology of cerebral ischemia / molecular imaging / prostaglandins / cyclooxygenase-2(COX-2) / positron CT (PET) / single photon CT (SPECT) / シクロオキシナーゼ(COX-2)|
In order to clarify 1)the roles of cyclooxygenase-2(COX-2) in the pathophysiology of cerebral ischemia and 2)the potentials of COX-2 molecular imaging in the patho-functional analysis of the disease, we planed the present project using molecular imaging technique. Our findings in this project were as follows :
1.Temporal changes of cerebral blood flow, metabolism, and neuro-receptor in animal models of cerebral ischemia
In ischemic regions where neuro-receptor function was preserved, neuronal DNA is still intact and cellular integrity is maintained. COX-2 expression was often observed in these regions.
2.Cyclooxygenase-2 expression in animal models of stroke
(1)The time course of COX-2 mRNA expression in the ischemic core was different from that of the peri-infarct area. The expression of COX-2 in focal ischemic tissues is determined by the depth and duration of CBF reduction.
(2)Upregulation of bilateral S-100A9 and ipsi-lateral IL-1β and IL-6 genes, induced by the Spreading Depression(SD) elicitation were demonstrated to be downregulated by a selective COX-2 inhibitor JTE-522.
3.Development of molecular probes for imaging COX-2 expression
We intended to develop a radioiodinated coxib as a SPECT tracer for imaging COX-2 expression and designed 5-(4-iodophenyl)-1-[4-(methylsulfonyl)phenyl]-3-(trifluoromethyl)-1H-pyrazole (IMTP). ^<125>I-IMTP was successfully synthesized with a high specific activity. Our results showed a high inhibitory potency and selectivity of IMTP for COX-2, indicating its potential as a SPECT tracer for imaging COX-2 expression.