| Co-Investigator(Kenkyū-buntansha) |
HORI KATSUYOSHI Institute of Development, Aging and Cancer, Dept.Vascular Biology, Associate Professor, 加齢医学研究所, 助教授 (00143032)
IDO TATSUO Cyclotron & Radioisotopecenter, Dept.Radiopharamcology, Professor, サイクロトロンラジオアイソトープセンター, 教授 (80134063)
齋藤 祥子 東北大学, 加齢医学研究所, 助手 (00125551)
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| Budget Amount *help |
¥11,400,000 (Direct Cost: ¥11,400,000)
Fiscal Year 2002: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2001: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2000: ¥5,700,000 (Direct Cost: ¥5,700,000)
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| Research Abstract |
Several new compounds targeting tumor vasculature have been reported. AC7700, a novel combretastain analogue has been known to induce irreversible stoppage of tumor blood flow. AC7700 induce collapse of microvessel in vivo resulted in tumor necrosis and inhibition of growth. In order to evaluate and to predict the whole body effect of AC7700 injection (AC) on tumor model, glucose metabolism by ^<18>Fluorodeoxy-glucose (FDG) uptake and blood flow by 14C-iodoantipyrine(IAP) and histopathology have been compared. AC 10mg/kg was I.v. injected to young male rats with subcutaneous tumor LY80: FDG uptake was measured 1hr after injection, 201TI and (IAP) uptake 5min after. Tumor volume, pathology, and autoradiography (ARG) were also evaluated. Tumor FDG uptake was dropped to 6% of the control at 1hr after AC and slight increase at 24hr, while 20ITI uptake to 20% at 1hr after AC, recovered completely at 24hr. Studies using FDG and 14C-IAP showed the same pattern, suggested the discordant changes. In ARG study, FDG uptake was matched to the viable tissue distribution, but not to the distribution of IAP. When AC was repeated 5 times at 0,2,4,7,9 days, tumor volume showed no significant changes, but FDG uptake decreased to 16% of the control. FDG uptake reflected the changes in tumor viability, was more sensitive indicator of AC therapy than the tumor volume. As the conclusion, metabolic evaluation with FDG is very sensitive for therapeutic effects on tumor with novel vascular targeting therapy.
We have tried radio-labeling of AC7739, active form of AC7700 using flurorine-18. However, this trial has not been successful due to unexpected reaction derived from complicated structure of this compound.
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