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PREDICTION OF TREATMENT EFFECTS OF ANTI-VASCULAR THERAPY OF TUMOR

肿瘤抗血管治疗的疗效预测

基本信息

批准号：
12470183
负责人：
KUBOTA KAZUO
金额：
$ 7.3万
依托单位：
TOHOKU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2002
项目状态：
已结题

项目摘要

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.

已经报道了几种靶向肿瘤血管的新化合物。AC 7700是一种新型的考布他汀类似物，已知其可诱导肿瘤血流的不可逆停止。AC 7700在体内诱导微血管塌陷，导致肿瘤坏死和生长抑制。为了评价和预测AC 7700注射液（AC）对肿瘤模型的全身作用，<18>通过14 C-碘安替比林（IAP）摄取葡萄糖代谢和血流量以及组织病理学进行了比较。用LY 80皮下移植瘤的幼龄雄性大鼠，静脉注射AC 10 mg/kg，1h后测定FDG摄取率，5 min后测定~（20）TI和（IAP）摄取率。还评价了肿瘤体积、病理学和放射自显影（ARG）。肿瘤FDG摄取在AC后1小时降至对照组的6%，24小时略有增加，而20 ITI摄取在AC后1小时降至20%，24小时完全恢复。FDG和14 C-IAP的研究显示了相同的模式，提示了不一致的变化。在ARG研究中，FDG摄取与活组织分布相匹配，但与IAP分布不匹配。AC重复5次（0、2、4、7、9d）后，肿瘤体积无明显变化，但FDG摄取量下降至对照组的16%。FDG摄取反映了肿瘤活力的变化，是比肿瘤体积更敏感的AC治疗指标。因此，FDG代谢评估对新型血管靶向治疗肿瘤的疗效非常敏感。我们尝试了使用氟-18放射性标记AC 7739，AC 7700的活性形式。然而，由于该化合物的复杂结构导致的意外反应，该试验尚未成功。