Enhancement of anti-neoplastic drug delivery into malignant brain tumors

增强抗肿瘤药物向恶性脑肿瘤的递送

• 批准号: 62480309
• 负责人: FUKUI Masashi
• 金额: $ 3.2万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1987
• 资助国家: 日本
• 起止时间: 1987 至 1988
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-62480309/
• 关键词: malignant brain tumor; chemotherapy; cerebral blood flow; ATP; rat; 経頚動脈的投与; ラット; ラット悪性脳腫瘍

We studied the effect of intravenous and intracaroted infusion of adenosine and adenosine triphosphate (ATP) on the regional blood flow of intracerebrally transplanted RG-C6 tumors in rats, using the hydrogen clearance method. The intracarotid administration of adenosine or ATP selectively increased blood flow in the tumor, but did not produce any significant change either in the regional cerebral blood flow of the extratumoral ipsilateral hemisphere or in the ipsilateral hemisphere without humor. The intracarotid administration of ATP at a dose of 10 mug/kg/min produced the most effective increase in the tumor blood flow (+51.5 16.8 %). In contrast, both the intravenous administration of adenosine or ATP failed to increase tumor blood flow.We also examined the effect of intravenous and intracarotid sdministration of adenosine triphosphate (ATP) on the regional blood flow of glioma patients, using positron emission tomography (PET). Intracarotid administration of ATP at a dose of 0.52 to 1.3 mug/kg/min selectively increased the blood flow in the tumor (+26.1 12.1 %). The side effects observed were tolerable. In contrast, intravenous administration of ATP failed to increase tumor blood flow. It is suggested that the intracarotid administration of ATP would serve to selectively enhance the delivery of anti-cancer agents to malignant brain tumors.

本实验采用氢清除率法研究了静脉和腔内输注腺苷和三磷酸腺苷（ATP）对大鼠脑内移植RG-C6肿瘤区域血流的影响。颈动脉内给予腺苷或ATP选择性地增加了肿瘤内的血流量，但对肿瘤外同侧半球或无房源的同侧半球的局部脑血流量没有产生任何显著变化。颈动脉内给药剂量为10马克杯/千克/分钟的ATP能最有效地增加肿瘤血流量（+51.5 - 16.8%）。相比之下，静脉注射腺苷或ATP均未能增加肿瘤血流量。我们还利用正电子发射断层扫描（PET）研究了静脉注射和颈动脉内注射三磷酸腺苷（ATP）对胶质瘤患者局部血流的影响。颈动脉内给药0.52 ~ 1.3 mg /kg/min的ATP选择性地增加了肿瘤内的血流量（+ 26.1% 12.1%）。观察到的副作用是可以忍受的。相反，静脉给药ATP不能增加肿瘤血流量。提示颈动脉内给药ATP可选择性地增强抗癌药物对恶性脑肿瘤的递送。

项目成果

Fukui M: Proceedings of the first internat.Symposium on pediatric Neurooncology. 44-50 (1987)

Fukui M：第一届国际儿科神经肿瘤学研讨会论文集。

福井仁士: 図説臨床「癌」シリーズ15脳腫瘍. 72-80 (1987)

Hitoshi Fukui：临床“癌症”系列 15 脑肿瘤图解 (1987)。

Fukui, M.: "Brain tumor" Nipponrinsho. 45. 2153-2160 (1987)

Fukui, M.：“脑肿瘤”Nipponrinsho。

Fukui, M.: "Brain tumor and blood-brain barrier" Oita Brain Tumor Conference. 10. 3-36 (1988)

Fukui, M.：“脑肿瘤和血脑屏障”大分脑肿瘤会议。

Fukui, M.: "Selective enhancement of intratumoral blood flow in malignant gliomas: Part 2. Positron emission tomographic study by intracarotid administration of adenosine triphosphate in human cases."

Fukui, M.：“恶性神经胶质瘤瘤内血流的选择性增强：第 2 部分。在人类病例中通过颈动脉内施用三磷酸腺苷进行正电子发射断层扫描研究。”