Enhancement of anti-neoplastic drug delivery into malignant brain tumors

用氢清除法研究了静脉和腔内注射腺苷和三磷酸腺苷(ATP)对大鼠RG-C6移植瘤局部血流量的影响。颈内动脉注射腺苷或三磷酸腺苷选择性地增加了肿瘤内的血流量，但对瘤外同侧大脑半球或无体液的同侧大脑半球的局部脑血流量均无明显影响。颈动脉内注射10µg/kg/min三磷酸腺苷对肿瘤血流量增加最有效(+51.5%，16.8%)。相反，静脉注射腺苷或三磷酸腺苷均不能增加肿瘤血流量。我们还利用正电子发射断层扫描(PET)检测了静脉和颈动脉注射三磷酸腺苷(ATP)对脑胶质瘤患者局部血流量的影响。颈动脉注射ATP0.52~1.3µg/kg/min可选择性增加肿瘤血流量(+26.1~12.1%)。观察到的副作用是可以耐受的。相反，静脉注射三磷酸腺苷未能增加肿瘤血流量。提示颈动脉内注射三磷酸腺苷可选择性增强抗癌药物对恶性脑肿瘤的转运。

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.