INTRACAROTID INFUSION OF RMP-7, A BRADYKININ ANALOG - A METHOD FOR SELECTIVE DRUG-DELIVERY TO BRAIN-TUMORS
INTRACAROTID INFUSION OF RMP-7, A BRADYKININ ANALOG - A METHOD FOR SELECTIVE DRUG-DELIVERY TO BRAIN-TUMORS
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DOI：
10.3171/jns.1994.81.5.0752
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发表时间：
1994-11-01
影响因子：
4.1
通讯作者：
BLACK, KL
中科院分区：
文献类型：
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作者：
INAMURA, T;NOMURA, T;BLACK, KL
研究缓激肽类似物RMP-7选择性增加RG 2神经胶质肿瘤中分子示踪剂摄取的能力。当以低剂量（0.1 μ g/kg/min）通过大鼠RG 2胶质瘤同侧颈动脉输注时，与颈动脉内单独输注溶媒相比，RMP-7显著增加了肿瘤毛细血管对甲氨蝶呤和其他4种不同分子量示踪剂的渗透性。用于检查渗透性的示踪剂包括放射性标记的α-氨基异丁酸（M（r）103 D）、蔗糖（M（r）342 D）、甲氨蝶呤（M（r）454.5 D）、菊粉（M（r）5000 D）和葡聚糖（M 70，000 D）。渗透性表示为单向转移;常数，Ki（μ l/gm/min）。与媒介物对照组相比，RMP-7组中肿瘤的渗透性（Ki）如下：α-氨基异丁酸，35.3 +/- 9.11对比12.7 +/- 4.56（p < 0.001）;蔗糖，16.5 +/- 3.83 vs 9.28 +/- 3.12（p < 0.05）;甲氨蝶呤，26.3 ± 10.3 vs 8.98 ± 6.78（p < 0.005）;菊粉，13.5 +/- 3.23对6.55 +/- 4.32（p < 0.005）;葡聚糖，15.2 +/- 3.42对1.47 +/- 1.24（p < 0.001）。RMP-7组RG 2胶质瘤对高分子量葡聚糖（70，000 D）的渗透性是溶剂对照组的10.3倍。颈动脉灌注RMP-7并没有显著增加肿瘤或脑组织中的血容量。正常脑毛细血管的渗透性不受颈动脉内输注0.1 μ g/kg/min RMP-7的影响。这些数据支持的想法，动脉内输注RMP-7将是一个有用的技术，选择性地提供抗肿瘤化合物的脑肿瘤。
The bradykinin analog, RMP-7, was investigated for its ability to selectively increase uptake of molecular tracers in RG2 glial tumors. When infused in low doses (0.1 mu g/kg/min) through the intracarotid artery ipsilateral to RG2 gliomas in rats, RMP-7 significantly increased the permeability of tumor capillaries to methotrexate and to four other tracers of varying molecular weights, compared to intracarotid infusion of vehicle alone. Tracers used to examine permeability included radiolabeled alpha-aminoisobutyric acid (M(r) 103 D), sucrose (M(r) 342 D), methotrexate (M(r) 454.5 D), inulin (M(r) 5000 D), and dextran (M 70,000 D). Permeability was expressed as the unidirectional transfer; constant, K-i (mu l/gm/min). The permeability (K-i) of tumors in the RMP-7 group compared to the vehicle control group was as follows: alpha-aminoisobutyric acid, 35.3 +/- 9.11 versus 12.7 +/- 4.56 (p < 0.001); sucrose, 16.5 +/- 3.83 versus 9.28 +/- 3.12 (p < 0.05); methotrexate, 26.3 +/- 10.3 versus 8.98 +/- 6.78 (p < 0.005); inulin, 13.5 +/- 3.23 versus 6.55 +/- 4.32 (p < 0.005); dextran, 15.2 +/- 3.42 versus 1.47 +/- 1.24 (p < 0.001). The permeability of RG2 gliomas to high-molecular-weight dextran (70,000 D) was 10.3-fold higher in the RMP-7 group than in the vehicle control group. Intracarotid infusion of RMP-7 did not significantly increase the blood volume in tumor or brain tissue. The permeability of normal brain capillaries was unaffected by intracarotid infusion of 0.1 mu g/kg/min RMP-7 relative to that achieved in tumor. These data support the idea that intracarotid infusion of RMP-7 will be a useful technique for selective delivery of antitumor compounds to brain tumors.