188Re-loaded lipid nanocapsules as a promising radiopharmaceutical carrier for internal radiotherapy of malignant gliomas
188Re-loaded lipid nanocapsules as a promising radiopharmaceutical carrier for internal radiotherapy of malignant gliomas
复制标题
DOI：
10.1007/s00259-008-0735-z
复制
发表时间：
2008-10-01
影响因子：
9.1
通讯作者：
Benoit, J-P.
中科院分区：
文献类型：
--
作者：
Allard, E.;Hindre, F.;Benoit, J-P.
目的研究Re-188（S3 CPh）（2）（S2 CPh）[Re-188-SSS]的脂质纳米胶囊（LNC）作为一种新型放射性药物载体对恶性胶质瘤的内照射治疗作用。本研究旨在评价Re-188-SSS LNC通过对流增强递送（CED）脑内给药对9 L大鼠脑肿瘤模型的疗效。将大鼠随机分为12、10、8、3Gy剂量组，与空白LNC、4Gy过氧化氢溶液和未处理组进行比较。通过测量CED注射后72 h内粪便和尿液中Re-188的消除来评价放射性核素脑滞留水平。结果Re-188-SSS LNC的CED药物清除迅速，脑T（1/2）为7 h。相比之下，当在LNC中给药时，Re-188组织保留时间大大延长，在72 h时仅消除了10%的注射剂量。与对照组和空白LNC处理动物相比，8 Gy Re-188-SSS LNC处理组的大鼠中位生存期显著改善。与对照组相比，中位生存时间增加约80%; 33%的动物是长期存活者。结论Re-188负载LNC的CED治疗恶性胶质瘤是一种安全有效的抗肿瘤系统。我们的数据是第一个显示在体内的Re-188内部放射治疗脑恶性肿瘤的疗效。
Purpose Lipid nanocapsules (LNC) entrapping lipophilic complexes of Re-188 (Re-188(S3CPh)(2)(S2CPh) [Re-188-SSS]) were investigated as a novel radiopharmaceutical carrier for internal radiation therapy of malignant gliomas. The present study was designed to evaluate the efficacy of intra-cerebral administration of Re-188-SSS LNC by means of convection-enhanced delivery (CED) on a 9L rat brain tumour model.Methods Female Fischer rats with 9L glioma were treated with a single injection of Re-188-SSS LNC by CED 6days after cell implantation. Rats were put into random groups according to the dose infused: 12, 10, 8 and 3Gy in comparison with blank LNC, perrhenate solution (4Gy) and non-treated animals. The radionuclide brain retention level was evaluated by measuring Re-188 elimination in faeces and urine over 72h after the CED injection. The therapeutic effect of Re-188-SSS LNC was assessed based on animal survival.Results CED of Re-188 perrhenate solution resulted in rapid drug clearance with a brain T (1/2) of 7h. In contrast, when administered in LNC, Re-188 tissue retention was greatly prolonged, with only 10% of the injected dose being eliminated at 72h. Rat median survival was significantly improved for the group treated with 8Gy Re-188-SSS LNC compared to the control group and blank LNC-treated animals. The increase in the median survival time was about 80% compared to the control group; 33% of the animals were long-term survivors. The dose of 8Gy proved to be a very effective dose, between toxic (10-12Gy) and ineffective (3-4Gy) doses.Conclusions These findings show that CED of Re-188-loaded LNC is a safe and potent anti-tumour system for treating malignant gliomas. Our data are the first to show the in vivo efficacy of Re-188 internal radiotherapy for the treatment of brain malignancy.