Uptake of a nido-carboranylporphyrin by human glioma xenografts in athymic nude mice and by syngeneic ovarian carcinomas in immunocompetent mice.
Uptake of a nido-carboranylporphyrin by human glioma xenografts in athymic nude mice and by syngeneic ovarian carcinomas in immunocompetent mice.
复制标题
无胸腺裸鼠中的人神经胶质瘤异种移植物和免疫活性小鼠中的同基因卵巢癌对 nido-carboranylporphyrin 的摄取。
DOI：
10.1073/pnas.87.18.7265
复制
发表时间：
1990
影响因子：
11.1
通讯作者：
Slatkin,DN
中科院分区：
文献类型：
--
作者：
Kahl,SB;Joel,DD;Nawrocky,MM;Micca,PL;Tran,KP;Finkel,GC;Slatkin,DN
以四（邻氨基苯基）卟啉和碳硼烷羰基氯为原料，通过碱辅助开笼和离子交换得到高水溶性钾盐，收率高，合成了含4个二羰基（[B9C2H11]-）笼的四苯基卟啉（BTPP）。初步研究表明，通过手术植入渗透微型泵皮下注射BTPP 6或7天的小鼠，BTPP在肝脏和同基因卵巢癌中积累，但在正常脑实质中没有积累。在这项研究中，我们测量了胸腺裸鼠皮下移植的人胶质瘤对硼的摄取情况，在这种情况下，BTPP通过类似的微型泵腹腔或皮下或同时输注3天或7天。同样输注具有免疫功能的同基因卵巢癌小鼠，以提供比较数据。当BTPP输注7天后肝脏组织中存在高达102微克/克的硼时，观察到胶质瘤中硼的体积浓度高达18微克/克，癌中硼的体积浓度高达45微克/克。胶质瘤硼浓度平均增加约80%（高达33微克/克），当相应的BTPP在3天内输注更多量时。单个小鼠血液样本的细胞计数和化学试验表明，BTPP引起中度肝毒性和血小板减少症。如果将BTPP或类似的药物用于人类恶性肿瘤的硼中子俘获治疗（BNCT），则应考虑到这种肝血毒性综合征。
A tetraphenylporphyrin bearing four dicarbollide ([B9C2H11]-) cages linked to the o-phenyl ring positions by anilide bonds, known as boronated tetraphenylporphyrin (BTPP), has been synthesized in excellent yield from tetra-(o-aminophenyl) porphyrin and carborane carbonyl chloride followed by base-assisted cage opening and ion exchange to give the highly water-soluble potassium salt. Preliminary studies showed that BTPP accumulates in liver and in a syngeneic ovarian carcinoma, but not in normal brain parenchyma, of mice infused with BTPP subcutaneously for 6 or 7 days via surgically implanted osmotic minipumps. In this study, the uptake of boron was measured in human gliomas xenografted subcutaneously to athymic nude mice in which BTPP was infused intraperitoneally or subcutaneously or both for 3 or 7 days by using similar minipumps. Immunocompetent mice bearing a syngeneic ovarian carcinoma were similarly infused to provide comparative data. Bulk concentrations of boron up to 18 micrograms/g of glioma and up to 45 micrograms/g of carcinoma were observed when up to 102 micrograms/g of tissue was present in the liver after 7 days of BTPP infusion. Glioma boron concentrations were increased by approximately 80% on the average (up to 33 micrograms/g) when correspondingly greater amounts of BTPP were infused in only 3 days. Cell counts and chemical tests on blood samples from individual mice indicate that BTPP causes moderate hepatotoxicity and thrombocytopenia. This hepatohematic toxicity syndrome should be taken into account if BTPP or a similar agent is used for boron neutron-capture therapy (BNCT) of human malignancies.