In vivo fate of folate-BSA in non-tumor- and tumor-bearing mice.
In vivo fate of folate-BSA in non-tumor- and tumor-bearing mice.
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叶酸-BSA 在非肿瘤和肿瘤小鼠中的体内命运。
DOI：
10.1021/js980215v
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发表时间：
1998
影响因子：
3.8
通讯作者：
M. Hashida
中科院分区：
文献类型：
--
作者：
T. Shinoda;Akira Takagi;Atsushi Maeda;S. Kagatani;Y. Konno;M. Hashida
KB肿瘤细胞在其膜上表现出数量增加的叶酸受体。该受体已被提出作为肿瘤药物靶向的有希望的靶点。因此，叶酸偶联牛血清白蛋白（叶酸-BSA）的处置作为药物靶向的模型系统进行了检查。接受KB肿瘤细胞移植的裸鼠静脉推注给予111 In标记的叶酸-BSA（111 In-叶酸-BSA; 1 mg/kg）或未修饰的111 In-BSA（111 In-BSA; 1 mg/kg）。比较了111 In-Folate-BSA和111 In-BSA的体内处置特性和药代动力学。111 In-叶酸-BSA在血浆中的β相半衰期为140 min。111 In-叶酸-BSA和111 In-BSA的肿瘤摄取速率指数分别为0.46 μ L/min/g和0.32 μ L/min/g。111 In-叶酸-BSA的该指数略高于体内111 In-BSA的指数，为1.4倍。体内实验表明叶酸-BSA具有相对较长的血浆持续时间。111 In-叶酸-BSA也显示出对肿瘤的选择性分布，但不如最近的体外实验结果那么大。因此，BSA进入实体瘤组织的低血管渗透性和抑制叶酸介导的肿瘤细胞从血液中摄取111 In-叶酸-BSA可能是分布的限速因素。
KB tumor cells exhibit an increased number of folate receptors on their membrane. This receptor has been proposed as a promising target for tumor drug targeting. Therefore, the disposition of folate-conjugated bovine serum albumin (folate-BSA) was examined as a model system for drug targeting. Nude mice which had received KB tumor cell transplants were given bolus intravenous administration of either 111In-labeled folate-BSA (111In-folate-BSA; 1 mg/kg) or unmodified 111In-BSA (111In-BSA; 1 mg/kg). The disposition characteristics and pharmacokinetics of 111In-folate-BSA were compared with those of the 111In-BSA as a control. The half-life of the beta-phase of 111ln-folate-BSA in plasma was 140 min. The tumor uptake rate index for 111In-folate-BSA was 0.46 microL/min/g, and that for 111In-BSA was 0.32 microL/min/g. This index of 111In-folate-BSA was slightly higher than that of 111In-BSA in vivo, by a factor of 1.4. In vivo experiments showed folate-BSA has a relatively long plasma duration. 111In-folate-BSA also showed selective distribution to tumors, but not as great as recent results from in vitro experiments. Therefore, the low vascular permeability of BSA into solid tumor tissue and inhibition of folate-mediated 111In-folate-BSA uptake by tumor cells from the blood may be the rate-limiting factor of distribution.
影响因子：
11.2
作者：
Steven D. Weitman;R. Lark;L. Coney;Daniel W. Fort;Verna Frasca;Vincent R. Zurawski;B. A. Kamen
通讯作者：
Steven D. Weitman;R. Lark;L. Coney;Daniel W. Fort;Verna Frasca;Vincent R. Zurawski;B. A. Kamen