使用chlorotoxin针对原发性脑瘤。

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Soroceanu L, Gillespie Y, Khazaeli MB, Sontheimer H

使用chlorotoxin针对原发性脑瘤。

癌症研究》1998年11月1日,58 (21):4871 - 9。

PubMed ID

9809993 (在PubMed

]

文摘

神经胶质瘤是原发性脑瘤,来自分化神经胶质细胞通过知之甚少恶性转变。虽然神经胶质瘤细胞保留一些基因和抗原特性常见的神经胶质细胞,他们显示出非凡的抗原异质性程度和可变的基因突变。近来发现神经胶质瘤细胞表达glioma-specific氯离子通道(GCC)敏感chlorotoxin (CTX),一个小肽纯化从Leiurus quinquestriatus蝎毒(N。乌尔里希et al Neuroreport 7: 1020 - 1024, 1996;n .乌尔里希和h . Sontheimer。j .杂志。(细胞杂志。),270:C1511-C1521, 1996]。使用本机和重组125标CTX,我们表明,神经胶质瘤细胞毒素绑定具体,涉及高亲和力(离解常数(Kd) = 4.2 nM)和低亲和力(Kd = 660核磁测井)结合位点。125年放射性受体化验,标CTX结合蛋白与奥= 72000,大概是GCC或受体调节GCC活动。体内靶向和biodistribution实验获得使用125 i -(131)标CTX注入严重联合免疫缺陷小鼠轴承异种移植神经胶质瘤。 CTX selectively accumulated in the brain of tumor-bearing mice with calculated brain: muscle ratios of 36.4% of injected dose/g (ID/g), as compared to 12.4% ID/g in control animals. In the tumor-bearing severe combined immunodeficient mice, the vast majority of the brain-associated radioactivity was localized within the tumor (tumor:muscle ratio, 39.13% ID/g; contralateral brain:muscle ratio, 6.68%ID/g). Moreover, (131)I-labeled CTX distribution, visualized through in vivo imaging by gamma ray camera scans, demonstrates specific and persistent intratumoral localization of the radioactive ligand. Immunohistochemical studies using biotinylated and fluorescently tagged CTX show highly selective staining of glioma cells in vitro, in situ, and in sections of patient biopsies. Comparison tissues including normal human brain, kidney, and colon were consistently negative for CTX immunostaining. These data suggest that CTX and CTX-conjugated molecules may serve as glioma-specific markers with diagnostic and therapeutic potential.

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药物

Chlorotoxin i - 131