Conjugation of phenyl isothiocyanate derivatives of carborane to antitumor antibody and in vivo localization of conjugates in nude mice.
Conjugation of phenyl isothiocyanate derivatives of carborane to antitumor antibody and in vivo localization of conjugates in nude mice.
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DOI：
10.1021/bc00008a005
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发表时间：
1991-03
影响因子：
4.7
通讯作者：
A. Varadarajan;R. Sharkey;D. Goldenberg;M. Hawthorne
中科院分区：
文献类型：
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作者：
A. Varadarajan;R. Sharkey;D. Goldenberg;M. Hawthorne
对1-（对-异硫氰酸基苯基）-1，2-二碳-闭合-[2- 3 H]十二硼烷（12）（3 H-1）和7-（对-异硫氰酸基苯基）十二氢-7，8-二碳-酰-[8- 3 H]十一硼酸盐（1-）离子（3 H-2）与鼠单克隆抗CSAp抗体Mu-9的偶联进行了系统研究，以比较带电和不带电硼笼对抗体负载的影响。大约一个中性笼和四个阴离子笼在两个单独的缀合物中成功地与抗体连接，随后将其放射性碘化并在体内评价。在两种情况下均未观察到抗体或其免疫反应性的显著损失。在携带GW-39肿瘤异种移植物的裸鼠中，含有阴离子碳硼烷衍生物的缀合物显示出降低的肿瘤摄取，尽管肿瘤：非肿瘤比率与天然抗体的相似。用125 I放射性标记2中的碳硼烷笼，然后尝试纯化产物4并将其缀合至模型山羊IgG蛋白。进行该探索性缀合研究作为将含有多个阴离子硼笼的新缀合试剂与抗肿瘤抗体连接的前奏。为了中子俘获治疗的目的，需要后一种缀合物来最大化硼负载。
A systematic study of the conjugation of 1-(p-isothiocyanatophenyl)-1,2-dicarba-closo-[2-3H]dodeca borane(12), 3H-1, and 7-(p-isothiocyanatophenyl)dodecahydro-7,8-dicarba-nido -[8-3H] undecaborate(1-)ion, 3H-2, to the murine monoclonal anti-CSAp antibody, Mu-9, was carried out to compare charged and uncharged boron cages in their effect upon antibody loading. Approximately one neutral cage and four of the anionic cages were successfully linked to antibody in two separate conjugates which were subsequently radioiodinated and evaluated in vivo. No significant loss of the antibody or its immunoreactivity was observed in either case. In nude mice bearing GW-39 tumor xenografts the conjugate containing the anionic carborane derivative showed a reduced tumor uptake although the tumor:non-tumor ratio was similar to that of the native antibody. The carborane cage in 2 was radiolabeled with 125I followed by attempts to purify and conjugate product 4 to a model goat IgG protein. This exploratory conjugation study was undertaken as a prelude to linking new conjugation reagents, which contain multiple anionic boron cages, to antitumor antibodies. The latter conjugates are required to maximize boron loading for the purpose of neutron-capture therapy.