Pimm M V, Clegg J A, Baldwin R W
Cancer Research Campaign Laboratories, University of Nottingham, U.K.
Eur J Cancer Clin Oncol. 1987 May;23(5):521-7. doi: 10.1016/0277-5379(87)90314-2.
The distribution in athymic nude mice of radiolabelled monoclonal antibody 791T/36 has been assessed during continuous infusion from subcutaneously implanted Alzet Osmotic Minipumps. During prolonged administration (up to 15 days) blood levels continued to rise. At 15 days, distribution of radiolabel was virtually identical to that seen after a single parenteral dose. Blood levels were in good agreement to those expected from whole body levels indicating satisfactory entry of antibody into the vascular compartment. Gel filtration chromatography of osmotic minipump contents and circulating radiolabel showed that the antibody had retained its structural integrity. In mice with human tumour xenografts examined a 5-day infusion of a mixture of 131I-791T/36 antibody and 125I-control IgG2b, blood levels of both radiolabels were comparable to those expected from whole body levels and there was effective tumour localization of the antibody to 2.5 times that of control IgG. These studies have demonstrated that prolonged administration of monoclonal antibody is feasible, that antibody enters the vascular compartment satisfactorily and that it can then localize in tumour deposits.
在通过皮下植入的Alzet渗透微型泵持续输注放射性标记的单克隆抗体791T/36期间,对无胸腺裸鼠体内的分布情况进行了评估。在长时间给药(长达15天)过程中,血液水平持续上升。在第15天,放射性标记的分布与单次肠胃外给药后观察到的情况几乎相同。血液水平与全身水平预期的情况高度一致,表明抗体能令人满意地进入血管腔室。对渗透微型泵内容物和循环放射性标记进行凝胶过滤色谱分析表明,抗体保持了其结构完整性。在对有人肿瘤异种移植的小鼠进行检查时,对131I-791T/36抗体和125I-对照IgG2b的混合物进行5天输注,两种放射性标记的血液水平与全身水平预期的情况相当,并且抗体在肿瘤中的定位效果是对照IgG的2.5倍。这些研究表明,长时间给予单克隆抗体是可行的,抗体能令人满意地进入血管腔室,然后可以在肿瘤沉积物中定位。