Goodwin D A, Meares C F, David G F, McTigue M, McCall M J, Frincke J M, Stone M R, Bartholomew R M, Leung J P
Int J Rad Appl Instrum B. 1986;13(4):383-91. doi: 10.1016/0883-2897(86)90015-2.
We have prepared monoclonal antibodies (MoAbs) with the specific ability to bind metal chelates such as 111In benzyl EDTA. One, 10, 50 and 100 micrograms MoAb CHA255 Kb = 4 X 10E9 was complexed with 111In BLEDTA II, BLEDTA IV, and benzyl EDTA and injected i.v. in Balb/c mice with KHJJ tumor. The biological half-life by whole body counting was profoundly altered for all three compounds; from minutes to hours with 10 micrograms; to days with 100 micrograms. Tumor uptake increased 50 fold at 24 h with increasing MoAb but satisfactory tumor concentrations (3% per g) and tumor/blood ratios (1.8:1) were obtained with an amount equivalent to 7 mg for a human. Blood level and whole body activity were decreased 30-50% within 3 h or i.v. injection of a "flushing" dose of unlabeled indium benzyl EDTA, increasing tumor/blood ratios to 50:1.
我们制备了具有特异性结合金属螯合物（如铟 - 111标记的苄基乙二胺四乙酸）能力的单克隆抗体（MoAbs）。将1、10、50和100微克单克隆抗体CHA255（解离常数Kb = 4×10⁹）与铟 - 111标记的二乙三胺五乙酸苄酯（BLEDTA II）、四乙五胺六乙酸苄酯（BLEDTA IV）以及苄基乙二胺四乙酸络合，然后静脉注射到患有KHJJ肿瘤的Balb/c小鼠体内。通过全身计数得出，这三种化合物的生物半衰期都发生了显著变化；10微克时从几分钟变为几小时；100微克时变为几天。随着单克隆抗体用量增加，24小时时肿瘤摄取量增加了50倍，但对于人类而言，使用相当于7毫克的量可获得令人满意的肿瘤浓度（每克3%）和肿瘤/血液比率（1.8:1）。静脉注射未标记的铟苄基乙二胺四乙酸的“冲洗”剂量后3小时内，血液水平和全身活性降低30 - 50%，肿瘤/血液比率提高到50:1。
