Rowlinson G, Snook D, Busza A, Epenetos A A
Department of Clinical Oncology, Royal Postgraduate Medical School, London, England.
Cancer Res. 1987 Dec 15;47(24 Pt 1):6528-31.
Intraperitoneal tumors from a human cancer cell line (LoVo) were established in nude mice by i.p. inoculation of a single cell suspension. Two preparations of the same monoclonal antibody, radiolabeled with 125I and 131I were injected i.p. and i.v. into the same animals. Localization was assessed by dissection and counting the activity in tumors and normal tissues. Tumor/tissue ratios 1 h after i.p. injection of antibody were approximately 50 times higher than after i.v. administration. This i.p./i.v. advantage fell to around 4 by 8 h and was just greater than 1 by 24 h. This effect was observed with both specific and nonspecific antibody, indicating that it is due to the route of administration. However, the absolute amounts of antibody bound to tumors depended on the specificity of the antibody. Twenty % of the injected dose of specific antibody was bound per gram to tumor 1 to 2 h after i.p. injection, falling to 10%/g by 24 h and remaining at this level up to 5 days after antibody administration. In contrast, less than 10%/g of nonspecific antibody was detected in tumors after 1 h; this fell rapidly to normal organ levels of less than 5%/g by 8 h. This study demonstrates a major advantage when administering radiolabeled monoclonal antibodies i.p. for targeting intraperitoneal tumors.
通过腹腔注射人癌细胞系(LoVo)的单细胞悬液,在裸鼠体内建立腹腔肿瘤模型。将两种用125I和131I放射性标记的相同单克隆抗体制剂分别经腹腔和静脉注射到同一批动物体内。通过解剖并计数肿瘤和正常组织中的放射性活性来评估定位情况。腹腔注射抗体后1小时,肿瘤/组织比值比静脉给药后高约50倍。这种腹腔/静脉给药的优势在8小时时降至约4倍,24小时时仅略大于1倍。特异性抗体和非特异性抗体均观察到这种效应,表明这是由于给药途径所致。然而,与肿瘤结合的抗体绝对量取决于抗体的特异性。腹腔注射后1至2小时,每克肿瘤结合20%的注射剂量的特异性抗体,24小时时降至10%/克,在抗体给药后长达5天内保持在该水平。相比之下,1小时后在肿瘤中检测到的非特异性抗体低于10%/克;8小时时迅速降至正常器官水平,低于5%/克。这项研究表明,腹腔注射放射性标记的单克隆抗体靶向腹腔肿瘤具有显著优势。