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碘-125和铟-111标记的OV-TL 3完整抗体及F(ab')2片段在荷瘤无胸腺小鼠体内的生物分布

Biodistribution of iodine-125 and indium-111 labeled OV-TL 3 intact antibodies and F(ab')2 fragments in tumor-bearing athymic mice.

作者信息

Massuger L F, Boerman O C, Corstens F H, Verheijen R H, Claessens R A, Poels L G, van den Broek W J, Kenemans P

机构信息

Department of Obstetrics and Gynecology, University Hospital Nijmegen, The Netherlands.

出版信息

Anticancer Res. 1991 Nov-Dec;11(6):2051-7.

PMID:1776839
Abstract

The monoclonal antibody OV-TL 3, directed against an ovarian carcinoma-associated antigenic determinant, was tested as a vehicle for radioimmunolocalization of ovarian carcinomas in athymic mice bearing NIH:OVCAR-3 xenografts. The biodistribution of intact. OV-TL 3 was compared with the distribution of OC 125. Tumor uptake with OV-TL 3 was significantly higher than with OC 125, and almost 7 times higher than with a non-specific control antibody (OV-TL 19). Administration of a mixture of intact OV-TL 3 and OC 125 did not improve tumor uptake in comparison with OV-TL 3 alone. Subsequently, intact OV-TL 3 and its F(ab')2 fragments were labeled with either 111In or 125I. The highest tumor uptake was obtained with 111In-labeled intact OV-TL 3 (14.7% ID/g, 48 hr p.i.). For both antibody forms uptake of 111In in liver, spleen and kidneys was very high. Furthermore, 111In cleared more slowly from most tissues than 125I. As a result, tumor/tissue ratios with 111In-labeled OV-TL 3 were lower than with 125I-labeled OV-TL 3. The highest tumor/tissue ratios (6.9 to 53) were obtained with 125I-labeled OV-TL 3 F(ab')2 fragments, 48 hr post injection. 111In-labeled OV-TL 3 F(ab')2 has already been shown to be a clinically useful label for the detection of ovarian cancer. The results of our comparative animal study suggest that these clinical results may even be improved by using 123I-labeled OV-TL 3 F(ab')2.

摘要

针对一种卵巢癌相关抗原决定簇的单克隆抗体OV-TL 3,在携带NIH:OVCAR-3异种移植瘤的无胸腺小鼠中,作为卵巢癌放射免疫定位的载体进行了测试。比较了完整的OV-TL 3与OC 125的生物分布。OV-TL 3的肿瘤摄取显著高于OC 125,几乎比非特异性对照抗体(OV-TL 19)高7倍。与单独使用OV-TL 3相比,给予完整的OV-TL 3和OC 125的混合物并没有提高肿瘤摄取。随后,完整的OV-TL 3及其F(ab')2片段用111In或125I进行标记。用111In标记的完整OV-TL 3获得了最高的肿瘤摄取(注射后48小时为14.7% ID/g)。对于两种抗体形式,111In在肝脏、脾脏和肾脏中的摄取都非常高。此外,111In从大多数组织中清除的速度比125I慢。因此,111In标记的OV-TL 3的肿瘤/组织比值低于125I标记的OV-TL 3。注射后48小时,用125I标记的OV-TL 3 F(ab')2片段获得了最高的肿瘤/组织比值(6.9至5)。111In标记的OV-TL 3 F(ab')2已被证明是检测卵巢癌的一种临床有用的标记物。我们的比较动物研究结果表明,使用123I标记的OV-TL 3 F(ab')2甚至可能改善这些临床结果。

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