Clarke K, Lee F T, Brechbiel M W, Smyth F E, Old L J, Scott A M
Tumour Targeting Program, Ludwig Institute for Cancer Research, Austin, Australia.
Cancer Res. 2000 Sep 1;60(17):4804-11.
The biodistribution characteristics of a humanized anti-Lewis(y) antibody (hu3S193) radiolabeled to three radioisotopes, 125I, 111In, and 90Y, were examined in a BALB/c nude mouse xenograft model of breast cancer. The immunoreactivity of both 125I- and 111In-bound hu3S193 exceeded 50% and was 20% for 90Y. In vivo, labeled antibody was shown by gamma camera imaging and immunohistochemical and autoradiographic techniques to localize to Lewis(y)-expressing breast xenografts with minimal normal tissue uptake. Maximal radioisotope uptake peaked at 48 h for all three isotopes; however, the percentage of injected dose/gram and tumor retention were greater for 111In- and 90Y-bound antibody than for 125I-bound antibody. Although immunoreactivity of 111In- and 125I-labeled hu3S193 in serum was stable over a 5-day period, the amount of unlabeled 111In in serum was lower than 125I, which together with higher tumor uptake indicates better retention of 111In-labeled hu3S193 and catabolites within the tumor cells. Superior tumor uptake and retention of 111In-labeled hu3S193 and similar blood clearance compared with 125I-labeled hu3S193, suggest that radiometals are the preferred radioisotope for this antibody-antigen system. Humanized 3S193 is a promising new construct for the targeting and potential therapy of Lewis(y)-expressing tumors.
在BALB/c裸鼠乳腺癌异种移植模型中，研究了用三种放射性同位素125I、111In和90Y标记的人源化抗Lewis(y)抗体（hu3S193）的生物分布特征。125I和111In标记的hu3S193的免疫反应性均超过50%，而90Y标记的hu3S193的免疫反应性为20%。在体内，通过γ相机成像、免疫组织化学和放射自显影技术显示，标记抗体定位于表达Lewis(y)的乳腺异种移植瘤，正常组织摄取极少。所有三种同位素的最大放射性同位素摄取在48小时达到峰值；然而，111In和90Y标记的抗体的注射剂量/克百分比和肿瘤滞留率高于125I标记的抗体。尽管111In和125I标记的hu3S193在血清中的免疫反应性在5天内保持稳定，但血清中未标记的111In含量低于125I，这与较高的肿瘤摄取一起表明111In标记的hu3S193及其代谢产物在肿瘤细胞内的保留更好。与125I标记的hu3S193相比，111In标记的hu3S193具有更好的肿瘤摄取和滞留以及相似的血液清除率，这表明放射性金属是该抗体-抗原系统的首选放射性同位素。人源化3S193是一种有前景的新构建体，可用于靶向和潜在治疗表达Lewis(y)的肿瘤。
