Fand I, Sharkey R M, Goldenberg D M
Center for Molecular Medicine and Immunology, University of Medicine and Dentistry of New Jersey, Newark 07103.
Cancer Res. 1990 Feb 1;50(3 Suppl):885s-891s.
Methods of single-tracer whole-body autoradiography (WBAR) have been developed in our laboratory which allow imaging and measurement of the zonal distribution of radioiodinated antibodies and their fragments within GW-39 colon carcinoma xenografts varying in size from large, cystic masses with necrotic cores to micrometastases. The whole-animal distribution of 90Y-labeled anti-carcinoembryonic antigen monoclonal antibody NP-2 was evaluated by WBAR in nude mice bearing s.c. implants of GW-39 colon cancer and revealed antitumor uptake specifically as well as significant accumulation of 90Y in the bones. Dual-tracer qualitative WBAR methods have also been applied in order to examine the biodistribution of labeled immunoglobulins in the GW-39 animal tumor model as a function of the underlying rapid cell proliferation index ([3H]-thymidine assay) in the same tumor. In addition, extension of the WBAR method was made to permit imaging of the biodistribution of 10B compounds in mice bearing Harding-Passey melanoma implants by using a track-etch procedure to produce alpha-particle WBAR. Further applications of single and multiple radionuclide WBAR are offered and discussed as an effective means of assessing the degree of penetration of immunoglobulins in tumors in which vascular patterns, local glucose metabolism, protein synthesis, and rapid cell proliferation indices may be characterized.
我们实验室已开发出单示踪全身放射自显影（WBAR）方法，该方法可对不同大小的GW - 39结肠癌异种移植物（从具有坏死核心的大囊性肿块到微转移灶）中放射性碘化抗体及其片段的区域分布进行成像和测量。通过WBAR评估了90Y标记的抗癌胚抗原单克隆抗体NP - 2在荷GW - 39结肠癌皮下植入物的裸鼠中的全身分布，结果显示其具有特异性抗肿瘤摄取以及90Y在骨骼中的显著蓄积。还应用了双示踪定性WBAR方法，以研究标记免疫球蛋白在GW - 39动物肿瘤模型中的生物分布，该分布是同一肿瘤中潜在的快速细胞增殖指数（[3H] - 胸腺嘧啶核苷测定）的函数。此外，对WBAR方法进行了扩展，通过使用径迹蚀刻程序产生α粒子WBAR，从而能够对荷Harding - Passey黑色素瘤植入物的小鼠中10B化合物的生物分布进行成像。本文提供并讨论了单放射性核素和多放射性核素WBAR的进一步应用，作为评估免疫球蛋白在肿瘤中渗透程度的有效手段，其中肿瘤的血管模式、局部葡萄糖代谢、蛋白质合成和快速细胞增殖指数可得以表征。
