Nuclear imaging of met-expressing human and canine cancer xenografts with radiolabeled monoclonal antibodies (MetSeek™)
Nuclear imaging of met-expressing human and canine cancer xenografts with radiolabeled monoclonal antibodies (MetSeek™)
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DOI：
10.1158/1078-0432.ccr-1004-0014
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发表时间：
2005-10-01
影响因子：
11.5
通讯作者：
Vande Woude, GF
中科院分区：
文献类型：
--
作者：
Hay, RV;Cao, B;Vande Woude, GF
目的：Met是一种致癌基因产物和受体酪氨酸激酶，是人类实体肿瘤恶性进展的关键分子。我们正在开发met定向成像和治疗剂，包括抗met单克隆抗体（MetSeek(TM)）。在这项研究中，我们比较了Met5和Met3两种抗体对表达met的人和犬异种肿瘤裸鼠的核成像。实验设计：异种移植物代表三种不同的人类组织来源的癌症和转移性犬前列腺癌在宿主胸腺裸鼠中培养。给动物注射了静脉注射。使用I-125-Met5或I-125-Met3，注射后几天获得全身后验伽马相机图像，并进行定量兴趣区活动分析。结果：将PC-3、SK-LMS-1/HGF和CNE-2异种移植物与PC-3、SK-LMS-1/HGF和DU145异种移植物与I-125-Met3成像的异种移植物进行比较。PC-3和SK-LMS-1/HGF宿主小鼠I-125-Met5和I-125-Met3的核成像对比质量相似。然而，通过感兴趣区域分析，用I-125-Met3成像的一组人类肿瘤显示出一种快速的初始肿瘤摄取模式，随后活性持续下降，而用I-125-Met5成像的一组人类肿瘤显示出缓慢的初始摄取，注射后1天达到肿瘤相关活性峰值，并且在异种移植物中持续活性至少5天。GN4犬前列腺癌异种移植物很容易用I-125-Met5成像。结论：我们得出结论，放射性碘化的Met3和Met5在异种移植小鼠中提供了质量相似的核图像，但定量考虑表明Met5可能对放射免疫治疗更有用。此外，犬前列腺癌似乎是Met5二期临床前评估的合适模型。
Purpose: Met, an oncogene product and receptor tyrosine kinase, is a keystone molecule for malignant progression in solid human tumors. We are developing Met-directed imaging and therapeutic agents, including anti-Met monoclonal antibodies (MetSeek(TM)). In this study, we compared two antibodies, Met5 and Met3, for nuclear imaging of human and canine Met-expressing tumor xenografts in nude mice.Experimental Design: Xenografts representing cancers of three different human tissue origins and metastatic canine prostate cancer were raised s.c. in host athymic nude mice. Animals were injected i.v.. with I-125-Met5 or I-125-Met3, posterior total body gamma camera images were acquired for several days postinjection, and quantitative region-of-interest activity analysis was done.Results: PC-3, SK-LMS-1/HGF, and CNE-2 xenografts imaged with I-125-Met5 were compared with PC-3, SK-LMS-1/HGF, and DU145 xenografts imaged with I-125-Met3. Nuclear imaging contrast was qualitatively similar for I-125-Met5 and I-125-Met3 in PC-3 and SK-LMS-1/HGF host mice. However, by region-of-interest analysis, the set of human tumors imaged with I-125-Met3 exhibited a pattern of rapid initial tumor uptake followed by a continuous decline in activity, whereas the set of human tumors imaged with I-125-Met5 showed slow initial uptake, peak tumor-associated activity at 1 day postinjection, and persistence of activity in xenografts for at least 5 days. GN4 canine prostate cancer xenografts were readily imaged with I-125-Met5.Conclusions: We conclude that radioiodinated Met3 and Met5 offer qualitatively similar nuclear images in xenograft-bearing mice, but quantitative considerations indicate that Met5 might be more useful for radioimmunotherapy. Moreover, canine prostate cancer seems to be a suitable model for second-stage preclinical evaluation of Met5.