Imaging of Prostate Cancer with Immuno-PET and Immuno-SPECT Using a Radiolabeled Anti-EGP-1 Monoclonal Antibody
Imaging of Prostate Cancer with Immuno-PET and Immuno-SPECT Using a Radiolabeled Anti-EGP-1 Monoclonal Antibody
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DOI：
10.2967/jnumed.110.086520
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发表时间：
2011-10-01
影响因子：
9.3
通讯作者：
Boerman, Otto C.
中科院分区：
文献类型：
--
作者：
van Rij, Catharina M.;Sharkey, Robert M.;Boerman, Otto C.
hRS 7是一种针对上皮糖蛋白-1（EGP-1;也称为TR 0 P2）的人源化IgG 1单克隆抗体。这种抗原存在于许多上皮癌中，包括前列腺癌，因此这种抗体可能适用于靶向这种癌症。在这项研究中，检查了hRS 7靶向前列腺癌的特征。使用具有人前列腺癌异种移植物的裸小鼠评估用Zr-89-hRS 7进行免疫PET和用In-111-hRS 7进行免疫SPECT的潜力。方法：EGP-1的表达进行了评估，在人类原发性和转移性前列腺癌样本和PC 3异种移植。在具有皮下PC 3异种移植物的裸鼠中检查用于前列腺癌靶向的最佳抗体蛋白剂量，然后在注射后1、3和7 d测定In-111-、I-125-和Zr-89-标记的hRS 7在皮下PC 3异种移植物中的生物分布。在皮下和前列腺内PC 3异种移植的小鼠中分别用Zr-89-hRS 7和In-111-hRS 7进行免疫PET和免疫SPECT。结果：免疫组化分析显示EGP-1在人原发性和转移性前列腺癌以及PC 3异种移植瘤中表达丰富。In-111-hRS 7和89 Zr-hRS 7优先并特异性地在PC 3异种移植物中积累，在每只小鼠0.1 μ g的蛋白剂量下，肿瘤摄取高达每克注射剂量的60%。裸鼠中的PC 3肿瘤用具有免疫-PET和免疫-SPECT的两种示踪剂清楚地可视化。结论：hRS 7在人前列腺癌异种移植物中显示出优异的体内肿瘤靶向性。因此，hRS 7是靶向前列腺癌的潜在载体。
hRS7 is a humanized IgG1 monoclonal antibody directed against the epithelial glycoprotein-1 (EGP-1; also known as TROP2). This antigen is found in many epithelial cancers, including prostate cancer, and therefore this antibody could be suitable for targeting this cancer. In this study, the characteristics of hRS7 for targeting prostate cancer were examined. The potential for immuno-PET with Zr-89-hRS7 and immuno-SPECT with In-111-hRS7 was assessed using nude mice with human prostate cancer xenografts. Methods: EGP-1 expression was assessed by immunohistology in human primary and metastatic prostate cancer samples and in PC3 xenografts. The optimal antibody protein dose for prostate cancer targeting was examined in nude mice with subcutaneous PC3 xenografts, and then the biodistribution of In-111-, I-125-, and Zr-89-labeled hRS7 was determined in subcutaneous PC3 xenografts at 1, 3, and 7 d after injection. Immuno-PET and immuno-SPECT were performed with Zr-89-hRS7 and In-111-hRS7 in mice with subcutaneous and intraprostatic PC3 xenografts, respectively. Results: Immunohistochemical analysis showed abundant EGP-1 expression in human primary and metastatic prostate cancers and in PC3 xenografts. In-111-hRS7 and 89Zr-hRS7 preferentially and specifically accumulated in PC3 xenografts, with tumor uptake as high as 60% injected dose per gram at a protein dose of 0.1 mu g per mouse. PC3 tumors in nude mice were clearly visualized with both tracers with immuno-PET and immuno-SPECT. Conclusion: hRS7 shows excellent in vivo tumor targeting in human prostate cancer xenografts. Therefore, hRS7 is a potential vehicle for targeting prostate cancer.