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177Lu 标记的抗 PSMA 抗体作为针对前列腺癌的新型放射性免疫治疗药物的体内测试。

In vivo testing of 177Lu-labelled anti-PSMA antibody as a new radioimmunotherapeutic agent against prostate cancer.

机构信息

Department of Nuclear Medicine, University Hospital Freiburg, 79106 Freiburg, Germany.

出版信息

In Vivo. 2011 Jan-Feb;25(1):55-9.

PMID:21282735
Abstract

AIM

The goal of the present study was to test the (177)Lu-labelled anti-PSMA monoclonal antibody 3/F11 ((177)Lu-DOTA-3/F11) as a new radioimmunotherapeutic agent in a prostate cancer SCID mouse xenograft model.

MATERIALS AND METHODS

The mAb 3/F11 was (177)Lu labelled using 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) as chelating agent. DOTA-3/F11 was tested for cell binding and serum immunoreactivity by flow cytometry. The biodistribution and the therapeutic efficacy of (177)Lu-DOTA-3/F11 in mice bearing PSMA-positive C4-2 prostate cancer xenografts were evaluated.

RESULTS

3/F11 and DOTA-3/F11 showed high and specific cell binding and similar serum half-lives of approximately seven days. Biodistribution studies revealed an increasing tumour uptake of (177)Lu DOTA-3/F11 over time with maximum tumour-to-muscle and tumour-to-blood ratios after 72 h. A single dose of 1 MBq (177)Lu-DOTA-3/F11 inhibited tumour growth and prolonged survival.

CONCLUSION

This study indicated that (177)Lu-DOTA-3/F11 may be a suitable radioimmunotherapeutic agent for the treatment of prostate cancer.

摘要

目的

本研究旨在测试（177）Lu 标记的抗 PSMA 单克隆抗体 3/F11（（177）Lu-DOTA-3/F11）作为一种新的放射性免疫治疗剂在前列腺癌 SCID 小鼠异种移植模型中的作用。

材料与方法

使用 1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸（DOTA）作为螯合剂对 mAb 3/F11 进行（177）Lu 标记。通过流式细胞术测试 DOTA-3/F11 的细胞结合和血清免疫反应性。评估（177）Lu-DOTA-3/F11 在携带 PSMA 阳性 C4-2 前列腺癌细胞异种移植的小鼠中的生物分布和治疗效果。

结果

3/F11 和 DOTA-3/F11 表现出高特异性的细胞结合和类似的血清半衰期，约为七天。生物分布研究表明，（177）Lu-DOTA-3/F11 的肿瘤摄取随时间增加，72 小时后肿瘤与肌肉和肿瘤与血液的比值最大。单次给予 1MBq（177）Lu-DOTA-3/F11 可抑制肿瘤生长并延长生存时间。

结论

本研究表明，（177）Lu-DOTA-3/F11 可能是治疗前列腺癌的一种合适的放射性免疫治疗剂。

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