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使用碘-125标记的生物素化单克隆抗体和冷抗生物素蛋白的放射免疫导向手术。

Radioimmunoguided surgery using iodine-125-labeled biotinylated monoclonal antibodies and cold avidin.

作者信息

Paganelli G, Stella M, Zito F, Magnani P, De Nardi P, Mangili F, Baratti D, Veglia F, Di Carlo V, Siccardi A G

机构信息

Department of Nuclear Medicine, University of Milan, Scientific Institute H S. Raffaele, Italy.

出版信息

J Nucl Med. 1994 Dec;35(12):1970-5.

PMID:7989979
Abstract

UNLABELLED

One of the limitations of intraoperative tumor detection with radiolabeled monoclonal antibody (Mab), by means of a gamma-detecting probe (GDP), is the long time interval needed between Mab injection and surgery to obtain low blood-pool activity. Such an interval can be shortened considerably, exploiting the high affinity between avidin and biotin.

METHODS

Twenty patients with colorectal cancer were injected with 1 mg of biotinylated 125I monoclonal antibodies followed, 48 hr later, by a chase of cold avidin. During surgery, the GDP was used to detect radioactive emissions from the tumor and normal tissue. Tumor tissue samples were analyzed in vitro by immunohistochemical tests for the presence of tumor antigens and in vivo antibody localization.

RESULTS

At the time of surgery (average 7 days postinjection), the mean value of circulating radioactivity was 6% +/- 3% of the injected dose. Of 20 patients studied, tumors were localized in 13 cases (65%). Subclinical tumors were detected in 3 patients (15%).

CONCLUSION

The use of 125I-labeled biotinylated Mabs followed by avidin as a chase enhances the applicability and effectiveness of radioimmunoguided surgery technology and will allow the use of radioisotopes with a shorter half-life than 125I.

摘要

未标记

通过γ探测探头(GDP)利用放射性标记单克隆抗体(Mab)进行术中肿瘤检测的局限性之一是,在Mab注射与手术之间需要较长的时间间隔以获得低血池活性。利用抗生物素蛋白和生物素之间的高亲和力可大大缩短这一间隔。

方法

给20例结直肠癌患者注射1毫克生物素化的125I单克隆抗体,48小时后再注射冷抗生物素蛋白进行追踪。手术期间,使用GDP检测肿瘤和正常组织的放射性发射。通过免疫组织化学试验在体外分析肿瘤组织样本中肿瘤抗原的存在情况,并在体内分析抗体定位情况。

结果

在手术时(平均注射后7天),循环放射性的平均值为注射剂量的6%±3%。在研究的20例患者中,13例(65%)肿瘤得到定位。3例(15%)检测到亚临床肿瘤。

结论

使用125I标记的生物素化Mab后再注射抗生物素蛋白进行追踪,可提高放射免疫导向手术技术的适用性和有效性,并将允许使用半衰期比125I短的放射性同位素。

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J Nucl Med. 1994 Dec;35(12):1970-5.
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引用本文的文献

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Gamma probes and their use in tumor detection in colorectal cancer.γ探测器及其在结直肠癌肿瘤检测中的应用。
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Avidin-biotin system pretargeting radioimmunoimaging and radioimmunotherapy and its application in mouse model of human colon carcinoma.抗生物素蛋白-生物素系统预靶向放射免疫显像和放射免疫治疗及其在人结肠癌小鼠模型中的应用
World J Gastroenterol. 2005 Oct 28;11(40):6288-94. doi: 10.3748/wjg.v11.i40.6288.
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Avidin chase reduces side effects of radioimmunotherapy in nude mice bearing human colon carcinoma.
抗生物素蛋白追踪可降低荷人结肠癌裸鼠放射免疫治疗的副作用。
World J Gastroenterol. 2005 Apr 7;11(13):1917-21. doi: 10.3748/wjg.v11.i13.1917.
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Biochemical modifications of avidin improve pharmacokinetics and biodistribution, and reduce immunogenicity.抗生物素蛋白的生化修饰改善了药代动力学和生物分布,并降低了免疫原性。
Br J Cancer. 1998 Jul;78(2):189-97. doi: 10.1038/bjc.1998.463.