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使用嵌合单克隆抗体U36进行的砹-211放射免疫疗法治疗头颈部鳞状细胞癌。

Radioimmunotherapy with astatine-211 using chimeric monoclonal antibody U36 in head and neck squamous cell carcinoma.

作者信息

Cheng Junping, Ekberg Tomas, Engström Mats, Nestor Marika, Jensen Holger J, Tolmachev Vladimir, Anniko Matti

机构信息

Department of Oto-Rhino-Laryngology and Head and Neck Surgery, Uppsala University Hospital (Akademiska Sjukhuset), Uppsala, Sweden.

出版信息

Laryngoscope. 2007 Jun;117(6):1013-8. doi: 10.1097/MLG.0b013e31804b1a6d.

DOI:10.1097/MLG.0b013e31804b1a6d
PMID:17440426
Abstract

OBJECTIVES

In advanced head and neck squamous cell carcinoma (HNSCC), there is a need for an adjuvant treatment. We aim to evaluate the biodistribution and therapeutic effect of radioimmunotherapy using the alpha emitting, astatine-211-labeled, chimeric monoclonal antibody U36 (U36) on the HNSCC cell line UT-SCC7 in vivo.

STUDY DESIGN

Xenograft tumors were inoculated subcutaneously in nude mice. Astatine-211-labeled U36 was injected intravenously with or without blocking of target with nonlabeled U36.

METHODS

In the biodistribution experiments, radioactivity was measured in tumors and various organs at set time points. In the therapeutic experiments, two groups (with or without blocking) received therapy, and the tumor growth was compared with that of controls. In addition, one group received nonlabeled U36 only.

RESULTS

The biodistribution experiments demonstrated that astatine-211-labeled U36 could target UT-SCC7 xenografts in nude mice. With time, uptake increased in tumors and decreased in normal organs. Nonlabeled U36 did not influence tumor growth. In the two therapy groups, 18 of 20 tumors responded to therapy by decreasing or stabilizing their volumes. Significant difference was seen between the treated groups and the controls (P < .05).

CONCLUSION

The study illustrates the specific binding of astatine-211-labeled U36 to HNSCC and suggests radioimmunotherapy with the alpha emitting radionuclide to be a useful treatment modality.

摘要

目的

在晚期头颈部鳞状细胞癌(HNSCC)中,需要一种辅助治疗方法。我们旨在评估使用发射α粒子的砹 - 211标记的嵌合单克隆抗体U36(U36)进行放射免疫治疗对HNSCC细胞系UT - SCC7在体内的生物分布和治疗效果。

研究设计

将异种移植瘤皮下接种于裸鼠体内。静脉注射砹 - 211标记的U36,同时或不同时用未标记的U36阻断靶点。

方法

在生物分布实验中,在设定的时间点测量肿瘤和各种器官中的放射性。在治疗实验中,两组(阻断组和非阻断组)接受治疗,并将肿瘤生长情况与对照组进行比较。此外,一组仅接受未标记的U36。

结果

生物分布实验表明,砹 - 211标记的U36可靶向裸鼠体内的UT - SCC7异种移植瘤。随着时间的推移,肿瘤摄取增加,正常器官摄取减少。未标记的U36不影响肿瘤生长。在两个治疗组中,20个肿瘤中有18个通过体积减小或稳定对治疗有反应。治疗组与对照组之间存在显著差异(P <.05)。

结论

该研究说明了砹 - 211标记的U36与HNSCC的特异性结合,并表明用发射α粒子的放射性核素进行放射免疫治疗是一种有用的治疗方式。

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