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用碘-131标记的抗神经细胞黏附分子单克隆抗体治疗小细胞肺癌异种移植瘤并评估组织中的吸收剂量。

Treatment of small-cell lung cancer xenografts with iodine-131-anti-neural cell adhesion molecule monoclonal antibody and evaluation of absorbed dose in tissue.

作者信息

Hosono M, Endo K, Hosono M N, Kobayashi H, Shirato M, Sakahara H, Ueda R, Konishi J

机构信息

Department of Nuclear Medicine, Kyoto University Faculty of Medicine, Japan.

出版信息

J Nucl Med. 1994 Feb;35(2):296-300.

PMID:8295002
Abstract

UNLABELLED

Human small-cell lung cancer (SCLC) is considered a feasible target for immunotherapy using a radiolabeled monoclonal antibody (Mab). A murine Mab, NE150 (IgG1), reacts with the neural cell adhesion molecule, which is identical to cluster 1 antigen of SCLC.

METHODS

To estimate their therapeutic effects, NE150 and an isotype-matched control Mab were labeled with 131I and administered intravenously as a single dose into athymic mice inoculated with a NCI-H69 SCLC xenograft. The absorbed dose in organs was also examined based upon a long-term biodistribution study of 131I-NE150.

RESULTS

Tumors (initial volume 563.4 +/- 223.5 mm3) treated with 11.1 MBq (300 microCi) of 131I-NE150 diminished and became invisible at days 30-33, demonstrating a 60-day mean growth delay to reach a tripled initial volume compared with sham-treated tumors. Cumulative absorbed doses were estimated to be 2310, 410, 500, 330, and 790 cGy for the tumor, liver, kidney, spleen and lung, respectively.

CONCLUSION

Iodine-131-NE150 had potent therapeutic effects against SCLC transplants in athymic mice, however, careful assessment of the side effects, improvement of radioiodination and chimerization of the Mab might be necessary to achieve efficient targeting in clinical therapeutic applications.

摘要

未标记

人小细胞肺癌(SCLC)被认为是使用放射性标记单克隆抗体(Mab)进行免疫治疗的可行靶点。一种鼠源单克隆抗体NE150(IgG1)与神经细胞黏附分子反应,该分子与SCLC的1簇抗原相同。

方法

为评估其治疗效果,将NE150和同型对照单克隆抗体用131I标记,并作为单剂量静脉注射给接种了NCI-H69 SCLC异种移植物的无胸腺小鼠。还基于131I-NE150的长期生物分布研究检查了各器官的吸收剂量。

结果

用11.1 MBq(300微居里)的131I-NE150治疗的肿瘤(初始体积563.4±223.5立方毫米)在第30-33天缩小并不可见,与假处理的肿瘤相比,平均生长延迟60天达到初始体积的三倍。肿瘤、肝脏、肾脏、脾脏和肺的累积吸收剂量估计分别为2310、410、500、330和790 cGy。

结论

碘-131-NE150对无胸腺小鼠中的SCLC移植瘤有显著治疗效果,然而,在临床治疗应用中要实现有效靶向,可能需要仔细评估副作用、改进放射性碘化以及对单克隆抗体进行人源化改造。

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