使用双特异性抗体和碘-125标记的二价半抗原对甲状腺髓样癌异种移植模型进行生物分布和剂量学研究。

Biodistribution and dosimetric study in medullary thyroid cancer xenograft using bispecific antibody and iodine-125-labeled bivalent hapten.

作者信息

Hosono M, Hosono M N, Kraeber-Bodéré F, Devys A, Thédrez P, Fiche M, Gautherot E, Barbet J, Chatal J F

机构信息

Saitama Medical Center, Saitama Medical School, Kawagoe, Japan.

出版信息

J Nucl Med. 1998 Sep;39(9):1608-13.

PMID:9744353

Abstract

UNLABELLED

The purpose of this study was to evaluate biodistributions and absorbed doses of anti-carcinoembryonic antigen (CEA)/anti-diethylenetriamine pentaacetic acid (DTPA)-indium (anti-DTPA-In) bispecific monoclonal antibody (BsMAb) F6-734 and 125I-labeled DTPA-indium dimer hapten (125I-di-DTPA-In hapten) in athymic mice xenografted with human medullary thyroid cancer.

METHODS

Bispecific monoclonal antibodies F6-679 (anti-CEA/antihistamine) and G7A5-734 (antimelanoma/anti-di-DTPA-In) were used as irrelevant BsMAbs. Athymic mice inoculated with TT medullary thyroid cancer cells expressing CEA were administered BsMAbs F6-734, F6-679 or G7A5-734 and then, 48 hr later, 125I-di-DTPA-In hapten. Iodine-125-labeled F6 F(ab')2 fragment was injected into other groups of mice. Biodistributions were examined at 30 min and 5, 24, 48 and 96 hr after injection of 125I-di-DTPA-In hapten or 125I-labeled F6 F(ab')2.

RESULTS

In mice injected with BsMAb F6-734 and 125I-di-DTPA-In hapten, tumor uptake was 9.1%+/-2.1%, 8.7%+/-3.5%, 8.0%+/-2.3%, 5.1%+/-0.9% and 3.5%+/-1.5% of the injected dose/g at 30 min and 5, 24, 48 and 96 hr, and tumor-to-blood, tumor-to-liver and tumor-to-kidney ratios were 37.0+/-12.5, 32.3+/-10.9 and 10.4+/-2.7 at 24 hr. Iodine-125-F6 F(ab')2 fragment showed a tumor uptake of 7.39% injected dose/g and tumor-to-blood, tumor-to-liver and tumor-to-kidney ratios of 1.8+/-0.6, 7.3+/-2.9 and 3.6+/-1.6 at 24 hr. In mice injected with F6-679 or G7A5-734, tumor uptake and tumor-to-normal tissue ratios were much lower than in the mice injected with F6-734. These results were confirmed by autoradiographic studies that demonstrated clear tumor-to-normal tissue contrast.

CONCLUSION

This two-step targeting method seems very potent for the diagnosis and therapy of human medullary thyroid cancer and other CEA-producing tumors because it combines high tumor uptake and low normal tissue background.

摘要

未标记

本研究的目的是评估抗癌胚抗原（CEA）/抗二乙烯三胺五乙酸（DTPA）-铟（抗-DTPA-In）双特异性单克隆抗体（BsMAb）F6-734和125I标记的DTPA-铟二聚体半抗原（125I-二-DTPA-In半抗原）在接种人甲状腺髓样癌的无胸腺小鼠中的生物分布和吸收剂量。

方法

双特异性单克隆抗体F6-679（抗CEA/抗组胺）和G7A5-734（抗黑色素瘤/抗二-DTPA-In）用作无关的BsMAb。给接种表达CEA的TT甲状腺髓样癌细胞的无胸腺小鼠注射BsMAb F6-734、F6-679或G7A5-734，然后在48小时后注射125I-二-DTPA-In半抗原。将125I标记的F6 F(ab')2片段注射到其他组小鼠中。在注射125I-二-DTPA-In半抗原或125I标记的F6 F(ab')2后30分钟、5、24、48和96小时检查生物分布。

结果

在注射BsMAb F6-734和125I-二-DTPA-In半抗原的小鼠中，在30分钟以及5、24、48和96小时时肿瘤摄取分别为注射剂量/克的9.1%±2.1%、8.7%±3.5%、8.0%±2.3%、5.1%±0.9%和3.5%±1.5%，在24小时时肿瘤与血液、肿瘤与肝脏以及肿瘤与肾脏的比率分别为37.0±12.5、32.3±10.9和10.4±2.7。125I-F6 F(ab')2片段在24小时时肿瘤摄取为注射剂量/克的7.39%，肿瘤与血液、肿瘤与肝脏以及肿瘤与肾脏的比率分别为1.8±0.6、7.3±2.9和3.6±1.6。在注射F6-679或G7A5-734的小鼠中，肿瘤摄取和肿瘤与正常组织的比率远低于注射F6-734的小鼠。这些结果通过放射自显影研究得到证实，该研究显示出清晰的肿瘤与正常组织对比。