Hosono M, Hosono M N, Kraeber-Bodéré F, Devys A, Thédrez P, Fiche M, Gautherot E, Barbet J, Chatal J F
Saitama Medical Center, Saitama Medical School, Kawagoe, Japan.
J Nucl Med. 1998 Sep;39(9):1608-13.
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.
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.
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.
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.
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。
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。
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。
这种两步靶向方法对于人甲状腺髓样癌和其他产生CEA的肿瘤的诊断和治疗似乎非常有效，因为它结合了高肿瘤摄取和低正常组织背景。
