Maeda M, Shoji M, Kawagoshi T, Futatsuya R, Honda T, Brady L W
Department of Radiological Sciences, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Japan.
Cancer. 1994 Feb 1;73(3 Suppl):800-7. doi: 10.1002/1097-0142(19940201)73:3+<800::aid-cncr2820731309>3.0.co;2-p.
The prognosis of pancreatic adenocarcinoma still remains poor because of the lack of reliable diagnostic tests for early stages of the disease. Monoclonal antibody 17-1A (MoAb 17-1A) has been studied extensively, and the antigen recognized by MoAb 17-1A is expressed by adenocarcinomas of the pancreas and stomach, as well as other normal and malignant epithelial tissues. The potential of MoAb 17-1A was investigated for its ability to detect pancreatic carcinomas. The use of MoAb 17-1A in treatment also was studied.
Immunoreactivity of MoAb 17-1A with human pancreatic carcinoma cell line HuP-T4 was examined histochemically by the avidin-biotinylated enzyme complex method. MoAb 17-1A was labeled with 125I by the Iodogen method and 111In using either diethylenetriaminepentaacetic anhydride (cDTPA) or 1-(p-benzyldiazonium) diethylenetriaminepentaacetic acid (aDTPA). After injection in nude mice bearing HuP-T4 xenografts, the biodistribution of 111In- and 125I-labeled MoAb 17-1A was examined at various time points.
Positive staining of MoAb 17-1A was noted for HuP-T4 cells. A statistically significant (P < 0.01) greater tumor uptake was observed at 3 days after intravenous injection of 125I-labeled MoAb 17-1A when compared with 125I-labeled nonspecific immunoglobulin G. 125I- and 111In-labeled MoAb 17-1A was concentrated in HuP-T4 carcinoma 1.9-4.8 times higher than in the spleen, heart, liver, and pancreas.
MoAb 17-1A was found to bind selectively to human pancreatic carcinoma HuP-T4. Tumor exhibited higher uptake of radiolabeled MoAb 17-1A compared with adjacent normal tissues. These results suggest that MoAb 17-1A may be applicable to the radioimmunodetection and radioimmunotherapy of pancreatic adenocarcinomas.
由于缺乏针对胰腺癌早期阶段的可靠诊断测试,胰腺癌的预后仍然很差。单克隆抗体17-1A(MoAb 17-1A)已得到广泛研究,MoAb 17-1A识别的抗原在胰腺癌、胃癌以及其他正常和恶性上皮组织中表达。研究了MoAb 17-1A检测胰腺癌的能力。还研究了MoAb 17-1A在治疗中的应用。
采用抗生物素蛋白-生物素化酶复合物法,通过组织化学检查MoAb 17-1A与人胰腺癌细胞系HuP-T4的免疫反应性。采用碘代法用125I标记MoAb 17-1A,并用二乙烯三胺五乙酸酐(cDTPA)或1-(对苄基重氮)二乙烯三胺五乙酸(aDTPA)用111In标记。在接种HuP-T4异种移植物的裸鼠中注射后,在不同时间点检查111In和125I标记的MoAb 17-1A的生物分布。
观察到MoAb 17-1A对HuP-T4细胞呈阳性染色。与125I标记的非特异性免疫球蛋白G相比,静脉注射125I标记的MoAb 17-1A后3天观察到肿瘤摄取有统计学意义的显著增加(P < 0.01)。125I和111In标记的MoAb 17-1A在HuP-T4癌中的富集程度比在脾脏、心脏、肝脏和胰腺中高1.9至4.8倍。
发现MoAb 17-1A与人胰腺癌细胞HuP-T4选择性结合。与相邻正常组织相比,肿瘤对放射性标记的MoAb 17-1A摄取更高。这些结果表明,MoAb 17-1A可能适用于胰腺癌的放射免疫检测和放射免疫治疗。