Lewis J C, Bagshawe K D, Keep P A
Oncodev Biol Med. 1982;3(2-3):161-8.
Autoradiography was used to identify the distribution of parenterally administered anti-CEA in human colorectal tumours xenografted to nude mice. Four xenograft lines were studied: three mucinous adenocarcinomas of various degrees of differentiation and one undifferentiated tumour. 125Iodine-labelled, affinity purified goat anti-CEA was given intravenously to xenograft-bearing mice, who were killed at intervals thereafter up to 7 days. Autoradiograms were prepared by both conventional methods and the Appleton 'diffusible compound' technique which is designed to avoid possible translocation and extraction of labelled antibody tracer during tissue processing. Control experiments were done using a non-specific goat gamma-globulin. By combining autoradiography with a PAP-immunoperoxidase method of demonstrating CEA, anti-CEA was found to be preferentially retained at extracellular sites of CEA-positive material within viable tumour areas. Cell surface retention was not observed. At all times following administration more antibody was detected within necrotic areas, extracellular spaces and stromal connective tissue than within the tumour cell compartment. These preliminary results are discussed in relation to the possibility of using anti-CEA as a carrier to deliver chemotherapeutic agents into colorectal tumours. The suitability of diffusible compound and conventional autoradiography for studies of this nature are also examined.
采用放射自显影法来确定经肠道外给药的抗癌胚抗原（CEA）在移植到裸鼠体内的人结肠直肠肿瘤中的分布情况。研究了四条移植瘤系：三个不同分化程度的黏液腺癌和一个未分化肿瘤。将125碘标记的、经亲和纯化的山羊抗CEA静脉注射给荷移植瘤小鼠，此后每隔一段时间处死小鼠，直至7天。通过传统方法和阿普尔顿“可扩散化合物”技术制备放射自显影片，该技术旨在避免在组织处理过程中标记抗体示踪剂可能发生的移位和提取。使用非特异性山羊γ球蛋白进行对照实验。通过将放射自显影与显示CEA的PAP免疫过氧化物酶方法相结合，发现抗CEA优先保留在存活肿瘤区域内CEA阳性物质的细胞外部位。未观察到细胞表面保留现象。给药后的所有时间里，在坏死区域、细胞外间隙和基质结缔组织中检测到的抗体都比肿瘤细胞区室中的多。结合使用抗CEA作为载体将化疗药物递送至结肠直肠肿瘤的可能性，对这些初步结果进行了讨论。还研究了可扩散化合物和传统放射自显影法用于此类研究的适用性。
