Pedley R B, Boden J A, Boden R W, Green A, Boxer G M, Bagshawe K D
Department of Medical Oncology, Charing Cross Hospital, London, UK.
Br J Cancer. 1989 Oct;60(4):549-54. doi: 10.1038/bjc.1989.311.
A human pancreatic adenocarcinoma was used to develop two histologically distinct xenograft lines, one associated with high levels (180-2000 ng ml-1) and one with low levels (greater than 2.0 less than 8.0 ng ml-1) of serum carcinoembryonic antigen (CEA). A strong correlation was found between tumour size and both circulating and tumour CEA levels in the former group, and also correlation at the 5% level between tumour size and serum CEA in the latter. Administration of either monoclonal or polyclonal 125I-anti-CEA antibody led to the formation of intravascular antigen-antibody immune complexes in mice with high CEA levels, and these were rapidly cleared by the liver, deiodination commencing within the first hour. Blood activity was reduced to 20% of the injected dose by 15 min, and by 24 h the radioactivity in all tissues except muscle was significantly below that found in either the low CEA group or in mice without tumours. No difference in radio-antibody clearance pattern was found between mice without tumours and the group with low levels of serum CEA. In spite of higher levels of CEA within the tumour in mice with elevated serum CEA, the rapid clearance of antigen-antibody complexes reduced tumour localisation to one quarter of that seen in mice with low serum, and correspondingly low tumour, CEA levels. Gamma-camera imaging confirmed these results. Possible implications to patient selection and treatment are discussed.
利用一株人胰腺腺癌建立了两个组织学特征不同的异种移植瘤系，其中一个系血清癌胚抗原（CEA）水平高（180 - 2000 ng/ml），另一个系血清CEA水平低（大于2.0小于8.0 ng/ml）。在前一组中，发现肿瘤大小与循环CEA水平及肿瘤CEA水平之间存在强相关性，在后一组中肿瘤大小与血清CEA之间也存在5%水平的相关性。给予单克隆或多克隆125I抗CEA抗体后，CEA水平高的小鼠体内形成血管内抗原 - 抗体免疫复合物，这些复合物被肝脏迅速清除，脱碘在第一小时内就开始。15分钟时血液活性降至注射剂量的20%，到24小时时，除肌肉外所有组织中的放射性均显著低于CEA水平低的组或无肿瘤小鼠。无肿瘤小鼠与血清CEA水平低的组之间在放射抗体清除模式上未发现差异。尽管血清CEA升高的小鼠肿瘤内CEA水平较高，但抗原 - 抗体复合物的快速清除使肿瘤定位降至血清CEA水平低且肿瘤CEA水平相应较低的小鼠的四分之一。γ相机成像证实了这些结果。文中讨论了对患者选择和治疗可能的影响。
