Beatty J D, Beatty B G, O'Conner-Tressel M, Do T, Paxton R J
Department of General Oncologic Surgery, City of Hope National Medical Center, Duarte, California 91010.
Cancer Res. 1990 Feb 1;50(3 Suppl):840s-845s.
Scintigraphic studies in animals and in humans have demonstrated uptake of radiolabeled antibody by both normal and tumor tissue. Normal tissues most commonly visualized are blood, liver, spleen, kidneys, lymph nodes, bone, and thyroid. A number of factors have been demonstrated to affect the uptake by normal and tumor tissue, including radioisotope properties, immunoglobulin characteristics, antibody specificity, tumor size, vascular permeability, and antigen expression. Clarification of the mechanisms of tumor and normal tissue uptake depends upon comparison of scintigraphic findings with analysis of tissue for such factors as radioactivity, antigen content, and tumor size. One of the major limitations of 111In labeled monoclonal antibody imaging has been extensive 111In uptake by histologically normal liver, especially in a host bearing a large tumor mass. By high performance liquid chromatography and sodium dodecyl sulfate-polyacrylamide-gel electrophoresis analysis of liver and blood it can be demonstrated that much of the liver uptake is related to the formation of antigen:antibody complexes. The normal liver intensity can be decreased by inhibition of radiolabeled complex formation. Understanding of the mechanisms of tissue uptake, both normal and tumor, and of radiolabeled antibody metabolism is crucial to the rational planning and use of radioimmunoconjugates for tumor imaging and treatment. Animal and human studies complement one another in examination of these mechanisms.
针对动物和人类的闪烁扫描研究表明，正常组织和肿瘤组织均可摄取放射性标记抗体。最常显影的正常组织是血液、肝脏、脾脏、肾脏、淋巴结、骨骼和甲状腺。已证实一些因素会影响正常组织和肿瘤组织对放射性标记抗体的摄取，这些因素包括放射性同位素特性、免疫球蛋白特征、抗体特异性、肿瘤大小、血管通透性和抗原表达。要阐明肿瘤组织和正常组织摄取的机制，需将闪烁扫描结果与针对放射性、抗原含量和肿瘤大小等因素的组织分析结果进行比较。¹¹¹铟标记的单克隆抗体成像的主要局限性之一是，组织学上正常的肝脏会大量摄取¹¹¹铟，尤其是在患有大肿瘤块的宿主体内。通过对肝脏和血液进行高效液相色谱分析以及十二烷基硫酸钠 - 聚丙烯酰胺凝胶电泳分析，可以证明肝脏的大量摄取与抗原：抗体复合物的形成有关。通过抑制放射性标记复合物的形成，可以降低正常肝脏的显影强度。了解正常组织和肿瘤组织摄取的机制以及放射性标记抗体的代谢，对于合理规划和使用放射免疫缀合物进行肿瘤成像和治疗至关重要。动物研究和人体研究在考察这些机制方面相辅相成。
