Slinkin M A, Curtet C, Faivre-Chauvet A, Sai-Maurel C, Gestin J F, Torchilin V P, Chatal J F
Laboratoire Biophysique-Cancerologie, INSERM U.211, Plateau Technique CHR, Nantes, France.
Nucl Med Biol. 1993 May;20(4):443-52. doi: 10.1016/0969-8051(93)90075-6.
F(ab')2 fragments of anti-carcinoembryonic antigen (CEA) monoclonal antibody (mAb) were modified with three chain-terminal polylysine-based chelating polymers so as to carry different electron charges. Immunoreactive conjugates labeled with 111In up to a specific radioactivity of 120-140 microCi/micrograms were injected into nude mice bearing human colorectal carcinoma, and the biodistribution patterns were compared with each other and with that of an anti-CEA F(ab')2-DTPA control. Immunoconjugate modified with positively-charged polymer produced the highest tumor uptake [up to 20% injected dose per gram (ID/g)], with very significant non-specific radioactivity in normal organs (particularly kidneys). When modified with a polymer carrying only a slight negative charge, the immunoconjugate also produced fairly high tumor uptake (up to 18% ID/g), with much lower non-specific radioactivity in normal organs. Highly negatively-charged conjugate produced the lowest tumor uptake (up to 8% ID/g), whereas blood and whole-body clearances were the fastest but slower than those of conventionally labeled F(ab')2 mAb. The possible mechanisms for the effects described are discussed.
用三种基于链端聚赖氨酸的螯合聚合物对抗癌胚抗原（CEA）单克隆抗体（mAb）的F(ab')2片段进行修饰，使其带有不同的电荷。将放射性比活度高达120 - 140微居里/微克的111In标记的免疫反应性缀合物注射到荷人结肠癌的裸鼠体内，并将其生物分布模式相互比较，同时与抗CEA F(ab')2 - DTPA对照的生物分布模式进行比较。用带正电荷聚合物修饰的免疫缀合物产生了最高的肿瘤摄取量[高达每克注射剂量的20%（ID/g）]，在正常器官（特别是肾脏）中有非常显著的非特异性放射性。当用仅带有轻微负电荷的聚合物修饰时，免疫缀合物也产生了相当高的肿瘤摄取量（高达18% ID/g），在正常器官中的非特异性放射性要低得多。带高度负电荷的缀合物产生的肿瘤摄取量最低（高达8% ID/g），而血液和全身清除速度最快，但比传统标记的F(ab')2 mAb慢。文中讨论了所描述效应的可能机制。
