Steinsträsser A, Berberich R, Kuhlmann L, Zabori S, Schwarz A
Radiochemisches Laboratorium, Hoechst AG, Frankfurt/Main, FRG.
Nuklearmedizin. 1992 Mar;31(2):57-63.
Lately, the specific binding of appropriate monoclonal antibodies to human granulocytes has been used for the scintigraphic detection of inflammatory foci. Using the antibody BW 250/183 we studied the underlying binding kinetics. As an important requirement for a specific cell binding it has been shown that the labelling procedure does not change the immunoreactivity of the antibody. An affinity constant of 2 x 10(9) l/mol has been calculated from binding studies. Usually, 0.25-1.0 mg of the 99mTc-labelled antibody are applied per patient. In the present study an equilibrium in blood appeared quickly after intravenous application; at steady state about one fourth of the activity was cell-bound. The rest of the activity circulated in the plasma in the form of labelled IgG and was able to react directly with those granulocytes which were already accumulated in the inflamed area. Even a drastic reduction of the applied protein mass did not change this equilibrium. The law of mass action seems not to be directly applicable to this problem. Interferences with components of the plasma can be excluded as explanation for this behaviour. After application of in-vitro labelled granulocytes from which unbound antibodies were removed completely by washing, an identical steady state was observed within 10 min after injection; however, in this situation the intravasal residence time of activity increased distinctly.
最近,合适的单克隆抗体与人粒细胞的特异性结合已被用于炎症病灶的闪烁显像检测。我们使用抗体BW 250/183研究了其潜在的结合动力学。作为特异性细胞结合的一个重要要求,已表明标记过程不会改变抗体的免疫反应性。通过结合研究计算出亲和常数为2×10⁹ l/mol。通常,每位患者应用0.25 - 1.0 mg的⁹⁹ᵐTc标记抗体。在本研究中,静脉注射后血液中很快出现平衡;在稳态时,约四分之一的活性与细胞结合。其余活性以标记IgG的形式在血浆中循环,并能够直接与已聚集在炎症区域的粒细胞反应。即使应用蛋白量大幅减少也不会改变这种平衡。质量作用定律似乎不适用于此问题。可以排除血浆成分的干扰作为这种行为的解释。应用经体外标记且通过洗涤完全去除未结合抗体的粒细胞后,注射后10分钟内观察到相同的稳态;然而,在这种情况下,活性在血管内的停留时间明显增加。