Quantitative considerations supporting the irrelevance of circulating serum CEA for the immunoscintigraphic...

Starting from the phenomenon that the amount of circulating CEA in patients' sera did not significantly influence immunoscintigraphic visualization of CEA expressing tumors, we built up an in vitro model to explain this phenomenon. Blocking experiments in this model system showed that the CEA specific MAbs BW 431/26 and BW 431/31 could not be inhibited in their binding to cell associated CEA, if they were preincubated with a 20 molar excess of serum CEA. In contrast, the CEA-NCA cross reactive MAbs could be inhibited in their binding to tumor associated CEA under identical conditions. These data combined with western blotting analysis of patients' sera and affinity constant determinations argue that conformational changes in serum CEA cause a decreased affinity of the CEA specific MAbs to serum CEA allowing a preferential binding to tumor associated CEA.