Quantitative Considerations Supporting the Irrelevance of Circulating Serum Carcinoembryonic Antigen for the Immunoscintigraphic Visualization of Carcinoembryonic Antigen-Expressing Carcinomas

Abstract

Since the first description of the carcinoembryonic antigen (CEA) in 1965 [14, 15] up to today, when the primary structure of CEA has been deduced from the cDNA sequence [22], CEA has become important as a tumor marker for the control of colorectal carcinomas [9, 13], as well as for the immunoscintigraphic visualization of CEA-expressing carcinomas [19]. In particular, the relatively new method of immunoscintigraphy requires the binding of monoclonal antibodies (MAb) to epitopes on CEA that are not detectable on the various nonspecific cross-reacting antigens (NCA) expressed on normal tissues [16, 24]. A so-called anti-CEA antibody with strong cross-reactivity to human granulocytes and erythrocytes (NCA) was not able to localize human colorectal carcinomas in vivo, but induced fever, rigors, emesis, and a short-term granulocytopenia [8]. Even those MAbs that are selective for protein epitopes on CEA [3, 6] and not cross-reactive with epitopes on NCAs or Y- or X-type carbohydrate moieties on CEA [21] are primarily confronted with high amounts of circulating CEA after their i. v. injection into the patient. The following in vitro experiments were conducted to explain why successful immunoscintigraphic localization of colorectal carcinomas using MAb binding to CEA are possible with a sensitivity of up to 90%, as shown in a multicenter study (100 patients) in the Federal Republic of Germany using the MAb BW 431/31 coupled via diethylene triamine penta-acetic acid (DTPA) to ¹¹¹ In [5].