COMPARATIVE TARGETING OF HUMAN COLON-CARCINOMA MULTICELL SPHEROIDS USING ONE-STEP AND 2-STEP (BISPECIFIC ANTIBODY) TECHNIQUES

In the perspective of radioimmunotherapy (RIT) of micrometastases, we compared, in multicell spheroids (MS), the uptake and retention kineti cs of I-125-F(ab)(2)(') F6 anti-carcinoembryonic antigen (CEA) monoclo nal antibody (MAb), and the affinity enhancement system (AES) using an anti-CEA/anti-DTPA-indium bispecific antibody (BsMAb) and a I-125-lab eled di-DTPA-In-tyrosine-lysine bivalent hapten. We used MS of colorec tal-tumor cell lines expressing CEA strongly (LS 174T), weakly (HT-29) or not at all (HRT-18). Uptake and retention kinetics of I-125-F(ab)( 2)(') F6 and I-125-BsMAb used alone gave similar results. The highest uptake values, obtained with LS 174T MS, were slightly lower with AES than with I-125-F(ab)(2)(') F6. However, effective retention half-live s were longer for AES than for I-125-F(ab)(2)(') F6 or for In-111-labe led monovalent hapten after pre-incubation of spheroids with BsMAb. Au toradiography showed the same slow and heterogeneous distribution of I -125-F(ab)(2)(') F6 and I-125-BsMAb. These results indicate that the 2 -step technique is more favorable for RIT: uptake values were approxim ately the same but uptake kinetics were more rapid, and retention half -life was longer than with the one-step technique.