Comparative targeting of human colon‐carcinoma multicell spheroids using one‐ and two‐step (bispecific antibody) techniques

In the perspective of radioimmunotherapy (RIT) of micrometastases, we compared, in multicell spheroids (MS), the uptake and retention kinetics of 125I‐F(ab)′2 F6 anti‐carcinoembryonic antigen (CEA) monoclonal antibody (MAb), and the affinity enhancement system (AES) using an anti‐CEA/anti‐DTPA‐indium bispecific antibody (BsMAb) and a 125I‐labeled di‐DTPA‐In‐tyrosine‐lysine bivalent hapten. We used MS of colorectal‐tumor cell lines expressing CEA strongly (LS 174T), weakly (HT‐29) or not at all (HRT‐18). Uptake and retention kinetics of 125I‐F(ab)′2 F6 and 125I‐BsMAb used alone gave similar results. The highest uptake values, obtained with LS 174T MS, were slightly lower with AES than with 125I‐F(ab)′2 F6. However, effective retention half‐lives were longer for AES than for 125I‐F(ab)′2 F6 or for 111In‐labeled monovalent hapten after pre‐incubation of spheroids with BsMAb. Autoradiography showed the same slow and heterogeneous distribution of 125I‐F(ab)′2 F6 and 125I‐BsMAb. These results indicate that the 2‐step technique is more favorable for RIT: uptake values were approximately the same but uptake kinetics were more rapid, and retention half‐life was longer than with the one‐step technique. © 1996 Wiley‐Liss, Inc.