Tumor targeting and pharmacokinetics of unmodified and modified F(ab)2 fragments of an anti-CEA murine monoclonal antibody (Immu-14).

Pharmacokinetic studies were performed with two different 111In-labeled F(ab)2 fragments of an anti-CEA murine monoclonal immunoglobulin G (Immun-14). Unmodified F(ab)2 and modified Fab-BMH-Fab fragments were compared in nude mice bearing a LS-174T human colon carcinoma tumor xenograft. Tumor accumulation is significantly higher for modified fragments than for unmodified fragments at all time points. At 24 h post injection, tumor uptake for modified and unmodified fragments reached 40 and 25% ID g, respectively. The retention of radioactivity in the liver was approx. 2-fold higher for modified fragments. Kidney uptake of modified fragments was at least 2-fold lower than that of unmodified fragments. Although blood radioactivity decreased rapidly for both fragments, the cumulative tumor activity was 40% higher for Fab-BMH-Fab fragment. Modified F(ab)2 fragments can deliver higher radiation doses to the tumor.