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 In-111-label ed F(ab)(2) fragments of an anti-CEA murine monoclonal immunoglobulin G (Immun-IL). Unmodified F(ab)(2) and modified Fab-BMH-Fab fragments w ere compared in nude mice bearing a LS-174T human colon carcinoma tumo r xenograft. Tumor accumulation is significantly higher for modified f ragments than for unmodified fragments at all time points. At 24 h pos t injection, tumor uptake for modified and unmodified fragments reache d 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 unmodifi ed fragments. Although blood radioactivity decreased rapidly for both fragments, the cumulative tumor activity was 40% higher for Fab-BMH-Fa b fragment. Modifred F(ab)(2) fragments can deliver higher radiation d oses to the tumor.