[Biodistribution of monoclonal antibody and Fab fragment and antitumor effect of their conjugates on hepatoma xenografts].

McAb 3A5, a rat monoclonal antibody directed against human hepatoma cells, and its Fab fragment were compared on their biodistribution and the therapeutic effects of their conjugates linked to C1027, a highly potent antitumor antibiotic, on the growth of human hepatoma xenografts in nude mice. Biodistribution study with 125I-labeled McAb 3A5 and its Fab fragment in hepatoma-bearing nude mice revealed that ID%/g values of McAb 3A5 were higher than those of the Fab fragment in tumor, liver, spleen and kidney; however, the T/NT ratios of Fab were higher than those of McAb 3A5. Imaging study with 131I-3A5 and 131I Fab showed that clear images of the tumor emerged 12h after injection of Fab and 40 h after that of McAb 3A5. IC50 values for McAb-C1027 and Fab-C1027 were 4.2 x 10(-14) mol/L, 8.6 x 10(-16) mol/L, respectively. Fab-C1027 conjugate was 49-fold more potent than McAb-C1027. Therapeutic effect of the conjugates was evaluated with hepatoma xenograft in nude mice. When treatment started 3 days after sc transplantation of the tumor with equivalent dose of C1027, 0.15 mg/kg, i.v., x3, tumor inhibition rates for McAb-C1027 and Fab-C1027 conjugates were 68% and 66%, respectively. When the treatment started on day 10 after transplantation with 0.10 mg/kg, i.v., x6, tumor inhibition rates for McAb-C1027 and Fab-C1027 conjugates were 24% and 54%, respectively. The results showed that compared with the intact McAb, Fab fragment displays higher specificity in biodistribution and exerts stronger inhibitory effect on the growth of established tumor xenografts.