TISSUE DISTRIBUTION OF MACROMOLECULAR CONJUGATE, ADRIAMYCIN LINKED TOOXIDIZED DEXTRAN, IN RAT AND MOUSE BEARING TUMOR-CELLS

Tissue distribution of the radioactivities after intravenous administr ation of [C-14]adriamycin ([C-14]ADM) or [C-14]ADM linked to oxidized dextran ([C-14]ADM-OXD) in mouse bearing Lewis lung carcinoma (LLC) an d rat bearing Walker 256 carcinosarcoma was studied. ADM conjugated wi th OXD increased plasma half-life and gave high area under the plasma concentration-time curve (AUC). The AUC values were 13.0 and 5.8 times higher than those of the [C-14]ADM group in mice and rats, respective ly. In the tumor tissues, AUC values of the [C-14]ADM-OXD group were a lso respectively 1.6 and 1.9 times higher than those of the [C-14]ADM group, However, the AUC values in the heart of the [C-14]ADM-OXD group were about half those of [C-14]ADM group in both animals. Thus the di stribution of ADM was changed by the conjugation with OXD. The excreti on profile of ADM was also changed by the conjugation. During 6 h afte r administration, [C-14]ADM-OSD was mainly excreted into rat urine at 45.2% of the original dose, but in the [C-14]ADM group recovery in uri nary excretion was 4.2%. Using [C-14]ADM-OXD and ADM-[C-14]OXD, the re spective tissue distribution of ADM and OXD portions in the ADM-OSD wa s studied in rats bearing Walker 256. The radioactivities of both [C-1 4]ADM-OXD and ADM-[C-14]OXD groups increased in tumor and liver within 1 h after administration. In the liver, both radioactivities were ret ained for 24 h, which suggested that ADM and OXD were retained as conj ugated form, however, different behavior was observed between the two groups in tumor tissues. Peak [C-14]ADM-OXD radioactivity was reached 6 h after administration and then decreased, while, ADM-[C-14]OXD was quickly cleared from the tumor after 1 h administration. The results s uggested that ADM was released from ADM-OXD and the remaining ADM-OXD, which was low in ADM content, was then cleared from the tumor tissues .