Intraportal injection of monoclonal antibody in nude mice bearing hepatic metastases

Abstract

Using a model for hepatic human colorectal carcinoma metastases in athymic mice, we compared the selective [intraportal (ip)] and systemic [intravenous (iv)] injection of radiolabeled monoclonal antibody (mAb) strongly reactive against the cell line. Percent injected dose of radiolabeled antibody per gram (%id/g) of tumor or normal tissues was measured at selected time points (up to 5 days postinjection) within 3 dose levels: 0.1, 1.0, and 2.0 micrograms (micrograms). At each dose level, 3-9 animals were studied in each of 3 groups: animals receiving ip injection (group HT-29-15 ip), those receiving intravenous injection (group HT-29-15 iv), and those receiving isotype-matched control antibody via the intraportal route (group BL-3 ip). Significantly greater (P < 0.005) %id/g in tumor was seen in group HT-29-15 ip at all time points and dose levels compared to those in groups HT-29-15 iv or BL-3 ip. However, immediately after injection of mAb, there was no difference in tumor %id/g between groups HT-29-15 ip and HT-29-15 iv at the highest dose level. There was no increase in %id/g of mAb in normal liver and blood after ip injection compared to iv injection beyond day 1. Therefore ip injection resulted in higher tumor to liver and tumor to blood ratios compared to iv (P < 0.005). We conclude that delivery of mAb to hepatic metastases can be enhanced by selective injection; this has important implications in the design of future clinical trials utilizing radiolabeled mAb in the diagnosis and treatment of hepatic metastases.