INTRAPORTAL INJECTION OF MONOCLONAL-ANTIBODY IN NUDE-MICE BEARING HEPATIC METASTASES

Using a model for hepatic human colorectal carcinoma metastases in ath ymic 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 radi olabeled antibody per gram (%id/g) of tumor or normal tissues was meas ured at selected time points (up to 5 days postinjection) within 3 dos e levels: 0. 1, 1.0, and 2.0 micrograms (mug). At each dose level, 3-9 animals were studied in each of 3 groups: animals receiving ip inject ion (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 < 0.0 05) %id/g in tumor was seen in group HT-29-15 ip at all time points an d dose levels compared to those in groups HT-29-15 iv or BL-3 ip. Howe ver, immediately after injection of mAb, there was no difference in tu mor %id/g between groups HT-29-15 ip and HT-29-15 iv at the highest do se level. There was no increase in %id/g of mAb in normal liver and bl ood after ip injection compared to iv injection beyond day 1. Therefor e ip injection resulted in higher tumor to liver and tumor to blood ra tios compared to iv (P < 0.005). We conclude that delivery of mAb to h epatic metastases can be enhanced by selective injection; this has imp ortant implications in the design of future clinical trials utilizing radiolabeled mAb in the diagnosis and treatment of hepatic metastases. (C) 1993 Wiley-Liss, Inc.