Radiolocalization of Human Pancreatic Tumors in Athymic Mice by Monoclonal Antibody DU-PAN 1

Abstract

Monoclonal antibodies that selectively bind to pancreatic tumors may be useful in the therapy and diagnosis of pancreatic carcinoma. In this study we have examined the tumor localization of radioiodinated DU-PAN 1, a mouse monoclonal antibody that is selective for a human pancreatic cancer-associated antigen. After radiolabeling, both DU-PAN 1 intact monoclonal antibody and F(ab′)₂ fragments retained immuno-reactivity and showed high affinity for the pancreatic tumor cell line CA13 in vitro. Paired-label biodistribution studies in nude mice bearing CA13 s.c. xenografts were performed. Mice received both ¹³¹I-labeled DU-PAN 1 immunoglobulin G2a or F(ab′)₂ fragment and ¹²⁵I-labeled mouse myeloma immunoglobulin G2a or F(ab′)₂ fragment. Tumor uptake for 5-µg doses of DU-PAN 1 immunoglobulin ranged from 4.8 to 11.83% injected dose/g. Tumor uptake values for mice given 5-µg doses of DU-PAN 1 F(ab′)₂ ranged from 3.9 to 6.9% injected dose/g. Tumor uptakes of the respective myeloma controls were lower in all cases when compared with the DU-PAN 1 preparations. Tumor localization indices for 5-µg doses of DU-PAN 1 immunoglobulin were 3.0 at 24 h and 2.9 at 48 h. For 5-µg doses of DU-PAN 1 F(ab′)₂, tumor localization indices were 29.9 at 24 h and 90.0 at 48 h. In most cases, tumor:normal tissue ratios were greater than 3 at all time points, indicative of tumor selectivity for both DU-PAN 1 preparations, but the ratios were considerably higher using the DU-PAN 1 F(ab′)₂. The F(ab′)₂ fragment thus displays better tumor localization characteristics when compared with the intact immunoglobulin. Protein doses of DU-PAN 1 F(ab′)₂ of between 5 and 10 µg gave the best localization, although protein doses of up to 100 µg could be administered before apparent tumor saturation was seen.