Localization of pancreatic cancer with radiolabeled monoclonal antibody PAM4.

Experimental animal studies were performed with (111)In-labeled PAM4 anti-MUC1 antibody along with (111)In-labeled control antibody. Tumor uptake of radiolabeled PAM4 was significantly higher than for the control antibody at all time points. When normalized to a blood dose of 1500 cGy as an estimate of myelotoxicity, (90)Y-labeled PAM4 would provide 5344 cGy to the tumor, whereas an equitoxic dose of (90)Y-labeled control antibody would provide only 862 cGy to the tumor. In addition to the animal studies, five patients with proven pancreatic cancer were administered either (131)I-PAM4 IgG (n=2) or 99mTc-PAM4 Fab' (n=3). Tumor targeting was observed in four out of five patients. By immunohistochemistry, PAM4 was non-reactive with tumor from the one patient not targeted. Dosimetry from the patients given (131)I-PAM4 predicted that tumors would receive 10-20 cGy/mCi with tumor/red marrow dose ratios ranging from 3 to 10. Based upon these results, we have established a phase-I (111)In-labeled PAM4 imaging and (90)Y-labeled PAM4 therapy trial.