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.
Gold
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The Garden State Cancer Center, 520 Belleville Avenue, Belleville, NJ 07109, USA. dvgold@att.net
Cardillo
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T
Goldenberg
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Sharkey
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RM
D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000912:Antibodies, Neoplasm / Q000627:therapeutic use*; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000276:immunology; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D018396:Mucin-1 / Q000276:immunology; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging* / Q000532:radiotherapy*; D010599:Pharmacokinetics; D016719:Radioimmunodetection / Q000379:methods; D016499:Radioimmunotherapy / Q000379:methods; D014055:Tomography, Emission-Computed
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D015295:Antigens, Tumor-Associated, Carbohydrate; D018396:Mucin-1