Therapeutic advantage of (90)yttrium- versus (131)iodine-labeled PAM4 antibody in experimental pancreatic cancer.
OBJECTIVE
Radioimmunotherapy studies using (131)I-PAM4 have demonstrated significant antitumor effects in mice bearing human pancreatic cancer xenografts. For several reasons (90)Y has been proposed as a more effective radionuclide for radioimmunotherapy of pancreatic cancer. The present study examined whether one radionuclide was more efficacious than the other in tumor-bearing mice.


METHODS
Athymic nude mice bearing CaPan1 xenograft tumors ( approximately 1.0 cm(3)) were given increasing doses of either (90)Y-PAM4 or (131)I-PAM4 up to their respective maximal tolerated doses [MTDs (260 and 700 microCi, respectively)].


RESULTS
(90)Y-PAM4 provided significantly greater growth inhibition than the (131)I-PAM4 (P < 0.035). Median survival time for the untreated mice was 6 weeks, whereas median survival times for the (131)I-treated mice and (90)Y-treated mice at their respective MTDs were 17.5 weeks and >26 weeks (the end of the study period), respectively. Within the (131)I-PAM4-treated group, two of eight mice were responders (>50% decrease in tumor size) for a median of 14 weeks. At the end of the study (26 weeks), 1 mouse was alive with no sign of tumor. All of the (90)Y-PAM4-treated mice were responders with a median duration of response of 20 weeks. Six of the seven mice were alive at week 26, with four mice having no evidence of disease.


CONCLUSIONS
These data demonstrate the advantage of (90)Y over (131)I as the radionuclide for PAM4-targeted radioimmunotherapy of xenografted pancreatic cancer. Furthermore, the duration and extent of the antitumor response suggests that multiple treatment cycles of (90)Y-PAM4 may provide an effective therapeutic for the control of pancreatic cancer.
Cardillo
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TM
The Garden State Cancer Center, 520 Belleville Avenue, Belleville, New Jersey 07109, USA. tmc_gscc@hotmail.com
Ying
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use; D051379:Mice; D008819:Mice, Nude; D009077:Mucins / Q000276:immunology; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000276:immunology / Q000401:mortality / Q000532:radiotherapy*; D016499:Radioimmunotherapy; D016019:Survival Analysis; D015996:Survival Rate; D013997:Time Factors; D014018:Tissue Distribution; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D015021:Yttrium Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes; D009077:Mucins; D015021:Yttrium Radioisotopes