Therapeutic advantage of (90)yttrium- versus (131)iodine-labeled PAM4 antibody in experimental pancreatic cancer.

OBJECTIVES: 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.