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Therapeutic Advantage of ⁹⁰Yttrium- versus ¹³¹Iodine-labeled PAM4 Antibody in Experimental Pancreatic Cancer¹

The Garden State Cancer Center [T. M. C., D. V. G.], Belleville, New Jersey 07109, and Department of Statistics, Columbia University [Z. Y.] New York, New York 08854

Objectives: Radioimmunotherapy studies using ¹³¹I-PAM4 have demonstrated significant antitumor effects in mice bearing human pancreatic cancer xenografts. For several reasons ⁹⁰Y 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 (1.0 cm³) were given increasing doses of either ⁹⁰Y-PAM4 or ¹³¹I-PAM4 up to their respective maximal tolerated doses [MTDs (260 and 700 µCi, respectively)].

Results: ⁹⁰Y-PAM4 provided significantly greater growth inhibition than the ¹³¹I-PAM4 (P < 0.035). Median survival time for the untreated mice was 6 weeks, whereas median survival times for the ¹³¹I-treated mice and ⁹⁰Y-treated mice at their respective MTDs were 17.5 weeks and >26 weeks (the end of the study period), respectively. Within the ¹³¹I-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 ⁹⁰Y-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 ⁹⁰Y over ¹³¹I 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 ⁹⁰Y-PAM4 may provide an effective therapeutic for the control of pancreatic cancer.

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