Experimental radioimmunotherapy of small peritoneal metastases of colorectal origin

Abstract

Radioimmunotherapy using radiolabeled monoclonal antibodies (MoAbs) directed against tumor-associated antigens might be an effective treatment modality for small volume disease. Our aim was to optimize an experimental model of radioimmunotherapy for small peritoneal metastases of colorectal origin using the anti-CEA MoAb MN-14. In nude mice with intraperitoneal (i.p.) LS174T tumors, a protein dose-escalation study was carried out to determine the maximal dose of radioiodinated MN-14 to be used in radioimmunotherapy. The biodistribution of radioiodinated MN-14 was determined after intravenous (i.v.) and i.p. administration. Finally, the therapeutic efficacy of escalating activity doses of ¹³¹I-labeled MN-14 (62.5–500 μCi) was assessed and compared to that of unlabeled MN-14 or 500 μCi of ¹³¹I-labeled irrelevant control antibody. At protein doses higher than 25 μg, uptake in tumor was reduced, presumably due to saturation of tumor antigen. During the first 24 hours i.p. administration led to higher tumor uptake and higher tumor:blood ratios than i.v. administration. Median survival of the control groups was 38 days (unlabeled MN-14) and 52 days (¹³¹I-labeled nonspecific antibody). Median survival of the groups treated with increasing activity doses of ¹³¹I-labeled MN-14 was 42 days (62.5 μCi), 49 days (125 μCi), 63 days (250 μCi) and 101 days (500 μCi), respectively (p < 0.0001 compared to unlabeled MN-14). The present study shows that the anti-CEA-antibody MN-14 preferentially accumulates in i.p. LS174T tumor xenografts after both i.p. and i.v. administration. Intraperitoneal radioimmunotherapy using ¹³¹I-labeled MN-14 delays significantly the outgrowth of peritoneal LS174T metastases, even at relatively low activity doses.