Toxicity and efficacy of radioimmunotherapy in carcinoembryonic antigen-producing medullary thyroid cancer xenograft: Comparison of iodine 131-labeled F(ab ')(2) and pretargeted bivalent hapten and evaluation of repeated injections

This study compared the toxicity and efficacy of I-131-labeled bivalent hap ten pretargeted by anti-carcinoembryonic antigen (CEA)/anti-N alpha-(diethy lenetriamine-N,N,N',N"- tetraacetic acid-indium(F6-734) bispecific antibody [affinity enhancement system (AES) reagents] with I-131-labeled anti-CEA F (ab')(2) (I-131-F6) in mice grafted with a human medullary thyroid carcinom a. Repeated injections of AES reagents were also evaluated. Mice bearing TT tumor xenografts were treated with 37, 74, or 92.5 MBq of A ES reagents, two injections of 74 MBq of AES reagents 45 days apart, or 37 or 92.5 MBq of I-131-F6. Control groups were treated with nonspecific I-131 -labeled F(ab')(2), nonspecific AES reagents, nonradiolabeled F6, F6-734 bi specific antibody, and nonradiolabeled bivalent hapten or received no injec tion. For AES treatments, bispecific antibody was injected 48 h before the hapten, Animal weight, hematological toxicity, tumor volume, and serum thyr ocalcitonin were monitored during 5 months. At 92.5 MBq, weight loss was significantly lower after AES than F6 treatmen t (P = 0.004). The percentages of leukocyte count changes were significantl y lower after AES than F6 at 37 and 92.5 MBq (P = 0.01 and 0.04, respective ly). The percentage of platelet count changes was significantly lower with AES at the 92.5-MBq dose level (P = 0.04). In the group injected twice with AES reagents, toxicity was not significantly increased after the second tr eatment. Tumor response was observed in all cases but was significantly lon ger with repeated treatments of 74 MBq AES reagents than with a single trea tment (P = 0.004). Two complete responses were observed with repeated treat ments. Changes in thyrocacitonin level paralleled those in tumor volume. These results indicate that pretargeted radioimmunotherapy was at least as efficient as one-step radioimmunotherapy and markedly less toxic. Repeated treatments with AES reagents increased efficacy without increasing toxicity .