The aim of this work is to compare the toxicity and efficacy of three-step pretargeting radioimmunotherapy involving administration of a biotinylated anti-carcinoembryonic antigen (CEA) antibody

followed by avidin followed finally by 153 Sm labelled biotin with 153 Sm directly labelled anti-CEA monoclonal antibody(McAb). CEA McAb and DTPA-biocytin (DB 2) was labelled with 153 Sm using the bifunctional chelate cyclic diethylenetriaminepentaacetic acid (DTPA) anhydride. Five groups of nude mice subcutaneously grafted with human colon carcinoma were treated 3 days after the graft. One group received the injection of 100μg McAb-Bt followed 2 days later by cold Av (80μg)and 11.1MBq 153 Sm-DB 2 after a further day. Four control groups were treated respectively with (1) 11.1MBq 153 Sm-CEA McAb

(2) 11.1MBq 153 Sm-mIgG

(3) 11.1MBq 153 Sm-DB 2

(4) 100μL physiological sodium chloride solution. Toxicity was evaluated by change of body weight and number of leukocytes

and efficacy was evaluated by variation in tumor volume. Histological analysis of tumors were performed. The results showed that pretargeting RIT and 153 Sm-CEA McAb had a strong tumor inhibition effect. The inhibitory rates of tumor were 80.67% and 78.44% respectively

five weeks after therapy. Histopathological evidence indicated that in tumor tissues radioactive damage was seen as necrosis of tumor cells

while in the other tissues such as liver and kindey tissues no radioactive damage was observed. Leukocyte counts were singnificantly decreased after treatment in groups of 153 Sm-CEA McAb and 153 Sm-mIgG

which indicated that the haemopoitic function of bone marrow may be affected. It was concluded that three-step pretargeting radioimmunotherapy was as efficient as 153 Sm-CEA McAb but was markedly less toxic.