EFFICACY AND TOXICITY OF CU-67-2IT-BAT-LYM-1 RADIOIMMUNOCONJUGATE IN MICE IMPLANTED WITH HUMAN BURKITTS-LYMPHOMA (RAJI)

Radioimmunotherapy has shown promising results for treatment of radios ensitive malignancies such as lymphoma. Positive responses have been r eported in patients with non-Hodgkin's lymphoma treated with I-131-rad iolabeled Lym-1, a mouse anti-lymphoma monoclonal antibody, In this st udy, the efficacy of Cu-67-radiolabeled Lym-1 was examined, Nude mice bearing human Burkitt's lymphoma (Raji) tumors (20-524 mm(3)) were tre ated with 12.4, 14.8, 18.5, and 23.3 MBq of Cu-67-2IT-BAT-Lym-1. Tumor size was measured to assess efficacy, and mouse weight, blood counts, and mortality were monitored to assess toxicity, In mice treated with 12,4, 14.8, and 18.5 MBq of Cu-67-2IT-BAT-Lym-1, 50% (9 of 18), 42% ( 5 of 12), and 50% (3 of 6) of tumors achieved remission or cure; 33% o f tumors were cured overall; and significant regrowth delay was observ ed, The 23.3 MBq dose group did not yield meaningful efficacy data bec ause of high mortality, In control groups receiving 14.8 and 18.5 MBq of the isotype-matched nonspecific monoclonal antibody radioimmunoconj ugate, Cu-67-2IT-BAT-L6, 0% (0 of 15) and 17% (2 of 12) of tumors achi eved a response; hence, targeted delivery of radiation was the dominan t antitumor mechanism of Cu-67-2IT-BAT-Lym-1. LD50/30 for mice treated with Cu-67-2IT-BAT-Lym-1 and -L6 were 21.6 and 20.6 MBq, respectively , In conclusion, Cu-67-2IT-BAT-Lym-1 provided a therapeutic and freque ntly curative dose of radiation to tumored mice with modest toxicity.