Radioimmunotherapy with a Cu-64-labeled monoclonal antibody: A comparison with Cu-67

Cu-67 t(1/2) = 62 h) has demonstrated potential as a radionuclide for radioimmunotherapy, but limited availability severely restricts its widespread use. Cu-64 (t1/2 = 12.8 h) has been shown to have comparable effectiveness in vitro and in vivo, The present study was undertaken to examine the therapeutic potential of Cu-64- and Cu-67-bromoacetamidobenzyl-1,4,8,11-tetraazacyclotetradecane-N,N',N '',N'''-tetraacetic acid (BAT)-2-iminathiolane (2IT)-1A3 (1A3 is a mouse anti-human colorectal cancel mAb) for treatment of GW39 human colon carcinoma carried in hamster thighs, Hamsters were injected with Cu-64- or Cu-67-BAT-2IT-1A3 or Cu-labeled nonspecific Ige (MOPC) or saline. Hamsters were killed 6-7 months after therapy or when tumors were greater than or equal to 10 g, Of the hamsters with small tumors (mean weight 0.43 +/- 0.25 g), 87.5% were disease-free 7 months after treatment with 2 mCi (1 Ci = 37 GBq) of Cu-64-BAT-2IT-1A3 or 0.4 mCi of Cu-67-BAT-2IT-1A3. The mean tumor doses at these activities of Cu-64- and Cu-67-BAT-2IT-1A3 were 586 and 1269 rad (1 rad = 0.01 GS), respectively, In contrast, 76% of hamsters treated with 2 mCi of Cu-64-BAT-2IT-MOPC or 0.4 mCi of Cu-67-BAT-2IT-MOPC had to he killed before 6 months because of tumor regrowth. When hamsters with larger tumors (mean weight 0.66 +/- 0.11 g) were treated with Cu-64- or Cu-67-BAT-2IT-1A3, survival was extended compared with controls, but only one animal remained tumor-free to 6 months. These results demonstrate that Cu-64- and Cu-67-BAT-2IT-1A3 given in a single administered dose ran eradicate small tumors without significant host toxicity, but additional strategies to deliver higher tumor doses will be needed for larger tumors.