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

⁶⁷Cu (t_1/2 = 62 h) has demonstrated potential as a radionuclide for radioimmunotherapy, but limited availability severely restricts its widespread use. ⁶⁴Cu (t_1/2 = 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 ⁶⁴Cu- and ⁶⁷Cu-bromoacetamidobenzyl-1,4,8,11-tetraazacyclotetradecane-N, N′,N″,N‴-tetraacetic acid (BAT)-2-iminothiolane (2IT)-1A3 (1A3 is a mouse anti-human colorectal cancer mAb) for treatment of GW39 human colon carcinoma carried in hamster thighs. Hamsters were injected with ⁶⁴Cu- or ⁶⁷Cu-BAT-2IT-1A3 or Cu-labeled nonspecific IgG (MOPC) or saline. Hamsters were killed 6-7 months after therapy or when tumors were ≥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 ⁶⁴Cu-BAT-2IT-1A3 or 0.4 mCi of ⁶⁷Cu-BAT-2IT-1A3. The mean tumor doses at these activities of ⁶⁴Cu- and ⁶⁷Cu-BAT-2IT-1A3 were 586 and 1269 rad (1 rad = 0.01 Gy), respectively. In contrast, 76% of hamsters treated with 2 mCi of ⁶⁴Cu-BAT-2IT-MOPC or 0.4 mCi of ⁶⁷Cu-BAT-2IT-MOPC had to be killed before 6 months because of tumor regrowth. When hamsters with larger tumors (mean weight 0.66 ± 0.11 g) were treated with ⁶⁴Cu- or ⁶⁷Cu-BAT-2IT-1A3, survival was extended compared with controls, but only one animal remained tumor-free to 6 months. These results demonstrate that ⁶⁴Cu- and ⁶⁷Cu-BAT-2IT-1A3 given in a single administered dose can eradicate small tumors without significant host toxicity, but additional strategies to deliver higher tumor doses will be needed for larger tumors.