Radioimmunotherapy with a 64Cu-Labeled Monoclonal Antibody: A Comparison with 67Cu

• Published in: Proceedings of the National Academy of Sciences - PNAS 1996-06, Vol.93 (13), p.6814-6818
• Main Authors: Connett, Judith M., Anderson, Carolyn J., Guo, Li-Wu, Schwarz, Sally W., Zinn, Kurt R., Rogers, Buck E., Siegel, Barry A., Philpott, Gordon W., Welch, Michael J.
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Antibodies, Monoclonal - therapeutic use; Cancer; Colonic Neoplasms - radiotherapy; Colorectal cancer; Copper Radioisotopes - therapeutic use; Cricetinae; Disease remission; Dosage; Dose fractionation; Dosimetry; Health care; Humans; Male; Medical research; Medical treatment; Mesocricetus; Neoplasm Transplantation; Radioimmunotherapy; Radionuclides; Radiotherapy; Radiotherapy Dosage; Tumors
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.93.13.6814

67Cu (t1/2 = 62 h) has demonstrated potential as a radionuclide for radioimmunotherapy, but limited availability severely restricts its widespread use. 64Cu (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 64Cu- and 67Cu-bromoacetamidobenzyl-1,4,8,11-tetraazacyclotetrade cane-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.