Radioimmunotherapy with a 64Cu-labeled monoclonal antibody: a comparison with 67Cu.
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-tetraazacyclotetradeca ne-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 > or = 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.
Connett
J M
JM
Department of Surgery, Washington University School of Medicine. St. Louis, MO 63110, USA.
Anderson
C J
CJ
Guo
L W
LW
Schwarz
S W
SW
Zinn
K R
KR
Rogers
B E
BE
Siegel
B A
BA
Philpott
G W
GW
Welch
M J
MJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000532:radiotherapy*; D003301:Copper Radioisotopes / Q000627:therapeutic use*; D006224:Cricetinae; D006801:Humans; D008297:Male; D008647:Mesocricetus; D009368:Neoplasm Transplantation; D016499:Radioimmunotherapy; D011879:Radiotherapy Dosage
D000911:Antibodies, Monoclonal; D003301:Copper Radioisotopes