Connett J M, Anderson C J, Guo L W, Schwarz S W, Zinn K R, Rogers B E, Siegel B A, Philpott G W, Welch M J
Department of Surgery, Washington University School of Medicine. St. Louis, MO 63110, USA.
Proc Natl Acad Sci U S A. 1996 Jun 25;93(13):6814-8. 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-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.
67铜（半衰期=62小时）已显示出作为放射性核素用于放射免疫治疗的潜力，但可获得性有限严重限制了其广泛应用。64铜（半衰期=12.8小时）已被证明在体外和体内具有相当的有效性。本研究旨在检测64铜和67铜标记的溴乙酰氨基苄基-1,4,8,11-四氮杂环十四烷-N,N',N",N"'-四乙酸（BAT）-2-亚氨基硫醇（2IT）-1A3（1A3是一种小鼠抗人结肠癌单克隆抗体）对仓鼠大腿携带的GW39人结肠癌的治疗潜力。给仓鼠注射64铜或67铜标记的BAT-2IT-1A3或铜标记的非特异性IgG（MOPC）或生理盐水。治疗后6至7个月或当肿瘤重量≥10克时处死仓鼠。对于小肿瘤（平均重量0.43±0.25克）的仓鼠，用2毫居里（1居里=37吉贝可）的64铜标记的BAT-2IT-1A3或0.4毫居里的67铜标记的BAT-2IT-1A3治疗后7个月，87.5%无疾病。64铜和67铜标记的BAT-2IT-1A3在这些活度下的平均肿瘤剂量分别为586和1269拉德（1拉德=0.01戈瑞）。相比之下，用2毫居里的64铜标记的BAT-2IT-MOPC或0.4毫居里的67铜标记的BAT-2IT-MOPC治疗的仓鼠中，76%由于肿瘤复发在6个月前不得不被处死。当用64铜或67铜标记的BAT-2IT-1A3治疗大肿瘤（平均重量0.66±0.11克）的仓鼠时，与对照组相比生存期延长，但只有一只动物在6个月时无肿瘤。这些结果表明，单次给药的64铜和67铜标记的BAT-2IT-1A3可根除小肿瘤而无明显的宿主毒性，但对于大肿瘤将需要额外的策略来给予更高的肿瘤剂量。
