Wilder R B, Langmuir V K, Mendonca H L, Goris M L, Knox S J
Department of Radiation Oncology, Stanford University, California 94305.
Cancer Res. 1993 Jul 1;53(13):3022-7.
Local hyperthermia and the hypoxic cytotoxin SR 4233 were administered to nude mice with 693 +/- 47 mm3 (mean +/- SE) s.c. HCT-8 human colonic adenocarcinoma xenografts in an attempt to enhance the antitumor effects of radioimmunotherapy. Biodistribution studies revealed preferential binding of NR-Lu-10, a murine monoclonal antibody, to the tumors compared with an isotype-matched control antibody, CCOO16-3.A single injection of 25 microCi 90Y-NR-Lu-10 significantly inhibited tumor growth (control versus 90Y-NR-Lu-10: P = 0.048). The administration of hyperthermia at 41.5 degrees C for 1 h immediately following the injection of 111In-labeled NR-Lu-10 up-regulated tumor-associated antigen expression and increased antibody uptake in the tumors by 73% (P = 0.001) without significantly affecting antibody uptake in normal tissues. However, the heat treatment did not produce a more homogeneous distribution of the antibodies in the tumors and did not significantly enhance the tumor growth delay produced by 90Y-NR-Lu-10 (P = 0.07). The administration of local hyperthermia at 43.0 degrees C for 1 h, on the other hand, had direct cytotoxic effects (P = 0.03) and enhanced the tumor growth delay produced by 90Y-NR-Lu-10 (P = 0.01). SR 4233 also enhanced the tumor growth delay produced by 90Y-NR-Lu-10 (P = 0.03). The greatest antitumor effects were observed when both hyperthermia at 43.0 degrees C and SR 4233 were administered in combination with 90Y-NR-Lu-10 (P = 0.002). No toxicity was produced by the local hyperthermia, and the only toxicities produced by 90Y-NR-Lu-10 and SR 4233 were neutropenia and weight loss.
对皮下接种有体积为693±47立方毫米（平均值±标准误）的HCT - 8人结肠腺癌异种移植物的裸鼠进行局部热疗，并给予低氧细胞毒素SR 4233，旨在增强放射免疫疗法的抗肿瘤效果。生物分布研究显示，与同型对照抗体CCOO16 - 3相比，鼠单克隆抗体NR - Lu - 10在肿瘤中有优先结合。单次注射25微居里的90Y - NR - Lu - 10可显著抑制肿瘤生长（对照组与90Y - NR - Lu - 10组比较：P = 0.048）。在注射111In标记的NR - Lu - 10后立即进行41.5℃、持续1小时的热疗，上调了肿瘤相关抗原的表达，使肿瘤中抗体摄取增加了73%（P = 0.001），且对正常组织中抗体摄取无显著影响。然而，热处理并未使抗体在肿瘤中的分布更均匀，也未显著增强90Y - NR - Lu - 10所产生的肿瘤生长延迟（P = 0.07）。另一方面，43.0℃、持续1小时的局部热疗具有直接细胞毒性作用（P = 0.03），并增强了90Y - NR - Lu - 10所产生的肿瘤生长延迟（P = 0.01）。SR 4233也增强了90Y - NR - Lu - 10所产生的肿瘤生长延迟（P = 0.03）。当43.0℃热疗和SR 4233都与90Y - NR - Lu - 10联合应用时，观察到最大的抗肿瘤效果（P = 0.002）。局部热疗未产生毒性，90Y - NR - Lu - 10和SR 4233仅产生中性粒细胞减少和体重减轻的毒性。
