Palm Stig, Bäck Tom, Claesson Ingela, Danielsson Anna, Elgqvist Jörgen, Frost Sofia, Hultborn Ragnar, Jensen Holger, Lindegren Sture, Jacobsson Lars
Department of Radiation Physics, Sahlgrenska Academy at Göteborg University, Göteborg, Sweden.
Int J Radiat Oncol Biol Phys. 2007 Oct 1;69(2):572-9. doi: 10.1016/j.ijrobp.2007.06.023.
To investigate the potential use of astatine-211 (211At)-labeled trastuzumab for the treatment of HER-2-positive, radioresistant ovarian carcinoma.
Four-week-old nude mice were inoculated intraperitoneally with 5 . 10(6) SKOV-3 cells in 0.4 mL saline on Day 0. The endpoint was the total tumor weight in each mouse on Day 63. Three experiments were performed in which the response to single-dose and fractionated treatment with unlabeled and 211At-labeled antibody was evaluated.
Experiment 1 showed, for the same total amount of trastuzumab, a dose-response relationship between 211At activity (0-400 kBq on Day 7) and therapeutic efficacy (p = 0.001). The effect of varying the amount of unlabeled trastuzumab was studied in Experiment 2. All mice, except for the controls, received 400 kBq 211At-trastuzumab, and different groups received 5, 50, or 500 microg trastuzumab on Day 7. The increase from 5 to 50 microg trastuzumab reduced the tumors by 78% in weight. No tumors were present in mice given 500 microg trastuzumab. In Experiment 3, the effect of a fractionated treatment regimen was studied. Mice that received 100 kBq 211At-trastuzumab on Days 7 and 8 had a 42% smaller tumor burden than did controls. Groups of mice injected with 200 + 100 kBq on Days 7 and 21 and mice injected with 100 kBq on Days 7, 8, and 21 both had 24% less tumor weight than the corresponding controls.
The combination of 500 microg trastuzumab and 400 kBq 211At-trastuzumab had the greatest effect, with complete eradication of the tumors in this nude mouse model.
研究211砹（211At）标记的曲妥珠单抗在治疗HER-2阳性、放射抗拒性卵巢癌方面的潜在应用。
在第0天，将5×10⁶个SKOV-3细胞接种于4周龄裸鼠的腹腔内，接种体积为0.4 mL生理盐水。终点指标为第63天每只小鼠的肿瘤总重量。进行了三项实验，评估未标记和211At标记抗体的单剂量及分次治疗的反应。
实验1表明，对于相同总量的曲妥珠单抗，211At活性（第7天为0 - 400 kBq）与治疗效果之间存在剂量反应关系（p = 0.001）。实验2研究了改变未标记曲妥珠单抗量的影响。除对照组外，所有小鼠在第7天接受400 kBq 211At - 曲妥珠单抗，不同组在第7天分别接受5、50或500 μg曲妥珠单抗。曲妥珠单抗量从5 μg增加到50 μg使肿瘤重量减少了78%。给予500 μg曲妥珠单抗的小鼠无肿瘤。在实验3中，研究了分次治疗方案的效果。在第7天和第8天接受100 kBq 211At - 曲妥珠单抗的小鼠，其肿瘤负荷比对照组小42%。在第7天和第21天注射200 + 100 kBq的小鼠组以及在第7天、第8天和第21天注射100 kBq的小鼠组，其肿瘤重量均比相应对照组少24%。
在该裸鼠模型中，500 μg曲妥珠单抗与400 kBq 211At - 曲妥珠单抗联合使用效果最佳，可完全消除肿瘤。
