213Bi (alpha-emitter)-antibody targeting of breast cancer metastases in the neu-N transgenic mouse model.
213Bi (alpha-emitter)-antibody targeting of breast cancer metastases in the neu-N transgenic mouse model.
复制标题
213Bi（α-发射体）抗体靶向 neu-N 转基因小鼠模型中的乳腺癌转移。
DOI：
10.1158/0008-5472.can-07-6308
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发表时间：
2008
期刊：
影响因子：
11.2
通讯作者：
Sgouros,George
中科院分区：
文献类型：
--
作者：
Song,Hong;Shahverdi,Karineh;Huso,DavidL;Esaias,Caroline;Fox,James;Liedy,Alyson;Liedy,Allison;Zhang,Zhe;Reilly,RTodd;Apostolidis,Christos;Morgenstern,Alfred;Sgouros,George
乳腺癌治疗失败主要是未能控制转移扩散。在这项研究中，我们研究了用 α 粒子发射器 213Bi 标记的针对 HER-2/neu 大鼠变体的抗体治疗转移性乳腺癌大鼠/中性转基因小鼠模型中广泛转移的功效。该模型显示肿瘤细胞广泛传播，导致溶骨性骨病变和肝转移，这是临床转移的常见部位。 213Bi-7.16.4 的最大耐受剂量为120 μCi。确定了骨髓抑制和随后恢复的动力学。左心室注射 105 只大鼠 HER-2/neu 表达同源肿瘤细胞三天后，用 (a) 120 μCi213Bi-7.16.4、(b) 90 μCi213Bi-7.16.4、(c) 120 μCi213Bi-Rituximab（无反应对照）和 (d) 未标记的治疗 neu-N 小鼠7.16.4。与未治疗对照组的 28 天相比，120 μCi213Bi-7.16.4 治疗将中位生存时间延长至 41 天（P < 0.0001）； b、c 和 d 组相应的中位生存时间分别为 36 天（P < 0.001）、31 天（P < 0.01）和 33 天（P = 0.05）。注射细胞数量减少 10 倍或接受多个疗程治疗的小鼠，相对于对照组，中位生存期并未显着改善。我们得出的结论是，针对 HER-2/neu 抗原的 α-emitter213Bi 标记单克隆抗体可有效治疗早期表达 HER-2/neu 的微转移。结果分析表明，进一步提高疗效可能需要更高比活性的构建体或在肿瘤细胞上更高表达的靶抗原。 [癌症研究 2008;68(10):3873–80]
Treatment failure in breast cancer is largely the failure to control metastatic dissemination. In this study, we investigated the efficacy of an antibody against the rat variant of HER-2/neu, labeled with the α-particle emitter213Bi to treat widespread metastases in a rat/neutransgenic mouse model of metastatic mammary carcinoma. The model manifests wide-spread dissemination of tumor cells leading to osteolytic bone lesions and liver metastases, common sites of clinical metastases. The maximum tolerated dose was 120 μCi of213Bi-7.16.4. The kinetics of marrow suppression and subsequent recovery were determined. Three days after left cardiac ventricular injection of 105rat HER-2/neu--expressing syngeneic tumor cells,neu-N mice were treated with (a) 120 μCi213Bi-7.16.4, (b) 90 μCi213Bi-7.16.4, (c) 120 μCi213Bi-Rituximab (unreactive control), and (d) unlabeled 7.16.4. Treatment with 120 μCi213Bi-7.16.4 increased median survival time to 41 days compared with 28 days for the untreated controls (P< 0.0001); corresponding median survival times for groups b, c, and d were 36 (P< 0.001), 31 (P< 0.01), and 33 (P= 0.05) days, respectively. Median survival relative to controls was not significantly improved in mice injected with 10-fold less cells or with multiple courses of treatment. We concluded that α-emitter213Bi-labeled monoclonal antibody targeting the HER-2/neuantigen was effective in treating early-stage HER-2/neu--expressing micrometastases. Analysis of the results suggests that further gains in efficacy may require higher specific activity constructs or target antigens that are more highly expressed on tumor cells. [Cancer Res 2008;68(10):3873–80]