Monitoring therapeutic response of human ovarian cancer to 17-DMAG by noninvasive PET imaging with (64)Cu-DOTA-trastuzumab.
Monitoring therapeutic response of human ovarian cancer to 17-DMAG by noninvasive PET imaging with (64)Cu-DOTA-trastuzumab.
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DOI：
10.1007/s00259-009-1158-1
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发表时间：
2009-09
影响因子：
9.1
通讯作者：
Chen, Xiaoyuan
中科院分区：
文献类型：
--
作者：
Niu, Gang;Li, Zibo;Cao, Qizhen;Chen, Xiaoyuan
关键词：
17-DMAG是一种热休克蛋白90（Hsp 90）抑制剂，已被广泛研究用于癌症治疗，并正在进行临床试验。人表皮生长因子受体2（HER-2）是Hsp 90的客户蛋白之一，并且其表达在17-DMAG处理后降低。在这项研究中，我们的目的是非侵入性监测HER-2对异种移植小鼠17-DMAG治疗的反应。MTT法检测人卵巢癌SKOV-3细胞对17-DMAG的体外敏感性。流式细胞术检测SKOV-3细胞HER-2表达。用17-DMAG治疗荷SKOV-3肿瘤的裸鼠，并通过测量肿瘤大小来评估治疗效果。使用64 Cu-DOTA-曲妥珠单抗和18F-FDG用microPET对治疗小鼠和对照小鼠进行成像。进行生物分布研究、免疫荧光染色以验证microPET结果。SKOV-3细胞对17-DMAG处理敏感，呈剂量依赖性，孵育72小时后的IC 50值为68.7 nM。肿瘤生长曲线支持17-DMAG对SKOV-3肿瘤的抑制作用。定量microPET成像显示64 Cu-DOTA-曲妥珠单抗在未处理的SKOV-3肿瘤中具有显著的肿瘤活性积累，其在17-DMAG处理的肿瘤中显著降低。FDG PET未检测到摄取差异。免疫荧光染色证实了17-DMAG治疗后肿瘤HER-2水平的显著降低。使用64 Cu-DOTA-曲妥珠单抗通过定量PET成功监测了抗Hsp 90治疗的早期反应。这种方法在监测HER-2阳性癌症患者在17-DMAG治疗下的治疗反应方面可能是有价值的。
17-DMAG, a heat shock protein 90 (Hsp90) inhibitor, has been intensively investigated for cancer therapy and is undergoing clinical trials. Human epidermal growth factor receptor 2 (HER-2) is one of the client proteins of Hsp90 and its expression is decreased upon 17-DMAG treatment. In this study, we aimed to non-invasively monitor the HER-2 response to 17-DMAG treatment in xenografted mice. The sensitivity of human ovarian cancer SKOV-3 cells to 17-DMAG in vitro was measured by MTT assay. HER-2 expression of SKOV-3 cells was determined by flow cytometry. Nude mice bearing SKOV-3 tumors were treated with 17-DMAG and the therapeutic efficacy was evaluated by tumor size measurement. Both treated and control mice were imaged with microPET using 64Cu-DOTA-trastuzumab and 18F-FDG. Biodistribution studies, immunofluorescence staining were performed to validate the microPET results. SKOV-3 cells are sensitive to 17-DMAG treatment, in a dose dependent manner, with an IC50 value of 68.7 nM after 72 h incubation. The tumor growth curve supported the inhibition effect of 17-DMAG on SKOV-3 tumors. Quantitative microPET imaging showed that 64Cu-DOTA-trastuzumab had prominent tumor activity accumulation in untreated SKOV-3 tumors, which was significantly reduced in 17-DMAG treated tumors. There was no uptake difference detected by FDG PET. Immunofluorescence staining confirmed the significant reduction in tumor HER-2 level upon 17-DMAG treatment. The early response to anti-Hsp90 therapy was successfully monitored by quantitative PET using 64Cu-DOTA-trastuzumab. This approach may be valuable in monitoring the therapeutic response in HER-2-positive cancer patients under 17-DMAG treatment.
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影响因子：
4.7
作者：
Gossett, DR;Bradley, MS;Lin, JY
通讯作者：
Lin, JY
影响因子：
82.9
作者：
Lee, Jae-Hyun;Huh, Yong-Min;Cheon, Jinwoo
通讯作者：
Cheon, Jinwoo
DOI：
10.1093/jnci/91.22.1940
发表时间：
1999-11-17
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
Kelland, LR;Sharp, SY;Workman, P
通讯作者：
Workman, P
影响因子：
4.8
作者：
Barzilay, E;Ben-Califa, N;Neumann, D
通讯作者：
Neumann, D
影响因子：
8
作者：
Basso, AD;Solit, DB;Rosen, N
通讯作者：
Rosen, N