Monitoring therapeutic response of human ovarian cancer to 17-DMAG by noninvasive PET imaging with <superscript>64</superscript>Cu-DOTA-trastuzumab.
In: European Journal of Nuclear Medicine & Molecular Imaging, Jg. 36 (2009-09-01), Heft 9, S. 1510-1519
Online
academicJournal
Zugriff:
17-Dimethylaminoethylamino-17-demethoxygeldanamycin (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 noninvasively 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 in 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 and 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 24.72 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 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. [ABSTRACT FROM AUTHOR]
Titel: |
Monitoring therapeutic response of human ovarian cancer to 17-DMAG by noninvasive PET imaging with <superscript>64</superscript>Cu-DOTA-trastuzumab.
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Autor/in / Beteiligte Person: | Niu, Gang ; Li, Zibo ; Cao, Qizhen ; Chen, Xiaoyuan |
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Zeitschrift: | European Journal of Nuclear Medicine & Molecular Imaging, Jg. 36 (2009-09-01), Heft 9, S. 1510-1519 |
Veröffentlichung: | 2009 |
Medientyp: | academicJournal |
ISSN: | 1619-7070 (print) |
DOI: | 10.1007/s00259-009-1158-1 |
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