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 64 Cu-DOTA-trastuzumab and 18 F-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 IC 50 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 64 Cu-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 64 Cu-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]
Copyright of European Journal of Nuclear Medicine & Molecular Imaging is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Titel: |
Monitoring therapeutic response of human ovarian cancer to 17-DMAG by noninvasive PET imaging with <superscript>64</superscript>Cu-DOTA-trastuzumab.
|
---|---|
Autor/in / Beteiligte Person: | Niu, Gang ; Li, Zibo ; Cao, Qizhen ; Chen, Xiaoyuan |
Link: | |
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 |
Schlagwort: |
|
Sonstiges: |
|