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Non-Invasive PET Imaging of EGFR Degradation Induced by a Heat Shock Protein 90 Inhibitor

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Abstract

Purpose

The aim of this study is to non-invasively monitor the epidermal growth factor receptor (EGFR) response to a Hsp90 inhibitor–17-AAG treatment in a PC-3 prostate cancer model.

Procedures

Nude mice bearing PC-3 tumor were injected intraperitoneally with 17-AAG and then imaged with micro positron emission tomography (microPET) using 64Cu-DOTA–cetuximab. Biodistribution studies, immunofluorescence staining, and Western blot were performed to validate the microPET results.

Results

PC-3 cells are sensitive to 17-AAG treatment in a dose-dependent manner. Quantitative microPET showed that 64Cu-DOTA–cetuximab has prominent tumor activity accumulation in untreated tumors (14.6 ± 2.6%ID/g) but significantly lower uptake in 17-AAG-treated tumors (8.9 ± 1.6% ID/g) at 24 h post-injection. Both immunofluorescence staining and Western blot confirmed the significantly lower EGFR expression level in the tumor tissue upon 17-AAG treatment.

Conclusions

The early response to anti-Hsp90 therapy was successfully monitored by quantitative PET using 64Cu-DOTA–cetuximab, which indicates that this approach may be valuable in monitoring the therapeutic response to Hsp90 inhibitor 17-AAG in EGFR-positive cancer patients.

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Acknowledgment

This project was financially supported by the National Institute of Biomedical Imaging and Bioengineering (NIBIB; R21 EB001785), National Cancer Institute (NCI; R21 CA102123, P50 CA114747, U54 CA119367, and R24 CA93862), Department of Defense (DOD; W81XWH-04-1-0697, W81XWH-06-1-0665, W81XWH-06-1-0042, and DAMD17-03-1-0143), and a DOD Prostate Cancer Training Award PC073549 (to G. Niu), and a Benedict Cassen Postdoctoral Fellowship from the Education and Research Foundation of the Society of Nuclear Medicine (to W. Cai).

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Authors and Affiliations

  1. The Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X Program, Stanford University School of Medicine, 1201 Welch Rd, P095, Stanford, CA, 94305-5484, USA

    Gang Niu, Weibo Cai, Kai Chen & Xiaoyuan Chen

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  1. Gang Niu
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  2. Weibo Cai
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  3. Kai Chen
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  4. Xiaoyuan Chen
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Correspondence to Xiaoyuan Chen.

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Niu, G., Cai, W., Chen, K. et al. Non-Invasive PET Imaging of EGFR Degradation Induced by a Heat Shock Protein 90 Inhibitor. Mol Imaging Biol 10, 99–106 (2008). https://doi.org/10.1007/s11307-007-0123-2

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  • DOI: https://doi.org/10.1007/s11307-007-0123-2

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