Gang Niu1, Weibo Cai, Kai Chen, Xiaoyuan Chen. 1. The Molecular Imaging Program at Stanford, Department of Radiology and Bio-X Program, Stanford University School of Medicine, 1201 Welch Rd, P095, Stanford, CA 94305-5484, USA.
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 (64)Cu-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 (64)Cu-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 (64)Cu-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.
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 (64)Cu-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 (64)Cu-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 (64)Cu-DOTA-cetuximab, which indicates that this approach may be valuable in monitoring the therapeutic response to Hsp90 inhibitor 17-AAG in EGFR-positive cancerpatients.
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