| Abstract: |
We compared 68Ga-DOTA-F(ab')2-herceptin (DOTA is 1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-tetraacetic acid [HER2 PET]) and 68F-FDG PET for imaging of tumor response to the heat shock protein 90 (Hsp90) inhibitor 17-allylamino-17-demethoxy-geldanamycin (17AAG). Methods: Mice bearing BT474 breast tumor xenografts were scanned with 68F-FDG PET and HER2 PET before and after 17AAG treatment and then biweekly for up to 3 wk. Results: Within 24 h after treatment, a significant decrease in HER2 was measured by HER2 PET, whereas 68F-FDG PET uptake, a measure of glycolysis, was unchanged. Marked growth inhibition occurred in treated tumors but became evident only by 11 d after treatment. Thus, Her2 downregulation occurs independently of changes in glycolysis after 17AAG therapy, and Her2 reduction more accurately predicts subsequent tumor growth inhibition. Conclusion: HER2 PET is an earlier predictor of tumor response to 17AAG therapy than 68F-FDG PET. |
| Keywords: |
controlled study; protein expression; treatment outcome; unclassified drug; human cell; nonhuman; comparative study; positron emission tomography; methodology; mouse; animal; metabolism; animals; mice; drug inhibition; breast cancer; epidermal growth factor receptor 2; animal experiment; animal model; tumor xenograft; drug effect; cell line, tumor; cancer inhibition; diagnostic agent; drug uptake; nude mouse; mice, nude; instrumentation; tumor cell line; fluorodeoxyglucose f 18; fluorodeoxyglucose f18; positron-emission tomography; drug derivative; heat shock protein 90 inhibitor; heat shock protein 90; hsp90 heat-shock proteins; down regulation; receptor, erbb-2; drug metabolism; neoplasm transplantation; trastuzumab; glycolysis; 1,4,7,10 tetraazacyclododecane 1,4,7,10 tetraacetic acid; gallium 68; benzoquinones; lactams, macrocyclic; rifabutin; cancer transplantation; 17-(allylamino)-17-demethoxygeldanamycin; benzoquinone derivative; macrocyclic lactam; 17 allylamino 17 demethoxygeldanamycin; 17 allylamino 17 demethoxy geldanamycin
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