Early tumor response to Hsp90 therapy using HER2 PET: Comparison with 18F-FDG

and 18F-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 18F-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 de-crease in HER2 was measured by HER2 PET, whereas 18F-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 18F-FDG PET. J Nucl Med 2006; 47:793–79