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Early Tumor Response to Hsp90 Therapy Using HER2 PET: Comparison with ¹⁸F-FDG PET

¹ Nuclear Medicine Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York; and ² Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York

Correspondence: For correspondence or reprints contact: Peter M. Smith-Jones, PhD, Nuclear Medicine Service, Box 77, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10021. E-mail: smith-jp{at}mskcc.org

We compared ⁶⁸Ga-DOTA-F(ab')₂-herceptin (DOTA is 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid [HER2 PET]) and ¹⁸F-FDG PET for imaging of tumor response to the heat shock protein 90 (Hsp90) inhibitor 17-allylamino-17-demethoxygeldanamycin (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 decrease 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.

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