Early tumor response to Hsp90 therapy using HER2 PET: comparison with 18F-FDG PET.
We compared (68)Ga-DOTA-F(ab')(2)-herceptin (DOTA is 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid [HER2 PET]) and (18)F-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 (18)F-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 (18)F-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.


CONCLUSIONS
HER2 PET is an earlier predictor of tumor response to 17AAG therapy than (18)F-FDG PET.
Smith-Jones
Peter M
PM
Nuclear Medicine Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA. smith-jp@mskcc.org
Solit
David
D
Afroze
Farzana
F
Rosen
Neal
N
Larson
Steven M
SM
D000818:Animals; D016227:Benzoquinones; D045744:Cell Line, Tumor; D019788:Fluorodeoxyglucose F18; D006019:Glycolysis; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D047029:Lactams, Macrocyclic; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D049268:Positron-Emission Tomography / Q000295:instrumentation* / Q000379:methods; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D017828:Rifabutin / Q000031:analogs & derivatives / Q000627:therapeutic use; D016896:Treatment Outcome
D016227:Benzoquinones; D019788:Fluorodeoxyglucose F18; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D018719:Erb-b2 Receptor Tyrosine Kinases; D017828:Rifabutin; C112765:tanespimycin