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

J Nucl Med. 2006 May;47(5):793-6.

Abstract

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.

Conclusion: HER2 PET is an earlier predictor of tumor response to 17AAG therapy than (18)F-FDG PET.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Benzoquinones
  • Cell Line, Tumor
  • Fluorodeoxyglucose F18*
  • Glycolysis
  • HSP90 Heat-Shock Proteins / metabolism*
  • Humans
  • Lactams, Macrocyclic
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Positron-Emission Tomography / instrumentation*
  • Positron-Emission Tomography / methods
  • Receptor, ErbB-2 / metabolism*
  • Rifabutin / analogs & derivatives
  • Rifabutin / therapeutic use
  • Treatment Outcome

Substances

  • Benzoquinones
  • HSP90 Heat-Shock Proteins
  • Lactams, Macrocyclic
  • Fluorodeoxyglucose F18
  • Rifabutin
  • tanespimycin
  • Receptor, ErbB-2