Imaging the pharmacodynamics of HER2 degradation in response to Hsp90 inhibitors Academic Article uri icon


MeSH Major

  • HSP90 Heat-Shock Proteins
  • Positron-Emission Tomography
  • Receptor, ErbB-2
  • Rifabutin


  • The development of therapeutic inhibitors of key signaling pathways has been hampered by the inability to assess the effect of a drug on its target in the patient. 17-allylaminogeldanamycin (17-AAG) is the first Hsp90 inhibitor to be tested in a clinical trial. It causes the degradation of HER2 and other Hsp90 targets, and has antitumor activity in preclinical models. We have developed a method for imaging the inhibition of Hsp90 by 17-AAG. We labeled an F(ab')2 fragment of the anti-HER2 antibody Herceptin with 68Ga, a positron emitter, which allows the sequential positron-emission tomographic imaging of HER2 expression. We have used this method to quantify as a function of time the loss and recovery of HER2 induced by 17-AAG in animal tumors. This approach allows noninvasive imaging of the pharmacodynamics of a targeted drug and will facilitate the rational design of combination therapy based on target inhibition.

publication date

  • June 2004



  • Academic Article



  • eng

Digital Object Identifier (DOI)

  • 10.1038/nbt968

PubMed ID

  • 15133471

Additional Document Info

start page

  • 701

end page

  • 6


  • 22


  • 6