Imaging of HER-2 overexpression in tumors for guiding therapy

Curr Pharm Des. 2008;14(28):2999-3019. doi: 10.2174/138161208786404290.


Human epidermal growth factor receptor type 2 (HER2) is a transmembrane tyrosine kinase receptor, which is overexpressed in a large fraction of breast, ovarian, urinary bladder and a number of other carcinomas. Overexpression of HER2 is associated with poor prognosis. Treatment of patients with HER2-expressing breast cancer with a humanized anti-HER2 monoclonal antibody trastuzumab has resulted in improved survival. Several kinds of other anti-HER2 therapies are under development. Radionuclide molecular imaging of HER2 expression may influence patient management by selecting patients, who would benefit form anti-HER2 therapy. Other applications, such as therapy response monitoring and follow-up are also possible. In this case, the use of radionuclide imaging may overcome problems associated with biopsies, including sampling errors and discordance of expression between primary tumors and metastases. Important preconditions for development of a successful tracer for radionuclide imaging are high affinity of a targeting agent and suitable chemistry of labeling. The paper reviews information concerning major classes of HER2-targeting agents, including full-length monoclonal antibodies, their enzymatically produced fragments, engineered immunoglobulin based tracers, and alternative high affinity binders. Available information suggests that Affibody molecules or other small non-immunoglobulin based tracers have the best potential for development of high-contrast imaging agents for visualization of HER2 in vivo.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Antineoplastic Agents / pharmacology
  • Drug Delivery Systems
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Neoplasms / diagnostic imaging*
  • Neoplasms / drug therapy
  • Neoplasms / metabolism*
  • Radionuclide Imaging
  • Radiopharmaceuticals*
  • Receptor, ErbB-2 / metabolism*
  • Recombinant Fusion Proteins


  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Radiopharmaceuticals
  • Recombinant Fusion Proteins
  • Receptor, ErbB-2