111Indium-trastuzumab visualises myocardial human epidermal growth factor receptor 2 expression shortly after anthracycline treatment but not during heart failure: a clue to uncover the mechanisms of trastuzumab-related cardiotoxicity

Eur J Cancer. 2007 Sep;43(14):2046-51. doi: 10.1016/j.ejca.2007.06.024. Epub 2007 Aug 24.


Aim: Trastuzumab can induce cardiotoxicity, particularly when combined with anthracyclines. Myocardial human epidermal growth factor receptor 2 (HER2) expression may be transiently upregulated by a compensatory mechanism following cardiac stress. 111In-DTPA-trastuzumab, scintigraphy can detect HER2 positive tumour lesions, however previously, we found myocardial uptake in only 1 of the 15 anthracycline-pre-treated patients with a median of 11 months after the last anthracycline administration. To evaluate whether myocardial HER2 expression is upregulated by anthracycline-induced cardiac stress or in case of heart failure by chronic pressure or volume overload, we performed 111In-DTPA-trastuzumab scans in patients shortly after anthracyclines and with non-anthracycline-related heart failure.

Methods: Patients within 3 weeks after undergoing 4-6 cycles first-line anthracycline-based chemotherapy and patients with heart failure due to cardiac disease underwent gammacamera imaging 48 and 96 h after 111In-DTPA-trastuzumab intravenously.

Results: Myocardial 111In-DTPA-trastuzumab uptake was observed in 5 out of 10 anthracycline-treated patients, who all were without symptomatic cardiac dysfunction. None of the 10 heart failure patients showed myocardial uptake.

Conclusion: Shortly after completion of anthracycline treatment, myocardial HER2 over-expression was detectable in 50% of the patients. 111In-DTPA-trastuzumab scintigraphy after anthracyclines prior to adjuvant trastuzumab potentially identifies patients susceptible for trastuzumab-related cardiotoxicity and thus may facilitate the optimal timing of trastuzumab therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anthracyclines / therapeutic use*
  • Antibodies, Monoclonal* / adverse effects
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents* / adverse effects
  • Chronic Disease
  • Female
  • Heart Diseases / chemically induced
  • Heart Failure / metabolism
  • Humans
  • Male
  • Middle Aged
  • Myocardium / metabolism*
  • Neoplasms / drug therapy*
  • Pentetic Acid
  • Receptor, ErbB-2 / metabolism*
  • Stress, Physiological / chemically induced
  • Tomography, Emission-Computed, Single-Photon / methods
  • Trastuzumab
  • Up-Regulation


  • Anthracyclines
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Pentetic Acid
  • Receptor, ErbB-2
  • Trastuzumab