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.

Abstract

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.

• Authors: M A de Korte, E G E de Vries, M N Lub-de Hooge, P L Jager, J A Gietema, W T A van der Graaf, W J Sluiter, D J van Veldhuisen, T M Suter, D T Sleijfer, P J Perik
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 43 Issue 14 Pg. 2046-51 (Sep 2007) ISSN: 0959-8049 [Print] England
• PMID: 17719768 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• 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