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.
OBJECTIVE
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.


CONCLUSIONS
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.
de Korte
M A
MA
Department of Medical Oncology, University of Groningen and University Medical Centre Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands.
de Vries
E G E
EG
Lub-de Hooge
M N
MN
Jager
P L
PL
Gietema
J A
JA
van der Graaf
W T A
WT
Sluiter
W J
WJ
van Veldhuisen
D J
DJ
Suter
T M
TM
Sleijfer
D T
DT
Perik
P J
PJ
D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000009:adverse effects; D002908:Chronic Disease; D005260:Female; D006331:Heart Diseases / Q000139:chemically induced; D006333:Heart Failure / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy*; D004369:Pentetic Acid; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D013312:Stress, Physiological / Q000139:chemically induced; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods; D000068878:Trastuzumab; D015854:Up-Regulation
D018943:Anthracyclines; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D004369:Pentetic Acid; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab