Indium-111-labeled trastuzumab scintigraphy in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer.
OBJECTIVE
The cardiac and antineoplastic effects of trastuzumab may be related to specific uptake of trastuzumab in myocardium and tumor tissue, respectively. We evaluated whether indium-111 (111In)-labeled trastuzumab scintigraphy can predict cardiotoxicity and identify tumor lesions. In addition, we evaluated whether plasma markers for cardiac dysfunction can be used to predict cardiotoxicity.


METHODS
Patients with human epidermal growth factor receptor 2 (HER2) -positive metastatic breast cancer underwent gamma camera imaging from 15 minutes to 7 days after injection of 150 MBq 111In-diethylenetriamine penta-acetic acid anhydride (DTPA) -trastuzumab, after loading-dose trastuzumab, and after once-a-week trastuzumab doses for 11 weeks, and concomitant paclitaxel once every 3 weeks. Cardiac assessments were performed before treatment, and after four and six cycles. Plasma N-terminal probrain natriuretic peptide (NT-proBNP) and serum troponin I were measured with immunoassay.


RESULTS
Fifteen of the 17 patients were available for cardiac and tumor uptake analysis. On the first scan, myocardial 111In-DTPA-trastuzumab uptake was observed in one patient with pre-existing cardiac arrhythmias, who did not develop heart failure during treatment. Severe cardiotoxicity occurred in three patients, without initial myocardial uptake, whereas one showed weak myocardial uptake after four cycles. The detection rate of single tumor lesions was 45%. New tumor lesions were discovered in 13 of 15 patients. Pretreatment plasma NT-proBNP levels were higher in patients with than without heart failure (mean, 534 [standard deviation, 236] v 105 [standard deviation, 79] ng/L; P = .009).


CONCLUSIONS
Radiolabeled trastuzumab scintigraphy was not valuable in predicting trastuzumab-related cardiotoxicity in metastatic breast cancer patients, but can identify HER2-positive tumors. Measurement of plasma NT-proBNP is promising regarding prediction of trastuzumab-related cardiotoxicity.
Perik
Patrick J
PJ
Department of Medical Oncology, Hospital Pharmacy, Nuclear Medicine and Cardiology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
Lub-De Hooge
Marjolijn N
MN
Gietema
Jourik A
JA
van der Graaf
Winette T A
WT
de Korte
M Alexander
MA
Jonkman
Sharon
S
Kosterink
Jos G W
JG
van Veldhuisen
Dirk J
DJ
Sleijfer
Dirk T
DT
Jager
Pieter L
PL
de Vries
Elisabeth G E
EG
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D018450:Disease Progression; D005260:Female; D006331:Heart Diseases / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis; D006338:Heart Neoplasms / Q000556:secondary; D006801:Humans; D007205:Indium Radioisotopes; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000008:administration & dosage; D004369:Pentetic Acid; D010446:Peptide Fragments / Q000097:blood; D011237:Predictive Value of Tests; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D015899:Tomography, Emission-Computed, Single-Photon; D000068878:Trastuzumab; D019210:Troponin I / Q000097:blood
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D007205:Indium Radioisotopes; D020097:Natriuretic Peptide, Brain; D017239:Paclitaxel; D004369:Pentetic Acid; D010446:Peptide Fragments; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; D019210:Troponin I; C109794:pro-brain natriuretic peptide (1-76)