This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Perik, P. J. Articles by de Vries, E. G.E. Search for Related Content PubMed PubMed Citation Articles by Perik, P. J. Articles by de Vries, E. G.E. Social Bookmarking                            What's this?

Indium-111–Labeled Trastuzumab Scintigraphy in Patients With Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer

Patrick J. Perik, Marjolijn N. Lub-De Hooge, Jourik A. Gietema, Winette T.A. van der Graaf, M. Alexander de Korte, Sharon Jonkman, Jos G.W. Kosterink, Dirk J. van Veldhuisen, Dirk T. Sleijfer, Pieter L. Jager, Elisabeth G.E. de Vries

From the Departments of Medical Oncology, Hospital Pharmacy, Nuclear Medicine and Cardiology, University of Groningen and University Medical Center Groningen, Groningen, the Netherlands.

Address reprint requests to Elisabeth G.E. de Vries, MD, PhD, Department of Medical Oncology, University Medical Center Groningen, PO Box 30.001, 9700 RB Groningen, the Netherlands; e-mail: e.g.e.de.vries{at}int.umcg.nl

Purpose 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.

Patients and 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).

Conclusion 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.

Supported by an unrestricted educational grant received from Hoffmann-La Roche Ltd, Basel, Switzerland.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				S. Nimmagadda, M. Pullambhatla, and M. G. Pomper Immunoimaging of CXCR4 Expression in Brain Tumor Xenografts Using SPECT/CT J. Nucl. Med., July 1, 2009; 50(7): 1124 - 1130. [Abstract] [Full Text] [PDF]

				E. C.F. Dijkers, J. G.W. Kosterink, A. P. Rademaker, L. R. Perk, G. A.M.S. van Dongen, J. Bart, J. R. de Jong, E. G.E. de Vries, and M. N. Lub-de Hooge Development and Characterization of Clinical-Grade 89Zr-Trastuzumab for HER2/neu ImmunoPET Imaging J. Nucl. Med., June 1, 2009; 50(6): 974 - 981. [Abstract] [Full Text] [PDF]

				J. H. Lee, E. L. Rosen, and D. A. Mankoff The Role of Radiotracer Imaging in the Diagnosis and Management of Patients with Breast Cancer: Part 2--Response to Therapy, Other Indications, and Future Directions J. Nucl. Med., May 1, 2009; 50(5): 738 - 748. [Abstract] [Full Text] [PDF]

				S. Ahlgren, H. Wallberg, T. A. Tran, C. Widstrom, M. Hjertman, L. Abrahmsen, D. Berndorff, L. M. Dinkelborg, J. E. Cyr, J. Feldwisch, et al. Targeting of HER2-Expressing Tumors with a Site-Specifically 99mTc-Labeled Recombinant Affibody Molecule, ZHER2:2395, with C-Terminally Engineered Cysteine J. Nucl. Med., May 1, 2009; 50(5): 781 - 789. [Abstract] [Full Text] [PDF]

				A. Orlova, H. Wallberg, S. Stone-Elander, and V. Tolmachev On the Selection of a Tracer for PET Imaging of HER2-Expressing Tumors: Direct Comparison of a 124I-Labeled Affibody Molecule and Trastuzumab in a Murine Xenograft Model J. Nucl. Med., March 1, 2009; 50(3): 417 - 425. [Abstract] [Full Text] [PDF]

				S. B. Lee, M. Hassan, R. Fisher, O. Chertov, V. Chernomordik, G. Kramer-Marek, A. Gandjbakhche, and J. Capala Affibody Molecules for In vivo Characterization of HER2-Positive Tumors by Near-Infrared Imaging Clin. Cancer Res., June 15, 2008; 14(12): 3840 - 3849. [Abstract] [Full Text] [PDF]

				D. A. Mankoff, J. M. Link, H. M. Linden, L. Sundararajan, and K. A. Krohn Tumor Receptor Imaging J. Nucl. Med., June 1, 2008; 49(Suppl_2): 149S - 163S. [Abstract] [Full Text] [PDF]

				P. P. Sengupta, D. W. Northfelt, F. Gentile, J. L. Zamorano, and B. K. Khandheria Trastuzumab-Induced Cardiotoxicity: Heart Failure at the Crossroads Mayo Clin. Proc., February 1, 2008; 83(2): 197 - 203. [Abstract] [Full Text] [PDF]

				B. R.J. H. Bird and S. M. Swain Cardiac Toxicity in Breast Cancer Survivors: Review of Potential Cardiac Problems Clin. Cancer Res., January 1, 2008; 14(1): 14 - 24. [Abstract] [Full Text] [PDF]

				G. A.M.S. van Dongen, G. W.M. Visser, M. N. Lub-de Hooge, E. G. de Vries, and L. R. Perk Immuno-PET: A Navigator in Monoclonal Antibody Development and Applications Oncologist, December 1, 2007; 12(12): 1379 - 1389. [Abstract] [Full Text] [PDF]

				L. Sampath, S. Kwon, S. Ke, W. Wang, R. Schiff, M. E. Mawad, and E. M. Sevick-Muraca Dual-Labeled Trastuzumab-Based Imaging Agent for the Detection of Human Epidermal Growth Factor Receptor 2 Overexpression in Breast Cancer J. Nucl. Med., September 1, 2007; 48(9): 1501 - 1510. [Abstract] [Full Text] [PDF]

				W. B. Nagengast, E. G. de Vries, G. A. Hospers, N. H. Mulder, J. R. de Jong, H. Hollema, A. H. Brouwers, G. A. van Dongen, L. R. Perk, and M. N. Lub-de Hooge In Vivo VEGF Imaging with Radiolabeled Bevacizumab in a Human Ovarian Tumor Xenograft J. Nucl. Med., August 1, 2007; 48(8): 1313 - 1319. [Abstract] [Full Text] [PDF]

				V. Cesson, K. Stirnemann, B. Robert, I. Luescher, T. Filleron, G. Corradin, J.-P. Mach, and A. Donda Active Antiviral T-Lymphocyte Response Can Be Redirected against Tumor Cells by Antitumor Antibody x MHC/Viral Peptide Conjugates Clin. Cancer Res., December 15, 2006; 12(24): 7422 - 7430. [Abstract] [Full Text] [PDF]