HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH RSS TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: jnumed.108.060392v1 50/6/974    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JNM Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Dijkers, E. C.F. Articles by Lub-de Hooge, M. N. Search for Related Content PubMed PubMed Citation Articles by Dijkers, E. C.F. Articles by Lub-de Hooge, M. N.

Development and Characterization of Clinical-Grade ⁸⁹Zr-Trastuzumab for HER2/neu ImmunoPET Imaging

¹ Department of Hospital and Clinical Pharmacy, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; ² Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; ³ Department of Otolaryngology/Head and Neck Surgery, VU University Medical Center, Amsterdam, The Netherlands; ⁴ Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; and ⁵ Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

Correspondence: For correspondence or reprints contact: Jos G.W. Kosterink, Department of Hospital and Clinical Pharmacy, University Medical Center Groningen, P.O. Box 30.001, Groningen 9700 RB, The Netherlands. E-mail: j.g.w.kosterink{at}apoth.umcg.nl

The anti–human epidermal growth factor receptor 2 (HER2/neu) antibody trastuzumab is administered to patients with HER2/neu-overexpressing breast cancer. Whole-body noninvasive HER2/neu scintigraphy could help to assess and quantify the HER2/neu expression of all lesions, including nonaccessible metastases. The aims of this study were to develop clinical-grade radiolabeled trastuzumab for clinical HER2/neu immunoPET scintigraphy, to improve diagnostic imaging, to guide antibody-based therapy, and to support early antibody development. The PET radiopharmaceutical ⁸⁹Zr-trastuzumab was compared with the SPECT tracer ¹¹¹In-trastuzumab, which we have tested in the clinic already. Methods: Trastuzumab was labeled with ⁸⁹Zr and (for comparison) with ¹¹¹In. The minimal dose of trastuzumab required for optimal small-animal PET imaging and biodistribution was determined with human HER2/neu-positive or -negative tumor xenograft–bearing mice. Results: Trastuzumab was efficiently radiolabeled with ⁸⁹Zr at a high radiochemical purity and specific activity. The antigen-binding capacity was preserved, and the radiopharmaceutical proved to be stable for up to 7 d in solvent and human serum. Of the tested protein doses, the minimal dose of trastuzumab (100 µg) proved to be optimal for imaging. The comparative biodistribution study showed a higher level of ⁸⁹Zr-trastuzumab in HER2/neu-positive tumors than in HER2/neu-negative tumors, especially at day 6 (33.4 ± 7.6 [mean ± SEM] vs. 7.1 ± 0.7 percentage injected dose per gram of tissue). There were good correlations between the small-animal PET images and the biodistribution data and between ⁸⁹Zr-trastuzumab and ¹¹¹In-trastuzumab uptake in tumors (R² = 0.972). Conclusion: Clinical-grade ⁸⁹Zr-trastuzumab showed high and HER2/neu-specific tumor uptake at a good resolution.

Key Words: HER2/neu • immunoPET • imaging • breast cancer

COPYRIGHT © 2009 by the Society of Nuclear Medicine, Inc.

Related articles in JNM:

This Month in JNM

JNM 2009 50: 11A-12A. [Full Text]