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.108.057919v1 50/3/417    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 Orlova, A. Articles by Tolmachev, V. Search for Related Content PubMed PubMed Citation Articles by Orlova, A. Articles by Tolmachev, V.

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

¹ Affibody AB, Bromma, Sweden; ² Division of Biomedical Radiation Sciences, Department of Oncology, Radiology and Clinical Immunology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden; ³ Karolinska Pharmacy at Karolinska University Hospital, Solna, and Department of Clinical Neurosciences, Karolinska Institutet, Stockholm, Sweden; and ⁴ Division of Nuclear Medicine, Department of Medical Sciences, Uppsala University, Uppsala, Sweden

Correspondence: For correspondence or reprints contact: Anna Orlova, Affibody AB, Box 20137, SE-16102, Bromma, Sweden. E-mail: anna.orlova{at}bms.uu.se

Human epidermal growth factor receptor type 2 (HER2) is a tyrosine kinase, which is often overexpressed in many carcinomas. Imaging HER2 expression in malignant tumors can provide important prognostic and predictive diagnostic information. The use of anti-HER2 tracers labeled with positron-emitting radionuclides may increase the sensitivity of HER2 imaging. The goal of this study was to compare directly 2 approaches for developing anti-HER2 PET tracers: a ¹²⁴I-labeled monoclonal antibody and a small (7-kDa) scaffold protein, the Affibody molecule. Methods: The anti-HER2 Affibody Z_HER2:342 and humanized monoclonal antibody trastuzumab were labeled with ^124/125I using p-iodobenzoate (PIB) as a linker. Cellular processing of both tracers by HER2-expressing cells was investigated. The biodistributions of ¹²⁴I-PIB-Z_HER2:342 and ¹²⁵I-PIB-trastuzumab were compared in BALB/C nu/nu mice bearing HER2-expressing NCI-N87 xenografts using paired labels. Small-animal PET of ¹²⁴I-PIB-Z_HER2:342 and ¹²⁴I-PIB-trastuzumab in tumor-bearing mice was performed at 6, 24, and 72 h after injection. Results: Both radioiodinated Z_HER2:342 and trastuzumab bound specifically to HER2-expressing cells in vitro and specifically targeted HER2-expressing xenografts in vivo. Radioiodinated trastuzumab was more rapidly internalized and degraded, which resulted in better retention of radioactivity delivered by Z_HER2:342. Total uptake of trastuzumab in tumors was higher than that of ¹²⁴I-PIB-Z_HER2:342. However, tumor-to-organ ratios were appreciably higher for ¹²⁴I-PIB-Z_HER2:342 due to the more rapid clearance of radioactivity from blood and normal organs. The ex vivo results were confirmed by small-animal PET. Conclusion: The use of the small scaffold targeting Affibody provides better contrast in HER2 imaging than does the monoclonal antibody.

Key Words: Affibody molecules • imaging • targeting • xenografts • HER2

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

Related articles in JNM:

This Month in JNM

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