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.108.060426v1 50/9/1500    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 HighWire Citing Articles via Google Scholar Google Scholar Articles by Olafsen, T. Articles by Wu, A. M. Search for Related Content PubMed PubMed Citation Articles by Olafsen, T. Articles by Wu, A. M.

Recombinant Anti-CD20 Antibody Fragments for Small-Animal PET Imaging of B-Cell Lymphomas

¹ Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California; ² Division of Hematology and Oncology, Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California; ³ Department of Radioimmunotherapy, City of Hope National Medical Center, Duarte, California; and ⁴ Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California

Correspondence: For correspondence or reprints contact: Tove Olafsen, UCLA Crump Institute for Molecular Imaging, California NanoSystems Institute, 570 Westwood Plaza, Building 114, Box 951770, Los Angeles, CA 90095-1770. E-mail: tolafsen{at}mednet.ucla.edu

The CD20 cell surface antigen is expressed at high levels by over 90% of B-cell non-Hodgkin lymphomas (NHL) and is the target of the anti-CD20 monoclonal antibody rituximab. To provide more sensitive, tumor-specific PET imaging of NHL, we sought to develop PET agents targeting CD20. Methods: Two recombinant anti-CD20 rituximab fragments, a minibody (scFv-C_H3 dimer; 80 kDa) and a modified scFv-Fc fragment (105 kDa), designed to clear rapidly, were generated. Both fragments were radiolabeled with ¹²⁴I, and the minibody was additionally labeled with ⁶⁴Cu (radiometal) after conjugation to 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA). The radioiodinated fragments and the radiometal-labeled minibody were evaluated in mice as small-animal PET imaging agents for the in vivo imaging of human CD20–expressing lymphomas. Results: Rapid and specific localization to CD20-positive tumors was observed with the radioiodinated fragments. However, the tumor uptake levels and blood activities differed, resulting in different levels of contrast in the images. The better candidate was the minibody, with superior uptake (2-fold higher than that obtained with scFv-Fc) in CD20-positive tumors and low uptake in CD20-negative tumors. Ratios of CD20-positive tumors to CD20-negative tumors at 21 h were 7.0 ± 3.1 (mean ± SD) and 3.9 ± 0.7 for the minibody and scFv-Fc, respectively. The ratio achieved with the ⁶⁴Cu-DOTA-minibody at 19 h was about 5-fold lower because of higher residual background activity in CD20-negative tumors. Conclusion: A radioiodinated minibody and a radioiodinated scFv-Fc fragment produced excellent, high-contrast images in vivo. These new immunoPET agents may prove useful for imaging CD20-positive lymphomas in preclinical models and in humans with NHL.

Key Words: lymphoma • CD20 • antibody fragments • immunoPET • rituximab

Guest Editor: Kenneth T. Cheng, National Institutes of Health

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

Related articles in JNM:

This Month in JNM

JNM 2009 50: 11A-12A. [Full Text]  

This article has been cited by other articles:

				T. Olafsen, S. J. Sirk, D. J. Betting, V. E. Kenanova, K. B. Bauer, W. Ladno, A. A. Raubitschek, J. M. Timmerman, and A. M. Wu ImmunoPET imaging of B-cell lymphoma using 124I-anti-CD20 scFv dimers (diabodies) Protein Eng. Des. Sel., April 1, 2010; 23(4): 243 - 249. [Abstract] [Full Text] [PDF]