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Affibody Molecules for Epidermal Growth Factor Receptor Targeting In Vivo: Aspects of Dimerization and Labeling Chemistry

¹ Unit of Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden; ² Affibody AB, Bromma, Sweden; ³ Department of Medical Sciences, Nuclear Medicine, Uppsala University, Uppsala, Sweden; ⁴ Division of Molecular Biotechnology, School of Biotechnology, Royal Institute of Technology, Stockholm, Sweden; and ⁵ Section of Hospital Physics, Department of Oncology, Uppsala University Hospital, Uppsala, Sweden

Correspondence: For correspondence or reprints contact: Vladimir Tolmachev, Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University, S-751 81 Uppsala, Sweden. E-mail: vladimir.tolmachev{at}bms.uu.se

Noninvasive detection of epidermal growth factor receptor (EGFR) expression in malignant tumors by radionuclide molecular imaging may provide diagnostic information influencing patient management. The aim of this study was to evaluate a novel EGFR-targeting protein, the Z_EGFR:1907 Affibody molecule, for radionuclide imaging of EGFR expression, to determine a suitable tracer format (dimer or monomer) and optimal label. Methods: An EGFR-specific Affibody molecule, Z_EGFR:1907, and its dimeric form, (Z_EGFR:1907)₂, were labeled with ¹¹¹In using benzyl-diethylenetriaminepentaacetic acid and with ¹²⁵I using p-iodobenzoate. Affinity and cellular retention of conjugates were evaluated in vitro. Biodistribution of radiolabeled Affibody molecules was compared in mice bearing EGFR-expressing A431 xenografts. Specificity of EGFR targeting was confirmed by comparison with biodistribution of non–EGFR-specific counterparts. Results: Head-to-tail dimerization of the Affibody molecule improved the dissociation rate. In vitro, dimeric forms demonstrated superior cellular retention of radioactivity. For both molecular set-ups, retention was better for the ¹¹¹In-labeled tracer than for the radioiodinated counterpart. In vivo, all conjugates accumulated specifically in xenografts and in EGFR-expressing tissues. The retention of radioactivity in tumors was better in vivo for dimeric forms; however, the absolute uptake values were higher for monomeric tracers. The best tracer, ¹¹¹In-labeled Z_EGFR:1907, provided a tumor-to-blood ratio of 100 (24 h after injection). Conclusion: The radiometal-labeled monomeric Affibody molecule Z_EGFR:1907 has a potential for radionuclide molecular imaging of EGFR expression in malignant tumors.

Key Words: Affibody molecules • EGFR • ¹²⁵I • ¹¹¹In • -camera imaging

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

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