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PET Imaging of Prostate Cancer Xenografts with a Highly Specific Antibody against the Prostate-Specific Membrane Antigen

¹ Department of Urology, University of Freiburg, Freiburg, Germany; ² Radiopharmacy, Department of Radiology, University of Tübingen, Tübingen, Germany; ³ Laboratory for Preclinical Imaging and Imaging Technology of the Werner Siemens-Foundation, Department of Radiology, University of Tübingen, Tübingen, Germany; ⁴ Faculty of Biology, University of Freiburg, Freiburg, Germany; and ⁵ Division of Immunology and Beckman Research Institute, City of Hope National Medical Center, Duarte, California

Correspondence: For correspondence or reprints contact: Bernd J. Pichler, Laboratory for Preclinical Imaging and Imaging Technology of the Werner Siemens-Foundation, Department of Radiology, University of Tübingen, Röntgenweg, 13 72076 Tübingen, Germany. E-mail: bernd.pichler{at}med.uni-tuebingen.de

Prostate-specific membrane antigen (PSMA), a transmembrane glycoprotein, is highly expressed by virtually all prostate cancers and is currently the focus of several diagnostic and therapeutic strategies. We have previously reported on the generation of several monoclonal antibodies (mAb) and antibody fragments that recognize and bind with high affinity to the extracellular domain of cell-adherent PSMA. This article reports the in vivo behavior and tumor uptake of the radiolabeled anti-PSMA mAb 3/A12 and its potential as a tracer for PET. Methods: The mAb 3/A12 was conjugated with the chelating agent 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA) and radiolabeled with ⁶⁴Cu. Severe combined immunodeficient mice bearing PSMA-positive C4-2 prostate carcinoma xenografts were used for small-animal PET imaging. Mice with PSMA-negative DU 145 tumors served as controls. For PET studies, each animal received 20–30 µg of radiolabeled mAb corresponding to an activity of 7.6–11.5 MBq. Imaging was performed 3, 24, and 48 h after injection. After the last scan, the mice were sacrificed and tracer in vivo biodistribution was measured by -counting. Results: Binding of the mAb 3/A12 on PSMA-expressing C4-2 cells was only minimally influenced by DOTA conjugation. The labeling efficiency using ⁶⁴Cu and DOTA-3/A12 was 95.3% ± 0.3%. The specific activity after ⁶⁴Cu labeling was between 327 and 567 MBq/mg. After tracer injection, static small-animal PET images of mice with PSMA-positive tumors revealed a tumor-to-background ratio of 3.3 ± 1.3 at 3 h, 7.8 ± 1.4 at 24 h, and 9.6 ± 2.7 at 48 h. In contrast, no significant tracer uptake occurred in the PSMA-negative DU 145 tumors. These results were confirmed by direct counting of tissues after the final imaging. Conclusion: Because of the high and specific uptake of ⁶⁴Cu-labeled mAb 3/A12 in PSMA-positive tumors, this ligand represents an excellent candidate for prostate cancer imaging and potentially for radioimmunotherapy.

Key Words: prostate-specific membrane antigen • radioimmunoimaging • tumor localization • PET

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

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