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High‐resolution animal PET imaging of prostate cancer xenografts with three different 64 Cu‐labeled antibodies against native cell‐adherent PSMA
Author(s) -
Alt Karen,
Wiehr Stefan,
Ehrlichmann Walter,
Reischl Gerald,
Wolf Philipp,
Pichler Bernd J.,
ElsässerBeile Ursula,
Bühler Patrick
Publication year - 2010
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.21176
Subject(s) - biodistribution , prostate cancer , in vivo , monoclonal antibody , glutamate carboxypeptidase ii , antibody , dota , prostate , medicine , pathology , nuclear medicine , cancer research , cancer , immunology , biology , microbiology and biotechnology
BACKGROUND The prostate specific membrane antigen (PSMA) is expressed by virtually all prostate cancers and represents an ideal target for diagnostic and therapeutic strategies. This article compares the in vivo behavior and tumor uptake of three different radiolabeled anti‐PSMA monoclonal antibodies (mAbs) and corresponding F(ab) 2 and Fab fragments thereof. METHODS The mAbs 3/A12, 3/F11, and 3/E7 and fragments of 3/A12 were conjugated with the chelating agent DOTA and radiolabeled with 64 Cu. For the microPET imaging studies, SCID mice bearing PSMA‐positive C4‐2 and PSMA‐negative DU 145 prostate cancer xenografts were used. Each animal received 20–30 µg radiolabeled mAb or fragment corresponding to an activity of 8–14 MBq. Imaging was performed 3, 24, and 48 hr post‐injection. After the last scan, mice were sacrificed and tracer in vivo biodistribution was measured by gamma‐counting. RESULTS Static microPET images of mice with PSMA‐positive tumors revealed a high uptake of the mAbs in the C4‐2 tumors at 24 and 48 hr after tracer injection and only a minimal distribution in the DU 145 tumors and other organs. In contrast, the F(ab) 2 and Fab fragments of 3/A12 were detected at a high extend in the kidney but not in the C4‐2 tumors. These results were confirmed by gamma counting of dissected organs after the final imaging. CONCLUSIONS Due to the high and specific uptake of the 64 Cu‐labeled mAbs in PSMA‐positive tumors, these antibodies represent excellent tools for prostate cancer imaging. Prostate 70: 1413–1421, 2010. © 2010 Wiley‐Liss, Inc.