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DOI: 10.1055/s-0029-1221633
PET Imaging of Anti-PSMA Antibodies as Novel Agents for Targeting Prostate Cancer
Ziele: The Prostate Specific Membrane Antigen (PSMA) has been shown to represent an excellent target for diagnosis and therapy of prostate cancer. We generated monoclonal antibodies (mAbs) against native cell-adherent PSMA. The aim of the present study was to show the specific binding of these mAbs in human prostate tumors in SCID mice and their use for PET imaging of prostate cancer. Methode: Specific binding of the mAbs to distinct extracellular epitopes of cell-adherent PSMA was determined by flow cytometry. For PET imaging the mAbs and F(ab)2-fragments were conjugated with the chelating agent DOTA and radiolabeled with 64Cu. The mAb were administered to SCID mice (20µg mAb corresponding to 7 MBq) bearing PSMA-positive or -negative human prostate carcinoma xenografts. To block the PSMA-specific receptors mice were injected once with 250 to 700µg non-radioactive mAb 3h prior to injection of the corresponding radiolabeled mAb. Mice were in vivo imaged using a small animal PET at 3, 24, and 48h post injection. After the last scan the ex vivo biodistribution was performed by gamma-counting. Ergebnis: The anti-PSMA mAbs called 3/A12 (IgG1), 3/F11 (IgG2a) and the fragment 3/A12-F(ab)2 showed a high and specific binding to PSMA-expressing prostate tissue and were not influenced by the DOTA-conjugation. Animal PET images of C4.2-tumors revealed 7.8, 8.1 and 4.7at 24h and 9.6, 13.2 and 3.1%ID/cc at 48h after injection of [64Cu]DOTA-3/A12, [64Cu]DOTA-3/F11 mAb or [64Cu]DOTA-3/A12-F(ab)2, respectively. The binding to PSMA was blocked already 3h after injection of 700µg of non-radioactive antibodies. A reduced tumor uptake was obtained with the corresponding F(ab)2-fragments, which showed a much faster blood clearance compared to the mAbs. Schlussfolgerung: Due to the high and specific binding to prostate cancer cells and their high uptake in PSMA-positive tumors the mAbs 3/A12, 3/F11 and the 3/A12-F(ab)2-fragment represent excellent candidates for prostate cancer imaging and radioimmunotherapy.
Korrespondierender Autor: Wiehr S
Universität Tübingen, Labor für Präklinische Bildgebung und Bildgebungstechnologie der Werner Siemens-Stiftung, Röntgenweg 13, 72076 Tübingen
E-Mail: Stefan.Wiehr@med.uni-tuebingen.de
small animal PET - oncology - PSMA