Effect of radiochemical modification on biodistribution of scFvD2B antibody fragment recognising prostate specific membrane antigen.

Antibody-based reagents represent a promising strategy as clinical diagnostic tools. Prostate cancer (PCa) is the second-leading cause of death in males in the Western population. There is a presently unmet need for accurate diagnostic tool to localize and define the extent of both primary PCa and occult recurrent disease.

One of the most suitable targets for PCa is the prostate-specific membrane antigen (PSMA) recognized by the monoclonal antibody D2B that we re-shaped into the single chain Fv (scFv format). Aim of this study was to evaluate in preclinical in vivo models the target specificity of scFvD2B after labelling with different radionuclides. (111)In radiolabelling was performed via the chelator Bz-NOTA, and (131)I radioiodination was performed using iodogen. The potential for molecular imaging and the biological behaviour of the radiolabelled scFvD2B were evaluated in mice bearing two subcutaneous PCa isogenic cell lines that differed only in PSMA expression. Biodistribution studies were performed at 3, 9, 15 and 24 h after injection to determine the optimal imaging time point. A significant kidney accumulation, as percentage of injected dose of tissue (%ID/g), was observed for (111)In-scFvD2B at 3 h after injection (45% ID/g) and it was maintained up to 24 h (26% ID/g). By contrast, kidney accumulation of (131)I-scFvD2B was only marginally (0. 3% ID/g at 24 h). At the optimal time point defined between 15 h and 24 h, regardless of the radionuclide used, the scFvD2B was able to localize significantly better in the PSMA expressing tumours compared to the negative control; with (131)I-scFvD2B yielding a significantly better target/background ratio compared to (111)In-scFvD2B. These data suggest that, besides antigen specificity, chemical modification may affect antibody fragment biodistribution.

Immunology letters. 2015 Sep 21 [Epub ahead of print]

Barbara Frigerio, Fabio Benigni, Elena Luison, Ettore Seregni, Claudio Pascali, Giulio Fracasso, Sara Morlino, Riccardo Valdagni, Delia Mezzanzanica, Silvana Canevari, Mariangela Figini

Unit of Molecular Therapies, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. , Division of Oncology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy. , Unit of Molecular Therapies, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. , S. C Nuclear Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. , S. C Nuclear Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. , Department of Pathology and Diagnostics, University of Verona, Verona, Italy. , Prostate Cancer Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. , Prostate Cancer Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. , Unit of Molecular Therapies, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. , Unit of Molecular Therapies, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. , Unit of Molecular Therapies, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.  

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