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. 111In radiolabelling was performed via the chelator Bz-NOTA, and 131I 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 111In-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 131I-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 131I-scFvD2B yielding a significantly better target/background ratio compared to 111In-scFvD2B. These data suggest that, besides antigen specificity, chemical modification may affect antibody fragment biodistribution.

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

FRACASSO, Giulio;
2015-01-01

Abstract

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. 111In radiolabelling was performed via the chelator Bz-NOTA, and 131I 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 111In-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 131I-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 131I-scFvD2B yielding a significantly better target/background ratio compared to 111In-scFvD2B. These data suggest that, besides antigen specificity, chemical modification may affect antibody fragment biodistribution.
Prostate Specific Membrane Antigen; antibody fragments single chain Fv; prostate cancer imaging; radiolabelling
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/934738
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