In the context of prostate cancer (PCa) imaging, the aim of this study was to optimize (in vitro) the specificity and assess preclinically (in vivo) the tumor targeting properties of the 123I-scFvD2B antibody specific for prostate-specific membrane antigen (PSMA).
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The 123I-labeling conditions of the antibody fragment scFvD2B, produced in an eukaryotic system under GMP-compliant conditions, were optimized and assessed for purity and immunoreactivity. The specificity and potency of tumor uptake were tested in three preclinical in vivo models of subcutaneously xenografted human tumors expressing different levels of PSMA (LNCaP, naturally expressing PSMA; PC3-PIP and LS174T-PSMA, transfected with PSMA) or PC3 and LS174T, as negative controls, to assess the clearance, biodistribution and imaging potential of 123I-scFvD2B.
The set conditions of production and radiolabeling yielded a reagent suitable for human delivery thanks to the purity of the formulation and the high immunoreactivity. In all preclinical models 123I-scFvD2B showed specific targeting only to PSMA-positive tumors with the final specific activity ranging up to 1500 MBq/mg. Despite different levels of PSMA expression, biodistribution analyses and SPECT/CT imaging demonstrated similar results and maximal signal-to-background ratios 24 hours after injection.
Due to its in vitro and in vivo properties, 123I-scFvD2B could be a promising tool for the early diagnosis of PCa, and may represent a molecular imaging option to monitor disease progression and assist in the clinical management of PCa patients.
Oncotarget. 2016 Dec 30 [Epub ahead of print]
Barbara Frigerio, Gerben Franssen, Elena Luison, Alessandro Satta, Ettore Seregni, Marco Colombatti, Giulio Fracasso, Riccardo Valdagni, Delia Mezzanzanica, Otto Boerman, Silvana Canevari, Mariangela Figini
Department of Experimental Oncology and Molecular Medicine, S.S. Molecular Therapies, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands., S.C. Nuclear Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Department of Medicine, University of Verona, Verona, Italy., Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, Radiation Oncology 1, Prostate Cancer Program, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.