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D2B is a new monoclonal antibody directed against an extracellular domain of prostate-specific membrane antigen (PSMA), which is overexpressed in prostate cancer. The potential of D2B IgG, and F(ab)(2) and Fab fragments of this antibody for targeting prostate cancer was determined in mice bearing subcutaneous prostate cancer xenografts. The optimal time point for imaging was determined in biodistribution and microSPECT imaging studies with In-111-D2B IgG, In-111-capromab pendetide, In-111-D2B F(ab)(2) and In-111-D2B Fab fragments in mice with PSMA-expressing LNCaP and PSMA-negative PC3 tumors at several time points after injection. All In-111-labeled antibody formats specifically accumulated in the LNCaP tumors, with highest uptake of In-111-D2B IgG and In-111-capromab pendetide at 168h p.i. (94.8 +/- 19.2% injected dose per gram (ID/g) and 16.7 +/- 2.2% ID/g, respectively), whereas uptake of In-111-D2B F(ab)(2) and In-111-D2B Fab fragments peaked at 24h p.i. (12.1 +/- 3.0% ID/g and 15.1 +/- 2.9% ID/g, respectively). Maximum LNCaP tumor-to-blood ratios were 13.0 +/- 2.3 (168h p.i.), 6.2 +/- 0.7 (24h p.i.), 23.0 +/- 4.0 (24h p.i.) and 4.5 +/- 0.6 (168h p.i.) for In-111-D2B IgG, In-111-F(ab)(2), In-111-Fab and In-111-capromab pendetide, respectively. LNCaP tumors were clearly visualized with microSPECT with all antibody formats. This study demonstrates the feasibility of D2B IgG, F(ab)(2) and Fab fragments for targeting PSMA-expressing prostate cancer xenografts. Copyright (c) 2014 John Wiley & Sons, Ltd.