Targeting human prostate cancer with 111 In‐labeled D2B IgG, F(ab′) 2 and Fab fragments in nude mice with PSMA‐expressing xenografts

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 111 In‐D2B IgG, 111 In‐capromab pendetide, 111 In‐D2B F(ab′) 2 and 111 In‐D2B Fab fragments in mice with PSMA‐expressing LNCaP and PSMA‐negative PC3 tumors at several time points after injection. All 111 In‐labeled antibody formats specifically accumulated in the LNCaP tumors, with highest uptake of 111 In‐D2B IgG and 111 In‐capromab pendetide at 168 h p.i. (94.8 ± 19.2% injected dose per gram (ID/g) and 16.7 ± 2.2% ID/g, respectively), whereas uptake of 111 In‐D2B F(ab′) 2 and 111 In‐D2B Fab fragments peaked at 24 h 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 (168 h p.i.), 6.2 ± 0.7 (24 h p.i.), 23.0 ± 4.0 (24 h p.i.) and 4.5 ± 0.6 (168 h p.i.) for 111 In‐D2B IgG, 111 In‐F(ab′) 2 , 111 In‐Fab and 111 In‐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 © 2014 John Wiley & Sons, Ltd.