Targeting human prostate cancer with 111In‐labeled D2B IgG, F(ab′)2 and Fab fragments in nude mice with PSMA‐expressing xenografts. (25th April 2014)

• Record Type: Journal Article
• Authors: Lütje, Susanne; van Rij, Catharina M.; Franssen, Gerben M.; Fracasso, Giulio; Helfrich, Wijnand; Eek, Annemarie; Oyen, Wim J.; Colombatti, Marco; Boerman, Otto C.
• Is Part Of: Contrast media & molecular imaging. Volume 10:Number 1(2015:Jan./Feb.)
• Page Start: 28
• Page End: 36
• Publication Date: 2014-04-25
• Subjects: Diagnostic imaging -- Periodicals; Magnetic resonance imaging -- Periodicals; Contrast media (Diagnostic imaging) -- Periodicals; Contrast Media -- Periodicals; Diagnostic Imaging -- Periodicals; Substances de contraste -- Périodiques; Diagnostics moléculaires -- Périodiques; Imagerie médicale; Substance de contraste; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.0754
• DOI: 10.1002/cmmi.1596
• Languages: English
• ISSNs: 1555-4309

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>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′)<sub>2</sub> 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 <sup>111</sup>In‐D2B IgG, <sup>111</sup>In‐capromab pendetide, <sup>111</sup>In‐D2B F(ab′)<sub>2</sub> and <sup>111</sup>In‐D2B Fab fragments in mice with PSMA‐expressing LNCaP and PSMA‐negative PC3 tumors at several time points after injection. All <sup>111</sup>In‐labeled antibody formats specifically accumulated in the LNCaP tumors, with highest uptake of <sup>111</sup>In‐D2B IgG and <sup>111</sup>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 <sup>111</sup>In‐D2B F(ab′)<sub>2</sub> and <sup>111</sup>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 <sup>111</sup>In‐D2B IgG, <sup>111</sup>In‐F(ab′)<sub>2</sub>, <sup>111</sup>In‐Fab and <sup>111</sup>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′)<sub>2</sub> and Fab fragments for targeting PSMA‐expressing prostate cancer xenografts. Copyright © 2014 John Wiley & Sons, Ltd.</p> </abstract>