Targeting human prostate cancer with 111In-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.
Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
Susanne
S
Lütje
Catharina M
CM
van Rij
Gerben M
GM
Franssen
Giulio
G
Fracasso
Wijnand
W
Helfrich
Annemarie
A
Eek
Wim J
WJ
Oyen
Marco
M
Colombatti
Otto C
OC
Boerman
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D000954:Antigens, Surface / Q000096:biosynthesis / Q000276:immunology*; D045744:Cell Line, Tumor; D043425:Glutamate Carboxypeptidase II / Q000096:biosynthesis / Q000276:immunology*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage / Q000276:immunology; D007074:Immunoglobulin G / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D008297:Male; D051379:Mice; D004369:Pentetic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000276:immunology; D011471:Prostatic Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D023041:Xenograft Model Antitumor Assays
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; C069971:DTPA-IgG complex; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D004369:Pentetic Acid; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II
D2B IgG; Fab fragments; capromab pendetide; prostate cancer imaging