Radiolabeled Anti-Claudin 4 and Anti-Prostate Stem Cell Antigen: Initial Imaging in Experimental Models of Pancreatic Cancer

• Published in: Molecular imaging Vol. 6; no. 2; pp. 131 - 139
• Main Authors: Foss, Catherine A., Fox, James J., Feldmann, Georg, Maitra, Anirban, Iacobuzio-Donohue, Christine, Kern, Scott E., Hruban, Ralph, Pomper, Martin G.
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01-03-2007
• Subjects: Animals; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - pharmacokinetics; Antigens, Neoplasm - analysis; Claudin-4; Epitopes - immunology; Fluorescent Antibody Technique; GPI-Linked Proteins; Humans; Iodine Radioisotopes - chemistry; Membrane Glycoproteins - analysis; Membrane Glycoproteins - immunology; Membrane Proteins - analysis; Membrane Proteins - immunology; Mice; Neoplasm Proteins - analysis; Neoplasm Proteins - immunology; Neoplasm Transplantation; Pancreatic Neoplasms - diagnosis; Radioimmunodetection - methods
• ISSN: 1535-3508; 1536-0121
• DOI: 10.2310/7290.2007.00010

Global expression profiling of pancreatic cancers has identified two cell surface molecules, claudin 4 and prostate stem cell antigen (PSCA), as being overexpressed in the vast majority of cases. Two antibodies, anti-claudin 4 and anti-PSCA, were radiolabeled with iodine 125 (125I) for imaging pancreatic cancer xenografts in mice using gamma scintigraphy and single-photon emission computed tomography-computed tomography (SPECT-CT). Immunofluorescence staining of intact and permeabilized Colo357 human pancreatic cancer cells showed strong extracellular staining by both anti-PSCA and anti-claudin 4. Biodistribution studies in claudin 4 and PSCA-expressing Colo357 and PANC-1 subcutaneous xenograft models in mice showed that [125I]anti-claudin 4 tumor to muscle ratio uptake was 4.3 in Colo357 at 6 days postinjection and 6.3 in PANC-1 xenografts at 4 days postinjection. Biodistribution of [125I]anti-PSCA showed tumor to muscle ratio uptake of 4.9 in Colo357 at 6 days postinjection. Planar gamma scintigraphic imaging in Colo357 xenograft-bearing mice showed clear tumor uptake of [125I]anti-claudin 4 by 24 hours postinjection and by 48 hours postinjection for [125I]anti-PSCA. SPECT-CT imaging with [125I]anti-claudin 4 and [125I]anti-PSCA in an L3.6PL orthotopic xenograft model showed strong tumor and spleen uptake at 5 days postinjection. Both anti-claudin 4 and anti-PSCA demonstrate promise as radiodiagnostic and possibly radiotherapeutic agents for human pancreatic cancers.