Radiolabeled anti-claudin 4 and anti-prostate stem cell antigen: initial imaging in experimental models of pancreatic cancer.

Abstract

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 ((125)I) 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 [(125)I]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 [(125)I]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 [(125)I]anti-claudin 4 by 24 hours postinjection and by 48 hours postinjection for [(125)I]anti-PSCA. SPECT-CT imaging with [(125)I]anti-claudin 4 and [(125)I]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.

• Authors: Catherine A Foss, James J Fox, Georg Feldmann, Anirban Maitra, Christine Iacobuzio-Donohue, Scott E Kern, Ralph Hruban, Martin G Pomper
• Journal: Molecular imaging (Mol Imaging) 2007 Mar-Apr Vol. 6 Issue 2 Pg. 131-9 ISSN: 1535-3508 [Print] England
• PMID: 17445507 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antigens, Neoplasm
• CLDN4 protein, human
• Claudin-4
• Cldn4 protein, mouse
• Epitopes
• GPI-Linked Proteins
• Iodine Radioisotopes
• Membrane Glycoproteins
• Membrane Proteins
• Neoplasm Proteins
• PSCA protein, human

Topics

• Animals
• Antibodies, Monoclonal (immunology, pharmacokinetics)
• Antigens, Neoplasm (analysis)
• Claudin-4
• Epitopes (immunology)
• Fluorescent Antibody Technique
• GPI-Linked Proteins
• Humans
• Iodine Radioisotopes (chemistry)
• Membrane Glycoproteins (analysis, immunology)
• Membrane Proteins (analysis, immunology)
• Mice
• Neoplasm Proteins (analysis, immunology)
• Neoplasm Transplantation
• Pancreatic Neoplasms (diagnosis)
• Radioimmunodetection (methods)