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

• Main Authors: Catherine A. Foss, James J. Fox, Georg Feldmann, Anirban Maitra, Christine Iacobuzio-Donohue, Scott E. Kern, Ralph Hruban, Martin G. Pomper
• Format: Article
• Language: English
• Published: Hindawi - SAGE Publishing 2007-03-01
• Series: Molecular Imaging
• Online Access: https://doi.org/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 ( 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.