Radiolabeled anti-claudin 4 and anti-prostate stem cell antigen: initial imaging in experimental models of pancreatic cancer.
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.
Foss
Catherine A
CA
Department of Radiology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Univeristy, Baltimore, MD 21287-2182, USA.
Fox
James J
JJ
Feldmann
Georg
G
Maitra
Anirban
A
Iacobuzio-Donohue
Christine
C
Kern
Scott E
SE
Hruban
Ralph
R
Pomper
Martin G
MG
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000493:pharmacokinetics; D000951:Antigens, Neoplasm / Q000032:analysis*; D062506:Claudin-4; D000939:Epitopes / Q000276:immunology; D005455:Fluorescent Antibody Technique; D058851:GPI-Linked Proteins; D006801:Humans; D007457:Iodine Radioisotopes / Q000737:chemistry; D008562:Membrane Glycoproteins / Q000032:analysis* / Q000276:immunology; D008565:Membrane Proteins / Q000032:analysis* / Q000276:immunology; D051379:Mice; D009363:Neoplasm Proteins / Q000032:analysis* / Q000276:immunology; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000175:diagnosis*; D016719:Radioimmunodetection / Q000379:methods*
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; C568157:CLDN4 protein, human; D062506:Claudin-4; C568158:Cldn4 protein, mouse; D000939:Epitopes; D058851:GPI-Linked Proteins; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C110843:PSCA protein, human