title: Improved targeting of pancreatic cancer: experimental studies of a new bispecific antibody, pretargeting enhancement system for immunoscintigraphy.
abstract: OBJECTIVE
  The early detection and diagnosis of pancreatic cancer remains a major clinical challenge in which imaging procedures have a central role. The purpose of this study was to evaluate a pretargeting method with a bispecific PAM4 (bsPAM4; anti-MUC1) antibody for radioimmunoscintigraphy of experimental human pancreatic cancer.
  
  
  METHODS
  A bispecific F(ab')(2) antibody was generated from chimeric PAM4 Fab' and murine 734 (anti-indium-diethylenetriaminepentaacetic acid) Fab' fragments and then used in conjunction with 2 peptide haptens ((111)In-IMP-156 and (99m)Tc-IMP-192). Biodistribution studies and radioimmunoscintigraphic imaging properties of the radiolabeled bsPAM4, and pretargeted, radiolabeled peptides were examined in the CaPan1 human pancreatic tumor grown as s.c. xenografts in athymic nude mice. Tumor uptake and tumor:nontumor ratios were compared with a nontargeting irrelevant anti-CD20, bispecific rituximab, radiolabeled peptides alone, and with directly labeled PAM4.
  
  
  RESULTS
  Biodistribution results indicated significantly greater tumor uptake of radiolabeled peptides at 3 h after injection when pretargeting was performed with bsPAM4 as compared with the bispecific rituximab [20.2 +/- 5.5 percentage of injected dose per gram of tissue (%ID/g) versus 0.9 +/- 0.1%ID/g, respectively, for (111)In-IMP-156, and 16.8 +/- 4.8%ID/g versus 1.1 +/- 0.2%ID/g, respectively, for (99m)Tc-IMP-192]. Similar results were obtained at the 24-h time point. Tumor:nontumor ratios were >30 for all of the tissues except the kidneys, where a ratio of 7.8 +/- 2.8 was observed. By immunoscintigraphy, tumors could be visualized as early as 30 min after injection of the radiolabeled peptide.
  
  
  CONCLUSIONS
  These studies demonstrate the feasibility of using the pretargeted, bispecific antibody technology for nuclear imaging of pancreatic cancer. The advantage of pretargeted bsPAM4 antibody as an imaging platform is the high specificity for pancreatic cancer as compared with the physicochemical parameters identified by current imaging technologies.
authors.affiliation: Garden State Cancer Center, Belleville, New Jersey 07109, USA.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Cardillo
authors.forename: Habibe
authors.initials: H
authors.lastname: Karacay
authors.forename: David M
authors.initials: DM
authors.lastname: Goldenberg
authors.forename: Dion
authors.initials: D
authors.lastname: Yeldell
authors.forename: Chien-Hsing
authors.initials: CH
authors.lastname: Chang
authors.forename: David E
authors.initials: DE
authors.lastname: Modrak
authors.forename: Robert M
authors.initials: RM
authors.lastname: Sharkey
authors.forename: David V
authors.initials: DV
authors.lastname: Gold
mesh_terms: D000818:Animals; D000906:Antibodies / Q000737:chemistry; D018033:Antibodies, Bispecific / Q000737:chemistry*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20 / Q000096:biosynthesis; D045744:Cell Line, Tumor; D006241:Haptens / Q000737:chemistry; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000276:immunology*; D010455:Peptides / Q000737:chemistry; D016719:Radioimmunodetection / Q000379:methods*; D000069283:Rituximab; D013997:Time Factors
chemical_list: D000906:Antibodies; D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D006241:Haptens; D010455:Peptides; D000069283:Rituximab