title: Preloading with Unlabeled CA19.9 Targeted Human Monoclonal Antibody Leads to Improved PET Imaging with89Zr-5B1.
abstract: CA19.9 is one of the most commonly occurring and highest density antigens in >90% of pancreatic cancers, making it an excellent target for monoclonal antibody (mAb)-based imaging and therapy applications. Preloading of unlabeled antibodies to enhance targeting of a radiolabeled mAb has been previously described both for imaging and radioimmunotherapy studies for other targets. We investigated the effect of preloading with the unmodified anti-CA19.9 antibody 5B1 on the uptake and contrast of the PET tracer89Zr-5B1 in subcutaneous and orthotopic murine models of pancreatic cancer utilizing Capan-2 xenografts, known to both express CA19.9 and shed antigen into circulation. Biodistribution and PET imaging studies with89Zr-5B1 alone showed high levels in the liver, spleen, and lymph nodes of mice with subcutaneous Capan-2 tumor xenografts when administered without preinjection of 5B1. When unlabeled 5B1 was administered prior to89Zr-5B1, the tracer significantly enhanced image contrast and tumor to tissue ratios in the same model, and the improvement was related to the time interval between the injections. Moreover, tumors were clearly delineated in an orthotopic pancreatic cancer model using our optimized approach. Taken together, these data suggest that preloading with 5B1 can improve89Zr-5B1 imaging of disease in a Capan-2 mouse model and that exploration of preloading may have clinical utility for ongoing clinical investigations.
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center , New York, New York 10065, United States.
authors.forename: Jacob L
authors.identifier: 0000-0003-4255-3044
authors.initials: JL
authors.lastname: Houghton
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center , New York, New York 10065, United States.
authors.forename: Dalya
authors.initials: D
authors.lastname: Abdel-Atti
authors.affiliation: MabVax Therapeutics , San Diego, California 92121, United States.
authors.forename: Wolfgang W
authors.initials: WW
authors.lastname: Scholz
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center , New York, New York 10065, United States.|Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center , New York, New York 10065, United States.
authors.forename: Jason S
authors.initials: JS
authors.lastname: Lewis
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry*; D018395:CA-19-9 Antigen / Q000737:chemistry*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000175:diagnosis*; D049268:Positron-Emission Tomography / Q000379:methods; D011868:Radioisotopes / Q000737:chemistry*; D019275:Radiopharmaceuticals / Q000737:chemistry*; D014018:Tissue Distribution; D015040:Zirconium / Q000737:chemistry*
chemical_list: D000911:Antibodies, Monoclonal; D018395:CA-19-9 Antigen; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D015040:Zirconium
keywords: 5B1; CA19.9; PET imaging; pancreatic cancer