title: Small-Animal PET Imaging of Pancreatic Cancer Xenografts Using a 64Cu-Labeled Monoclonal Antibody, MAb159.
abstract: Overexpression of the GRP78 receptor on cell surfaces has been linked with tumor growth, metastasis, and resistance to therapy. We developed a (64)Cu-labeled probe for PET imaging of tumor GRP78 expression based on a novel anti-GRP78 monoclonal antibody, MAb159.
  
  
  METHODS
  MAb159 was conjugated with the (64)Cu-chelator DOTA through lysines on the antibody. DOTA-human IgG was also prepared as a control that did not bind to GRP78. The resulting PET probes were evaluated in BXPC3 pancreatic cancer xenografts in athymic nude mice.
  
  
  RESULTS
  The radiotracer was synthesized with a specific activity of 0.8 MBq/μg of antibody. In BXPC3 xenografts, (64)Cu-DOTA-MAb159 demonstrated prominent tumor accumulation (4.3 ± 1.2, 15.4 ± 2.6, and 18.3 ± 1.0 percentage injected dose per gram at 1, 17, and 48 after injection, respectively). In contrast, (64)Cu-DOTA-human IgG had low BXPC3 tumor accumulation (4.8 ± 0.5, 7.5 ± 0.7, and 4.6 ± 0.8 percentage injected dose per gram at 1, 17, and 48 h after injection, respectively).
  
  
  CONCLUSIONS
  We demonstrated that GRP78 can serve as a valid target for pancreatic cancer imaging. The success of this approach will be valuable for evaluating disease course and therapeutic efficacy at the earliest stages of anti-GRP78 treatment. Moreover, these newly developed probes may have important applications in other types of cancer overexpressing GRP78.
authors.affiliation: Department of Radiology and Biomedical Research Imaging Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Radiology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China Molecular Imaging Center, Department of Radiology, University of Southern California, Los Angeles, California Guangdong Provincial Engineering Research Center of Molecular Imaging, Guangzhou, China ziboli@med.unc.edu shanhong@mail.sysu.edu.cn.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.affiliation: Molecular Imaging Center, Department of Radiology, University of Southern California, Los Angeles, California.
authors.forename: Shuanglong
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Pathology, University of Southern California, Los Angeles, California; and.
authors.forename: Ren
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of Radiology and Biomedical Research Imaging Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Hong
authors.initials: H
authors.lastname: Yuan
authors.affiliation: Vasgene Therapeutics Inc., Los Angeles, California.
authors.forename: Valery
authors.initials: V
authors.lastname: Krasnoperov
authors.affiliation: Department of Radiology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China Guangdong Provincial Engineering Research Center of Molecular Imaging, Guangzhou, China ziboli@med.unc.edu shanhong@mail.sysu.edu.cn.
authors.forename: Hong
authors.initials: H
authors.lastname: Shan
authors.affiliation: Molecular Imaging Center, Department of Radiology, University of Southern California, Los Angeles, California.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Conti
authors.affiliation: Department of Pathology, University of Southern California, Los Angeles, California; and.
authors.forename: Parkash S
authors.initials: PS
authors.lastname: Gill
authors.affiliation: Department of Radiology and Biomedical Research Imaging Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina Molecular Imaging Center, Department of Radiology, University of Southern California, Los Angeles, California ziboli@med.unc.edu shanhong@mail.sysu.edu.cn.
authors.forename: Zibo
authors.initials: Z
authors.lastname: Li
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000737:chemistry*; D045744:Cell Line, Tumor; D003301:Copper Radioisotopes; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D006360:Heat-Shock Proteins / Q000737:chemistry; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D014018:Tissue Distribution
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D003301:Copper Radioisotopes; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D006573:Heterocyclic Compounds, 1-Ring; C000717248:Hspa5 protein, mouse; D007074:Immunoglobulin G; D019275:Radiopharmaceuticals; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
keywords: 64Cu; GRP78; PET; pancreatic cancer