title: Preclinical 89Zr Immuno-PET of High-Grade Serous Ovarian Cancer and Lymph Node Metastasis.
abstract: The elevation of cancer antigen 125 (CA125) levels in the serum of asymptomatic patients precedes the radiologic detection of high-grade serous ovarian cancer by at least 2 mo and the final clinical diagnosis by 5 mo. PET imaging of CA125 expression by ovarian cancer cells may enhance the evaluation of the extent of disease and provide a roadmap to surgery as well as detect recurrence and metastases.
  
  
  
  (89)Zr-labeled mAb-B43.13 was synthesized to target CA125 and evaluated via PET imaging and biodistribution studies in mice bearing OVCAR3 human ovarian adenocarcinoma xenografts. Ex vivo analysis of tumors and lymph nodes was performed via autoradiography, histopathology, and immunohistochemistry.
  
  
  
  PET imaging using (89)Zr-DFO-mAb-B43.13 (DFO is desferrioxamine) clearly delineated CA125-positive OVCAR3 xenografts as early as 24 h after the administration of the radioimmunoconjugate. Biodistribution studies revealed accretion of (89)Zr-DFO-mAb-B43.13 in the OVCAR3 tumors, ultimately reaching 22.3 ± 6.3 percentage injected dose per gram (%ID/g) at 72 h after injection. Most interestingly, activity concentrations greater than 50 %ID/g were observed in the ipsilateral lymph nodes of the xenograft-bearing mice. Histopathologic analysis of the immuno-PET-positive lymph nodes revealed the presence of grossly metastasized ovarian cancer cells within the lymphoid tissues. In control experiments, only low-level, non-specific uptake of (89)Zr-labeled isotype IgG was observed in OVCAR3 tumors; similarly, low-activity concentrations of (89)Zr-DFO-mAb-B43.13 accumulated in CA125-negative SKOV3 tumors.
  
  
  
  Immuno-PET with (89)Zr-labeled mAb-B43.13 is a potential strategy for the noninvasive delineation of extent of disease and may add value in treatment planning and treatment monitoring of high-grade serous ovarian cancer.
authors.affiliation: Department of Radiology and the Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, New York Department of Oncology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Sai Kiran
authors.initials: SK
authors.lastname: Sharma
authors.affiliation: Department of Radiology and the Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Kuntal K
authors.initials: KK
authors.lastname: Sevak
authors.affiliation: Tri-Institutional Laboratory of Comparative Pathology, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, and The Rockefeller University, New York, New York.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Monette
authors.affiliation: Department of Radiology and the Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Sean D
authors.initials: SD
authors.lastname: Carlin
authors.affiliation: Department of Oncology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: James C
authors.initials: JC
authors.lastname: Knight
authors.affiliation: Department of Oncology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Frank R
authors.initials: FR
authors.lastname: Wuest
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York; and.
authors.forename: Evis
authors.initials: E
authors.lastname: Sala
authors.affiliation: Department of Chemistry, Hunter College and the Graduate Center of the City University of New York, New York, New York bz102@hunter.cuny.edu lewisj2@mskcc.org.
authors.forename: Brian M
authors.initials: BM
authors.lastname: Zeglis
authors.affiliation: Department of Radiology and the Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, New York bz102@hunter.cuny.edu lewisj2@mskcc.org.
authors.forename: Jason S
authors.initials: JS
authors.lastname: Lewis
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D018394:CA-125 Antigen / Q000276:immunology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000276:immunology / Q000493:pharmacokinetics*; D008207:Lymphatic Metastasis; D008565:Membrane Proteins / Q000276:immunology; D051379:Mice; D010051:Ovarian Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology*; D049268:Positron-Emission Tomography / Q000379:methods*; D011868:Radioisotopes; D014018:Tissue Distribution; D015040:Zirconium
chemical_list: D000911:Antibodies, Monoclonal; D018394:CA-125 Antigen; D018796:Immunoconjugates; C451759:MUC16 protein, human; D008565:Membrane Proteins; D011868:Radioisotopes; D015040:Zirconium
keywords: 89Zr; CA125; ovarian cancer; positron emission tomography
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