title: Biodistribution and PET Imaging of Labeled Bispecific T Cell-Engaging Antibody Targeting EpCAM.
abstract: AMG 110, a bispecific T cell engager (BiTE) antibody construct, induces T cell-mediated cancer cell death by cross-linking epithelial cell adhesion molecule (EpCAM) on tumor cells with a cluster of differentiation 3 ε (CD3ε) on T cells. We labeled AMG 110 with (89)Zr or near-infrared fluorescent dye (IRDye) 800CW to study its tumor targeting and tissue distribution.
  
  
  
  Biodistribution and tumor uptake of (89)Zr-AMG 110 was studied up to 6 d after intravenous administration to nude BALB/c mice bearing high EpCAM-expressing HT-29 colorectal cancer xenografts. Tumor uptake of (89)Zr-AMG 110 was compared with uptake in head and neck squamous cell cancer FaDu (intermediate EpCAM) and promyelocytic leukemia HL60 (EpCAM-negative) xenografts. Intratumoral distribution in HT-29 tumors was studied using 800CW-AMG 110.
  
  
  
  Tumor uptake of (89)Zr-AMG 110 can be clearly visualized using small-animal PET imaging up to 72 h after injection. The highest tumor uptake of (89)Zr-AMG 110 at the 40-μg dose level was observed at 6 and 24 h (respectively, 5.35 ± 0.22 and 5.30 ± 0.20 percentage injected dose per gram; n = 3 and 4). Tumor uptake of (89)Zr-AMG 110 was EpCAM-specific and correlated with EpCAM expression. 800CW-AMG 110 accumulated at the tumor cell surface in viable EpCAM-expressing tumor tissue.
  
  
  
  PET and fluorescent imaging provided real-time information about AMG 110 distribution and tumor uptake in vivo. Our data support using (89)Zr and IRDye 800CW to evaluate tumor and tissue uptake kinetics of bispecific T cell engager antibody constructs in preclinical and clinical settings.
authors: Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors: Frank J
authors: FJ
authors: Warnders
authors: Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors: Stijn J H
authors: SJ
authors: Waaijer
authors: Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors: Martin
authors: M
authors: Pool
authors: Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors: Marjolijn N
authors: MN
authors: Lub-de Hooge
authors: Amgen Research (Munich) GmbH, Munich, Germany.
authors: Matthias
authors: M
authors: Friedrich
authors: Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors: Anton G T
authors: AG
authors: Terwisscha van Scheltinga
authors: Amgen Research (Munich) GmbH, Munich, Germany.
authors: Petra
authors: P
authors: Deegen
authors: Amgen Research (Munich) GmbH, Munich, Germany.
authors: Sabine K
authors: SK
authors: Stienen
authors: Amgen, Thousand Oaks, California; and.
authors: Peter C
authors: PC
authors: Pieslor
authors: Amgen, Thousand Oaks, California; and.
authors: H Kam
authors: HK
authors: Cheung
authors: Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands Department of Pharmacy, Section of Pharmacotherapy and Pharmaceutical Care, University of Groningen, Groningen, The Netherlands.
authors: Jos G W
authors: JG
authors: Kosterink
authors: Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands e.g.e.de.vries@umcg.nl.
authors: Elisabeth G E
authors: EG
authors: de Vries
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000493:pharmacokinetics*; D000071858:Epithelial Cell Adhesion Molecule / Q000276:immunology*; D018922:HL-60 Cells; D019073:HT29 Cells; D006801:Humans; D007553:Isotope Labeling; D008297:Male; D051379:Mice; D049268:Positron-Emission Tomography / Q000379:methods*; D011868:Radioisotopes; D013601:T-Lymphocytes / Q000276:immunology*; D014018:Tissue Distribution; D015040:Zirconium
chemical_list: D000911:Antibodies, Monoclonal; D000071858:Epithelial Cell Adhesion Molecule; D011868:Radioisotopes; D015040:Zirconium
keywords: 89Zr; BiTE; PET; fluorescence; imaging