title: ImmunoPET and biodistribution with human epidermal growth factor receptor 3 targeting antibody ⁸⁹Zr-RG7116.
abstract: The humanized monoclonal antibody with high affinity for the human epidermal growth factor receptor (HER) 3, RG7116, is a glycoengineered, IgG1 class antibody. By labeling RG7116 with zirconium-89 ((89)Zr) we aimed to visualize in vivo HER3 expression and study the biodistribution of this antibody in human tumor-bearing mice. Biodistribution of (89)Zr-RG7116 was studied in subcutaneously xenografted FaDu tumor cells (HER3-positive). Dose-dependency of (89)Zr-RG7116 organ distribution and specific tumor uptake was assessed by administering doses ranging from 0.05 to 10 mg/kg RG7116 to SCID/Beige mice. Biodistribution was analyzed at 24 and 144 h after injection. MicroPET imaging was performed at 1, 3, and 6 days after injection of 1.0 mg/kg (89)Zr-RG7116 in the FaDu, H441, QG-56 and Calu-1 xenografts with varying HER3 expression. The excised tumors were analyzed for HER3 expression. Biodistribution analyses showed a dose- and time-dependent (89)Zr-RG7116 tumor uptake in FaDu tumors. The highest tumor uptake of (89)Zr-RG7116 was observed in the 0.05 mg/kg dose group with 27.5%ID/g at 144 h after tracer injection. MicroPET imaging revealed specific tumor uptake of (89)Zr-RG7116 in FaDu and H441 models with an increase in tumor uptake over time. Biodistribution data was consistent with the microPET findings in FaDu, H441, QG56 and Calu-1 xenografts, which correlated with HER3 expression levels. In conclusion, (89)Zr-RG7116 specifically accumulates in HER3 expressing tumors. PET imaging with this tracer provides real-time non-invasive information about RG7116 distribution, tumor targeting and tumor HER3 expression levels.
authors.affiliation: Department of Medical Oncology; University of Groningen; Groningen, The Netherlands; Department of Hospital and Clinical Pharmacy; University of Groningen; Groningen, The Netherlands.
authors.forename: Anton G T
authors.initials: AG
authors.lastname: Terwisscha van Scheltinga
authors.affiliation: Department of Hospital and Clinical Pharmacy; University of Groningen; Groningen, The Netherlands; Department of Nuclear Medicine and Molecular Imaging; University of Groningen; Groningen, The Netherlands.
authors.forename: Marjolijn N
authors.initials: MN
authors.lastname: Lub-de Hooge
authors.affiliation: Pharma Research & Early Development (pRED); F. Hoffmann-La Roche AG; Basel, Switzerland.
authors.forename: Keelara
authors.initials: K
authors.lastname: Abiraj
authors.affiliation: Department of Medical Oncology; University of Groningen; Groningen, The Netherlands.
authors.forename: Carolien P
authors.initials: CP
authors.lastname: Schröder
authors.affiliation: Department of Medical Oncology; University of Groningen; Groningen, The Netherlands.
authors.forename: Linda
authors.initials: L
authors.lastname: Pot
authors.affiliation: Pharma Research & Early Development (pRED); Roche Diagnostics GmbH; Penzberg, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Bossenmaier
authors.affiliation: Pharma Research & Early Development (pRED); Roche Diagnostics GmbH; Penzberg, Germany.
authors.forename: Marlene
authors.initials: M
authors.lastname: Thomas
authors.affiliation: Pharma Research & Early Development (pRED); Roche Diagnostics GmbH; Penzberg, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Hölzlwimmer
authors.affiliation: Pharma Research & Early Development (pRED); Roche Diagnostics GmbH; Penzberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Friess
authors.affiliation: Department of Hospital and Clinical Pharmacy; University of Groningen; Groningen, The Netherlands.
authors.forename: Jos G W
authors.initials: JG
authors.lastname: Kosterink
authors.affiliation: Department of Medical Oncology; University of Groningen; Groningen, The Netherlands.
authors.forename: Elisabeth G E
authors.initials: EG
authors.lastname: de Vries
mesh_terms: D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000276:immunology / Q000494:pharmacology*; D064593:Heterografts; D006801:Humans; D018796:Immunoconjugates / Q000276:immunology / Q000493:pharmacokinetics*; D007554:Isotopes / Q000276:immunology / Q000494:pharmacology*; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000276:immunology; D049268:Positron-Emission Tomography / Q000379:methods*; D011859:Radiography; D019275:Radiopharmaceuticals / Q000276:immunology / Q000494:pharmacology*; D020893:Receptor, ErbB-3 / Q000276:immunology*; D015040:Zirconium / Q000276:immunology / Q000494:pharmacology*
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D018796:Immunoconjugates; D007554:Isotopes; D019275:Radiopharmaceuticals; D015040:Zirconium; C581292:ERBB3 protein, human; D020893:Receptor, ErbB-3
keywords: 89Zr; HER3; imaging; immunoPET; mAbs