title: Multimodal imaging analysis of an orthotopic head and neck cancer mouse model and application of anti-CD137 tumor immune therapy.
abstract: BACKGROUND
  Recent technical progress makes sophisticated noninvasive imaging methods available for murine models. For the first time, in this study, we applied fluorodeoxyglucose (FDG)-positron emission tomography (PET)-CT and FDG-PET-MRI to a murine orthotopic model of head and neck cancer immunotherapy.
  
  
  METHODS
  Tumor growth of floor of the mouth tumors was evaluated by multimodal small-animal imaging using FDG-PET-CT and FDG-PET-MRI. The immunotherapeutic effects of anti-CD137 antibody therapy were examined on body weight, tumor growth, and tumor-infiltrating immune cells in longitudinal imaging studies and immunohistochemical analyses.
  
  
  RESULTS
  Imaging revealed aggressive, fast-growing tumors without evidence of local or distant metastases. CD137 immunotherapy decreased tumor take and growth and stabilized body weight over time. A clear case of tumor regression was demonstrated by longitudinal PET-CT.
  
  
  CONCLUSIONS
  The murine model mimics the characteristics of head and neck cancer in humans and offers excellent opportunities to investigate immunomodulatory anticancer drugs. The CD137 antibody showed antitumor effects in some therapy-responsive mice.
authors.affiliation: Department of Otorhinolaryngology, University Hospital Essen, Essen, Germany.
authors.forename: Anne-Kristin
authors.initials: AK
authors.lastname: Vahle
authors.affiliation: European Institute for Molecular Imaging, University of Münster, Münster, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Hermann
authors.affiliation: European Institute for Molecular Imaging, University of Münster, Münster, Germany.|Department of Nuclear Medicine, University Hospital Münster, Germany.|Cluster of Excellence EXC 1003 "CiM - Cells in Motion,", University of Münster, Münster, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Schäfers
authors.affiliation: Department of Otorhinolaryngology, University Hospital Essen, Essen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Wildner
authors.affiliation: Department of Otorhinolaryngology, University Hospital Essen, Essen, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kerem
authors.affiliation: Department of Otorhinolaryngology, University Hospital Essen, Essen, Germany.
authors.forename: Ender
authors.initials: E
authors.lastname: Öztürk
authors.affiliation: Bristol-Myers Squibb Company, New York, New York.
authors.forename: Maria
authors.initials: M
authors.lastname: Jure-Kunkel
authors.affiliation: Department of Otorhinolaryngology, University Hospital Essen, Essen, Germany.
authors.forename: Cindy
authors.initials: C
authors.lastname: Franklin
authors.affiliation: Department of Otorhinolaryngology, University Hospital Essen, Essen, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Lang
authors.affiliation: Department of Otorhinolaryngology, University Hospital Essen, Essen, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Brandau
mesh_terms: D053330:4-1BB Ligand / Q000037:antagonists & inhibitors*; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging* / Q000473:pathology / Q000628:therapy; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D019788:Fluorodeoxyglucose F18; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology / Q000628:therapy; D007150:Immunohistochemistry; D007167:Immunotherapy / Q000379:methods*; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods; D051379:Mice; D008809:Mice, Inbred C3H; D009062:Mouth Neoplasms / Q000000981:diagnostic imaging* / Q000628:therapy*; D064847:Multimodal Imaging / Q000379:methods*; D000072078:Positron Emission Tomography Computed Tomography / Q000379:methods; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D053330:4-1BB Ligand; C505975:Tnfsf9 protein, mouse; D019788:Fluorodeoxyglucose F18
keywords: 4-1BB; head and neck squamous cell carcinoma; immunotherapy; longitudinal positron emission tomography (PET)-MRI; small-animal positron emission tomography (PET)-CT