title: TGF-β Antibody Uptake in Recurrent High-Grade Glioma Imaged with 89Zr-Fresolimumab PET.
abstract: Transforming growth factor-β (TGF-β) signaling is involved in glioma development. The monoclonal antibody fresolimumab (GC1008) can neutralize all mammalian isoforms of TGF-β, and tumor uptake can be visualized and quantified with (89)Zr-fresolimumab PET in mice. The aim of this study was to investigate the fresolimumab uptake in recurrent high-grade gliomas using (89)Zr-fresolimumab PET and to assess treatment outcome in patients with recurrent high-grade glioma treated with fresolimumab.
  
  
  METHODS
  Patients with recurrent glioma were eligible. After intravenous administration of 37 MBq (5 mg) of (89)Zr-fresolimumab, PET scans were acquired on day 2 or day 4 after tracer injection. Thereafter, patients were treated with 5 mg of fresolimumab per kilogram intravenously every 3 wk. (89)Zr-fresolimumab tumor uptake was quantified as maximum standardized uptake value (SUVmax). MR imaging for response evaluation was performed after 3 infusions or as clinically indicated.
  
  
  RESULTS
  Twelve patients with recurrent high-grade glioma were included: 10 glioblastomas, 1 anaplastic oligodendroglioma, and 1 anaplastic astrocytoma. All patients underwent (89)Zr-fresolimumab PET 4 d after injection. In 4 patients, an additional PET scan was obtained on day 2 after injection. SUVmax on day 4 in tumor lesions was 4.6 (range, 1.5-13.9) versus a median SUVmean of 0.3 (range, 0.2-0.5) in normal brain tissue. All patients showed clinical or radiologic progression after 1-3 infusions of fresolimumab. Median progression-free survival was 61 d (range, 25-80 d), and median overall survival was 106 d (range, 37-417 d).
  
  
  CONCLUSIONS
  (89)Zr-fresolimumab penetrated recurrent high-grade gliomas very well but did not result in clinical benefit.
authors.affiliation: Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Martha W
authors.initials: MW
authors.lastname: den Hollander
authors.affiliation: Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Frederike
authors.initials: F
authors.lastname: Bensch
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University of Groningen, Groningen, The Netherlands.
authors.forename: Andor W J M
authors.initials: AW
authors.lastname: Glaudemans
authors.affiliation: Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Thijs H
authors.initials: TH
authors.lastname: Oude Munnink
authors.affiliation: Department of Neurology, University Medical Center Groningen, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Roelien H
authors.initials: RH
authors.lastname: Enting
authors.affiliation: Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Wilfred F A
authors.initials: WF
authors.lastname: den Dunnen
authors.affiliation: Department of Radiotherapy, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Mart A A M
authors.initials: MA
authors.lastname: Heesters
authors.affiliation: Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Frank A E
authors.initials: FA
authors.lastname: Kruyt
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University of Groningen, Groningen, The Netherlands Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Marjolijn N
authors.initials: MN
authors.lastname: Lub-de Hooge
authors.affiliation: Department of Radiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; and.
authors.forename: Jan
authors.initials: J
authors.lastname: Cees de Groot
authors.affiliation: Sanofi-Aventis Oncology, Cambridge, Massachusetts.
authors.forename: Joseph
authors.initials: J
authors.lastname: Pearlberg
authors.affiliation: Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Jourik A
authors.initials: JA
authors.lastname: Gietema
authors.affiliation: Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Elisabeth G E
authors.initials: EG
authors.lastname: de Vries
authors.affiliation: Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands a.walenkamp@umcg.nl.
authors.forename: Annemiek M E
authors.initials: AM
authors.lastname: Walenkamp
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000532:radiotherapy; D045744:Cell Line, Tumor; D005260:Female; D005910:Glioma / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000532:radiotherapy*; D049268:Positron-Emission Tomography / Q000379:methods; D011868:Radioisotopes / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D014018:Tissue Distribution; D016212:Transforming Growth Factor beta / Q000276:immunology; D015040:Zirconium / Q000493:pharmacokinetics
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D016212:Transforming Growth Factor beta; C560928:fresolimumab; D015040:Zirconium
keywords: 89Zr-fresolimumab; PET imaging; TGF-β; recurrent high-grade glioma