Martha W den Hollander1, Frederike Bensch1, Andor W J M Glaudemans2, Thijs H Oude Munnink1, Roelien H Enting3, Wilfred F A den Dunnen4, Mart A A M Heesters5, Frank A E Kruyt1, Marjolijn N Lub-de Hooge6, Jan Cees de Groot7, Joseph Pearlberg8, Jourik A Gietema1, Elisabeth G E de Vries1, Annemiek M E Walenkamp9. 1. Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. 2. Department of Nuclear Medicine and Molecular Imaging, University of Groningen, Groningen, The Netherlands. 3. Department of Neurology, University Medical Center Groningen, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. 4. Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. 5. Department of Radiotherapy, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. 6. 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. 7. Department of Radiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; and. 8. Sanofi-Aventis Oncology, Cambridge, Massachusetts. 9. Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands a.walenkamp@umcg.nl.
Abstract
UNLABELLED: 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). CONCLUSION: (89)Zr-fresolimumab penetrated recurrent high-grade gliomas very well but did not result in clinical benefit.
UNLABELLED: 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-fresolimumabtumor 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). CONCLUSION: (89)Zr-fresolimumab penetrated recurrent high-grade gliomas very well but did not result in clinical benefit.
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