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TGF-beta Antibody Uptake in Recurrent High-Grade Glioma Imaged with Zr-89-Fresolimumab PET

den Hollander, M. W., Bensch, F., Glaudemans, A. W. J. M., Oude Munnink, T. H., Enting, R. H., den Dunnen, W. F. A., Heesters, M. A. A. M., Kruyt, F. A. E., Lub-de Hooge, M. N., de Groot, J. C., Pearlberg, J., Gietema, J. A., de Vries, E. G. E. & Walenkamp, A. M. E., Sep-2015, In : Journal of Nuclear Medicine. 56, 9, p. 1310-1314 5 p.

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  • TGF-beta Antibody Uptake in Recurrent High-Grade Glioma Imaged with Zr

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DOI

Transforming growth factor-beta (TGF-beta) signaling is involved in glioma development. The monoclonal antibody fresolimumab (GC1008) can neutralize all mammalian isoforms of TGF-beta, and tumor uptake can be visualized and quantified with Zr-89-fresolimumab PET in mice. The aim of this study was to investigate the fresolimumab uptake in recurrent high-grade gliomas using Zr-89-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 Zr-89-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. Zr-89-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 Zr-89-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: Zr-89-fresolimumab penetrated recurrent high-grade gliomas very well but did not result in clinical benefit.

Original languageEnglish
Pages (from-to)1310-1314
Number of pages5
JournalJournal of Nuclear Medicine
Volume56
Issue number9
Publication statusPublished - Sep-2015

    Keywords

  • PET imaging, recurrent high-grade glioma, Zr-89-fresolimumab, TGF-beta, MALIGNANT GLIOMA, GLIOBLASTOMA, RECEPTOR, CANCER, FRESOLIMUMAB, ACTIVATION, EXPRESSION, THERAPY, TUMORS, BRAIN

ID: 22359312