TY - JOUR T1 - TGF-β Antibody Uptake in Recurrent High-Grade Glioma Imaged with <sup>89</sup>Zr-Fresolimumab PET JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 1310 LP - 1314 DO - 10.2967/jnumed.115.154401 VL - 56 IS - 9 AU - Martha W. den Hollander AU - Frederike Bensch AU - Andor W.J.M. Glaudemans AU - Thijs H. Oude Munnink AU - Roelien H. Enting AU - Wilfred F.A. den Dunnen AU - Mart A.A.M. Heesters AU - Frank A.E. Kruyt AU - Marjolijn N. Lub-de Hooge AU - Jan Cees de Groot AU - Joseph Pearlberg AU - Jourik A. Gietema AU - Elisabeth G.E. de Vries AU - Annemiek M.E. Walenkamp Y1 - 2015/09/01 UR - http://jnm.snmjournals.org/content/56/9/1310.abstract N2 - 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 89Zr-fresolimumab PET in mice. The aim of this study was to investigate the fresolimumab uptake in recurrent high-grade gliomas using 89Zr-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 89Zr-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. 89Zr-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 89Zr-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: 89Zr-fresolimumab penetrated recurrent high-grade gliomas very well but did not result in clinical benefit. ER -