PT  - JOURNAL ARTICLE
AU  - den Hollander, Martha W.
AU  - Bensch, Frederike
AU  - Glaudemans, Andor W.J.M.
AU  - Oude Munnink, Thijs H.
AU  - Enting, Roelien H.
AU  - den Dunnen, Wilfred F.A.
AU  - Heesters, Mart A.A.M.
AU  - Kruyt, Frank A.E.
AU  - Lub-de Hooge, Marjolijn N.
AU  - Cees de Groot, Jan
AU  - Pearlberg, Joseph
AU  - Gietema, Jourik A.
AU  - de Vries, Elisabeth G.E.
AU  - Walenkamp, Annemiek M.E.
TI  - TGF-β Antibody Uptake in Recurrent High-Grade Glioma Imaged with <sup>89</sup>Zr-Fresolimumab PET
AID  - 10.2967/jnumed.115.154401
DP  - 2015 Sep 01
TA  - Journal of Nuclear Medicine
PG  - 1310--1314
VI  - 56
IP  - 9
4099  - http://jnm.snmjournals.org/content/56/9/1310.short
4100  - http://jnm.snmjournals.org/content/56/9/1310.full
SO  - J Nucl Med2015 Sep 01; 56
AB  - 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.