TY - JOUR
T1 - TGF-beta Antibody Uptake in Recurrent High-Grade Glioma Imaged with Zr-89-Fresolimumab PET
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 - de Groot, Jan Cees
AU - Pearlberg, Joseph
AU - Gietema, Jourik A.
AU - de Vries, Elisabeth G. E.
AU - Walenkamp, Annemiek M. E.
N1 - Copyright © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
PY - 2015/9
Y1 - 2015/9
N2 - 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.
AB - 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.
KW - PET imaging
KW - recurrent high-grade glioma
KW - Zr-89-fresolimumab
KW - TGF-beta
KW - MALIGNANT GLIOMA
KW - GLIOBLASTOMA
KW - RECEPTOR
KW - CANCER
KW - FRESOLIMUMAB
KW - ACTIVATION
KW - EXPRESSION
KW - THERAPY
KW - TUMORS
KW - BRAIN
U2 - 10.2967/jnumed.115.154401
DO - 10.2967/jnumed.115.154401
M3 - Article
C2 - 26135113
SN - 0161-5505
VL - 56
SP - 1310
EP - 1314
JO - Journal of Nuclear Medicine
JF - Journal of Nuclear Medicine
IS - 9
ER -