2015
DOI: 10.2967/jnumed.115.154401
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TGF-β Antibody Uptake in Recurrent High-Grade Glioma Imaged with 89Zr-Fresolimumab PET

Abstract: Transforming growth factor-b (TGF-b) signaling is involved in glioma development. The monoclonal antibody fresolimumab (GC1008) can neutralize all mammalian isoforms of TGF-b, 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… Show more

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Cited by 81 publications
(54 citation statements)
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“…For imaging of a number of antibodies without dose-dependent PK, such as bevacizumab, fresolizumab or the mesothelin-targeting antibody MMOT0530A, a dose of 5 or 10 mg unlabeled antibody was already sufficient for optimal PET imaging (24,29,32,42). However, for HER2 imaging with 89 Zr-trastuzumab, an antibody with clear dose-dependent PK, an additional dose of 50 mg unlabeled trastuzumab is needed for optimal imaging (43, 44).…”
Section: Discussionmentioning
confidence: 99%
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“…For imaging of a number of antibodies without dose-dependent PK, such as bevacizumab, fresolizumab or the mesothelin-targeting antibody MMOT0530A, a dose of 5 or 10 mg unlabeled antibody was already sufficient for optimal PET imaging (24,29,32,42). However, for HER2 imaging with 89 Zr-trastuzumab, an antibody with clear dose-dependent PK, an additional dose of 50 mg unlabeled trastuzumab is needed for optimal imaging (43, 44).…”
Section: Discussionmentioning
confidence: 99%
“…As often, an additional dose of unlabeled antibody was required for imaging to guarantee sufficient circulating labeled antibody and thereby to improve tumor visualization (23,26,29,32). We first verified the tracer biodistribution with escalating doses of 10, 50 and 100 mg of unlabeled lumretuzumab.…”
Section: Methodsmentioning
confidence: 99%
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“…Another phase I trial of fresolimumab was conducted with 12 patients: 10 patients with glioblastomas and one patient each with anaplastic oligodendroglioma or anaplastic astrocytoma. PET scans used to monitor treatment efficacy showed radiologic progression in all patients in the trial after one to three infusions of fresolimumab [65].…”
Section: Tgfβ Antibodiesmentioning
confidence: 99%
“…Galunisertib (LY2157299), a TGF-β receptor I kinase inhibitor, failed to demonstrate improved overall survival as compared to lomustine in patients with recurrent GBM (135) but is now being tested in combination with nivolumab in patients with GBM and recurrent pancreatic cancer and hepatocellular carcinoma (NCT02423343; Table 3). Similarly, fresolimumab, a pan-TGF-β antibody failed to show survival benefit in patients with glioma (136). Although these results are quite discouraging, it is important to pursue investigation of TGF-β targeting.…”
Section: Targeting the Tumor Environmentmentioning
confidence: 99%