Brain tumors account for only 2% of all cancers but result in a disproportionate share of
cancer morbidity and mortality. The five-year survival rates for the most common histologic
subtypes, anaplastic astrocytoma and glioblastoma (glioblastoma multiforme, GBM), are 30% and
10%, respectively.
Drugs affecting transforming growth factor-β (TGF-β) might be of great interest for malignant
glioma treatment. TGF-β is an oncogenic factor in advanced tumors where it induces
proliferation, angiogenesis, invasion, and metastasis as well as suppresses the antitumoral
immune response. In addition TGF-β and its TGF-β receptors, TβRI and TβRII, are overexpressed
in GBMs. TGF-β signaling is involved in multiple steps of GBM development. GC1008 is an
antibody that is capable of neutralizing TGF-β and may therefore offer a new treatment option
for patients with malignant glioma.
For therapeutic success, it may be essential for GC1008 to reach the target site, in this
case located in the brain. We will be able to prove this with 89Zr-GC1008 PET imaging. This
imaging method also allows quantification of the amount of GC1008 reaching the tumor.
This study consists of 2 parts. In part 1, patients with a suspicion of a malignant glioma
undergo an 89Zr-GC1008 PET scan before standard (surgical)treatment. In part 2, patients with
relapsed malignant glioma will undergo an 89Zr-GC1008 PET scan and will be treated with
GC1008 in a phase II study as there is no standard treatment for these patients.
We hypothesize that GC1008 uptake in brain tumors can be visualized and quantified using the
89Zr-GC1008 PET scan and GC1008 might offer a new treatment option for patients with relapsed
malignant gliomas.