Improvement of Malignant Glioma Treatment: Preclinical evaluation of adenoviral gene therapy and PRRT

Glioblastoma multiforme (GBM) is the most aggressive type of malignant glioma (WHO grade 4). Patients suffering from a GBM have a median survival of less than a year after diagnosis despite the recent developments in neurosurgery, radiotherapy and chemotherapy. This poor prognosis has led to the investigation of new treatment modalities. Locoregional treatment modalities are potentially attractive for GBMs because these tumors are generally confined to the central nervous system and only rarely metastasize outside the nervous system. Examples of such locoregional treatment modalities are gene therapy and peptide receptor radionuclide therapy (PRRT). As will be discussed in chapter 1.2, after successful gene therapy treatment experiments in animal models, the clinical results of GBM gene therapy have been disappointing, showing the need for improvement of this modality. PRRT could also be beneficial for GBM patients since small radiolabeled peptide molecules can migrate from the injection site to the tumor, and target to their corresponding receptor on the cell membrane of these cells. At this moment, however, it is not clear which peptide receptors are expressed on human GBM tissues. The goal of this thesis was to identify bottlenecks limiting the efficacy of glioma gene therapy using molecular imaging techniques. In addition, we explored the possibility of PRRT treatment for GBM patients.

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