Glioblastoma is the most common primary malignant neoplasm of the adult brain. Even after multimodal therapy, outcomes remain poor, with a median survival of one year. Although advanced imaging methods have been suggested as molecular markers of prognosis and therapeutic response, these methods have not been validated for clinical use. In this exploratory, imaging-based, trial, thirty patients with a pathological diagnosis of glioblastoma will be followed prospectively for two years. The study examines how PET and MR imaging signals change following administration of a standard radio-chemotherapy treatment regimen to determine whether these imaging modalities can provide early indicators of response to therapeutic intervention. The investigators hypothesize that decreases in uptake of an investigational 18F-FLT PET tracer following treatment with radiation and chemotherapy will be a reliable predictor of glioblastoma response. In a more exploratory fashion, the investigators also will identify changes in diffusion and hypoxia MR imaging that may also correlate well with treatment response.

Patients with glioblastoma will be imaged with FLT PET/CT followed by MRI. The FLT uptake will be correlated with advanced MRI markers of tumor progression to determine the ability of using FLT PET and MRI for predicting response to treatment.

Inclusion Criteria:

• Adult patients (> 18 yo) with a pathological diagnosis of malignant glioma (WHO grades III and IV, including all histological subtypes)
• Surgical intervention includes subtotal resection or biopsy with MRI evidence of residual disease after resection
• Patients with plan to undergo standard chemotherapy and radiation protocols including a combination of fractionated radiation and temozolomide
• Preoperative Karnofsky performance score (KPS) of > 60
• Willingness of patient and his/her partner to use contraceptive measures for duration of trial that will include PET studies.

Exclusion Criteria:

• Patient refuses adjunctive therapy
• Pregnancy
• Karnofsky scale < 60
• Inability to undergo MR imaging studies
• Estimated GFR ≤ 60 ml/min (using GFR = 0.85*[140 - age(y)]*[bodyweight(kg)]/[72*Cr(mg/dl)] for women and GFR = [140 - age(y)]*[bodyweight(kg)]/[72*Cr(mg/dl)] for men).
• Inability or unwillingness to follow instructions for both PET and MR imaging sessions.

Patients with WHO grade III or IV glioma