18F PPRGD2 PET/CT, 18F FDG PET/CT and MRI Evaluation of Response to Anti-Angiogenesis Therapy in Recurrent Glioblastoma Multiforme

18F PPRGD2 PET/CT, 18F FDG PET/CT and MRI Evaluation of Response to Anti-Angiogenesis Therapy in Recurrent Glioblastoma Multiforme

Award: $1,479,171 over 3 years

Principal Investigator: Sanjiv Gambhir, MD, PhD; Co-Investigator: Andrei Iagaru, MD

Background: Bevacizumab is a therapeutic antibody designed to specifically inhibit vascular endothelial growth factor (VEGF). Phase II clinical trials of bevacizumab administered alone or in combination with irinotecan chemotherapy demonstrated encouraging six-month progression-free survival and objective response rates in patients with recurrent GBM. Brain MRI is currently the imaging modality of choice for evaluation of recurrent GBM and response to therapy. However, anatomic imaging may not detect early responses to anti-angiogenesis therapy such as bevacizumab. Fluorine-18 2-Fluoro 2-deoxyglucose (18F FDG) positron emission tomography and computed tomography (PET/CT) is a powerful imaging tool for cancer detection and monitoring response to therapy in various malignancies, but evaluation of response to therapy may be negatively influenced by its non-specificity (uptake in inflammatory/reactive cells) and normal high uptake in the brain. In this context, 18F-labeled dimeric RGD peptide [18F]FPA-PEG3-E[c(RGDyK)]2 ([18F] FPPRGD2), a novel radiopharmaceutical recently developed at Stanford for imaging of tumor integrin expression, may provide more accurate evaluation of response to anti-angiogenesis therapy in subjects with recurrent GBM.

Hypothesis: FPPRGD2 PET/CT scanning in patients with recurrent GBM is feasible and can reliably detect  (within 1 week after initiation of bevacizumab treatment) which patients will respond to anti-angiogenesis therapy early on.

Primary objective: To develop a non-invasive molecular imaging strategy for the early identification of patients with recurrent GBM who are most likely to respond to anti-angiogenesis therapy

Specific Aims:
1: Evaluate the feasibility of [18F] FPPRGD2 PET/CT scanning in patients with recurrent GBM
2: Compare [18F] FPPRGD2 PET/CT vs. 18F FDG PET/CT vs. brain MRI for evaluating response to anti-angiogenesis therapy (bevacizumab) in patients with recurrent GBM