Tumor Hypoxia and Proliferation in Patients With High-Grade Glioma

Overview

This is a pilot study to assess a new methodology developed for High Grade Glioma (HGG). FMISO PET (Fluoromisonidazole-PET) allows researchers to study whether tumor cells lack oxygen (hypoxia). FLT PET (Fluorodeoxythymidine-PET) allows researchers to study the increase in the number of cells as a result of cell growth and cell division (proliferation). Tumors that have low oxygen levels and/or are dividing fast shall resist to standard cancer treatment. The study will compare FMISO PET and FLT PET imaging techniques with molecular biomarkers of hypoxia, angiogenesis, and cellular proliferation in tissue. proliferation).This information could help researchers develop new treatment techniques to better treat cancer.

This is a pilot study to assess a novel methodology recently developed to simultaneously image tumor hypoxia and proliferation by means of simultaneous FMISO and FLT PET acquisition. FMISO (18F-Fluoromisonidazole) PET is a non-invasive method for detecting tumor hypoxia in solid tumors. FLT (3'-deoxy-3'\[(18)F\]-fluorothymidine) PET is a non-invasive method to image Cell proliferation rate. Imaging of tumor hypoxia and proliferation with FMISO and FLT PET respectively are two very well established techniques in in high-grade glioma. The long-term goal of this proposal is to establish clinically robust methodology to simultaneously image multiple tumor hallmarks. The central hypothesis is that combined information from multiple tumor hallmarks will offer complementary information about the underlying physiological processes, and will yield synergistic prognostic and predictive values. The rationale is that these findings will enhance the understanding of the underlying biology and pathophysiology, and will open new therapeutic strategies to target radioresistant and highly aggressive regions within the tumor, as well as aiding in the development of imaging theragnostics. The method used in this proposal is based on our previous work on simultaneous imaging of FMISO/FLT PET, and is facilitated by prior knowledge of the tissue pharmacokinetics, and an ability to distinguish the two radiotracers fractions in blood by thin-layer chromatography (TLC). The study will compare FMISO and FLT imaging findings with those from molecular biomarkers of hypoxia, angiogenesis, and cellular proliferation in tissue.