Approaches to PET Imaging of Glioblastoma

Glioblastoma multiforme (GBM) is the deadliest type of brain tumor, affecting approximately three in 100,000 adults annually. Positron emission tomography (PET) imaging provides an important non-invasive method of measuring biochemically specific targets at GBM lesions. These powerful data can characterize tumors, predict treatment effectiveness, and monitor treatment. This review will discuss the PET imaging agents that have already been evaluated in GBM patients so far, and new imaging targets with promise for future use. Previously used PET imaging agents include the tracers for markers of proliferation ([¹¹C]methionine; [¹⁸F]fluoro-ethyl-L-tyrosine, [¹⁸F]Fluorodopa,[¹⁸F]fluoro-thymidine, and [¹⁸F]clofarabine), hypoxia sensing ([¹⁸F]FMISO, [¹⁸F]FET-NIM, [¹⁸F]EF5, [¹⁸F]HX4, and [⁶⁴Cu]ATSM), and ligands for inflammation. As cancer therapeutics evolve toward personalized medicine and therapies centered on tumor biomarkers, the development of complimentary selective PET agents can dramatically enhance these efforts. Newer biomarkers for GBM PET imaging are discussed, with some already in use for PET imaging other cancers and neurological disorders. These targets include Sigma 1, Sigma 2, programmed death ligand 1, poly-ADP-ribose polymerase, and isocitrate dehydrogenase. For GBM, these imaging agents come with additional considerations such as blood-brain barrier penetration, quantitative modeling approaches, and nonspecific binding.