Investigational PET tracers for high-grade gliomas

High-grade gliomas (HGGs) are the most common primary malignant tumors of the brain, with glioblastoma (GBM) constituting over 50% of all the gliomas in adults. The disease carries very high mortality, and even with optimal treatment, the median survival is 2-5 years for anaplastic tumors and 1-2 years for GBMs. Neuroimaging is critical to managing patients with HGG for diagnosis, treatment planning, response assessment, and detecting recurrent disease. Magnetic resonance imaging (MRI) is the cornerstone of imaging in neuro-oncology, but molecular imaging with positron emission tomography (PET) can overcome some of the inherent limitations of MRI. Additionally, PET has the potential to target metabolic and molecular alterations in HGGs relevant to prognosis and therapy that cannot be assessed with anatomic imaging. Many classes of PET tracers have been evaluated in HGG including agents that target cell membrane biosynthesis, protein synthesis, amino acid transport, DNA synthesis, the tricarboxylic acid (TCA) cycle, hypoxic environments, cell surface receptors, blood flow, vascular endothelial growth factor (VEGF), epidermal growth factor (EGFR), and the 18-kDa translocator protein (TSPO), among others. This chapter will provide an overview of PET tracers for HGG that have been evaluated in human subjects with a focus on tracers that are not yet in widespread use for neuro-oncology.