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The role of molecular imaging with positron emission tomography (PET) for diagnosis, treatment planning and post-treatment monitoring of brain tumors has grown substantially in the last decades. In the last 25 years, almost 50 different PET agents have been developed and tested in human clinical studies. While some of these PET agents are yet to make their way into clinical practice, others have already established pivotal roles in brain tumor imaging. Although all these agents share an affinity for brain tumor cells, they target different tumor-altered molecular pathways within these cells: some agents are taken up by the cell through overexpressed transporters and become trapped, altered, or incorporated into upregulated metabolic pathways, while other agents bind to overexpressed receptors or to cells present in the tumor microenvironment. In this monograph, we explore the major genetic and molecular changes characteristic of brain tumors, how they are used by PET agents to gain access to tumor cells and their environment, and how this translates to uptake in clinical practice. Gaining insight in these processes is essential for correct image interpretation and helps to understand why some agents are more successful than others.
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