Cranial radiotherapy (CRT) refers to radiation to the head or neck to kill localized cancer cells. Although effective in controlling tumors, damage to the surrounding tissues limits its therapeutic benefit. Among other side effects, injury to normal brain cells can lead to acute and long-term cognitive decline. Pediatric patients are particularly vulnerable to CRT-induced neurodegeneration due to their ongoing brain development. Brain inflammation is thought to be driven by brain immune cells (microglia). Microglia are the sentinels of the brain. They are tasked with responding to damage by eating invading pathogens and destroying them via a mechanism known as respiratory burst. We developed...

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Cranial radiotherapy (CRT) refers to radiation to the head or neck to kill localized cancer cells. Although effective in controlling tumors, damage to the surrounding tissues limits its therapeutic benefit. Among other side effects, injury to normal brain cells can lead to acute and long-term cognitive decline. Pediatric patients are particularly vulnerable to CRT-induced neurodegeneration due to their ongoing brain development. Brain inflammation is thought to be driven by brain immune cells (microglia). Microglia are the sentinels of the brain. They are tasked with responding to damage by eating invading pathogens and destroying them via a mechanism known as respiratory burst. We developed a Position Emission Tomography (PET) imaging agent ([18F]4FN) that can detect respiratory burst. We hypothesize that [18F]4FN will inform on neuroinflammation after CRT. We will test this hypothesis in mouse models of CRT and will also determine whether [18F]4FN is a better tool than a commonly used brain PET agent, 18F-PBR06. We aim to discover if PET can visualize the amelioration of neuroinflammation upon treatment with an anti-inflammatory drug (TAT-NBD peptide) previously used in this model. We expect that, after treatment, we will observe a decrease in the PET signal and an improvement in cognitive and behavioral functions in these animals. Finally, we aim to investigate the inflammatory status of the peritumoral region in a rat model of brain cancer (glioma). Since these animals can be cured of their cancer with CRT, and survive long-term, they will provide the opportunity to observe how inflammation evolves around the tumor during its progression or regression. We hope to show that [18F]4FN PET is a suitable method to monitor CRT-mediated neuroinflammation before the onset of neuropathies and cognitive impairments. Since [18F]4FN is already undergoing a first-in-human clinical trial, we hope to provide a further clinical indication for this promising PET agent.

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