The Molecular Effects of Ionizing Radiations on Brain Cells: Radiation Necrosis vs. Tumor Recurrence

The central nervous system (CNS) is generally resistant to the effects of radiation, but higher doses, such as those related to radiation therapy, can cause both acute and long-term brain damage. The most important results is a decline in cognitive function that follows, in most cases, cerebral radionecrosis. The essence of radio-induced brain damage is multifactorial, being linked to total administered dose, dose per fraction, tumor volume, duration of irradiation and dependent on complex interactions between multiple brain cell types. Cognitive impairment has been described following brain radiotherapy, but the mechanisms leading to this adverse event remain mostly unknown. In the event of a brain tumor, on follow-up radiological imaging often cannot clearly distinguish between recurrence and necrosis, while, especially in patients that underwent radiation therapy (RT) post-surgery, positron emission tomography (PET) functional imaging, is able to differentiate tumors from reactive phenomena. More recently, efforts have been done to combine both morphological and functional data in a single exam and acquisition thanks to the co-registration of PET/MRI. The future of PET imaging to differentiate between radionecrosis and tumor recurrence could be represented by a third-generation PET tracer already used to reveal the spatial extent of brain inflammation. The aim of the following review is to analyze the effect of ionizing radiations on CNS with specific regard to effect of radiotherapy, focusing the attention on the mechanism underling the radionecrosis and the brain damage, and show the role of nuclear medicine techniques to distinguish necrosis from recurrence and to early detect of cognitive decline after treatment.