Abstract
Radiotherapy is one of the most frequently applied treatments in oncology. Tissue-absorbed ionizing radiation damages not only targeted cells but the surrounding cells too. The consequent long-term induced oxidative stress, irreversible tissue damage, or second malignancies draw attention to the urgent need of a follow-up medical method by which personalized treatment could be attained and the actually dose-limiting organ could be monitored in the clinical practice. We worked out a special hemisphere irradiation technique for mice which mimics the radiation exposure during radiotherapy. We followed up the changes of possible brain imaging biomarkers of side effects, such as cerebral blood flow, vascular endothelial function, and cellular metabolic processes for 60 days. BALB/c mice were divided into two groups (n=6 per group) based on the irradiation doses (5 and 20 Gy). After the irradiation procedure arterial spin labeling (ASL), diffusion-weighted imaging (DWI) in magnetic resonance modality and [18F]fluoro-deoxy-D-glucose positron emission tomography (FDG-PET) scans of the brain were obtained at several time points (3, 7, 30, and 60 days after the irradiation). Significant physiological changes were registered in the brain of animals following the irradiation by both applied doses. Elevated standard uptake values were detected all over the brain by FDG-PET studies 2 months after the irradiation. The apparent diffusion coefficients from DWI scans significantly decreased one month after the irradiation procedure, while ASL studies did not show any significant perfusion changes in the brain. Altogether, our sensitive multimodal imaging protocol seems to be an appropriate method for follow-up of the health status after radiation therapy. The presented approach makes possible parallel screening of healthy tissues and the effectiveness of tumor therapy without any additional radiation exposure.
Highlights
Radiotherapy is one of the most widely spread anticancer treatments in the eld of clinical oncology. e paradigm of radiotherapy declares the therapeutic e ect is based on indirect and direct DNA damages [1, 2]
Every cell has well-developed repair mechanisms for DNA impairments, the less-di erentiated cancerous cells have diminished ability to repair their broken DNA double-strand based on their uncontrolled and fast reproduction. is unique physiological property serves as the base of radiation therapy where the accumulated absorbed dose determines the severity of the evolving damages [1]
[18F]FDG-positron emission tomography (PET) scans made possible to follow up brain glucose use of animals after the irradiation [27]. e [18F] FDG uptake and the calculated SUV strictly correlate with local glucose metabolism, reflecting different constituents of brain glucose uptake: glial metabolism, neuronal and synaptic activity, and local immune processes [28]
Summary
Radiotherapy is one of the most widely spread anticancer treatments in the eld of clinical oncology. e paradigm of radiotherapy declares the therapeutic e ect is based on indirect and direct DNA damages [1, 2]. Is unique physiological property serves as the base of radiation therapy where the accumulated absorbed dose determines the severity of the evolving damages (slowed down reproduction, necrosis, or cell death) [1]. E persistence of these stressful e ects has Contrast Media & Molecular Imaging significant consequences Among others, they are responsible for long-term health risks of irradiation such as cardiovascular disease, vascular cell damage, neuropathy, and nerve demyelination as well [1,2,3,4,5,6,7,8,9,10,11,12,13]. In the case of neuro-oncological irradiation treatments, the healthy brain and spinal cord are critical dose-limiting organs during therapy [1, 17,18,19,20]
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