Contrast-enhanced T1-weighted MRI, 11C-DPA-713 PET and 11C-CPPC PET as predictive imaging biomarkers of neuroinflammation in radiotherapy-induced brain injury.

Radiotherapy-induced brain injury (RIBI) is a chronic side effect that affects brain tumor survivors treated with radiotherapy. Neuroinflammation is a key contributor to RIBI. Thus, imaging methods capable of noninvasively monitoring neuroinflammation are needed. Although positron emission tomography (PET)-based radiotracers exist for imaging neuroinflammation, PET involves ionizing radiation which could be detrimental to pediatric patients already facing the risk of RIBI. Here, we evaluated the feasibility of developing contrast-enhanced T1W MRI as a predictive biomarker of neuroinflammation in RIBI. Four groups of eight-week-old female BALB/c mice were stereotactically irradiated at 80 Gy and monitored longitudinally for neuroinflammation using 11C-DPA-713 PET; 11C-CPPC PET; gadoteridol-based contrast-enhanced T1-weighted MRI; and TSPO, CD68, IBA1 immunohistochemistry. Our results showed that contrast-enhanced T1W MRI was as effective as 11C-DPA-713 PET; 11C-CPPC PET and immunohistochemistry (P < 0.05, n = 3) in predicting neuroinflammation, by detecting subtle changes in the blood-brain barrier permeability that affected neuroinflammation changes.