Radiation-induced brain injury in non-human primates: A dual tracer PET study with [11C]MPC-6827 and [11C]PiB

Radiation-induced brain injury (RIBI) and Alzheimer's disease (AD) share key pathological features, including β-amyloid (Aβ) plaque formation and microtubule (MT) destabilization, both contributing to neurodegeneration. This pilot study assessed Aβ deposition and MT stability in non-human primates (NHPs) exposed to ionizing radiation, utilizing [¹¹C]PiB and [¹¹C]MPC-6827 PET imaging to explore neurodegenerative mechanisms. Fourteen rhesus macaques, seven irradiated and seven controls underwent PET imaging. Tracers were synthesized and brain regions (ex. cingulate, hippocampus, and occipital lobe) were analyzed for tracer uptake. Although no statistically significant whole-brain differences in tracer uptake were found between irradiated and control groups, significant regional differences were observed in the occipital lobe, where irradiated NHPs exhibited higher [¹¹C]MPC-6827 uptake (p < 0.0001), suggesting MT destabilization. No significant differences were found in [¹¹C]PiB uptake. Correlation analysis revealed a slight positive association (Pearson r = 0.2866) between irradiation dose and [¹¹C]MPC-6827 uptake. These findings suggest that irradiation-induced MT destabilization may be region-specific, offering insights into shared neurodegenerative pathways in RIBI and AD, highlighting the potential of [¹¹C]MPC-6827 as a marker for early neuronal dysfunction in irradiated brains.