TAU IMAGING USING FLUORINE-19 MRI IN A MOUSE MODEL OF TAUOPATHY

Recent advances in neuroimaging techniques allow us to evaluate the pathological features in Alzheimer's disease, such as amyloid deposition and neurofibrillary tangles. Here we have developed a novel imaging technique to detect neurofibrillary tangles using fluorine-19 magnetic resonance imaging. All experimental procedures in this study were approved by the Committee on Animal Care of Shiga University of Medical Science. We synthesized a buta-1,3-diene derivative with PEG side chain bearing CF3 group, named Shiga-X35, as a fluorine-19 MRI probe. Female rTg4510 mice (a mouse model of tauopathy) and wild-type mice, under anesthesia with sodium pentobarbital, were intravenously injected Shiga-X35 at a dose of 200 mg/kg via the tail vein by continuous infusion. And then, MR imaging of mouse head was conducted with a 7.0 T horizontal-bore MR scanner. The fluorine-19 MR image in the wild-type mice showed two strong signals around the olfactory bulb and the hindbrain, suggesting the accumulation of Shiga-X35 in the adipose tissues around the regions. On the other hand, in rTg4510 mice, we observed an intense signal in the forebrain region located between the two signals. Semi-quantitative analysis of the signal intensity in the forebrain region revealed a significant accumulation of fluorine-19 MR signal in the rTg4510 mice, compared with the wild-type mice. Histological analysis showed fluorescent signals of Shiga-X35 binding to the neurofibrillary tangles in the brain sections of rTg4510 mice. Our data indicate that fluorine-19 MRI using Shiga-X35 would be a powerful tool to evaluate the accumulation of neurofibrillary tangles in the brain.