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Alzheimer's disease (AD) is the most common cause of dementia. Neuroinflammation appears to play an important role in AD pathogenesis. Ligands of the 18 kDa translocator protein (TSPO), a marker for activated microglia, have been used as positron emission tomography (PET) tracers to reflect neuroinflammation in humans and mouse models. Here, we used the novel TSPO-targeted PET tracer (18)F-GE180 (flutriciclamide) to investigate differences in neuroinflammation between young and old WT and APP/PS1dE9 transgenic (Tg) mice. In vivo PET scans revealed an overt age-dependent elevation in whole-brain uptake of (18)F-GE180 in both WT and Tg mice, and a significant increase in whole-brain uptake of (18)F-GE180 (peak-uptake and retention) in old Tg mice compared with young Tg mice and all WT mice. Similarly, the (18)F-GE180 binding potential in hippocampus was highest to lowest in old Tg &gt; old WT &gt; young Tg &gt; young WT mice using MRI coregistration. Ex vivo PET and autoradiography analysis further confirmed our in vivo PET results: enhanced uptake and specific binding (SUV75%) of (18)F-GE180 in hippocampus and cortex was highest in old Tg mice followed by old WT, young Tg, and finally young WT mice. (18)F-GE180 specificity was confirmed by an in vivo cold tracer competition study. We also examined (18)F-GE180 metabolites in 4-month-old WT mice and found that, although total radioactivity declined over 2 h, of the remaining radioactivity, ∼90% was due to parent (18)F-GE180. In conclusion, (18)F-GE180 PET scans may be useful for longitudinal monitoring of neuroinflammation during AD progression and treatment.

the journal of neuroscience/the journal of neuroscience

<i>In Vivo</i>Detection of Age- and Disease-Related Increases in Neuroinflammation by<sup>18</sup>F-GE180 TSPO MicroPET Imaging in Wild-Type and Alzheimer's Transgenic Mice

In VivoDetection of Age- and Disease-Related Increases in Neuroinflammation by18F-GE180 TSPO MicroPET Imaging in Wild-Type and Alzheimer's Transgenic Mice

In VivoDetection of Age- and Disease-Related Increases in Neuroinflammation by¹⁸F-GE180 TSPO MicroPET Imaging in Wild-Type and Alzheimer's Transgenic Mice