Background: Neuroinflammation is associated with neurodegenerative disease. PET radioligands targeting the 18 kDa translocator protein (TSPO) has been used as in vivo markers of neuroinflammation, but there is an urgent need for novel probes with an improved signal-to-noise ratio. Flutriciclamide ( 18 F-GE180) is a recently developed third generation TSPO ligand. In this first study, we evaluated the optimum scan duration and kinetic modeling strategies for 18 F-GE180 PET in (older) healthy controls. Methods: Ten healthy controls, six TSPO high affinity binders (HABs) and four mixed affinity binders (MABs), were recruited. All subjects had detailed neuropsychological tests and MRI, followed by a 210 min 18 F-GE180 dynamic PET/CT scan using a metabolite corrected arterial plasma input function. Five different kinetic models describing brain 18 F-GE180 uptake were interrogated: irreversible and reversible two-tissue compartment models, a reversible one-tissue model and two models with an extra irreversible vascular compartment. The optimum scan length was investigated based on 210 min scan data. The feasibility of generating parametric maps was also investigated using graphical analysis. Results: 18 F-GE180 concentration was higher in plasma than in whole blood during the entire scan duration. Using the kinetic models, the volume of distribution (V T ) was 0.17 in HABs and 0.12 in MABs. The model that best represented brain 18 F-GE180 kinetics across regions was the reversible two-tissue model and 90 min was determined as the optimum scan length required to obtain stable estimates. Logan graphical analysis with arterial input function gave a V T highly consistent with 2TCM4k, which could be used for voxel-wise analysis. Conclusions: We report here for the first time the kinetic properties of the novel 3 nd generation TSPO PET ligand, 18 F-GE180, in humans: 2TCM4k is the optimal method to quantify the brain uptake and 90 min is the optimal scan length, and Logan approach could be used to generate parametric maps. While these control subjects have shown relatively low V T , the methodology presented in this study forms the basis for quantification of future PET studies using 18 F-GE180 in different pathologies.Background: Variants in the triggering receptor expressed on myeloid cells 2 (TREM2) gene increase the risk of developing Alz-heimer's disease (AD). In the brain, TREM2 is highly expressed by microglia. TREM2 appears to mediate microglial phagocytosis and the expression of an anti-inflammatory phenotype. Loss of this function may contribute to the pathogenesis of AD and shift cell behaviour towards a more harmful pro-inflammatory phenotype. An important goal is to establish whether AD patients with/without a TREM2 risk variant share a similar microglial response to pathology. Methods:Human brain sections containing the hippocampal regions CA1 and CA4 were obtained from comparable AD cases with (AD/TREM2+) and without (AD/TREM2-) TREM2 variants, and Control/healthy cases without TREM2 variants (Control/TREM2-). ...
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