P100 - LONGITUDINAL IN VIVO PET IMAGING OF P2X7 RECEPTOR IN THE APP/PS1-21 MOUSE MODEL OF ALZHEIMER’S DISEASE USING THE NOVEL RADIOTRACER [11C]SMW139 (ID 941)
Abstract
Aims
To image P2X7 receptor expression using the novel PET tracer, [11C]SMW139, and compare [11C]SMW139 to the TSPO receptor tracer, [18F]F-DPA, in a mouse model of Aβ deposition.
Methods
APP/PS1-21 transgenic (TG) mice (N=7), and wild-type (WT) healthy control mice (N=7) had a baseline PET scan at 5 months old and three follow-up scans at 8, 11 and 14 months with [11C]SMW139. The same animals were imaged with [18F]F-DPA at 14 months. Expression of P2X7 and TSPO receptors was investigated using immunohistochemical staining.
Results
Time activity curves in TG and WT mice at baseline and follow-up scans indicated fast clearance and low retention of [11C]SMW139 in the brain neocortex during PET dynamic acquisition at 0-60 min. The averaged (3-15 min) standard uptake values (SUVs) showed similar [11C]SMW139 uptake in the neocortex and hippocampus of TG and their age-matched WT mice at baseline and all follow-up scans. On the other hand, averaged (25-50 min) SUVs showed higher [18F]F-DPA uptake in the neocortex and hippocampus of TG compared to their age-matched WT mice at 14 months. Findings from immunohistochemical staining did not show, in contrast to TSPO expression, notable change in the expression of P2X7 receptor with age.
Conclusions
Preliminary results of this study showed that [18F]F-DPA is better to monitor neuroinflammation in the APP/PS1-21 mouse model than [11C]SMW139. This may be explained by more limited expression of P2X7 compared to TSPO in this animal model.
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