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Published on: June 14, 2018
[11C]PBR28 PET imaging is sensitive to neuroinflammation in the aged rat
Matthew D Walker1, Katherine Dinelle2, Rick Kornelsen2
1Department of Physics and Astronomy, University of British Columbia, Vancouver, British Columbia, Canada.
Abstract:
Neuroinflammation in the aging rat brain was investigated using [(11)C]PBR28 microPET (positron emission tomography) imaging. Normal rats were studied alongside LRRK2 p.G2019S transgenic rats; this mutation increases the risk of Parkinson's disease in humans. Seventy [(11)C]PBR28 PET scans were acquired. Arterial blood sampling enabled tracer kinetic modeling and estimation of VT. In vitro autoradiography was also performed. PBR28 uptake increased with age, without differences between nontransgenic and transgenic rats. In 12 months of aging (4 to 16 months), standard uptake value (SUV) increased by 56% from 0.44 to 0.69 g/mL, whereas VT increased by 91% from 30 to 57 mL/cm(3). Standard uptake value and VT were strongly correlated (r = 0.52, 95% confidence interval (CI) = 0.31 to 0.69, n = 37). The plasma free fraction, fp, was 0.21 ± 0.03 (mean ± standard deviation, n = 53). In vitro binding increased by 19% in 16 months of aging (4 to 20 months). The SUV was less variable across rats than VT; coefficients of variation were 13% (n = 27) and 29% (n = 12). The intraclass correlation coefficient for SUV was 0.53, but was effectively zero for VT. These data show that [(11)C]PBR28 brain uptake increases with age, implying increased microglial activation in the aged brain.
Insights
Brain imaging with [(11)C]PBR28 shows increased microglial activation in aging rats. This neuroinflammation marker rises with age, regardless of Parkinson's disease risk genes, suggesting aging itself drives these changes.
Area of Science:
- Neuroscience
- Radiochemistry
- Gerontology
Background:
- Aging is associated with increased neuroinflammation, a key factor in neurodegenerative diseases.
- Microglial activation is a primary indicator of neuroinflammation.
- Positron Emission Tomography (PET) imaging offers a non-invasive method to study brain changes in vivo.
Purpose of the Study:
- To investigate age-related changes in neuroinflammation using [(11)C]PBR28 PET imaging in rats.
- To assess the impact of the LRRK2 p.G2019S mutation, a risk factor for Parkinson's disease, on age-related neuroinflammation.
- To correlate in vivo PET findings with in vitro autoradiography data.
Main Methods:
- Utilized [(11)C]PBR28 microPET imaging in normal and LRRK2 p.G2019S transgenic rats across different ages.
- Acquired 70 PET scans and performed arterial blood sampling for tracer kinetic modeling to estimate total volume of distribution (VT).
- Conducted in vitro autoradiography to validate PET findings and measured plasma free fraction (fp).
Main Results:
- [(11)C]PBR28 uptake in the brain significantly increased with age in both normal and transgenic rats.
- Standard Uptake Value (SUV) increased by 56% and VT by 91% over 12 months of aging (4 to 16 months).
- In vitro binding showed a 19% increase with aging (4 to 20 months), correlating with PET data.
Conclusions:
- Brain uptake of [(11)C]PBR28, a marker of microglial activation, increases with age in rats.
- Aging, rather than the LRRK2 p.G2019S mutation, appears to be the primary driver of increased neuroinflammation in this model.
- These findings highlight the utility of [(11)C]PBR28 PET imaging for studying age-related neuroinflammation.
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