[11C] PBR28 PET imaging is sensitive to neuroinflammation in the aged rat

Abstract

Neuroinflammation in the aging rat brain was investigated using [11C] 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 [11C] PBR28 PET scans were acquired. Arterial blood sampling enabled tracer kinetic modeling and estimation of V T. 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 V T increased by 91% from 30 to 57 mL/cm 3. Standard uptake value and V T were strongly correlated (r=0.52, 95% confidence interval (CI)=0.31 to 0.69, n=37). The plasma free fraction, f p, 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 V T; 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 V T. These data show that [11C] PBR28 brain uptake increases with age, implying increased microglial activation in the aged brain.