title: [11C]PBR28 PET imaging is sensitive to neuroinflammation in the aged rat.
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.
authors.affiliation: Department of Physics and Astronomy, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Walker
authors.affiliation: Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Katherine
authors.initials: K
authors.lastname: Dinelle
authors.affiliation: Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Rick
authors.initials: R
authors.lastname: Kornelsen
authors.affiliation: Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Nathan V
authors.initials: NV
authors.lastname: Lee
authors.affiliation: TRIUMF, Vancouver, British Columbia, Canada.
authors.forename: Qing
authors.initials: Q
authors.lastname: Miao
authors.affiliation: TRIUMF, Vancouver, British Columbia, Canada.
authors.forename: Mike
authors.initials: M
authors.lastname: Adam
authors.affiliation: TRIUMF, Vancouver, British Columbia, Canada.
authors.forename: Christine
authors.initials: C
authors.lastname: Takhar
authors.affiliation: Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Edwin
authors.initials: E
authors.lastname: Mak
authors.affiliation: Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Schulzer
authors.affiliation: Department of Medical Genetics, Centre for Applied Neurogenetics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Farrer
authors.affiliation: Department of Physics and Astronomy, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Vesna
authors.initials: V
authors.lastname: Sossi
mesh_terms: D000081:Acetamides / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000375:Aging / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D002247:Carbon Isotopes / Q000493:pharmacokinetics / Q000494:pharmacology; D007249:Inflammation / Q000000981:diagnostic imaging / Q000378:metabolism; D008297:Male; D017628:Microglia / Q000000981:diagnostic imaging / Q000378:metabolism; D049268:Positron-Emission Tomography; D011725:Pyridines / Q000493:pharmacokinetics* / Q000494:pharmacology*; D011859:Radiography; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic
chemical_list: D000081:Acetamides; D002247:Carbon Isotopes; C526798:N-(2-methoxybenzyl)-N-(4-phenoxypyridin-3-yl)acetamide; D011725:Pyridines
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