Preclinical Evaluation of TSPO and MAO-B PET Radiotracers in an LPS Model of Neuroinflammation

Vidya Narayanaswami; Junchao Tong; Christin Schifani; Peter M Bloomfield; Kenneth Dahl; Neil Vasdev

doi:10.1016/j.cpet.2020.12.003

Preclinical Evaluation of TSPO and MAO-B PET Radiotracers in an LPS Model of Neuroinflammation

PET Clin. 2021 Apr;16(2):233-247. doi: 10.1016/j.cpet.2020.12.003.

Authors

Vidya Narayanaswami¹, Junchao Tong², Christin Schifani³, Peter M Bloomfield⁴, Kenneth Dahl⁵, Neil Vasdev⁶

Affiliations

¹ Azrieli Centre for Neuro-Radiochemistry, Brain Health Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Room 270, Toronto, Ontario M5T 1R8, Canada.
² Brain Health Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Room 339, Toronto, Ontario M5T 1R8, Canada.
³ Brain Health Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Room 270, Toronto, Ontario M5T 1R8, Canada.
⁴ Brain Health Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Room B26A, Toronto, Ontario M5T 1R8, Canada.
⁵ Azrieli Centre for Neuro-Radiochemistry, Brain Health Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Room B02, Toronto, Ontario M5T 1R8, Canada.
⁶ Department of Psychiatry, Brain Health Imaging Centre, Azrieli Centre for Neuro-Radiochemistry, Centre for Addiction and Mental Health, University of Toronto, 250 College Street, Room PET G2, Toronto, Ontario M5T 1R8, Canada. Electronic address: [email protected].

PMID: 33648665
DOI: 10.1016/j.cpet.2020.12.003

Abstract

Discovery of novel PET radiotracers targeting neuroinflammation (microglia and astrocytes) is actively pursued. Employing a lipopolysaccharide (LPS) rat model, this longitudinal study evaluated the translocator protein 18-kDa radiotracer [¹⁸F]FEPPA (primarily microglia) and monoamine oxidase B radiotracers [¹¹C]L-deprenyl and [¹¹C]SL25.1188 (astrocytes preferred). Increased [¹⁸F]FEPPA binding peaked at 1 week in LPS-injected striatum whereas increased lazabemide-sensitive [¹¹C]L-deprenyl binding developed later. No increase in radiotracer uptake was observed for [¹¹C]SL25.1188. The unilateral intrastriatal LPS rat model may serve as a useful tool for benchmarking PET tracers targeted toward distinct phases of neuroinflammatory reactions involving both microglia and astrocytes.

Keywords: LPS rat model; MAO-B; Neuroinflammation; PET biomarkers; TSPO.

Publication types

Review

MeSH terms

Animals
Brain / diagnostic imaging
Carrier Proteins
Humans
Lipopolysaccharides*
Longitudinal Studies
Microglia / metabolism
Monoamine Oxidase*
Positron-Emission Tomography
Rats
Receptors, GABA / metabolism
Receptors, GABA-A

Substances

Carrier Proteins
Lipopolysaccharides
Receptors, GABA
Receptors, GABA-A
TSPO protein, human
Tspo protein, rat
Monoamine Oxidase