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[F-18]GE-180 PET Detects Reduced Microglia Activation After LM11A-31 Therapy in a Mouse Model of Alzheimer's Disease THERANOSTICS James, M. L., Belichenko, N. P., Shuhendler, A. J., Hoehne, A., Andrews, L. E., Condon, C., Nguyen, T. V., Reiser, V., Jones, P., Trigg, W., Rao, J., Gambhir, S. S., Longo, F. M. 2017; 7 (6): 1422-1436

Abstract

Microglial activation is a key pathological feature of Alzheimer's disease (AD). PET imaging of translocator protein 18 kDa (TSPO) is a strategy to detect microglial activation in vivo. Here we assessed flutriciclamide ([(18)F]GE-180), a new second-generation TSPO-PET radiotracer, for its ability to monitor response to LM11A-31, a novel AD therapeutic in clinical trials. AD mice displaying pathology were treated orally with LM11A-31 for 3 months. Subsequent [(18)F]GE-180-PET imaging revealed significantly lower signal in cortex and hippocampus of LM11A-31-treated AD mice compared to those treated with vehicle, corresponding with decreased levels of TSPO immunostaining and microglial Iba1 immunostaining. In addition to detecting decreased microglial activation following LM11A-31 treatment, [(18)F]GE-180 identified activated microglia in AD mice with greater sensitivity than another second-generation TSPO radiotracer, [(18)F]PBR06. Together, these data demonstrate the promise of [(18)F]GE-180 as a potentially sensitive tool for tracking neuroinflammation in AD mice and for monitoring therapeutic modulation of microglial activation.

View details for DOI 10.7150/thno.17666

View details for PubMedID 28529627