[F]GE-180 PET Detects Reduced Microglia Activation After LM11A-31 Therapy in a Mouse Model of Alzheimer's Disease

Overview

Journal Theranostics

Date 2017 May 23

PMID 28529627

Citations 42

Authors

Michelle L James

Nadia P Belichenko

Adam J Shuhendler

Aileen Hoehne

Lauren E Andrews

Christina Condon

Thuy-Vi V Nguyen

Vladimer Reiser

Paul Jones

William Trigg

Jianghong Rao

Sanjiv S Gambhir

Frank M Longo

Affiliations

Soon will be listed here.

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 . Here we assessed flutriciclamide ([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 [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, [F]GE-180 identified activated microglia in AD mice with greater sensitivity than another second-generation TSPO radiotracer, [F]PBR06. Together, these data demonstrate the promise of [F]GE-180 as a potentially sensitive tool for tracking neuroinflammation in AD mice and for monitoring therapeutic modulation of microglial activation.

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