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

Theranostics. 2017 Mar 24;7(6):1422-1436. doi: 10.7150/thno.17666. eCollection 2017.

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 ([18F]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 [18F]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, [18F]GE-180 identified activated microglia in AD mice with greater sensitivity than another second-generation TSPO radiotracer, [18F]PBR06. Together, these data demonstrate the promise of [18F]GE-180 as a potentially sensitive tool for tracking neuroinflammation in AD mice and for monitoring therapeutic modulation of microglial activation.

Keywords: Alzheimer's disease; LM11A-31.; PET; TSPO; [18F]GE-180; flutriciclamide; neuroinflammation.

Publication types

  • Evaluation Study

MeSH terms

  • Alzheimer Disease / diagnostic imaging*
  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / pathology*
  • Animals
  • Carbazoles / administration & dosage*
  • Cerebral Cortex / pathology
  • Disease Models, Animal
  • Hippocampus / pathology
  • Isoleucine / analogs & derivatives*
  • Isoleucine / therapeutic use
  • Mice
  • Microglia / drug effects*
  • Morpholines / therapeutic use*
  • Radiopharmaceuticals / administration & dosage*
  • Receptors, GABA / analysis*
  • Sensitivity and Specificity

Substances

  • Bzrp protein, mouse
  • Carbazoles
  • GE-180
  • LM11A-31
  • Morpholines
  • Radiopharmaceuticals
  • Receptors, GABA
  • Isoleucine