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Biomarkers

Jannatun Namme1, Yulong Xu2, Changning Wang3

  • 1Virginia Commonwealth University, Richmond, VA, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 25, 2025
PubMed
Abstract

Insights

Researchers developed a novel PET radiotracer targeting mitochondrial complex I defects, crucial in Alzheimer's disease (AD) and related dementias (ADRD). This tracer shows promise for visualizing neurodegeneration in mouse models.

Area of Science:

  • Neuroscience
  • Biochemistry
  • Radiochemistry

Background:

  • Mitochondrial dysfunction is implicated in Alzheimer's disease and related dementias (AD/ADRD).
  • Complex I defects in the electron transport chain (ETC) are linked to reactive oxygen species (ROS) production and neurodegeneration.

Purpose of the Study:

  • To synthesize and characterize novel mitochondrial complex I inhibitors as Positron Emission Tomography (PET) radiotracers.
  • To develop a PET imaging agent for visualizing complex I activity in the brain.

Main Methods:

  • Synthesis of novel mitochondrial complex I inhibitors.
  • Radiolabeling of an inhibitor with Fluorine-18 (F-18).
  • Characterization of the F-18 radiotracer in mice using PET/CT imaging for biodistribution and brain penetration.

Main Results:

  • The F-18 radiotracer demonstrated rapid brain entry and favorable clearance kinetics.
  • Blocking studies confirmed the specificity of the radiotracer for its target, mitochondrial complex I.

Conclusions:

  • A novel F-18 labeled PET radiotracer targeting mitochondrial complex I was successfully synthesized.
  • In vivo PET/CT studies in mice validated the radiotracer's potential for imaging brain complex I activity.

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