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Association between FDG- and TSPO-PET signals across human and animal studies investigating neurodegenerative

Luiza S Machado1,2, Pedro Vidor1, Lavínia Perquim1

  • 1Graduate Program in Biological Sciences: Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS), Rua Ramiro Barcelos 2500, 90035-003, Porto Alegre, Rio Grande do Sul, Brazil.

Molecular Psychiatry
|September 4, 2025
PubMed
Abstract

Insights

This review explores the link between brain metabolism (FDG-PET) and microglial activity (TSPO-PET) in neurodegeneration. Findings suggest a complex relationship, varying by disease and imaging tracer, necessitating further research.

Area of Science:

  • Neuroimaging
  • Neurodegeneration Biomarkers
  • Neuroinflammation

Background:

  • Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET) hypometabolism is a key indicator of neurodegeneration.
  • Glial cells, particularly microglia, influence the FDG-PET signal.
  • 18-kDa translocator protein (TSPO)-PET radiopharmaceuticals assess microglial activation, but FDG- and TSPO-PET associations are debated.

Purpose of the Study:

  • To systematically review preclinical and clinical studies using both FDG- and TSPO-PET.
  • To investigate the association between metabolic changes and neuroinflammation in neurodegenerative conditions.

Main Methods:

  • Systematic literature review of studies employing both FDG-PET and TSPO-PET.
  • Inclusion of 14 preclinical (mouse models of amyloid, tau, neurotoxins) and 7 clinical studies (Alzheimer's, Parkinson's, frontotemporal lobar degeneration).

Main Results:

  • Most clinical studies reported a negative association between FDG-PET and TSPO-PET signals.
  • Preclinical studies showed mixed results, influenced by the specific TSPO-PET radiotracer used.
  • Evidence supports a link between glial activity and brain metabolism, with species-specific differences.

Conclusions:

  • Glial heterogeneity and TSPO-PET radiotracer specificities impact the observed associations.
  • Longitudinal studies in early neurodegeneration stages are crucial.
  • Development of more accurate preclinical models is needed to clarify FDG- and TSPO-PET dynamics.

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