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Distinct [18F]THK5351 binding patterns in primary progressive aphasia variants.

Jolien Schaeverbeke1,2, Charlotte Evenepoel1,2, Lieven Declercq3,4

  • 1Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Herestraat 49, 3000, Leuven, Belgium.

European Journal of Nuclear Medicine and Molecular Imaging
|June 28, 2018
PubMed
Summary

Positron emission tomography (PET) tracer [18F]THK5351 binding patterns in primary progressive aphasia (PPA) variants align with predicted pathologies. This tau PET imaging correlates with clinical deficits, aiding in understanding PPA subtypes.

Keywords:
AgrammatismMotor speechNonfluent variantPrimary progressive aphasiaTau[18F]THK5351 binding

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Area of Science:

  • Neuroimaging
  • Neurology
  • Radiochemistry

Background:

  • Primary progressive aphasia (PPA) comprises heterogeneous subtypes with distinct underlying pathologies.
  • Nonfluent variant (NFV) and logopenic variant (LV) PPA often involve tauopathy, while semantic variant (SV) PPA is linked to TDP-43 proteinopathy.
  • Accurate in vivo assessment of these pathologies is crucial for diagnosis and therapeutic development.

Purpose of the Study:

  • To evaluate the binding patterns of the tau PET tracer [18F]THK5351 in patients with different PPA variants.
  • To investigate the correlation between [18F]THK5351 binding and specific clinical deficits in PPA.

Main Methods:

  • 20 PPA patients (12 NFV, 5 SV, 3 LV) and 20 healthy controls underwent neurolinguistic assessment, MRI, and amyloid biomarker tests.
  • [18F]THK5351 PET scans were analyzed using standardized uptake value ratio (SUVR) with statistical parametric mapping.
  • Voxel-wise regression analysis explored associations between [18F]THK5351 SUVR and neurolinguistic scores.

Main Results:

  • NFV patients showed increased [18F]THK5351 binding in motor and subcortical areas compared to controls and SV patients.
  • SV patients exhibited increased binding in temporal and ventromedial frontal regions compared to controls and NFV patients.
  • Agrammatism and motor speech impairment correlated with [18F]THK5351 binding in the left supplementary motor area and postcentral gyrus.

Conclusions:

  • [18F]THK5351 PET imaging reveals topographical binding patterns consistent with the predicted underlying pathologies in NFV and SV PPA.
  • The tracer's binding intensity correlates with the severity of clinical impairments observed in PPA patients.
  • [18F]THK5351 demonstrates potential as a valuable tool for characterizing PPA subtypes and their associated neuropathology.