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[18F]-AV-1451 PET imaging for tau pathology has non-specific binding in unexpected brain areas. This study identifies these off-target binding sites and provides code for improved analysis and partial volume correction.

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Area of Science:

  • Neuroimaging
  • Radiochemistry
  • Neuropathology

Background:

  • [18F]-AV-1451 is a key positron emission tomography (PET) tracer for quantifying tau pathology.
  • Non-specific binding of [18F]-AV-1451 can occur in brain regions not associated with aggregated tau.
  • Understanding and correcting for non-specific binding is crucial for accurate tau PET imaging.

Purpose of the Study:

  • To identify and characterize non-specific binding sites of [18F]-AV-1451.
  • To define appropriate reference regions for PET data analysis.
  • To provide computational tools for partial volume correction (PVC) of PET data.

Main Methods:

  • Analysis of [18F]-AV-1451 PET scans to identify unexpected binding.
  • Definition of novel reference regions, including the inferior cerebellar gray matter.
  • Implementation of the Rousset geometric transfer matrix (GTM) method for PVC.
  • Development and release of open-source code for region of interest (ROI) creation and PVC.

Main Results:

  • Non-specific binding was observed in the superior cerebellum, choroid plexus, skull, and meninges (extra-cortical hotspots).
  • Specific brain regions identified with off-target binding include orbitofrontal, occipital, temporal, and parietal areas.
  • The inferior cerebellar gray matter was established as a suitable reference region.
  • Code for ROI generation and GTM-based PVC is publicly available.

Conclusions:

  • [18F]-AV-1451 exhibits significant non-specific binding in several brain regions and extra-cortical areas.
  • Careful selection of reference regions and application of PVC are essential for accurate [18F]-AV-1451 quantification.
  • The provided code facilitates improved analysis of tau PET data, enhancing its utility in aging and Alzheimer's disease research.