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Developments in Tau PET Imaging

  • Eduardo Rigon Zimmer (a1) (a2) (a3), Antoine Leuzy (a1) (a2), Serge Gauthier (a2) and Pedro Rosa-Neto (a1) (a2)
Abstract

The presence of neurofibrillary tangles in the brain is a hallmark feature of several neurodegenerative diseases termed “tauopathies,” including Alzheimer’s disease (AD) and the tau molecular subgroup of frontotemporal lobar degeneration (FTLD-tau). Recently, several positron emission tomography (PET) radiopharmaceuticals targeting abnormal conformations of the tau protein have been developed. To date, six novel tau imaging agents—[18F]THK523, [18F]THK5105, [18F]THK5117, [18F]T807, [18F]T808, and [11C]PBB3—have been described and are considered promising as potential tau radioligands. Tau imaging agents offer the opportunity of in vivo topographical mapping and quantification of tau aggregates in parallel with clinical and cognitive assessments. As such, tau imaging is considered of key importance for progress toward earlier and more accurate diagnosis of tauopathies as well as for the monitoring of therapeutic interventions and drug development. Here, we shed light on the most important developments in tau radiopharmaceuticals, highlighting challenges, possibilities and future directions.

La présence d’enchevêtrements neurofibrillaires dans le cerveau est une des caractéristiques dans plusieurs maladies neurodégénératives appelées «tauopathies» dont font partie la maladie d’Alzheimer (MA) et le sous-moléculaire de la protéine tau de la dégénérescence fronto-temporale lobaire (DFTL-tau). Récemment, plusieurs tomographies par émission de positons (TEP) radiopharmaceutiques ont été mises au point afin de cibler avec précision les conformations anormales de la protéine tau. Six nouveaux agents d’imagerie tau [18F]THK523, [18F]THK5105, [18F]THK5117, [18F] T807, [18F]T808, et [11C]PBB3 ont été décrits à ce jour et sont considérés très prometteurs en tant que radioligands tau potentiels. Les agents d’imagerie tau ouvrent de nouvelles voies à la cartographie topographique et à la quantification in vivo des agrégats de la protéine tau en parallèle avec les évaluations cliniques et cognitives en cours. L’imagerie de la protéine tau est considérée en tant que telle comme ayant une importance capitale pour faire progresser les diagnostics actuels vers des diagnostics plus précoces et plus précis de tauopathies, ainsi que pour le suivi des interventions thérapeutiques et le développement de médicaments. La suite de cet article permettra, nous l’espérons, d’apporter plus de lumière sur les développements radiopharmaceutiques les plus importants de la protéine tau, les défis et possibilités, tout en mettant en évidence les orientations futures de cette imagerie.

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Corresponding author
Correspondence to: Pedro Rosa-Neto, McGill Center for Studies in Aging, 6825 LaSalle Blvd., Montreal, Canada H4H 1R3. Email: pedro.rosa@mcgill.ca
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