[18F]-T807 tauopathy PET imaging in chronic traumatic encephalopathy

Correspondence

We recently reported the case of a retired NFL player with a clinical diagnosis of chronic traumatic encephalopathy (CTE); the diagnosis was based on clinical characteristics of his progressive cognitive disorder and negative [18F]-florbetapir PET brain imaging indicating absence of amyloid plaques in his brain (Mitsis et al. 2014)¹. An [18F]-T807 PET imaging study revealed retention of [18F]-T807 in the substantia nigra (SN), globus pallidi (GP), and hippocampi, bilaterally. Key images from that paper were reproduced in a recent review by Gandy et al. (2014)². The pattern of retention was interpreted by the original authors as potentially consistent with the clinical diagnosis of CTE¹.

The anatomical distribution of [18F]-T807 retention was interpreted as atypical and suggestive of the distribution of pathology in Progressive Supranuclear Palsy (PSP). That interpretation was noted in the Mitsis et al. (2014) paper¹ in light of a recent case report linking CTE and PSP³ and because the subject in the Mitsis et al. (2014)¹ case manifested nasal speech, hypomimia, and impaired upgaze, all features of PSP. These facts notwithstanding, we emphasize that we cannot exclude the possibility that the pattern of [18F]-T807 binding observed in the retired NFL player could be the result of nonspecific retention of [18F]-T807 in these same regions of brain. Indeed, some as-yet unpublished experience with [18F]-T807 has demonstrated a propensity of the ligand to bind to the SN and GP in what appears to be a non-specific fashion (http://www.alzforum.org/news/conference-coverage/tau-tracers-shine-boston-conference). The [18F]-T807 binding to the hippocampi in¹ could fall within the spectrum of aging-related tauopathy, the known deposition of NFT in this region (http://www.alzforum.org/news/conference-coverage/tau-tracers-shine-boston-conference). We write here to emphasize the point that proof of the histological underpinnings of [18F]-T807 binding awaits the presentation of a sufficiently powered study of in vivo-radiological/postmortem-histological correlation relationships, and as a reminder that while the development of several putative tau-binding ligands has opened new possibilities for research and clinical use, that none have been validated to the extent necessary for reliable use and such validation should be a top priority.