. In Vivo Tau Imaging. Human Amyloid Imaging Abstract. 2012 Jan 1;

Abstract:

Definitive diagnosis of tauopathies such as Alzheimer’s disease (AD), some variants of frontotemporal lobe degeneration, (FTLD) progressive supranuclear palsy and corticobasal degeneration, is still reliant upon post-mortem examination of the human brain. Furthermore, these diseases are often difficult to differentiate clinically due to overlapping phenotypes, especially at early stages of their development. In vivo imaging with PET will allow new insights into tau deposition in the human brain, facilitating research into causes, diagnosis and treatment of taupathies, as is now available for Aβ. We have characterized8F-THK523, a novel tau imaging agent developed at Tohoku University in Sendai, Japan, demonstrating its selectivity and specificity for tau pathology both in vitro and in vivo. In vitro binding studies demonstrated that8F-THK523 binds with higher affinity to a greater number of binding sites on recombinant tau compared with Aβ1-42 fibrils. Autoradiographic and histofluorescence analysis of human AD hippocampal brain sections, demonstrated that THK523 co-localized with immunoreactive tau pathology, but failed to highlight Aβ plaques. In small animal PET studies, there was a significantly higher (48%) brain retention of8F-THK523 in tau transgenic (rTg4510) mice compared with their wild-type littermates or APP/PS1 mice. The preclinical examination of THK523, with its high affinity and selectivity for tau pathology both in vitro and in vivo, along with toxicity studies, indicated that8F-THK523 fullfilled criteria for human PET studies. Initial human PET studies comparing8F-THK523 and1C-PiB have shown that8F-THK523 does not bind to Aβ in AD. While no cortical retention was observed in healthy controls and Semantic Dementia (SD) patients, higher retention, albeit much lower than the observed with1C-PiB, was detected in AD. Further studies are needed to confirm these initial findings.

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