THK5351 can be radiolabeled and used as a radiotracer for in vivo imaging of tau pathology in the brain.
In Vitro
Aggregated tau protein is a major neuropathological substrate central to the pathophysiology of neurodegenerative diseases such as Alzheimer's disease (AD). 18 F-THK5351 binds to Alzheimer disease hippocampal homogenates with high affinity (K d =2.9 nM; maximum number of binding sites=368.3 pmol/g tissue). It has fast dissociation from white-matter tissue. The THK5351 binding amount correlates with the amount of tau deposits in tissue. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
THK5351 exhibits favorable pharmacokinetics and no defluorination in mice. 18 F-THK5351 enters the brain immediately after intravenous injection and shows a fast washout from the brain. At 0.1 and 1 mg/kg, no animals died and no treatment-related changes in any animal are noted in clinical observations, body weight measurement, and pathologic examination . Autoradiography in the brain sections of patients with PSP demonstrates [ 3 H]THK-5351 binding to tau deposits with a high selectivity. Although patients with PSP exhibits no remarkable [ 18 F]THK-5351 retention in the temporal cortex, significantly higher tracer retention is observed in the globus pallidus and midbrain. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
