THK5351

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). ¹⁸F-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^[1]. In Vivo: THK5351 exhibits favorable pharmacokinetics and no defluorination in mice. ¹⁸F-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^[1]. Autoradiography in the brain sections of patients with PSP demonstrates [³H]THK-5351 binding to tau deposits with a high selectivity. Although patients with PSP exhibits no remarkable [¹⁸F]THK-5351 retention in the temporal cortex, significantly higher tracer retention is observed in the globus pallidus and midbrain^[2].