Novel tau PET tracer exhibits high sensitivity and specificity, allowing for earlier identification of Alzheimer's disease

Tau lesions are the neuropathologic hallmarks of Alzheimer's disease, and tau accumulation is closely associated with future cognitive decline. PET imaging with specific tau radiotracers provides information on the progression of the tau burden, which can help to assess disease activity, determine treatment, and predict therapeutic outcomes.

"Much effort over the past decade has been focused on generating PET radiotracers to visualize tau lesions in vivo," said Nobuyuki Okamura, MD, PhD, professor of Division of Pharmacology, Faculty of Medicine at Tohoku Medical and Pharmaceutical University in Sendai, Japan. "While progress has been made, existing tau PET radiotracers have problems with insufficient sensitivity to early lesions and the presence of off-target binding. To address these issues, our research team created an optimized tau PET tracer, ¹⁸F-SNFT-1, with high sensitivity and specificity to tau pathology in Alzheimer's disease."

In the study, researchers compared the binding profile of ¹⁸F-SNFT-1 with those of other reported tau PET radiotracers. In vitro binding properties of ¹⁸F-labeled tau tracers were evaluated through the autoradiography of frozen human brain tissues from patients with diverse neurodegenerative diseases. Pharmacokinetics, metabolism, and radiation dosimetry were assessed in normal mice after intravenous administration of ¹⁸F-SNFT-1.

In vitro binding assays demonstrated that ¹⁸F-SNFT-1 possesses high selectivity and high affinity for tau lesions in the brain tissue of patients with Alzheimer's disease. Autoradiographic analysis of tau deposits in medial temporal brain sections from patients with Alzheimer's disease showed a higher signal-to-background ratio for ¹⁸F-SNFT-1 than for the other tau PET tracers and no significant off-target binding. ¹⁸F-SNFT-1 also showed a high initial brain uptake and rapid washout from the brains of normal mice without radiolabeled metabolites.

"Therapeutic agents targeting tau protein are under development, and treatment with anti-tau drugs should be initiated as early as possible," noted Okamura. "Early detection of tau lesions using ¹⁸F-SNFT-1 may accelerate the initiation of therapy with anti-tau drugs and improve the lives of people with Alzheimer's disease."

This study was made available online in June 2023.