First-in-human PET neuroimaging of [¹⁸F]OXD-2314

Area of Science:

• Nuclear Medicine
• Radiopharmaceutical Chemistry
• Neuroimaging

Background:

• Tauopathies are a group of neurodegenerative diseases characterized by the abnormal aggregation of tau protein in the brain.
• Non-Alzheimer's disease tauopathies represent a significant unmet medical need for diagnostic and therapeutic advancements.
• Positron emission tomography (PET) imaging offers a non-invasive method to visualize in vivo molecular targets, including tau pathology.

Purpose of the Study:

• To evaluate the safety and feasibility of [¹⁸F]OXD-2314, a novel PET radiotracer, in first-in-human studies.
• To assess the biodistribution and pharmacokinetic properties of [¹⁸F]OXD-2314 in healthy control subjects.
• To establish the potential of [¹⁸F]OXD-2314 for imaging tau in non-Alzheimer's disease tauopathies.

Main Methods:

• Automated synthesis of [¹⁸F]OXD-2314 was performed using a commercial module and validated for human administration.
• Dynamic PET imaging was conducted in a cohort of healthy control subjects (2 female, 2 male, ages 49-65).
• Quantitative analysis involved kinetic modeling using arterial input functions to determine total distribution volumes (V_T) in various brain regions.

Main Results:

• [¹⁸F]OXD-2314 demonstrated favorable characteristics, meeting all release criteria for human use.
• PET imaging showed an initial peak uptake in the whole brain, followed by a consistent washout pattern.
• The radiotracer exhibited uniform distribution across brain regions, with V_T values ranging from 2.21 ± 0.29 to 2.81 ± 0.43 mL/cm³.

Conclusions:

• [¹⁸F]OXD-2314 has been successfully translated into first-in-human PET imaging with no reported adverse events.
• The promising safety and imaging profile supports its further investigation in patient populations with non-Alzheimer's tauopathies.
• Clinical trials in patients with non-Alzheimer's tauopathies are currently in progress.