First-in-human PET neuroimaging of [<sup>18</sup>F]OXD-2314.

Murrell, Emily; Narciso, Lucas; Desmond, Kimberly L; Chow, Caitlin; Lindberg, Anton; Garcia, Armando; Mathis, Chester A; Svensson, Samuel et al. · Eur J Nucl Med Mol Imaging · 2025

basic_science · Level V

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Abstract

This first-in-human positron emission tomography (PET) study evaluates [<sup>18</sup>F]OXD-2314, a radiopharmaceutical designed for imaging tau in non-Alzheimer's disease tauopathies. Synthesis of [<sup>18</sup>F]OXD-2314 was automated using a commercial module and validated for human use. Dynamic PET imaging was performed in healthy control subjects (2 female, 2 male, ages 49-65 years). Kinetic modelling was performed from brain time-activity curves and radiometabolite-corrected arterial input functions to estimate total distribution volumes (V<sub>T</sub>) in each region of interest. [<sup>18</sup>F]OXD-2314 met all release criteria for human use. PET imaging revealed an initial whole brain peak of 2.3 standardized uptake value, followed by a steady washout. Distribution of radioactivity was uniform among brain regions (V<sub>T</sub> range: 2.21 ± 0.29 to 2.81 ± 0.43 mL/cm<sup>3</sup>). [<sup>18</sup>F]OXD-2314 was successfully translated to first-in-human PET imaging. No adverse events were reported and PET imaging in patient populations of non-AD tauopathies is underway.

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