Fig. 1: Synthesis of [¹⁸F]FEDV and in vitro characterization.

a, Under homeostasis, RONS production and elimination are tightly regulated (eustress). Disruption of this balance, oxidative stress, results in high levels of RONS that are damaging to biological systems. b, Scheme of a hypothesized mechanism of intracellular retention of [¹⁸F]F-OPB after [¹⁸F]FEDV reacts with RONS. We propose that, like its parent chemical edaravone, [¹⁸F]FEDV freely diffuses through the plasma membrane, reacts with intracellular RONS at physiological pH and produces unstable intermediates leading to [¹⁸F]F-OPB. The [¹⁸F]F-OPB cannot pass through the plasma membrane and is retained within the cell, thereby providing a PET signal. c, Scheme of the radiosynthesis of [¹⁸F]FEDV, a radiopharmaceutical analogue of edaravone. d, Quantification of the [¹⁹F]FEDV-to-[¹⁹F]F-OPB conversion after exposure to various oxidants for 5 min, 10 min, 15 min or 20 min. The tested oxidants, arranged in order of increasing reduction potential, included hydrogen peroxide (H₂O₂), tert-butyl hydroperoxide (t-BuOOH), nitroxyl (NO^•), hypochlorite (ClO^–), tert-butoxide (t-BuO^•), water-soluble lipid peroxyl radicals [LOO^•(aq)], and lipid-soluble lipid peroxyl radicals [LOO^•(lip)], peroxynitrite (ONOO^–) and hydroxide (OH^•). Shown are the mean of three replicates. e, Quantification of cellular uptake (Bq per mg protein) of [¹⁸F]FEDV in N2a cells after exposure to 3 mM TBHP or TBHP with co-incubation of 100 μM edaravone. Shown are the mean ± s.e.m. of six replicates. f, Stability of [¹⁸F]FEDV in the final product reformulation solvent (5% ethanol in saline) and in human plasma. Shown are the mean ± s.e.m.; *P = 0.0386, ***P = 1.2 × 10⁻⁹, two-way ANOVA with Bonferroni post hoc test for significance.