A positron emission tomography tracer for the imaging of oxidative stress in the central nervous system
Justin H. Wilde, Yu Sun, Spenser R. Simpson, Ethan Hill, Zhongxiao Fu, Emily Bian, Melissa M. Kinkaid, Paulina Villanueva, Aden Weybright, William Terrell, Zoraiz Qureshi, Shashika S. Perera, Heather S. Sheppard, James R. Stone, Bijoy Kundu, Chia-Yi Kuan, Kiel D. Neumann
Abstract
Reactive oxygen and nitrogen species (RONS) contribute to the pathogenesis of neurodegeneration, but the inability to detect RONS in vivo in the central nervous system has confounded the interpretation of results of clinical trials of antioxidants. Here we report the synthesis and characterization of a positron emission tomography (PET) probe, [18F]fluoroedaravone ([18F]FEDV), for the in vivo quantification of oxidative stress. Derived from the antioxidant edaravone, the probe can diffuse through the blood–brain barrier and is stable in human plasma. In mice, PET imaging with [18F]FEDV allowed for the detection of RONS after intrastriatal injection of sodium nitroprusside, in the middle cerebral artery after stroke by photothrombosis, and in brains with tauopathy. When using dynamic PET imaging coupled with parametric mapping, the sensitivity of [18F]FEDV-PET to RONS allowed for the detection of increased oxidative stress. [18F]FEDV-PET could be used to quantify RONS longitudinally in vivo and to assess the results of clinical studies of antioxidants. A positron emission tomography tracer of reactive oxygen and nitrogen species enables the in vivo quantification of oxidative stress, as shown in mouse models of oxidative stress, stroke and tauopathy.