@article {KANG113, author = {LEI KANG and Dawei Jiang and Dalong NI and Emily Ehlerding and Rongfu Wang and Weibo Cai}, title = {Antioxidative neuroprotective role of iron-gallic acid coordination nanoparticles and PET/MR usage in an ischemia stroke model}, volume = {60}, number = {supplement 1}, pages = {113--113}, year = {2019}, publisher = {Society of Nuclear Medicine}, abstract = {113Purpose: For ischaemic stroke, thrombolysis is usually be chosen to improve the clinical outcome, however the induced reperfusion injury is a potential factor of poorer recovery. Oxidative stress is one factor which can leading to cell damage and death via reactive oxygen species (ROS) thus antioxidant strategies have been used in the treatment of stroke. In this study, Fe-GA coordination polymer nanoparticles (Fe-GA NCPs) were developed for an antioxidative neuroprotector in the ischemia stroke rat model and evaluated using PET/MR imaging. Methods: The ultra-small Fe-GA NCPs were synthesized and tested by transmission electric microscope (TEM) and dynamic light scattering. Their antioxidative effect were further evaluated by the degradation of methylene blue (MB), the coloration of tetramethylbenzidine (TMB), the reduction of 1,1-diphenyl-2-picrylhydrazyl (DPPH) and the electron spin resonance (ESR) spectroscopy in vitro. To investigate the neuroprotective effects of Fe-GA NCPs nanoparticles in vivo, we induced ischemic stroke in rats and subsequently injection before reperfusion which mimicked the pathologic process in clinic. Adult Sprague-Dawley male rats were performed middle cerebral artery occlusion (MCAO), and reperfusion was performed 90 min after MCAO. Fe-GA encephalic injection was performed 1h before reperfusion under standard operation. 24 h after reperfusion, all rats underwent neurologic testing followed by neurologic function scale, 18F-FDG small animal PET (Philips), PET/MR (Siemens) scanning, 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin-eosin (HE) staining and oxidative stress testing. Normal, sham operation, MCAO only, saline (NS), and edaravone were performed as control groups and evaluated as well. Results: Fe-GA NCPs were synthesized using a simple chemical process. TEM images revealed discrete and uniform 7 nm-sized nanoparticles. As proved by MB, TMB, DPPH, and ESR spectroscopy, the ultra-small Fe-GA NCPs could significantly scavenge the reactive oxygen/nitrogen species. After treated with Fe-GA NCPs, the neurological score was better than other control groups. For MCAO model, 18F-FDG PET/MR could show the low FDG uptake in the region of brain infarct and high signal in T2-weighted MRI imaging. We found that brain infarct volumes in rats treated with Fe-GA NCPs decreases significantly than other negative groups. Its therapeutic effect was even better than same concentration of edaravone which is used in clinic for same purpose. Further, TTC staining verified these in vivo imaging results. The areas of infarct lesion showed by PET/MRI were correlated with TTC staining results, suggesting PET/MRI could be effectively used for evaluation. HE staining also showed the shape and structure of infarct brain were abnormal. Finally, oxidative stress was tested for oblated brain tissue and found less ROS level in Fe-GA NCPs treated rats. Conclusions: Fe-GA CPNs exhibit an impressive antioxidative neuroprotective role in ischemia stroke, which might have the potential to be translated into clinical applications for improved treatment of patients with stroke. PET/MRI is effective and accurate method for ischemic evaluation.}, issn = {0161-5505}, URL = {https://jnm.snmjournals.org/content/60/supplement_1/113}, eprint = {https://jnm.snmjournals.org/content}, journal = {Journal of Nuclear Medicine} }