Real-Time Trafficking of PEGylated Liposomes in the Rodent Focal Brain Ischemia Analyzed by Positron Emission Tomography

A liposomal drug delivery system was previously applied to ischemic brain model rats for the treatment of brain ischemia, and we observed that 100-nm-sized liposomes could extravasate and accumulate in the ischemic brain region even when cerebral blood flow was markedly reduced in permanent middle cerebral artery occlusion (p-MCAO) model rats. In the present study, we investigated the real-time cerebral distribution of polyethylene glycol (PEG)-modified liposomes (PEG-liposomes) labeled with 1-[F-18]fluoro-3,6-dioxatetracosane in p-MCAO rats by positron emission tomography (PET). [F-18]-Labeled PEG-liposomes were intravenously injected into p-MCAO rats 1 h after the onset of occlusion, and then a PET scan was performed for 2 h. The PET scan showed that the signal intensity of [F-18] gradually increased in the ischemic region despite the drastic reduction in cerebral perfusion, suggesting that PEG-liposomes had accumulated in and around the ischemic region. Therefore, drug delivery to the ischemic region by use of liposomes would be possible under ischemic conditions, and a liposomal drug delivery system could be a promising strategy for protecting the ischemic brain from damage before recovery from ischemia.