Effects of hypoxic–ischemic brain injury on striatal dopamine transporter in newborn piglets: evaluation of 11C-CFT PET/CT for DAT quantification

Abstract

Alterations of dopamine in striatal presynaptic terminals play an important role in the hypoxic-ischemic (HI) brain injury. Quantification of DAT levels in the presynaptic site using (11)C-N-2-carbomethoxy-3-(4-fluorophenyl)-tropane ((11)C-CFT) with positron emission tomography (PET) was applied in studies for Parkinson's disease. The current study investigated the changes in striatal DAT following HI brain injury in newborn piglets using (11)C-CFT PET. Newborn piglets were subjected to occlusion of bilateral common carotid arteries for 30 min and simultaneous peripheral hypoxia. Brain DAT imaging was performed using PET/CT with (11)C-CFT as the probe in each group (including the control group and HI insult groups). Brain tissues were collected for DAT immunohistochemical (IHC) analysis at each time point post the PET/CT procedure. Sham controls had some operation without HI procedure. A few minutes after intravenous injection of (11)C-CFT, radioactive signals for DAT clearly appeared in the cortical area, striatum and cerebellum of newborn piglets of sham control group and HI insult groups. HI brain insult markedly increased striatal DAT at an early period (P<.05 vs. sham controls) when neuronal pathological changes were mild. Changes in striatal DAT were absent at later period post-HI insult when neuronal injury became more severe. (11)C-CFT PET imaging data and IHC DAT staining data were highly correlated (r=0.844, P<.05). HI brain injury resulted in a transient increase in striatal DAT. (11)C-CFT PET/CT imaging data reflected the dynamic changes of DAT in the striatum in vivo.