Visualization of early infarction in rat brain after ischemia using a translocator protein (18 kDa) PET ligand [11C]DAC with ultra-high specific activity

Abstract

The aim of this study was to visualize early infarction in the rat brain after ischemia using a translocator protein (TSPO) (18kDa) PET ligand [11C]DAC with ultra-high specific activity (SA) of 3670–4450GBq/μmol. An infarction model of rat brain was prepared by ischemic surgery and evaluated 2days after ischemia using small-animal PET and in vitro autoradiography. Early infarction with a small increase of TSPO expression in the brain was visualized using PET with high SA [11C]DAC (average 4060GBq/μmol), but was not distinguished clearly with usually reported SA [11C]DAC (37GBq/μmol). Infarction in the rat brain 4days after ischemia was visualized using high and usually reported SAs [11C]DAC. Displacement experiments with unlabeled TSPO-selective AC-5216 or PK11195 diminished the difference in radioactivity between ipsilateral and contralateral sides, confirming that the increased uptake on the infracted brain was specific to TSPO. In vitro autoradiography with high SA [11C]DAC showed that the TSPO expression increased on early infarction in the rat brain. High SA [11C]DAC is a useful and sensitive biomarker for the visualization of early infarction and the characterization of TSPO expression which was slightly elevated in the infarcted brain using PET.