Early MRI and outcomes of untreated patients with mild or improving ischemic stroke

Abstract

A novel ¹⁸F-labeled tracer, LMI1195 (<i>N</i>-[3-bromo-4-(3-¹⁸F-fluoro-propoxy)-benzyl]-guanidine), is being developed for sympathetic nerve imaging; its high specificity for neural uptake-1 mechanism has previously been demonstrated in cell associative studies and in rabbit and nonhuman primate studies assessing heart uptake. The aim of this study was to investigate the mechanisms of ¹⁸F-LMI1195 cardiac uptake in the rat, which is known to contain norepinephrine uptake mechanisms beyond uptake-1. <b>Methods:</b> Tracer accumulation in the heart was studied over time after intravenous administration of ¹⁸F-LMI1195 in healthy male Wistar rats by quantitative in vivo PET imaging. The uptake mechanism was assessed by pretreatment with the nonselective norepinephrine uptake-1 and norepinephrine uptake-2 inhibitor phenoxybenzamine (50 mg/kg intravenously; <i>n</i> = 4), the selective norepinephrine uptake-1 inhibitor desipramine (2 mg/kg intravenously; <i>n</i> = 4), or saline control (intravenously; <i>n</i> = 4). <b>Results:</b>¹⁸F-LMI1195 produced high and sustained heart uptake allowing clear delineation of the left ventricular wall over 60 min after tracer administration. Pretreatment with phenoxybenzamine markedly reduced the ¹⁸F-LMI1195 cardiac uptake when compared with controls. In contrast, there was preserved ¹⁸F-LMI1195 uptake after desipramine pretreatment. <b>Conclusion:</b> In rats, cardiac uptake of ¹⁸F-LMI1195 was significantly inhibited by phenoxybenzamine but not desipramine, suggesting ¹⁸F-LMI1195 is a substrate for the uptake-2 mechanism and is consistent with the rat heart having a dominant level of the mechanism.