Test–retest repeatability of quantitative cardiac 11C-meta-hydroxyephedrine measurements in rats by small animal positron emission tomography

IntroductionThe norepinephrine analogue 11C-meta-hydroxyephedrine (HED) has been used to interrogate sympathetic neuronal reuptake in cardiovascular disease. Application for longitudinal studies in small animal models of disease necessitates an understanding of test–retest variability. This study evaluated the repeatability of multiple quantitative cardiac measurements of HED retention and washout and the pharmacological response to reuptake blockade and enhanced norepinephrine levels.MethodsSmall animal PET images were acquired over 60 min following HED administration to healthy male Sprague Dawley rats. Paired test and retest scans were undertaken in individual animals over 7 days. Additional HED scans were conducted following administration of norepinephrine reuptake inhibitor desipramine or continuous infusion of exogenous norepinephrine. HED retention was quantified by retention index, standardized uptake value (SUV), monoexponential and one-compartment washout. Plasma and cardiac norepinephrine were measured by high performance liquid chromatography.ResultsTest retest variability was lower for retention index (15% ± 12%) and SUV (19% ± 15%) as compared to monoexponential washout rates (21% ± 13%). Desipramine pretreatment reduced myocardial HED retention index by 69% and SUV by 85%. Chase treatment with desipramine increased monoexponential HED washout by 197% compared to untreated controls. Norepinephrine infusion dose-dependently reduced HED accumulation, reflected by both retention index and SUV, with a corresponding increase in monoexponential washout. Plasma and cardiac norepinephrine levels correlated with HED quantitative measurements.ConclusionThe repeatability of HED retention index, SUV, and monoexponential washout supports its suitability for longitudinal PET studies in rats. Uptake and washout of HED are sensitive to acute increases in norepinephrine concentration.