Abstract
We aimed to explore the impact of ageing on 11C-hydroxyephedrine (11C-HED) uptake in the healthy rat heart in a longitudinal setting. To investigate a potential cold mass effect, the influence of specific activity on cardiac 11C-HED uptake was evaluated: 11C-HED was synthesized by N-methylation of (−)-metaraminol as the free base (radiochemical purity >95%) and a wide range of specific activities (0.2–141.9 GBq/μmol) were prepared. 11C-HED (48.7 ± 9.7MBq, ranged 0.2–60.4 μg/kg cold mass) was injected in healthy Wistar Rats. Dynamic 23-frame PET images were obtained over 30 min. Time activity curves were generated for the blood input function and myocardial tissue. Cardiac 11C-HED retention index (%/min) was calculated as myocardial tissue activity at 20–30 min divided by the integral of the blood activity curves. Additionally, the impact of ageing on myocardial 11C-HED uptake was investigated longitudinally by PET studies at different ages of healthy Wistar Rats. A dose-dependent reduction of cardiac 11C-HED uptake was observed: The estimated retention index as a marker of norepinephrine function decreased at a lower specific activity (higher amount of cold mass). This observed high affinity of 11C-HED to the neural norepinephrine transporter triggered a subsequent study: In a longitudinal setting, the 11C-HED retention index decreased with increasing age. An age-related decline of cardiac sympathetic innervation could be demonstrated. The herein observed cold mass effect might increase in succeeding scans and therefore, 11C-HED microPET studies should be planned with extreme caution if one single radiosynthesis is scheduled for multiple animals.
Highlights
As the predominant disorder of the ageing population, heart failure (HF) is the major cause of death in both the United States and Europe[1,2]
HED uptake with different specific activities was observed (Fig. 1A, representative axial Positron Emission Tomography (PET) images): With a low dose of 0.2 μg/kg, uptake in the left ventricular myocardium could be clearly visualized, while a slight decrease could be observed at a dose of 1 μg/kg
The estimated retention index as a marker of norepinephrine re-uptake function decreased with lower specific activity
Summary
As the predominant disorder of the ageing population, heart failure (HF) is the major cause of death in both the United States and Europe[1,2]. The diagnostic use of cardiac radionuclide imaging probes such as 123I-metaiodobenzylguanidine (123I-mIBG) for Single Photon Emission Computed Tomography (SPECT) or 11C-hydroxyephedrine (11C-HED) for Positron Emission Tomography (PET) is currently expanding[14,15,16,17]. Both radiotracers are considered to reflect sympathetic presynaptic function, as they share NE pathways and interact with uptake-1 mechanism, which recovers exocitotically released NE from the synaptic cleft[18,19,20,21]. Given the expected broadened use of 11C-HED outside of controlled clinical trials as well as the alterations of myocardial sympathetic nerve function in the elderly, we aimed to explore the potential impact of ageing on cardiac 11C-HED uptake in healthy rats in a longitudinal setting
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