The Impact of Ageing on 11C-Hydroxyephedrine Uptake in the Rat Heart

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.

Molecular Imaging-Derived Biomarker of Cardiac Nerve Integrity — Introducing High NET Affinity PET Probe 18F-AF78

“…Another factor affecting uptake and retention is the specific activity of the radiotracer, as has been demonstrated by our research on 11 C-HED in rat hearts. 38 . The cold mass effect should certainly be addressed after establishing a fully repeatable radiolabeling protocol suitable for clinical application.…”

Cardiac11C-Donepezil Binding Increases With Age in Healthy Humans: Potentially Signifying Sigma-1 Receptor Upregulation

“…The density of sympathetic nerve terminals, as assessed by 123 I-MIBG scintigraphy and 11 C-HED PET, remains stable or declines with age. [40][41][42] In contrast, several 11 C-methylquinuclidinyl benzilate PET studies have shown that muscarinic cholinergic receptors are upregulated in patients with dilated cardiac myopathy and also in remote nondamaged territories in patients with myocardial infarction. [43][44][45] Thus, cholinergic cardiac receptor upregulation is clearly an adaptive response in several types of heart disease.…”

Optimization of the Automated Synthesis of [11C]mHED—Administered and Apparent Molar Activities

“…On the other hand, different doses of m HED were applied with constant concentrations of metaraminol in a recently published study. A washout or decreased time activity curve was observed from an applied concentration of 10 µg/kg bodyweight m HED [16]. The IC 50 value of m HED towards NET drug inhibition was reported as 0.42 µM (competitive inhibition) by Foley at al.…”