16482
2018
eng
11120
8
article
1
2018-07-19
--
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The Impact of Ageing on 11C-Hydroxyephedrine Uptake in the Rat Heart
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. \(^{11}\)C-HED (48.7±9.7MBq, ranged 0.2–60.4μg/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 11CHED 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.
Scientific Reports
10.1038/s41598-018-29509-0
2281-5872
urn:nbn:de:bvb:20-opus-164826
Johns Hopkins School of Medicine
Scientific Reports (2018) 8:11120. DOI:10.1038/s41598-018-29509-0
701983
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Rudolf A. Werner
Xinyu Chen
Yoshifumi Maya
Christoph Eissler
Mitsuru Hirano
Naoko Nose
Hiroshi Wakabayashi
Constantin Lapa
Mehrbod S. Javadi
Takahiro Higuchi
eng
uncontrolled
ageing
deu
swd
Positronen-Emissions-Tomografie
eng
uncontrolled
11C-HED
eng
uncontrolled
11C-Hydroxyephedrine
eng
uncontrolled
cardiac sympathetic nervous system
eng
uncontrolled
myocardial sympathetic innervation imaging
eng
uncontrolled
PET
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
OpenAIRE
Förderzeitraum 2018
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/16482/Werner_Rudolf_Aging_11C-Hydroxyephedrine_SciRep_2018.pdf
17176
2018
eng
17631
8
article
1
2018-11-13
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Left Ventricular Diastolic Dysfunction in a Rat Model of Diabetic Cardiomyopathy using ECG-gated \(^{18}\)F-FDG PET
In diabetic cardiomyopathy, left ventricular (LV) diastolic dysfunction is one of the earliest signs of cardiac involvement prior to the definitive development of heart failure (HF). We aimed to explore the LV diastolic function using electrocardiography (ECG)-gated \(^{18}\)F-fluorodeoxyglucose positron emission tomography (\(^{18}\)F-FDG PET) imaging beyond the assessment of cardiac glucose utilization in a diabetic rat model. ECG-gated \(^{18}\)F-FDG PET imaging was performed in a rat model of type 2 diabetes (ZDF fa/fa) and ZL control rats at age of 13 weeks (n=6, respectively). Under hyperinsulinemic-euglycemic clamp to enhance cardiac activity, \(^{18}\)F-FDG was administered and subsequently, list-mode imaging using a dedicated small animal PET system with ECG signal recording was performed. List-mode data were sorted and reconstructed into tomographic images of 16 frames per cardiac cycle. Left ventricular functional parameters (systolic: LV ejection fraction (EF), heart rate (HR) vs. diastolic: peak filling rate (PFR)) were obtained using an automatic ventricular edge detection software. No significant difference in systolic function could be obtained (ZL controls vs. ZDF rats: LVEF, 62.5±4.2 vs. 59.4±4.5%; HR: 331±35 vs. 309±24 bpm; n.s., respectively). On the contrary, ECG-gated PET imaging showed a mild but significant decrease of PFR in the diabetic rats (ZL controls vs. ZDF rats: 12.1±0.8 vs. 10.2±1 Enddiastolic Volume/sec, P<0.01). Investigating a diabetic rat model, ECG-gated \(^{18}\)F-FDG PET imaging detected LV diastolic dysfunction while systolic function was still preserved. This might open avenues for an early detection of HF onset in high-risk type 2 diabetes before cardiac symptoms become apparent.
Scientific Reports
10.1038/s41598-018-35986-0
urn:nbn:de:bvb:20-opus-171765
Scientific Reports 8:17631 (2018). DOI: 10.1038/s41598-018-35986-0
701983
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Rudolf A. Werner
Christoph Eissler
Nobuyuki Hayakawa
Paula Arias-Loza
Hiroshi Wakabayashi
Mehrbod S. Javadi
Xinyu Chen
Tetsuya Shinaji
Constantin Lapa
Theo Pelzer
Takahiro Higuchi
eng
uncontrolled
diabetic cardiomyopathy
eng
uncontrolled
personalized treatment
eng
uncontrolled
precision medicine
eng
uncontrolled
ZDF rats
eng
uncontrolled
ECG
eng
uncontrolled
PET
eng
uncontrolled
\(^{18}\)F-fluorodeoxyglucose
eng
uncontrolled
\(^{18}\)F-FDG
eng
uncontrolled
diabetes
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Medizinische Klinik und Poliklinik I
OpenAIRE
Förderzeitraum 2018
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/17176/Werner_Scientific_Reports.pdf