TY  - JOUR
A1  - Werner, Rudolf A.
A1  - Eissler, Christoph
A1  - Hayakawa, Nobuyuki
A1  - Arias-Loza, Paula
A1  - Wakabayashi, Hiroshi
A1  - Javadi, Mehrbod S.
A1  - Chen, Xinyu
A1  - Shinaji, Tetsuya
A1  - Lapa, Constantin
A1  - Pelzer, Theo
A1  - Higuchi, Takahiro
T1  - Left Ventricular Diastolic Dysfunction in a Rat Model of Diabetic Cardiomyopathy using ECG-gated \(^{18}\)F-FDG PET
JF  - Scientific Reports
N2  - 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.
KW  - diabetic cardiomyopathy
KW  - personalized treatment
KW  - precision medicine
KW  - ZDF rats
KW  - ECG
KW  - PET
KW  - \(^{18}\)F-fluorodeoxyglucose
KW  - \(^{18}\)F-FDG
KW  - diabetes
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-171765
VL  - 8
IS  - 17631
ER  - 
TY  - JOUR
A1  - Werner, Rudolf A.
A1  - Chen, Xinyu
A1  - Maya, Yoshifumi
A1  - Eissler, Christoph
A1  - Hirano, Mitsuru
A1  - Nose, Naoko
A1  - Wakabayashi, Hiroshi
A1  - Lapa, Constantin
A1  - Javadi, Mehrbod S.
A1  - Higuchi, Takahiro
T1  - The Impact of Ageing on 11C-Hydroxyephedrine Uptake in the Rat Heart
JF  - Scientific Reports
N2  - 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.
KW  - ageing
KW  - Positronen-Emissions-Tomografie
KW  - 11C-HED
KW  - 11C-Hydroxyephedrine
KW  - cardiac sympathetic nervous system
KW  - myocardial sympathetic innervation imaging
KW  - PET
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164826
SN  - 2281-5872
VL  - 8
IS  - 11120
ER  -