16112
2017
eng
i1-i3
Supplement
18
conferenceobject
Oxford University Press
1
2018-04-25
--
--
PET-Guided Histological Characterization of Myocardial Infiltrating Cells in a Rat Model of Myocarditis
No abstract available.
European Heart Journal - Cardiovascular Imaging
2047-2404
10.1093/ehjci/jex071
urn:nbn:de:bvb:20-opus-161127
This is a pre-copyedited, author-produced version of an article accepted for publication in European Heart Journal Cardiovascular Imaging following peer review. The version of record . Eur Heart J Cardiovasc Imaging. ISSN: 2047-2404. Supplement, vol. 18, i1-i3, May 2017 is available online at: 10.1093/ehjci/jex071.
European Heart Journal - Cardiovascular Imaging, Volume 18, Issue suppl_1, May 2017, Pages i1–i3, https://doi.org/10.1093/ehjci/jex071
701983
Johns Hopkins School of Medicine, Baltimore, MD, U.S.
Deutsches Urheberrecht
Rudolf Werner
Hiroshi Wakabayashi
Roland Jahns
Süleyman Ergün
Valerie Jahns
Takahiro Higuchi
deu
swd
Myokarditis
eng
uncontrolled
positron emission tomography
eng
uncontrolled
myocarditis
eng
uncontrolled
PET
eng
uncontrolled
18F-FDG
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Institut für Pharmakologie und Toxikologie
Institut für Anatomie und Zellbiologie
Medizinische Klinik und Poliklinik I
OpenAIRE
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/16112/Werner_Rudolf_Myocarditis.pdf
16560
2018
eng
1-8
article
1
2018-07-24
--
--
Longitudinal \(^{18}\)F-FDG PET imaging in a Rat Model of Autoimmune Myocarditis
Aims: Although mortality rate is very high, diagnosis of acute myocarditis remains challenging with conventional tests. We aimed to elucidate the potential role of longitudinal 2-Deoxy-2-\(^{18}\)F-fluoro-D-glucose (\(^{18}\)F-FDG) positron emission tomography (PET) inflammation monitoring in a rat model of experimental autoimmune myocarditis.
Methods and results: Autoimmune myocarditis was induced in Lewis rats by immunizing with porcine cardiac myosin emulsified in complete Freund’s adjuvant. Time course of disease was assessed by longitudinal \(^{18}\)F-FDG PET imaging. A correlative analysis between in- and ex vivo \(^{18}\)F-FDG signalling and macrophage infiltration using CD68 staining was conducted. Finally, immunohistochemistry analysis of the cell-adhesion markers CD34 and CD44 was performed at different disease stages determined by longitudinal \(^{18}\)F-FDG PET imaging. After immunization, myocarditis rats revealed a temporal increase in 18F-FDG uptake (peaked at week 3), which was followed by a rapid decline thereafter. Localization of CD68 positive cells was well correlated with in vivo \(^{18}\)F-FDG PET signalling (R\(^2\) = 0.92) as well as with ex vivo 18F-FDG autoradiography (R\(^2\) = 0.9, P < 0.001, respectively). CD44 positivity was primarily observed at tissue samples obtained at acute phase (i.e. at peak 18F-FDG uptake), while CD34-positive staining areas were predominantly identified in samples harvested at both sub-acute and chronic phases (i.e. at \(^{18}\)F-FDG decrease).
Conclusion: \(^{18}\)F-FDG PET imaging can provide non-invasive serial monitoring of cardiac inflammation in a rat model of acute myocarditis.
European Heart Journal Cardiovascular Imaging
2047-2404
10.1093/ehjci/jey119
urn:nbn:de:bvb:20-opus-165601
Johns Hopkins School of Medicine
701983
European Heart Journal - Cardiovascular Imaging (2018) 0, 1–8 doi:10.1093/ehjci/jey119
CC BY-NC: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell 4.0 International
Rudolf Werner
Hiroshi Wakabayashi
Jochen Bauer
Claudia Schütz
Christina Zechmeister
Nobuyuki Hayakawa
Mehrbod S. Javadi
Constantin Lapa
Roland Jahns
Süleyman Ergün
Valerie Jahns
Takahiro Higuchi
eng
uncontrolled
positron emission tomography
deu
swd
Myokarditis
eng
uncontrolled
myocarditis
eng
uncontrolled
inflammation
eng
uncontrolled
18F-FDG
eng
uncontrolled
PET
eng
uncontrolled
personalized treatment
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Institut für Pharmakologie und Toxikologie
Institut für Anatomie und Zellbiologie
OpenAIRE
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/16560/Werner_EHJ_Cardiovascular_Imaging_2018.pdf
16111
2017
eng
i52-53
Supplement
18
conferenceobject
Oxford University Press
1
2018-04-25
--
--
Effect of Antidepressants on Radiolabeled Metaiodobenzylguanidine (MIBG) Uptake
No abstract available.
European Heart Journal - Cardiovascular Imaging
10.1093/ehjci/jex080
2047-2404
urn:nbn:de:bvb:20-opus-161116
This is a pre-copyedited, author-produced version of an article accepted for publication in European Heart Journal Cardiovascular Imaging following peer review. The version of
record Eur Heart J Cardiovasc Imaging. ISSN: 2047-2404. Supplement, vol. 18, i52-53, May 2017 is available online at: 10.1093/ehjci/jex080.
701983
European Heart Journal - Cardiovascular Imaging. Supplement, vol. 18, i52-53, May 2017. doi: 10.1093/ehjci/jex080
Johns Hopkins School of Medicine, Baltimore, MD, U.S.
Deutsches Urheberrecht
Rudolf Werner
Ryohei Kobayashi
Hiroshi Wakabayashi
Constantin Lapa
Andreas Menke
Takahiro Higuchi
deu
swd
MIBG
eng
uncontrolled
Metaiodobenzylguanidine
eng
uncontrolled
mIBG
eng
uncontrolled
antidepressants
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie
OpenAIRE
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/16111/Werner_Rudolf_mIBG .pdf
16139
2017
deu
Abstract Nr.: V119
2
56
conferenceobject
Schattauer Verlag
1
2018-05-02
--
--
Bildgebung der frühen linksventrikulären Dysfunktion mit ECG-gated F-18-FDG PET in einem Diabetes-Ratten-Modell
Einleitung: Die linksventrikuläre diastolische Dysfunktion (LVDD) ist bei Diabetikern noch vor Entwicklung einer klinisch apparenten Herzinsuffizienz eines der ersten Anzeichen einer kardialen Beteiligung. Daher soll in dieser Studie untersucht werden, ob die LVDD mit ECG-gated F-18-FDG PET in einem Diabetes-Rattenmodell dargestellt werden kann.
Methodik: Es wurden F-18-FDG PET Scans in einem Typ-2-Diabetes Rattenmodell (ZDF fa/fa, n=6) und in ZL Kontrollen (n=6) vorgenommen (Alter, jeweils 13 Wochen). Unter Hyperinsulinemic-Euglycemic Clamp-Technik wurden 37 MBq 18F-FDG über die Schwanzvene appliziert. 15-35 Minuten nach Tracergabe wurden mittels eines Kleintier-PET-Scanners sowie unter EKG-Ableitung PET Scans angefertigt (16 frames/cardiac cycle). Die linksventrikuläre Ejektionsfraktion (EF) und die Peak Füllrate (PFR) wurden mittels einer geeigneten Software (Heart Function View) gemessen, wobei die Software an die Größe des Rattenherzes angepasst wurde.
Ergebnisse: Im Alter von 13 Wochen entwickeln ZDF Diabetes-Ratten eine im Vergleich zu Kontrolltieren eine signifikante myokardiale Hypertrophie, bestätigt durch post-mortem Analyse des Herzgewichtes (994±78mg vs. 871±44mg in ZDF Diabetes-Ratten vs. ZL Kontrollen, p<0.01). ECG-gated PET zeigte eine signifikante Abnahme der LV diastolischen PFR (10.4±0.5 vs. 11.8±0.4 EDV/sec in ZDF Diabetes-Ratten vs. ZL Kontrollen, p<0.001), jedoch zeigte sich kein signifikanter Unterschied zwischen LVEF und der Herzfrequenz in den untersuchten ZDF Diabetes-Ratten und Kontrollen (LVEF: 60.0±4.5 vs. 63.7±4.1%, n.s. und HR: 305±25 vs. 323±24 bpm, n.s.).
Schlussfolgerung: Im Diabetes-Ratten-Modell kann unter Verwendung eines ECG-gated FDG-PET Protokolls die diastolische Dysfunktion als Parameter der frühen diabetischen Kardiomyopathie nachgewiesen werden.
Nuklearmedizin
http://www.nuklearmedizin.de/jahrestagungen/abstr_online2017/print_abstract_pdf.php
0029-5566
10.3413/Nukmed-0880-17-02
urn:nbn:de:bvb:20-opus-161396
This article is not an exact copy of the original published article in Nuklearmedizin.
The definitive publisher-authenticated version of „Bildgebung der frühen linksventrikulären Dysfunktion mit ECG-gated F-18-FDG PET in einem Diabetes-Ratten-Modell. Nuklearmedizin 2017; 56 (Abstract Nr.: V119).“ is available online at http://www.nuklearmedizin.de/jahrestagungen/abstr_online2017/print_abstract_pdf.php
Johns Hopkins School of Medicine
701983
Nuklearmedizin 2017 (Vol. 56): Heft 2 (A41-A42). doi:10.3413/Nukmed-0880-17-02
Deutsches Urheberrecht
Rudolf Werner
Nobuyuki Hayakawa
Paula-Anah Arias-Loza
Hiroshi Wakabayashi
Tetsuya Shinaji
Constantin Lapa
Theo Pelzer
Takahiro Higuchi
deu
swd
Positronen-Emissions-Tomografie
deu
uncontrolled
Diabetes
deu
uncontrolled
diabetische Kardiomyopathie
deu
uncontrolled
Positronen-Emissions-Tomografie
deu
uncontrolled
PET
deu
uncontrolled
EKG
deu
uncontrolled
ECG
deu
uncontrolled
ECG-gated
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Medizinische Klinik und Poliklinik I
OpenAIRE
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/16139/Werner_Rudolf_Diabetische Kardiomyopathie_accepted_version.pdf
20270
2019
eng
17026
9
article
1
2020-04-09
--
--
Ventricular distribution pattern of the novel sympathetic nerve PET radiotracer \(^{18}\)F-LMI1195 in Rabbit Hearts
We aimed to determine a detailed regional ventricular distribution pattern of the novel cardiac nerve PET radiotracer \(^{18}\)F-LMI1195 in healthy rabbits. Ex-vivo high resolution autoradiographic imaging was conducted to identify accurate ventricular distribution of \(^{18}\)F-LMI1195. In healthy rabbits, \(^{18}\)F-LMI1195 was administered followed by the reference perfusion marker \(^{201}\)Tl for a dual-radiotracer analysis. After 20 min of \(^{18}\)F-LMI1195 distribution time, the rabbits were euthanized, the hearts were extracted, frozen, and cut into 20-μm short axis slices. Subsequently, the short axis sections were exposed to a phosphor imaging plate to determine \(^{18}\)F-LMI1195 distribution (exposure for 3 h). After complete \(^{18}\)F decay, sections were re-exposed to determine 201Tl distribution (exposure for 7 days). For quantitative analysis, segmental regions of Interest (ROIs) were divided into four left ventricular (LV) and a right ventricular (RV) segment on mid-ventricular short axis sections. Subendocardial, mid-portion, and subepicardial ROIs were placed on the LV lateral wall. \(^{18}\)F-LMI1195 distribution was almost homogeneous throughout the LV wall without any significant differences in all four LV ROIs (anterior, posterior, septal and lateral wall, 99 ± 2, 94 ± 5, 94 ± 4 and 97 ± 3%LV, respectively, n.s.). Subepicardial \(^{201}\)Tl uptake was significantly lower compared to the subendocardial portion (subendocardial, mid-portion, and subepicardial activity: 90 ± 3, 96 ± 2 and *80 ± 5%LV, respectively, *p < 0.01 vs. mid-portion). This was in contradistinction to the transmural wall profile of \(^{18}\)F-LMI1195 (90 ± 4, 96 ± 5 and 84 ± 4%LV, n.s.). A slight but significant discrepant transmural radiotracer distribution pattern of \(^{201}\)Tl in comparison to \(^{18}\)F-LMI1195 may be a reflection of physiological sympathetic innervation and perfusion in rabbit hearts.
Scientific Reports
10.1038/s41598-019-53596-2
urn:nbn:de:bvb:20-opus-202707
Scientific Reports (2019) 9:17026. https://doi.org/10.1038/s41598-019-53596-2
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Rudolf A. Werner
Hiroshi Wakabayashi
Xinyu Chen
Nobuyuki Hayakawa
Constantin Lapa
Steven P. Rowe
Mehrbod S. Javadi
Simon Robinson
Takahiro Higuchi
eng
uncontrolled
Cardiovascular diseases
eng
uncontrolled
Heart failure
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Deutsches Zentrum für Herzinsuffizienz (DZHI)
Förderzeitraum 2019
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/20270/Werner_ScientificReports_2019.pdf
16128
2018
eng
article
1
2018-04-29
--
--
Impact of Novel Antidepressants on Cardiac Metaiodobenzylguanidine (mIBG) Uptake: Experimental Studies in SK-N-SH Cells and Healthy Rabbits
Background: \(^{123}\)I-metaiodobenzylguanidine (mIBG) provides independent prognostic value for risk stratification among heart failure patients, but the use of concomitant medication should not impact its quantitative information. We aimed to evaluate the four most-prescribed antidepressants currently used as a first‑line treatment for patients with major depressive disorder (MDD) and their potential on altering mIBG imaging results.
Methods: The inhibition effect of four different types of antidepressants (desipramine, escitalopram, venlafaxine and bupropion) for MDD treatment on \(^{131}\)I-mIBG uptake was assessed by in-vitro cell uptake assays using human neuroblastoma SK-N-SH cells. The half maximal inhibitory concentration (IC50) of tracer uptake was determined from dose-response curves. To evaluate the effects of IV pretreatment with desipramine (1.5 mg/kg) and escitalopram (2.5, 15 mg/kg) on mIBG cardiac uptake, in-vivo planar 123I-mIBG scans in healthy New Zealand White Rabbits were conducted. Results: The IC50 values of desipramine, escitalopram, venlafaxine and bupropion on \(^{131}\)I-mIBG cellular uptake were 11.9 nM, 7.5 μM, 4.92 μM, and 12.9 μM, respectively. At the maximum serum concentration (Cmax, as derived by previous clinical trials), the inhibition rates of 131I-mIBG uptake were 90.6 % for desipramine, 25.5 % for venlafaxine, 11.7 % for bupropion and 0.72 % for escitalopram. A low inhibition rate for escitalopram in the cell uptake study triggered investigation of an in-vivo rabbit model: with dosage considerably higher than clinical practice, the non-inhibitory effect of escitalopram was confirmed. Furthermore, pretreatment with desipramine led to a marked reduction of cardiac 123I-mIBG uptake.
Conclusions: In the present in-vitro binding assay and in-vivo rabbit study, the selective-serotonin reuptake inhibitor escitalopram had no major impact on neuronal cardiac mIBG uptake within therapeutic dose ranges, while other types of first-line antidepressants for MDD treatment led to a significant decrease. These preliminary results warrant further confirmatory clinical trials regarding the reliability of cardiac mIBG imaging, in particular, if the patient’s neuropsychiatric status would not tolerate withdrawal of a potentially norepinephrine interfering antidepressant.
Journal of Nuclear Medicine
10.2967/jnumed.117.206045
0161-5505
29496989
urn:nbn:de:bvb:20-opus-161280
This research was originally published in JNM. Rudolf A. Werner, Ryohei Kobayashi, Mehrbod Som Javadi, Zoe Köck, Hiroshi Wakabayashi, Stefan Unterecker, Kenichi Nakajima, Constantin Lapa, Andreas Menke, Takahiro Higuchi. Impact of Novel Antidepressants on Cardiac Metaiodobenzylguanidine (mIBG) Uptake: Experimental Studies in SK-N-SH Cells and Healthy Rabbits. J. Nucl. Med. July 1, 2018, vol. 59, no. 7, 1099-1103. © SNMMI.
Johns Hopkins University School of Medicine
Department of Nuclear Medicine, Kanazawa University
Journal of Nuclear Medicine July 1, 2018 vol. 59, no. 7, 1099-1103 © SNMMI
701983
Deutsches Urheberrecht
Rudolf A. Werner
Ryohei Kobayashi
Mehrbod Som Javadi
Zoe Köck
Hiroshi Wakabayashi
Stefan Unterecker
Kenichi Nakajima
Constantin Lapa
Andreas Menke
Takahiro Higuchi
eng
uncontrolled
MDD
deu
swd
Antidepressants
eng
uncontrolled
depression
eng
uncontrolled
123I-mIBG
eng
uncontrolled
antidepressant
eng
uncontrolled
cardiac sympathetic nerve system
eng
uncontrolled
major depressive disorder
eng
uncontrolled
myocardial sympathetic innervation imaging
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie
OpenAIRE
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/16128/Werner_Rudolf_Antidepressants_JNM_accepted_version.pdf
17176
2018
eng
17631
8
article
1
2018-11-13
--
--
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
16482
2018
eng
11120
8
article
1
2018-07-19
--
--
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
15906
2017
eng
16795
7
article
1
2018-03-16
--
--
Whitening and impaired glucose utilization of brown adipose tissue in a rat model of type 2 diabetes mellitus
Brown adipose tissue (BAT) is an attractive therapeutic target to combat diabetes and obesity due to its ability to increase glucose expenditure. In a genetic rat model (ZDF fa/fa) of type-2 diabetes and obesity, we aimed to investigate glucose utilization of BAT by \(^{18}\)F-FDG PET imaging. Male Zucker diabetic fatty (ZDF) and Male Zucker lean (ZL) control rats were studied at 13 weeks. Three weeks prior to imaging, ZDF rats were randomized into a no-restriction (ZDF-ND) and a mild calorie restriction (ZDF-CR) group. Dynamic \(^{18}\)F-FDG PET using a dedicated small animal PET system was performed under hyperinsulinemic-euglycemic clamp. \(^{18}\)F-FDG PET identified intense inter-scapular BAT glucose uptake in all ZL control rats, while no focally increased \(^{18}\)F-FDG uptake was detected in all ZDF-ND rats. Mild but significant improved BAT tracer uptake was identified after calorie restriction in diabetic rats (ZDF-CR). The weight of BAT tissue and fat deposits were significantly increased in ZDF-CR and ZDF-ND rats as compared to ZL controls, while UCP-1 and mitochondrial concentrations were significantly decreased. Whitening and severely impaired insulin-stimulated glucose uptake in BAT was confirmed in a rat model of type-2 diabetes. Additionally, calorie restriction partially restored the impaired BAT glucose uptake.
Scientific Reports
10.1038/s41598-017-17148-w
urn:nbn:de:bvb:20-opus-159066
Scientific Reports 7:16795 (2017). DOI: 10.1038/s41598-017-17148-w
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Constantin Lapa
Paula Arias-Loza
Nobuyuki Hayakawa
Hiroshi Wakabayashi
Rudolf A. Werner
Xinyu Chen
Tetsuya Shinaji
Ken Herrmann
Theo Pelzer
Takahiro Higuchi
eng
uncontrolled
molecular medicine
eng
uncontrolled
endocrinology
Krankheiten
open_access
Klinik und Poliklinik für Nuklearmedizin
Medizinische Klinik und Poliklinik I
Förderzeitraum 2017
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/15906/Lapa_Scientific_Reports.pdf