16222
2018
eng
100
Supplement No 1
59
conferenceobject
1
2018-05-27
--
--
The Impact of Ageing on [\(^{11}\)C]meta-Hydroxyephedrine Uptake in the Rat Heart
No abstract available.
Journal of Nuclear Medicine
0161-5505
http://jnm.snmjournals.org/content/59/supplement_1/100.abstract
urn:nbn:de:bvb:20-opus-162228
Johns Hopkins School of Medicine
Journal of Nuclear Medicine May 1, 2018 vol. 59 no. supplement 1 100
701983
Deutsches Urheberrecht
Rudolf A. Werner
Xinyu Chen
Mitsuru Hirano
Naoko Nose
Constantin Lapa
Mehrbod S. Javadi
Takahiro Higuchi
deu
swd
Positronen-Emissions-Tomografie
eng
uncontrolled
moycardial sympathetic innervation
deu
uncontrolled
Positronen-Emissions-Tomografie
eng
uncontrolled
positron emission tomography
eng
uncontrolled
PET
eng
uncontrolled
11C-HED
eng
uncontrolled
hydroxyephedrine
eng
uncontrolled
ageing
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
OpenAIRE
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/16222/Werner_Rudolf_11C-HED_JNM_Kongressbeitrag_accepted_version.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
14920
2015
eng
545-558
6
5
article
1
2017-05-24
--
--
Radionuclide imaging of neurohormonal system of the heart
Heart failure is one of the growing causes of death especially in developed countries due to longer life expectancy. Although many pharmacological and instrumental therapeutic approaches have been introduced for prevention and treatment of heart failure, there are still limitations and challenges. Nuclear cardiology has experienced rapid growth in the last few decades, in particular the application of single photon emission computed tomography (SPECT) and positron emission tomography (PET), which allow non-invasive functional assessment of cardiac condition including neurohormonal systems involved in heart failure; its application has dramatically improved the capacity for fundamental research and clinical diagnosis. In this article, we review the current status of applying radionuclide technology in non-invasive imaging of neurohormonal system in the heart, especially focusing on the tracers that are currently available. A short discussion about disadvantages and perspectives is also included.
Theranostics
10.7150/thno.10900
urn:nbn:de:bvb:20-opus-149205
Theranostics 5(6), 545-558 (2015). DOI: 10.7150/thno.10900
CC BY-NC: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell 4.0 International
Xinyu Chen
Rudolf A. Werner
Mehrbod S. Javadi
Yoshifumi Maya
Michael Decker
Constantin Lapa
Ken Herrmann
Takahiro Higuchi
eng
uncontrolled
SPECT
eng
uncontrolled
radiotracer
eng
uncontrolled
heart failure
eng
uncontrolled
cardiac neurohormonal system
eng
uncontrolled
nuclear cardiology
eng
uncontrolled
PET
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Institut für Pharmazie und Lebensmittelchemie
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/14920/065_Chen_Theranostics.pdf
16913
2018
eng
article
1
2018-10-12
--
--
Moving into the Next Era of PET Myocardial Perfusion Imaging - Introduction of Novel \(^{18}\)F-labeled Tracers
The heart failure (HF) epidemic continues to rise with coronary artery disease (CAD) as one of its main causes. Novel concepts for risk stratification to guide the referring cardiologist towards revascularization procedures are of significant value. Myocardial perfusion imaging (MPI) using single-photon emission computed tomography (SPECT) agents has demonstrated high accuracy for the detection of clinically relevant stenoses. With positron emission tomography (PET) becoming more widely available, mainly due to its diagnostic performance in oncology, perfusion imaging with that modality is more practical than in the past and overcomes existing limitations of SPECT MPI. Advantages of PET include more reliable quantification of absolute myocardial blood flow, the routine use of computed tomography for attenuation correction, a higher spatiotemporal resolution and a higher count sensitivity. Current PET radiotracers such as rubidium-82 (half-life, 76 sec), oxygen-15 water (2 min) or nitrogen-13 ammonia (10 min) are labeled with radionuclides with very short half-lives, necessitating that stress imaging is performed under pharmacological vasodilator stress instead of exercise testing. However, with the introduction of novel 18F-labeled MPI PET radiotracers (half-life, 110 min), the intrinsic advantages of PET can be combined with exercise testing. Additional advantages of those radiotracers include, but are not limited to: potentially improved cost-effectiveness due to the use of pre-existing delivery systems and superior imaging qualities, mainly due to the shortest positron range among available PET MPI probes. In the present review, widely used PET MPI radiotracers will be reviewed and potential novel 18F-labeled perfusion radiotracers will be discussed.
The International Journal of Cardiovascular Imaging
1569-5794
10.1007/s10554-018-1469-z
urn:nbn:de:bvb:20-opus-169134
Johns Hopkins University, Baltimore, MD, U.S.
International Journal of Cardiovascular Imaging (2019) 35: 569. https://doi.org/10.1007/s10554-018-1469-z
701983
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Rudolf A. Werner
Xinyu Chen
Steven P. Rowe
Constantin Lapa
Mehrbod S. Javadi
Takahiro Higuchi
eng
uncontrolled
heart failure with mid-range ejection fraction
deu
swd
Positronenemissionstomografie
eng
uncontrolled
coronary artery disease
eng
uncontrolled
precision medicine
eng
uncontrolled
positron emission tomography
eng
uncontrolled
PET
eng
uncontrolled
SPECT
eng
uncontrolled
myocardial perfusion imaging
eng
uncontrolled
MPI
eng
uncontrolled
18F-flurpiridaz
eng
uncontrolled
18FFBnTP
eng
uncontrolled
HFmrEF
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
OpenAIRE
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/16913/Werner2018_IJCI_PETMyocardialPerfusionImaging.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
16708
2018
eng
12
8
article
1
2018-08-10
--
--
Subcellular storage and release mode of the novel \(^{18}\)F-labeled sympathetic nerve PET tracer LMI1195
Background: \(^{18}\)F-N-[3-bromo-4-(3-fluoro-propoxy)-benzyl]-guanidine (\(^{18}\)F-LMI1195) is a new class of PET tracer designed for sympathetic nervous imaging of the heart. The favorable image quality with high and specific neural uptake has been previously demonstrated in animals and humans, but intracellular behavior is not yet fully understood. The aim of the present study is to verify whether it is taken up in storage vesicles and released in company with vesicle turnover.
Results: Both vesicle-rich (PC12) and vesicle-poor (SK-N-SH) norepinephrine-expressing cell lines were used for in vitro tracer uptake studies. After 2 h of \(^{18}\)F-LMI1195 preloading into both cell lines, effects of stimulants for storage vesicle turnover (high concentration KCl (100 mM) or reserpine treatment) were measured at 10, 20, and 30 min. \(^{131}\)I-meta-iodobenzylguanidine (\(^{131}\)I-MIBG) served as a reference. Both high concentration KCl and reserpine enhanced \(^{18}\)F-LMI1195 washout from PC12 cells, while tracer retention remained stable in the SK-N-SH cells. After 30 min of treatment, 18F-LMI1195 releasing index (percentage of tracer released from cells) from vesicle-rich PC12 cells achieved significant differences compared to cells without treatment condition. In contrast, such effect could not be observed using vesicle-poor SK-N-SH cell lines. Similar tracer kinetics after KCl or reserpine treatment were also observed using 131I-MIBG. In case of KCl exposure, Ca\(^{2+}\)-free buffer with the calcium chelator, ethylenediaminetetracetic acid (EDTA), could suppress the tracer washout from PC12 cells. This finding is consistent with the tracer release being mediated by Ca\(^{2+}\) influx resulting from membrane depolarization.
Conclusions: Analogous to \(^{131}\)I-MIBG, the current in vitro tracer uptake study confirmed that \(^{131}\)F-LMI1195 is also stored in vesicles in PC12 cells and released along with vesicle turnover. Understanding the basic kinetics of \(^{18}\)FLMI1195 at a subcellular level is important for the design of clinical imaging protocols and imaging interpretation.
EJNMMI Research
10.1186/s13550-018-0365-9
2191-219X
29411169
urn:nbn:de:bvb:20-opus-167081
Johns Hopkins School of Medicine
701983
EJNMMI Research (2018) 8:12 https://doi.org/10.1186/s13550-018-0365-9
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Xinyu Chen
Rudolf A. Werner
Constantin Lapa
Naoko Nose
Mitsuru Hirano
Mehrbod S. Javadi
Simon Robinson
Takahiro Higuchi
eng
uncontrolled
phaeochromocytoma
deu
swd
Positronen-Emissions-Tomografie
eng
uncontrolled
heart failure
eng
uncontrolled
sympathetic nervous system
eng
uncontrolled
storage vesicle turnover
eng
uncontrolled
positron emission tomography
eng
uncontrolled
18F-LMI1195
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
OpenAIRE
Förderzeitraum 2018
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/16708/Werner Rudolf LMI1195.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
16362
2018
eng
article
1
2018-06-30
--
--
SPECT vs. PET in Cardiac Innervation Imaging: Clash of the Titans
Purpose: We aim to provide an overview of the conventional single photon emission computed tomography (SPECT) and emerging positron emission tomography (PET) catecholamine analogue tracers for assessing myocardial nerve integrity, in particular focusing on \(^{18}\)F-labeled tracers.
Results: Increasingly, the cardiac sympathetic nervous system (SNS) is being studied by non-invasive molecular imaging approaches. Forming the backbone of myocardial SNS imaging, the norepinephrine (NE) transporter at the sympathetic nerve terminal plays a crucial role for visualizing denervated myocardium: in particular, the single-photon-emitting NE analogue \(^{123}\)I-meta-Iodobenzylguanidine (\(^{123}\)I-mIBG) has demonstrated favorable results in the identification of patients at a high risk for cardiac death. However, cardiac neuronal PET agents offer several advantages inlcuding improved spatio-temporal resolution and intrinsic quantifiability. Compared to their \(^{11}\)C-labeled counterparts with a short half-life (20.4 min), novel \(^{18}\)F-labeled PET imaging agents to assess myocardial nerve integrity have the potential to revolutionize the field of SNS molecular imaging: The longer half-life of \(^{18}\)F (109.8 min) allows for more flexibility in the study design and delivery from central cyclotron facilities to smaller hospitals may lead to further cost reduction. A great deal of progress has been made by the first in-human studies of such \(^{18}\)F-labeled SNS imaging agents. Moreover, dedicated animal platforms open avenues for further insights into the handling of radiolabeled catecholamine analogues at the sympathetic nerve terminal. Conclusions: \(^{18}\)F-labeled imaging agents demonstrate key properties for mapping cardiac sympathetic nerve integrity and might outperform current SPECT-based or \(^{11}\)C-labeled tracers in the long run.
Clinical and Translational Imaging
10.1007/s40336-018-0289-4
2281-5872
urn:nbn:de:bvb:20-opus-163628
Johns Hopkins School of Medicine, Baltimore, MD, USA
National Cardiovascular and Cerebral Center, Suita, Japan
Clinical and Translational Imaging (2018) 6, 4, 293–303. https://doi.org/10.1007/s40336-018-0289-4
701983
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Rudolf A. Werner
Xinyu Chen
Mitsuru Hirano
Steven P. Rowe
Constantin Lapa
Mehrbod S. Javadi
Takahiro Higuchi
eng
uncontrolled
single photon emission computed tomography: sympathetic nerve
deu
swd
Positronen-Emissions-Tomografie
eng
uncontrolled
18F-LMI1195
eng
uncontrolled
11C-hydroxyephedrine
eng
uncontrolled
123I-metaiodobenzylguanidine
eng
uncontrolled
positron emission tomography
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
OpenAIRE
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/16362/Werner_2018_SPECTVsPETInCardiacInnervation.pdf