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
16125
2018
eng
article
1
2018-04-29
--
--
Predictive value of \(^{18}\)F-FDG PET in patients with advanced medullary thyroid carcinoma treated with vandetanib
Introduction: Therapeutic options in advanced medullary thyroid carcinoma (MTC) have markedly improved since the introduction of tyrosine kinase inhibitors (TKI). We
aimed to assess the role of metabolic imaging using 2-deoxy-2-(\(^{18}\)F)fluoro-D-glucose (\(^{18}\)F-FDG) positron emission tomography/computed tomography (PET/CT) shortly before and 3 months after initiation of TKI treatment.
Methods: Eighteen patients with advanced and progressive MTC scheduled for vandetanib treatment underwent baseline \(^{18}\)F-FDG PET/CT prior to and 3 months after TKI treatment initiation. During follow-up, CT scans were performed every 3 months and analyzed according to Response Evaluation Criteria In Solid Tumors (RECIST). The predictive value for estimating progression-free (PFS) and overall survival (OS) was examined by investigating \(^{18}\)F-FDG mean/maximum standardized uptake values (SUVmean/max) of the metabolically most active lesion as well as by analyzing clinical parameters (tumor marker doubling times {calcitonin, carcinoembryonic antigen (CEA)}, prior therapies, RET (rearranged during transfection) mutational status, and disease type).
Results: Within a median follow-up of 5.2 years, 9 patients experienced disease progression after a median time interval of 2.1y whereas the remainder had ongoing disease control (n=5 partial response and n=4 stable disease). Eight of the 9 patients with progressive disease died from MTC after a median of 3.5y after TKI initiation.
Pre-therapeutic SUVmean >4.0 predicted a significantly shorter PFS (PFS: 1.9y vs. 5.2y; p=0.04). Furthermore, sustained high 18F-FDG uptake at 3 months with a SUVmean>2.8 tended to portend an unfavorable prognosis with a PFS of 1.9y (vs. 3.5y; p=0.3). Prolonged CEA doubling times were significantly correlated with longer PFS (r=0.7) and OS (r=0.76, p<0.01, respectively). None of the other clinical parameters had prognostic significance.
Conclusions: Pre-therapeutic \(^{18}\)F-FDG PET/CT holds prognostic information in patients with advanced MTC scheduled for treatment with the TKI vandetanib. Low tumor metabolism of SUVmean < 4.0 prior to treatment predicts longer progression-free survival.
Journal of Nuclear Medicine
10.2967/jnumed.117.199778
0161-5505
https://www.ncbi.nlm.nih.gov/pubmed/29025983
urn:nbn:de:bvb:20-opus-161256
This research was originally published in JNM. Rudolf A. Werner, Jan-Stefan Schmid, Takahiro Higuchi, Mehrbod S. Javadi, Steven P. Rowe, Bruno Märkl, Christoph Aulmann, Martin Fassnacht, Matthias Kroiss, Christoph Reiners, Andreas K. Buck, Michael C. Kreissl, Constantin Lapa. Predictive value of 18F-FDG PET in patients with advanced medullary thyroid carcinoma treated with vandetanib. J Nucl Med. May 1, 2018;vol. 59 no. 5: 756-761. © SNMMI.
Johns Hopkins University School of Medicine
Journal of Nuclear Medicine May 1, 2018 vol. 59 no. 5 756-761. doi:10.2967/jnumed.117.199778
701983
Deutsches Urheberrecht
Rudolf Werner
Jan-Stefan Schmid
Takahiro Higuchi
Mehrbod S. Javadi
Steven P. Rowe
Bruno Märkl
Christoph Aulmann
Martin Fassnacht
Matthias Kroiß
Christoph Reiners
Andreas Buck
Michael Kreissl
Constantin Lapa
eng
uncontrolled
positron emission tomography
deu
swd
Medullärer Schilddrüsenkrebs
deu
swd
Positronen-Emissions-Tomografie
eng
uncontrolled
medullary thyroid carcinoma
eng
uncontrolled
tyrosine kinase inhibitor
eng
uncontrolled
vandetanib
eng
uncontrolled
2- deoxy-2-(18F)fluoro-D-glucose
eng
uncontrolled
18F-FDG
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/16125/Werner_Rudolf_Vandetanib_JNM_accepted_version.pdf
16127
2018
eng
article
1
2018-04-29
--
--
Functional renal imaging with \(^{18}\)F-FDS PET in rat models of renal disorders
Background: Precise regional quantitative assessment of renal function is limited with conventional \(^{99m}\)Tc-labeled renal radiotracers. A recent study reported that the positron emission tomography (PET) radiotracer 2-deoxy-2-(\(^{18}\)F-fluorosorbitol (\(^{18}\)F-FDS) has ideal pharmacokinetics for functional renal imaging. Furthermore, (\(^{18}\)F-FDS is available via simple reduction from routinely used 2-deoxy-2-(\(^{18}\)F-fluoro-D-glucose ((\(^{18}\)F-FDG). We aimed to further investigate the potential of (\(^{18}\)F-FDS PET as a functional renal imaging agent using rat models of kidney diseases.
Methods: Two different rat models of renal impairment were investigated: Glycerol induced acute renal failure (ARF) by intramuscular administration of glycerol in hind legs and unilateral ureteral obstruction (UUO) by ligation of the left ureter. 24h after these treatments, dynamic 30 min 18F-FDS PET data were acquired using a dedicated small animal PET system. Urine 18F-FDS radioactivity 30 min after radiotracer injection was measured together with co-injected \(^{99m}\)Tc-diethylenetriaminepentaacetic acid (\(^{99m}\)Tc-DTPA) urine activity. Results: Dynamic PET imaging demonstrated rapid (\(^{18}\)F-FDS accumulation in the renal cortex and rapid radiotracer excretion via kidneys in control healthy rats. On the other hand, significantly delayed renal radiotracer uptake (continuous slow uptake) was observed in ARF rats and UUO-treated kidneys. Measured urine radiotracer concentrations of (\(^{18}\)F-FDS and \(^{99m}\)Tc-DTPA were well correlated (R=0.84, P<0.05).
Conclusions: (\(^{18}\)F-FDS PET demonstrated favorable kinetics for functional renal imaging in rat models of kidney diseases. Advantages of high spatiotemporal resolution of PET imaging and simple tracer production could potentially complement or replace conventional renal scintigraphy in select cases and significantly improve the diagnostic performance of renal functional imaging.
Journal of Nuclear Medicine
10.2967/jnumed.117.203828
0161-5505
29242399
urn:nbn:de:bvb:20-opus-161279
This research was originally published in JNM. Rudolf A. Werner, Hiroshi Wakabayashi, Xinyu Chen, Mitsuru Hirano, Tetsuya Shinaji, Constantin Lapa, Steven P. Rowe, Mehrbod S. Javadi and Takahiro Higuchi. Functional renal imaging with 18F-FDS PET in rat models of renal disorders. J Nucl Med. May 1, 2018;vol. 59 no. 5: 828-832. © SNMMI.
Johns Hopkins University School of Medicine
Journal of Nuclear Medicine May 1, 2018 vol. 59 no. 5 828-832. doi:10.2967/jnumed.117.203828
701983
Deutsches Urheberrecht
Rudolf Werner
Hiroshi Wakabyashi
Xinyu Chen
Mitsuru Hirano
Tetsuya Shinaji
Constantin Lapa
Steven Rowe
Mehrbod Javadi
Takahiro Higuchi
eng
uncontrolled
unilateral ureteral obstruction
deu
swd
Nierenfunktionsstörung
deu
swd
Positronen-Emissions-Tomografie
eng
uncontrolled
18F-FDS
eng
uncontrolled
99mTc-DTPA
eng
uncontrolled
PET
eng
uncontrolled
renal failure
eng
uncontrolled
Glomerular filtration
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
OpenAIRE
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/16127/Werner_Rudolf_Kidney_JNM_accepted_version.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
16129
2018
eng
article
1
2018-04-29
--
--
SSTR-RADS Version 1.0 as a Reporting System for SSTR-PET Imaging and Selection of Potential PRRT Candidates: A Proposed Standardization Framework
Reliable standards and criteria for somatostatin receptor (SSTR) positron emission tomography (PET) are still lacking. We herein propose a structured reporting system on a 5-point scale for SSTR-PET imaging, titled SSTR-RADS version 1.0, which might serve as a standardized assessment for both diagnosis and treatment planning in neuroendocrine tumors (NET). SSTR-RADS could guide the imaging specialist in interpreting SSTR-PET scans, facilitate communication with the referring clinician so that appropriate work-up for equivocal findings is pursued, and serve as a reliable tool for patient selection for planned Peptide Receptor Radionuclide Therapy.
Journal of Nuclear Medicine
10.2967/jnumed.117.206631
0161-5505
29572257
urn:nbn:de:bvb:20-opus-161298
This research was originally published in JNM. Rudolf A. Werner, Lilja B. Solnes, Mehrbod Som Javadi, Alexander Weich, Michael A. Gorin, Kenneth J. Pienta, Takahiro Higuchi, Andreas K. Buck, Martin G. Pomper, Steven P. Rowe, Constantin Lapa. SSTR-RADS Version 1.0 as a Reporting System for SSTR-PET Imaging and Selection of Potential PRRT Candidates: A Proposed Standardization Framework. J. Nucl. Med. July 1, 2018, vol. 59, no. 7, 1085-1091. © SNMMI
Johns Hopkins University School of Medicine
701983
Journal of Nuclear Medicine July 1, 2018 vol. 59 no. 7 1085-1091 © SNMMI
Deutsches Urheberrecht
Rudolf Werner
Lilja Solnes
Mehrbod Javadi
Alexander Weich
Michael Gorin
Kenneth Pienta
Takahiro Higuchi
Andreas Buck
Martin Pomper
Steven Rowe
Constantin Lapa
eng
uncontrolled
Radionuclide Therapy
deu
swd
Standardisierung
deu
swd
Positronen-Emissions-Tomografie
eng
uncontrolled
68Ga-DOTATATE/-TOC
eng
uncontrolled
Gastrointestinal
eng
uncontrolled
Neuroendocrine
eng
uncontrolled
Neuroendocrine Tumor
eng
uncontrolled
Oncology
eng
uncontrolled
GI
eng
uncontrolled
PET
eng
uncontrolled
PET/CT
eng
uncontrolled
PRRT
eng
uncontrolled
RADS
eng
uncontrolled
SSTR
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Medizinische Klinik und Poliklinik II
OpenAIRE
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/16129/Werner_Rudolf_Standardization_JNM_accepted_version.pdf
16220
2018
eng
626
Supplement No. 1
59
conferenceobject
1
2018-05-27
--
--
Diagnostic Accuracy of Visual Assessment of an Initial DaT-Scan in Comparison to a Fully Automatic Semiquantitative Method
No abstract available.
Journal of Nuclear Medicine
0161-5505
http://jnm.snmjournals.org/content/59/supplement_1/626.abstract
urn:nbn:de:bvb:20-opus-162208
This research was originally published in JNM. Rudolf A. Werner, Charles Marcus, Sara Sheikhbahaei, Takahiro Higuchi, Lilja B. Solnes, Steven P. Rowe, Andreas K. Buck, Constantin Lapa, Mehrbod S. Javadi. Diagnostic Accuracy of Visual Assessment of an Initial DaT-Scan in Comparison to a Fully Automatic Semiquantitative Method. J Nucl Med. May 1, 2018; vol. 59 no. supplement 1:626. © SNMMI.
Johns Hopkins School of Medicine
701983
Journal of Nuclear Medicine May 1, 2018 vol. 59 no. supplement 1 626
Deutsches Urheberrecht
Rudolf A. Werner
Charles Marcus
Sara Sheikhbahaei
Takahiro Higuchi
Lilja B. Solnes
Steven P. Rowe
Andreas K. Buck
Constantin Lapa
Mehrbod S. Javadi
deu
swd
Parkinson-Krankheit
eng
uncontrolled
SPECT
eng
uncontrolled
Parkinson
eng
uncontrolled
Parkinson Disease
eng
uncontrolled
DaTscan
eng
uncontrolled
Ioflupane
eng
uncontrolled
molecular imaging
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
OpenAIRE
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/16220/Werner_Rudolf_Accuracy_DaT-Scan_JNM_accepted_version.pdf
16221
2018
eng
1646
Supplement No 1
59
conferenceobject
1
2018-05-27
--
--
The Impact of Ageing on Dopamine Transporter Imaging
No abstract available.
Journal of Nuclear Medicine
0161-5505
urn:nbn:de:bvb:20-opus-162213
http://jnm.snmjournals.org/content/59/supplement_1/1646.abstract
This research was originally published in JNM. Rudolf A. Werner, Charles Marcus, Sara Sheikhbahaei, Takahiro Higuchi, Lilja B. Solnes, Steven P. Rowe, Andreas K. Buck, Constantin Lapa, Mehrbod S. Javadi. The Impact of Ageing on Dopamine Transporter Imaging. J Nucl Med. May 1, 2018; vol. 59 no. supplement 1:1646. © SNMMI.
Johns Hopkins School of Medicine
701983
Journal of Nuclear Medicine May 1, 2018 vol. 59 no. supplement 1 1646
Deutsches Urheberrecht
Rudolf A. Werner
Charles Marcus
Sara Sheikhbahaei
Takahiro Higuchi
Lilja B. Solnes
Steven P. Rowe
Andreas K. Buck
Constantin Lapa
Mehrbod S. Javadi
deu
swd
Parkinson-Krankheit
eng
uncontrolled
Parkinson
eng
uncontrolled
Parkinson Disease
eng
uncontrolled
DaTscan
eng
uncontrolled
Ioflupane
eng
uncontrolled
SPECT
eng
uncontrolled
molecular imaging
eng
uncontrolled
ageing
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
OpenAIRE
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/16221/Werner_Rudolf_Ageing_DaTscan_JNM_accepted_version.pdf
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
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
16462
2018
eng
preprint
1
2018-07-17
--
--
Pre-therapy Somatostatin-Receptor-Based Heterogeneity Predicts Overall Survival in Pancreatic Neuroendocrine Tumor Patients Undergoing Peptide Receptor Radionuclide Therapy
Purpose: Early identification of aggressive disease could improve decision-support in pancreatic neuroendocrine tumor (pNET) patients prior to peptide receptor radionuclide therapy (PRRT). The prognostic value of intratumoral textural features (TF) determined by baseline somatostatin receptor (SSTR)-PET before PRRT was analyzed.
Procedures: 31 patients with G1/G2 pNET were enrolled (G2, n=23/31). Prior to PRRT with [\(^{177}\)Lu]DOTATATE (mean, 3.6 cycles), baseline SSTR-PET/CT was performed. By segmentation of 162 (median per patient, 5) metastases, intratumoral TF were computed. The impact of conventional PET parameters (SUV\(_{mean/max}\)), imaging-based TF as well as clinical parameters (Ki67, CgA) for prediction of both progression-free (PFS) and overall survival (OS) after PRRT was evaluated.
Results: Within a median follow-up of 3.7y, tumor progression was detected in 21 patients (median, 1.5y) and 13/31 deceased (median, 1.9y). In ROC analysis, the TF Entropy, reflecting derangement on a voxel-by-voxel level, demonstrated predictive capability for OS (cutoff=6.7, AUC=0.71, p=0.02). Of note, increasing Entropy could predict a longer survival (>6.7, OS=2.5y, 17/31), whereas less voxel-based derangement portended inferior outcome (<6.7, OS=1.9y, 14/31). These findings were supported in a G2 subanalysis (>6.9, OS=2.8y, 9/23 vs. <6.9, OS=1.9y, 14/23). Kaplan-Meier analysis revealed a significant distinction between high- and low-risk groups using Entropy (n=31, p<0.05). For those patients below the ROC-derived threshold, the relative risk of death after PRRT was 2.73 (n=31, p=0.04). Ki67 was negatively associated with PFS (p=0.002); however, SUVmean/max failed in prognostication (n.s.).
Conclusions: In contrast to conventional PET parameters, assessment of intratumoral heterogeneity demonstrated superior prognostic performance in pNET patients undergoing PRRT. This novel PET-based strategy of outcome prediction prior to PRRT might be useful for patient risk stratification.
Molecular Imaging and Biology
https://doi.org/10.1007/s11307-018-1252-5
https://link.springer.com/article/10.1007/s11307-018-1252-5
1536-1632
urn:nbn:de:bvb:20-opus-164624
This is a post-peer-review, pre-copyedit version of an article published in Molecular Imaging and Biology. The final authenticated version is available online at: http://dx.doi.org/s11307-018-1252-5
Die finale Version dieses Artikels steht unter https://doi.org/10.1007/s11307-018-1252-5 bzw. http://nbn-resolving.org/urn:nbn:de:bvb:20-opus-167168 open access zur Verfügung.
Johns Hopkins School of Medicine
Molecular Imaging and Biology (2018). https://doi.org/10.1007/s11307-018-1252-5
701983
Deutsches Urheberrecht
Rudolf A. Werner
Harun Ilhan
Sebastian Lehner
László Papp
Norbert Zsótér
Imke Schatka
Dirk O. Muegge
Mehrbod S. Javadi
Takahiro Higuchi
Andreas K. Buck
Peter Bartenstein
Frank Bengel
Markus Essler
Constantin Lapa
Ralph A. Bundschuh
eng
uncontrolled
Pancreas
deu
swd
Positronen-Emissions-Tomografie
eng
uncontrolled
PET
eng
uncontrolled
neuroendocrine tumor
eng
uncontrolled
tumor heterogeneity
eng
uncontrolled
[68Ga]
eng
uncontrolled
[177Lu]-DOTATATE/-DOTATOC
eng
uncontrolled
PET/CT
eng
uncontrolled
SSTR
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
OpenAIRE
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/16462/Werner_Radiomics_Molecular_Imaging_Biology_accepted_version.pdf