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
16998
2017
eng
96732-96737
57
8
article
1
2018-10-25
--
--
Targeting CXCR4 with [\(^{68}\)Ga]Pentixafor: a suitable theranostic approach in pleural mesothelioma?
C-X-C motif chemokine receptor 4 (CXCR4) is a key factor for tumor growth and metastasis in several types of human cancer. This study investigated the feasibility of CXCR4-directed imaging with positron emission tomography/computed tomography (PET/CT) using [\(^{68}\)Ga]Pentixafor in malignant pleural mesothelioma.
Six patients with pleural mesothelioma underwent [\(^{68}\)Ga]Pentixafor-PET/CT. 2′-[\(^{18}\)F]fluoro-2′-deoxy-D-glucose ([\(^{18}\)F]FDG)-PET/CT (4/6 patients) and immunohistochemistry obtained from biopsy or surgery (all) served as standards of reference. Additionally, 9 surgical mesothelioma samples were available for histological work-up.
Whereas [\(^{18}\)F]FDG-PET depicted active lesions in all patients, [\(^{68}\)Ga]Pentixafor-PET/CT recorded physiologic tracer distribution and none of the 6 patients presented [\(^{68}\)Ga]Pentixafor-positive lesions. This finding paralleled results of immunohistochemistry which also could not identify relevant CXCR4 surface expression in the samples analyzed.
In contrast to past reports, our data suggest widely absence of CXCR4 expression in pleural mesothelioma. Hence, robust cell surface expression should be confirmed prior to targeting this chemokine receptor for diagnosis and/or therapy.
Oncotarget
10.18632/oncotarget.18235
29228566
urn:nbn:de:bvb:20-opus-169989
Oncotarget, 2017, Vol. 8, No. 57, 96732-96737. DOI: 10.18632/oncotarget.18235
false
true
Constantin Lapa
Stefan Kircher
Andreas Schirbel
Andreas Rosenwald
Saskia Kropf
Theo Pelzer
Thorsten Walles
Andreas K. Buck
Wolfgang A. Weber
Hans-Juergen Wester
Ken Herrmann
Katharina Lückerath
eng
uncontrolled
PET
eng
uncontrolled
CXCR4
eng
uncontrolled
[\(^{68}\)Ga] pentixafor
eng
uncontrolled
pleural mesothelioma
eng
uncontrolled
theranostics
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Pathologisches Institut
Medizinische Klinik und Poliklinik I
Förderzeitraum 2017
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/16998/010_Lapa_ONCOTARGET.pdf