TY  - JOUR
A1  - Werner, Rudolf
A1  - Wakabayashi, Hiroshi
A1  - Bauer, Jochen
A1  - Schütz, Claudia
A1  - Zechmeister, Christina
A1  - Hayakawa, Nobuyuki
A1  - Javadi, Mehrbod S.
A1  - Lapa, Constantin
A1  - Jahns, Roland
A1  - Ergün, Süleyman
A1  - Jahns, Valerie
A1  - Higuchi, Takahiro
T1  - Longitudinal \(^{18}\)F-FDG PET imaging in a Rat Model of Autoimmune Myocarditis
JF  - European Heart Journal Cardiovascular Imaging
N2  - 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.
KW  - positron emission tomography
KW  - Myokarditis
KW  - myocarditis
KW  - inflammation
KW  - 18F-FDG
KW  - PET
KW  - personalized treatment
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165601
SN  - 2047-2404
ER  - 
TY  - JOUR
A1  - Rossow, Leonie
A1  - Veitl, Simona
A1  - Vorlová, Sandra
A1  - Wax, Jacqueline K.
A1  - Kuhn, Anja E.
A1  - Maltzahn, Verena
A1  - Upcin, Berin
A1  - Karl, Franziska
A1  - Hoffmann, Helene
A1  - Gätzner, Sabine
A1  - Kallius, Matthias
A1  - Nandigama, Rajender
A1  - Scheld, Daniela
A1  - Irmak, Ster
A1  - Herterich, Sabine
A1  - Zernecke, Alma
A1  - Ergün, Süleyman
A1  - Henke, Erik
T1  - LOX-catalyzed collagen stabilization is a proximal cause for intrinsic resistance to chemotherapy
JF  - Oncogene
N2  - The potential of altering the tumor ECM to improve drug response remains fairly unexplored. To identify targets for modification of the ECM aiming to improve drug response and overcome resistance, we analyzed expression data sets from pre-treatment patient cohorts. Cross-evaluation identified a subset of chemoresistant tumors characterized by increased expression of collagens and collagen-stabilizing enzymes. We demonstrate that strong collagen expression and stabilization sets off a vicious circle of self-propagating hypoxia, malignant signaling, and aberrant angiogenesis that can be broken by an appropriate auxiliary intervention: Interfering with collagen stabilization by inhibition of lysyl oxidases significantly enhanced response to chemotherapy in various tumor models, even in metastatic disease. Inhibition of collagen stabilization by itself can reduce or enhance tumor growth depending on the tumor type. The mechanistical basis for this behavior is the dependence of the individual tumor on nutritional supply on one hand and on high tissue stiffness for FAK signaling on the other.
KW  - Cancer models
KW  - Cancer therapeutic resistance
KW  - Targeted therapies
KW  - Tumour angiogenesis
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227008
VL  - 37
ER  -