14868
2015
eng
8418-8429
10
6
article
1
2017-05-17
--
--
\(^{11}\)C-Methionine-PET: a novel and sensitive tool for monitoring of early response to treatment in multiple myeloma
Multiple myeloma (MM) remains an essentially incurable hematologic malignancy. However, new treatment modalities and novel drugs have been introduced and thus additional tools for therapy monitoring are increasingly needed. Therefore, we evaluated the radiotracers \(^{11}\)C-Methionine (paraprotein-biosynthesis) and \(^{18}\)F-FDG (glucose-utilization) for monitoring response to anti-myeloma-therapy and outcome prediction. Influence of proteasome-inhibition on radiotracer-uptake of different MM cell-lines and patient-derived CD138\(^{+}\) plasma cells was analyzed and related to tumor-biology. Mice xenotransplanted with MM. 1S tumors underwent MET- and FDG-\(\mu\)PET. Tumor-to-background ratios before and after 24 h, 8 and 15 days treatment with bortezomib were correlated to survival. Treatment reduced both MET and FDG uptake; changes in tracer-retention correlated with a switch from high to low CD138-expression. In xenotransplanted mice, MET-uptake significantly decreased by 30-79% as early as 24 h after bortezomib injection. No significant differences were detected thus early with FDG. This finding was confirmed in patient-derived MM cells. Importantly, early reduction of MET-but not FDG-uptake correlated with improved survival and reduced tumor burden in mice. Our results suggest that MET is superior to FDG in very early assessment of response to anti-myeloma-therapy. Early changes in MET-uptake have predictive potential regarding response and survival. MET-PET holds promise to individualize therapies in MM in future.
Oncotarget
10.18632/oncotarget.3053
urn:nbn:de:bvb:20-opus-148688
Oncotarget, 2015, 6(10), 8418-8429. DOI: 10.18632/oncotarget.3053
Katharina Lückerath
Constantin Lapa
Christa Albert
Ken Herrmann
Gerhard Jörg
Samuel Samnick
Herrmann Einsele
Stefan Knop
Andreas K. Buck
eng
uncontrolled
positron emission tomography
eng
uncontrolled
imaging techniques
eng
uncontrolled
experience
eng
uncontrolled
\(^{11}\)C-Methionine-PET
eng
uncontrolled
treatment response
eng
uncontrolled
molecular imaging
eng
uncontrolled
multiple myeloma
eng
uncontrolled
management
eng
uncontrolled
\(^{18}\)F-FDG PET/CT
eng
uncontrolled
bone disease
eng
uncontrolled
stem-cell transplantation
eng
uncontrolled
esophagogastric junction
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Abteilung für Molekulare Innere Medizin (in der Medizinischen Klinik und Poliklinik II)
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/14868/038_Lueckerath_Oncotarget.pdf
12549
2015
eng
e0122269
3
10
article
1
2016-01-26
--
--
Tumor-Associated Macrophages in Glioblastoma Multiforme—A Suitable Target for Somatostatin Receptor-Based Imaging and Therapy?
Background
Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults. Tumor-associated macrophages (TAM) have been shown to promote malignant growth and to correlate with poor prognosis. [1,4,7,10-tetraazacyclododecane-NN′,N″,N′″-tetraacetic acid]-d-Phe1,Tyr3-octreotate (DOTATATE) labeled with Gallium-68 selectively binds to somatostatin receptor 2A (SSTR2A) which is specifically expressed and up-regulated in activated macrophages. On the other hand, the role of SSTR2A expression on the cell surface of glioma cells has not been fully elucidated yet. The aim of this study was to non-invasively assess SSTR2A expression of both glioma cells as well as macrophages in GBM.
Methods
15 samples of patient-derived GBM were stained immunohistochemically for macrophage infiltration (CD68), proliferative activity (Ki67) as well as expression of SSTR2A. Anti-CD45 staining was performed to distinguish between resident microglia and tumor-infiltrating macrophages. In a subcohort, positron emission tomography (PET) imaging using \(^{68}Ga-DOTATATE\) was performed and the semiquantitatively evaluated tracer uptake was compared to the results of immunohistochemistry.
Results
The amount of microglia/macrophages ranged from <10% to >50% in the tumor samples with the vast majority being resident microglial cells. A strong SSTR2A immunostaining was observed in endothelial cells of proliferating vessels, in neurons and neuropile. Only faint immunostaining was identified on isolated microglial and tumor cells. Somatostatin receptor imaging revealed areas of increased tracer accumulation in every patient. However, retention of the tracer did not correlate with immunohistochemical staining patterns.
Conclusion
SSTR2A seems not to be overexpressed in GBM samples tested, neither on the cell surface of resident microglia or infiltrating macrophages, nor on the surface of tumor cells. These data suggest that somatostatin receptor directed imaging and treatment strategies are less promising in GBM.
PLoS One
10.1371/journal.pone.0122269
urn:nbn:de:bvb:20-opus-125498
PLoS ONE 10(3): e0122269. doi:10.1371/journal.pone.0122269
Constantin Lapa
Thomas Linsenmann
Katharina Lückerath
Samuel Samnick
Ken Herrmann
Carolin Stoffer
Ralf-Ingo Ernestus
Andreas K. Buck
Mario Löhr
Camelia-Maria Monoranu
eng
uncontrolled
glioma
eng
uncontrolled
positron emission tomography
eng
uncontrolled
glioblastoma multiforme
eng
uncontrolled
macrophages
eng
uncontrolled
somatostatin
eng
uncontrolled
microglial cells
eng
uncontrolled
immunostaining
eng
uncontrolled
magnetic resonance imaging
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Förderzeitraum 2015
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/12549/Lapa_journal.pone.0122269.pdf
14873
2015
eng
477-487
4
7
article
1
2017-05-17
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--
In vivo molecular imaging of chemokine receptor CXCR4 expression in patients with advanced multiple myeloma
CXCR4 is a G-protein-coupled receptor that mediates recruitment of blood cells toward its ligand SDF-1. In cancer, high CXCR4 expression is frequently associated with tumor dissemination andpoor prognosis. We evaluated the novel CXCR4 probe [\(^{68}\)Ga]Pentixafor for invivo mapping of CXCR4 expression density in mice xenografted with human CXCR4-positive MM cell lines and patients with advanced MM by means of positron emission tomography (PET). [\(^{68}\)Ga]Pentixafor PET provided images with excellent specificity and contrast. In 10 of 14 patients with advanced MM [\(^{68}\)Ga]Pentixafor PET/CT scans revealed MM manifestations, whereas only nine of 14 standard [\(^{18}\)F]fluorodeoxyglucose PET/CT scans were rated visually positive. Assessment of blood counts and standard CD34\(^{+}\) flow cytometry did not reveal significant blood count changes associated with tracer application. Based on these highly encouraging data on clinical PET imaging of CXCR4 expression in a cohort of MM patients, we conclude that [\(^{68}\)Ga]Pentixafor PET opens a broad field for clinical investigations on CXCR4 expression and for CXCR4-directed therapeutic approaches in MM and other diseases.
EMBO Molecular Medicine
10.15252/emmm.201404698
urn:nbn:de:bvb:20-opus-148738
EMBO Molecular Medicine 7(4), 477-487 (2015). DOI: 10.15252/emmm.201404698
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Kathrin Philipp-Abbrederis
Ken Herrmann
Stefan Knop
Margret Schottelius
Matthias Eiber
Katharina Lückerath
Elke Pietschmann
Stefan Habringer
Carlos Gerngroß
Katharina Franke
Martina Rudelius
Andreas Schirbel
Constantin Lapa
Kristina Schwamborn
Sabine Steidle
Elena Hartmann
Andreas Rosenwald
Saskia Kropf
Ambros J Beer
Christian Peschel
Hermann Einsele
Andreas K Buck
Markus Schwaiger
Katharina Götze
Hans-Jürgen Wester
Ulrich Keller
eng
uncontrolled
FDG PET/CT
eng
uncontrolled
cells
eng
uncontrolled
CXCR4/SDF-1
eng
uncontrolled
CXCR4
eng
uncontrolled
multiple myeloma
eng
uncontrolled
positron emission tomography
eng
uncontrolled
chemokine receptor
eng
uncontrolled
in vivo imaging
eng
uncontrolled
malignancies
eng
uncontrolled
involvement
eng
uncontrolled
microenvironment
eng
uncontrolled
survival
eng
uncontrolled
cancer
eng
uncontrolled
autologous transplantation
eng
uncontrolled
bone disease
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Pathologisches Institut
Abteilung für Molekulare Innere Medizin (in der Medizinischen Klinik und Poliklinik II)
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/14873/043_Philipp-Abbrederis_EMBO_Molecular_Medicine.pdf