TY  - JOUR
A1  - Philipp-Abbrederis, Kathrin
A1  - Herrmann, Ken
A1  - Knop, Stefan
A1  - Schottelius, Margret
A1  - Eiber, Matthias
A1  - Lückerath, Katharina
A1  - Pietschmann, Elke
A1  - Habringer, Stefan
A1  - Gerngroß, Carlos
A1  - Franke, Katharina
A1  - Rudelius, Martina
A1  - Schirbel, Andreas
A1  - Lapa, Constantin
A1  - Schwamborn, Kristina
A1  - Steidle, Sabine
A1  - Hartmann, Elena
A1  - Rosenwald, Andreas
A1  - Kropf, Saskia
A1  - Beer, Ambros J
A1  - Peschel, Christian
A1  - Einsele, Hermann
A1  - Buck, Andreas K
A1  - Schwaiger, Markus
A1  - Götze, Katharina
A1  - Wester, Hans-Jürgen
A1  - Keller, Ulrich
T1  - In vivo molecular imaging of chemokine receptor CXCR4 expression in patients with advanced multiple myeloma
JF  - EMBO Molecular Medicine
N2  - 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.
KW  - FDG PET/CT
KW  - cells
KW  - CXCR4/SDF-1
KW  - CXCR4
KW  - multiple myeloma
KW  - positron emission tomography
KW  - chemokine receptor
KW  - in vivo imaging
KW  - malignancies
KW  - involvement
KW  - microenvironment
KW  - survival
KW  - cancer
KW  - autologous transplantation
KW  - bone disease
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-148738
VL  - 7
IS  - 4
ER  - 
TY  - JOUR
A1  - Werner, Rudolf A.
A1  - Weich, Alexander
A1  - Higuchi, Takahiro
A1  - Schmid, Jan S.
A1  - Schirbel, Andreas
A1  - Lassmann, Michael
A1  - Wild, Vanessa
A1  - Rudelius, Martina
A1  - Kudlich, Theodor
A1  - Herrmann, Ken
A1  - Scheurlen, Michael
A1  - Buck, Andreas K.
A1  - Kropf, Saskia
A1  - Wester, Hans-Jürgen
A1  - Lapa, Constantin
T1  - Imaging of Chemokine Receptor 4 Expression in Neuroendocrine Tumors - a Triple Tracer Comparative Approach
JF  - Theranostics
N2  - C-X-C motif chemokine receptor 4 (CXCR4) and somatostatin receptors (SSTR) are overexpressed in gastro-entero-pancreatic neuroendocrine tumors (GEP-NET). In this study, we aimed to elucidate the feasibility of non-invasive CXCR4 positron emission tomography/computed tomography (PET/CT) imaging in GEP-NET patients using [\(^{68}\)Ga]Pentixafor in comparison to \(^{68}\)Ga-DOTA-D-Phe-Tyr3-octreotide ([\(^{68}\)Ga]DOTATOC) and \(^{18}\)F-fluorodeoxyglucose ([\(^{18}\)F]FDG). Twelve patients with histologically proven GEP-NET (3xG1, 4xG2, 5xG3) underwent [\(^{68}\)Ga]DOTATOC, [\(^{18}\)F]FDG, and [\(^{68}\)Ga]Pentixafor PET/CT for staging and planning of the therapeutic management. Scans were analyzed on a patient as well as on a lesion basis and compared to immunohistochemical staining patterns of CXCR4 and somatostatin receptors SSTR2a and SSTR5. [\(^{68}\)Ga]Pentixafor visualized tumor lesions in 6/12 subjects, whereas [\(^{18}\)F]FDG revealed sites of disease in 10/12 and [\(^{68}\)Ga]DOTATOC in 11/12 patients, respectively. Regarding sensitivity, SSTR-directed PET was the superior imaging modality in all G1 and G2 NET. CXCR4-directed PET was negative in all G1 NET. In contrast, 50% of G2 and 80% of G3 patients exhibited [\(^{68}\)Ga]Pentixafor-positive tumor lesions. Whereas CXCR4 seems to play only a limited role in detecting well-differentiated NET, increasing receptor expression could be non-invasively observed with increasing tumor grade. Thus, [\(^{68}\)Ga]Pentixafor PET/CT might serve as non-invasive read-out for evaluating the possibility of CXCR4-directed endoradiotherapy in advanced dedifferentiated SSTR-negative tumors.
KW  - SSTR
KW  - peptide receptor radionuclide therapy
KW  - neuroendocrine tumor
KW  - [\(^{68}\)Ga]Pentixafor
KW  - CXCR4
KW  - chemokine receptor
KW  - PET/CT
KW  - DOTATOC
KW  - PRRT
KW  - Positronen-Emissions-Tomografie
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158008
VL  - 7
IS  - 6
ER  -