TY  - JOUR
A1  - Weich, Alexander
A1  - Rogoll, Dorothee
A1  - Gawlas, Sophia
A1  - Mayer, Lars
A1  - Weich, Wolfgang
A1  - Pongracz, Judit
A1  - Kudlich, Theodor
A1  - Meining, Alexander
A1  - Scheurlen, Michael
T1  - Wnt/β-catenin signaling regulates CXCR4 expression and [\(^{68}\)Ga] Pentixafor internalization in neuroendocrine tumor cells
JF  - Diagnostics
N2  - Loss of Somatostatin Receptor 2 (SSTR2) expression and rising CXC Chemokine Receptor Type 4 (CXCR4) expression are associated with dedifferentiation in neuroendocrine tumors (NET). In NET, CXCR4 expression is associated with enhanced metastatic and invasive potential and worse prognosis but might be a theragnostic target. Likewise, activation of Wnt/β-catenin signaling may promote a more aggressive phenotype in NET. We hypothesized an interaction of the Wnt/β-catenin pathway with CXCR4 expression and function in NET. The NET cell lines BON-1, QGP-1, and MS-18 were exposed to Wnt inhibitors (5-aza-CdR, quercetin, and niclosamide) or the Wnt activator LiCl. The expressions of Wnt pathway genes and of CXCR4 were studied by qRT-PCR, Western blot, and immunohistochemistry. The effects of Wnt modulators on uptake of the CXCR4 ligand [\(^{68}\)Ga] Pentixafor were measured. The Wnt activator LiCl induced upregulation of CXCR4 and Wnt target gene expression. Treatment with the Wnt inhibitors had opposite effects. LiCl significantly increased [\(^{68}\)Ga] Pentixafor uptake, while treatment with Wnt inhibitors decreased radiopeptide uptake. Wnt pathway modulation influences CXCR4 expression and function in NET cell lines. Wnt modulation might be a tool to enhance the efficacy of CXCR4-directed therapies in NET or to inhibit CXCR4-dependent proliferative signaling. The underlying mechanisms for the interaction of the Wnt pathway with CXCR4 expression and function have yet to be clarified.
KW  - neuroendocrine tumor
KW  - NET
KW  - Wnt
KW  - β-catenin
KW  - CXCR4
KW  - [\(^{68}\)Ga] Pentixafor
KW  - BON-1
KW  - QGP-1
KW  - MS-18
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-228914
SN  - 2075-4418
VL  - 11
IS  - 2
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  -