TY - JOUR
A1 - Breun, Maria
A1 - Monoranu, Camelia M.
A1 - Kessler, Almuth F.
A1 - Matthies, Cordula
A1 - Löhr, Mario
A1 - Hagemann, Carsten
A1 - Schirbel, Andreas
A1 - Rowe, Steven P.
A1 - Pomper, Martin G.
A1 - Buck, Andreas K.
A1 - Wester, Hans-Jürgen
A1 - Ernestus, Ralf-Ingo
A1 - Lapa, Constantin
T1 - [\(^{68}\)Ga]-Pentixafor PET/CT for CXCR4-mediated imaging of vestibular schwannomas
JF - Frontiers in Oncology
N2 - We have recently demonstrated CXCR4 overexpression in vestibular schwannomas (VS). This study investigated the feasibility of CXCR4-directed positron emission tomography/computed tomography (PET/CT) imaging of VS using the radiolabeled chemokine ligand [\(^{68}\)Ga]Pentixafor.
Methods: 4 patients with 6 primarily diagnosed or pre-treated/observed VS were enrolled. All subjects underwent [\(^{68}\)Ga]Pentixafor PET/CT prior to surgical resection. Images were analyzed visually and semi-quantitatively for CXCR4 expression including calculation of tumor-to-background ratios (TBR). Immunohistochemistry served as standard of reference in three patients.
Results: [\(^{68}\)Ga]Pentixafor PET/CT was visually positive in all cases. SUV\(_{mean}\) and SUV\(_{max}\) were 3.0 ± 0.3 and 3.8 ± 0.4 and TBR\(_{mean}\) and TBR\(_{max}\) were 4.0 ± 1.4 and 5.0 ± 1.7, respectively. Histological analysis confirmed CXCR4 expression in tumors.
Conclusion: Non-invasive imaging of CXCR4 expression using [\(^{68}\)Ga]Pentixafor PET/CT of VS is feasible and could prove useful for in vivo assessment of CXCR4 expression.
KW - vestibular schwannoma
KW - CXCR4
KW - PET/CT
KW - molecular imaging
KW - Pentixafor
Y1 - 2019
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-201863
VL - 9
IS - 503
ER -
TY - JOUR
A1 - Lapa, Constantin
A1 - Lückerath, Katharina
A1 - Kleinlein, Irene
A1 - Monoranu, Camelia Maria
A1 - Linsenmann, Thomas
A1 - Kessler, Almuth F.
A1 - Rudelius, Martina
A1 - Kropf, Saskia
A1 - Buck, Andreas K.
A1 - Ernestus, Ralf-Ingo
A1 - Wester, Hans-Jürgen
A1 - Löhr, Mario
A1 - Herrmann, Ken
T1 - \(^{68}\)Ga-Pentixafor-PET/CT for Imaging of Chemokine Receptor 4 Expression in Glioblastoma
JF - Theranostics
N2 - Chemokine receptor-4 (CXCR4) has been reported to be overexpressed in glioblastoma (GBM) and to be associated with poor survival. This study investigated the feasibility of non-invasive CXCR4-directed imaging with positron emission tomography/computed tomography (PET/CT) using the radiolabelled chemokine receptor ligand \(^{68}\)Ga-Pentixafor.
15 patients with clinical suspicion on primary or recurrent glioblastoma (13 primary, 2 recurrent tumors) underwent \(^{68}\)Ga-Pentixafor-PET/CT for assessment of CXCR4 expression prior to surgery. O-(2-\(^{18}\)F-fluoroethyl)-L-tyrosine (\(^{18}\)F-FET) PET/CT images were available in 11/15 cases and were compared visually and semi-quantitatively (SUV\(_{max}\), SUV\(_{mean}\)). Tumor-to-background ratios (TBR) were calculated for both PET probes. \(^{68}\)Ga-Pentixafor-PET/CT results were also compared to histological CXCR4 expression on neuronavigated surgical samples.
\(^{68}\)Ga-Pentixafor-PET/CT was visually positive in 13/15 cases with SUV\(_{mean}\) and SUV\(_{max}\) of 3.0±1.5 and 3.9±2.0 respectively. Respective values for \(^{18}\)F-FET were 4.4±2.0 (SUV\(_{mean}\)) and 5.3±2.3 (SUV\(_{max}\)). TBR for SUV\(_{mean}\) and SUV\(_{max}\) were higher for \(^{68}\)Ga-Pentixafor than for \(^{18}\)F-FET (SUV\(_{mean}\) 154.0±90.7 vs. 4.1±1.3; SUV\(_{max}\) 70.3±44.0 and 3.8±1.2, p<0.01), respectively. Histological analysis confirmed CXCR4 expression in tumor areas with high \(^{68}\)Ga-Pentixafor uptake; regions of the same tumor without apparent \(^{68}\)Ga-Pentixafor uptake showed no or low receptor expression.
In this pilot study, \(^{68}\)Ga-Pentixafor retention has been observed in the vast majority of glioblastoma lesions and served as readout for non-invasive determination of CXCR4 expression. Given the paramount importance of the CXCR4/SDF-1 axis in tumor biology, \(^{68}\)Ga-Pentixafor-PET/CT might prove a useful tool for sensitive, non-invasive in-vivo quantification of CXCR4 as well as selection of patients who might benefit from CXCR4-directed therapy.
KW - imaging
KW - chemokine receptor-4
KW - glioblastoma
KW - positron emission tomography/computed tomography
KW - \(^{68}\)Ga-Pentixafor
Y1 - 2016
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-168174
VL - 6
IS - 3
ER -
TY - JOUR
A1 - Weich, Alexander
A1 - Werner, Rudolf A.
A1 - Buck, Andreas K.
A1 - Hartrampf, Philipp E.
A1 - Serfling, Sebastian E.
A1 - Scheurlen, Michael
A1 - Wester, Hans-Jürgen
A1 - Meining, Alexander
A1 - Kircher, Stefan
A1 - Higuchi, Takahiro
A1 - Pomper, Martin G.
A1 - Rowe, Steven P.
A1 - Lapa, Constantin
A1 - Kircher, Malte
T1 - CXCR4-Directed PET/CT in Patients with Newly Diagnosed Neuroendocrine Carcinomas
JF - Diagnostics
N2 - We aimed to elucidate the diagnostic potential of the C-X-C motif chemokine receptor 4 (CXCR4)-directed positron emission tomography (PET) tracer \(^{68}\)Ga-Pentixafor in patients with poorly differentiated neuroendocrine carcinomas (NEC), relative to the established reference standard \(^{18}\)F-FDG PET/computed tomography (CT). In our database, we retrospectively identified 11 treatment-naïve patients with histologically proven NEC, who underwent \(^{18}\)F-FDG and CXCR4-directed PET/CT for staging and therapy planning. The images were analyzed on a per-patient and per-lesion basis and compared to immunohistochemical staining (IHC) of CXCR4 from PET-guided biopsies. \(^{68}\)Ga-Pentixafor visualized tumor lesions in 10/11 subjects, while \(^{18}\)F-FDG revealed sites of disease in all 11 patients. Although weak to moderate CXCR4 expression could be corroborated by IHC in 10/11 cases, \(^{18}\)F-FDG PET/CT detected significantly more tumor lesions (102 vs. 42; total lesions, n = 107; p < 0.001). Semi-quantitative analysis revealed markedly higher 18F-FDG uptake as compared to \(^{68}\)Ga-Pentixafor (maximum and mean standardized uptake values (SUV) and tumor-to-background ratios (TBR) of cancerous lesions, SUVmax: 12.8 ± 9.8 vs. 5.2 ± 3.7; SUVmean: 7.4 ± 5.4 vs. 3.1 ± 3.2, p < 0.001; and, TBR 7.2 ± 7.9 vs. 3.4 ± 3.0, p < 0.001). Non-invasive imaging of CXCR4 expression in NEC is inferior to the reference standard \(^{18}\)F-FDG PET/CT.
KW - CXCR4
KW - NET
KW - NEC
KW - 68Ga-Pentixafor
KW - 18F-FDG
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-234231
SN - 2075-4418
VL - 11
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 -
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 - Herrmann, Ken
A1 - Buck, Andreas K.
A1 - Schuster, Tibor
A1 - Abbrederis, Kathrin
A1 - Blümel, Christina
A1 - Santi, Ivan
A1 - Rudelius, Martina
A1 - Wester, Hans-Jürgen
A1 - Peschel, Christian
A1 - Schwaiger, Markus
A1 - Dechow, Tobias
A1 - Keller, Ulrich
T1 - Week one FLT-PET response predicts complete remission to R-CHOP and survival in DLBCL
JF - Oncotarget
N2 - Despite improved survival in the Rituximab (R) era, a considerable number of patients with diffuse large B-cell lymphoma (DLBCL) ultimately die from the disease. Functional imaging using [18F]fluorodeoxyglucose-PET is suggested for assessment of residual viable tumor very early during treatment but is compromised by non-specific tracer retention in inflammatory lesions. The PET tracer [18F]fluorodeoxythymidine (FLT) as surrogate marker of tumor proliferation may overcome this limitation. We present results of a prospective clinical study testing FLT-PET as superior and early predictor of response to chemotherapy and outcome in DLBCL. 54 patients underwent FLT-PET prior to and one week after the start of R-CHOP chemotherapy. Repetitive FLT-PET imaging was readily implemented into the diagnostic work-up. Our data demonstrate that the reduction of FLT standard uptake valuemean (SUVmean) and SUVmax one week after chemotherapy was significantly higher in patients achieving complete response (CR, n=48; non-CR, n=6; p<0.006). Martingale-residual and Cox proportional hazard analyses showed a significant monotonous decrease of mortality risk with increasing change in SUV. Consistent with these results, early FLT-PET response showed relevant discriminative ability in predicting CR. In conclusion, very early FLT-PET in the course of R-CHOP chemotherapy is feasible and enables identification of patients at risk for treatment failure.
KW - [18F]Fluorodeoxythymidine
KW - FLT-PET
KW - positron emission tomography
KW - DLBCL
KW - lymphoma
Y1 - 2014
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-120659
SN - 1949-2553
VL - 5
IS - 12
ER -