16998
2017
eng
96732-96737
57
8
article
1
2018-10-25
--
--
Targeting CXCR4 with [\(^{68}\)Ga]Pentixafor: a suitable theranostic approach in pleural mesothelioma?
C-X-C motif chemokine receptor 4 (CXCR4) is a key factor for tumor growth and metastasis in several types of human cancer. This study investigated the feasibility of CXCR4-directed imaging with positron emission tomography/computed tomography (PET/CT) using [\(^{68}\)Ga]Pentixafor in malignant pleural mesothelioma.
Six patients with pleural mesothelioma underwent [\(^{68}\)Ga]Pentixafor-PET/CT. 2′-[\(^{18}\)F]fluoro-2′-deoxy-D-glucose ([\(^{18}\)F]FDG)-PET/CT (4/6 patients) and immunohistochemistry obtained from biopsy or surgery (all) served as standards of reference. Additionally, 9 surgical mesothelioma samples were available for histological work-up.
Whereas [\(^{18}\)F]FDG-PET depicted active lesions in all patients, [\(^{68}\)Ga]Pentixafor-PET/CT recorded physiologic tracer distribution and none of the 6 patients presented [\(^{68}\)Ga]Pentixafor-positive lesions. This finding paralleled results of immunohistochemistry which also could not identify relevant CXCR4 surface expression in the samples analyzed.
In contrast to past reports, our data suggest widely absence of CXCR4 expression in pleural mesothelioma. Hence, robust cell surface expression should be confirmed prior to targeting this chemokine receptor for diagnosis and/or therapy.
Oncotarget
10.18632/oncotarget.18235
29228566
urn:nbn:de:bvb:20-opus-169989
Oncotarget, 2017, Vol. 8, No. 57, 96732-96737. DOI: 10.18632/oncotarget.18235
false
true
Constantin Lapa
Stefan Kircher
Andreas Schirbel
Andreas Rosenwald
Saskia Kropf
Theo Pelzer
Thorsten Walles
Andreas K. Buck
Wolfgang A. Weber
Hans-Juergen Wester
Ken Herrmann
Katharina Lückerath
eng
uncontrolled
PET
eng
uncontrolled
CXCR4
eng
uncontrolled
[\(^{68}\)Ga] pentixafor
eng
uncontrolled
pleural mesothelioma
eng
uncontrolled
theranostics
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Pathologisches Institut
Medizinische Klinik und Poliklinik I
Förderzeitraum 2017
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/16998/010_Lapa_ONCOTARGET.pdf
15800
2017
eng
1489-1498
6
7
article
1
2018-02-23
--
--
Imaging of Chemokine Receptor 4 Expression in Neuroendocrine Tumors - a Triple Tracer Comparative Approach
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.
Theranostics
10.7150/thno.18754
urn:nbn:de:bvb:20-opus-158008
Theranostics 2017; 7(6): 1489-1498. doi: 10.7150/thno.18754
701983
CC BY-NC: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell 4.0 International
Rudolf A. Werner
Alexander Weich
Takahiro Higuchi
Jan S. Schmid
Andreas Schirbel
Michael Lassmann
Vanessa Wild
Martina Rudelius
Theodor Kudlich
Ken Herrmann
Michael Scheurlen
Andreas K. Buck
Saskia Kropf
Hans-Jürgen Wester
Constantin Lapa
eng
uncontrolled
SSTR
eng
uncontrolled
peptide receptor radionuclide therapy
eng
uncontrolled
neuroendocrine tumor
eng
uncontrolled
[\(^{68}\)Ga]Pentixafor
eng
uncontrolled
CXCR4
eng
uncontrolled
chemokine receptor
eng
uncontrolled
PET/CT
eng
uncontrolled
DOTATOC
eng
uncontrolled
PRRT
deu
swd
Positronen-Emissions-Tomografie
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Pathologisches Institut
Medizinische Klinik und Poliklinik II
OpenAIRE
Förderzeitraum 2017
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/15800/Werner_Theranostics.pdf
17209
2017
eng
1589-1597
6
7
article
1
2018-11-19
--
--
CXCR4-directed endoradiotherapy induces high response rates in extramedullary relapsed multiple myeloma
C-X-C-motif chemokine receptor 4 (CXCR4) is a key factor for tumor growth and metastasis in several types of human cancer. We have recently reported promising first-in-man experience with CXCR4-directed endoradiotherapy (ERT) in multiple myeloma (MM).
Eight heavily pretreated MM patients underwent a total of 10 ERT cycles (7 patients with 1 cycle and a single patient with 3 cycles). ERT was administered in combination with chemotherapy and autologous stem cell support. End points were occurrence and timing of adverse events, progression-free and overall survival.
ERT was overall well tolerated without any unexpected acute adverse events or changes in vital signs. With absorbed tumor doses >30-70 Gy in intra- or extramedullary lesions, significant anti-myeloma activity was observed with 1 patient achieving complete remission and 5/8 partial remission. Directly after ERT major infectious complications were seen in one patient who died from sepsis 22 days after ERT, another patient with high tumor burden experienced lethal tumor lysis syndrome. Median progression-free survival was 54 days (range, 13-175), median overall survival was 223 days (range, 13-313). During follow-up (6 patients available), one patient died from infectious complications, 2/8 from disease progression, the remaining 3/8 patients are still alive.
CXCR4-directed ERT was well-tolerated and exerted anti-myeloma activity even at very advanced stage MM with presence of extramedullary disease. Further assessment of this novel treatment option is highly warranted.
Theranostics
10.7150/thno.19050
28529638
urn:nbn:de:bvb:20-opus-172095
Theranostics (2017) 7:6, pp. 1589-1597. https://www.thno.org/v07p1589.htm
true
true
CC BY-NC: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell 4.0 International
Constantin Lapa
Ken Herrmann
Andreas Schirbel
Heribert Hänscheid
Katharina Lückerath
Margret Schottelius
Malte Kircher
Rudolf A. Werner
Martin Schreder
Samuel Samnick
Saskia Kropf
Stefan Knop
Andreas K. Buck
Hermann Einsele
Hans-Juergen Wester
K. Martin Kortüm
eng
uncontrolled
medicine
eng
uncontrolled
multiple myeloma
eng
uncontrolled
PET
eng
uncontrolled
CXCR4
eng
uncontrolled
theranostics
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Medizinische Klinik und Poliklinik II
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/17209/Lapa_v07p1589.pdf
17210
2017
eng
205-212
1
7
article
1
2018-11-19
--
--
[\(^{68}\)Ga]Pentixafor-PET/CT for imaging of chemokine receptor CXCR4 expression in multiple myeloma - comparison to [\(^{18}\)F]FDG and laboratory values
Chemokine (C-X-C motif) receptor 4 (CXCR4) is a key factor for tumor growth and metastasis in several types of human cancer including multiple myeloma (MM). Proof-of-concept of CXCR4-directed radionuclide therapy in MM has recently been reported. This study assessed the diagnostic performance of the CXCR4-directed radiotracer [\(^{68}\)Ga]Pentixafor in MM and a potential role for stratifying patients to CXCR4-directed therapies.
Thirty-five patients with MM underwent [\(^{68}\)Ga]Pentixafor-PET/CT for evaluation of eligibility for endoradiotherapy. In 19/35 cases, [\(^{18}\)F]FDG-PET/CT for correlation was available. Scans were compared on a patient and on a lesion basis. Tracer uptake was correlated with standard clinical parameters of disease activity.
[\(^{68}\)Ga]Pentixafor-PET detected CXCR4-positive disease in 23/35 subjects (66%). CXCR4-positivity at PET was independent from myeloma subtypes, cytogenetics or any serological parameters and turned out as a negative prognostic factor. In the 19 patients in whom a comparison to [\(^{18}\)F]FDG was available, [\(^{68}\)Ga]Pentixafor-PET detected more lesions in 4/19 (21%) subjects, [\(^{18}\)F]FDG proved superior in 7/19 (37%). In the remaining 8/19 (42%) patients, both tracers detected an equal number of lesions. [\(^{18}\)F]FDG-PET positivity correlated with [\(^{68}\)Ga]Pentixafor-PET positivity (p=0.018).
[\(^{68}\)Ga]Pentixafor-PET provides further evidence that CXCR4 expression frequently occurs in advanced multiple myeloma, representing a negative prognostic factor and a potential target for myeloma specific treatment. However, selecting patients for CXCR4 directed therapies and prognostic stratification seem to be more relevant clinical applications for this novel imaging modality, rather than diagnostic imaging of myeloma.
Theranostics
10.7150/thno.16576
28042328
urn:nbn:de:bvb:20-opus-172106
Theranostics (2017) 7:1, pp. 205-212. https://www.thno.org/v07p0205.htm
true
true
CC BY-NC: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell 4.0 International
Constantin Lapa
Martin Schreder
Andreas Schirbel
Samuel Samnick
Klaus Martin Kortüm
Ken Herrmann
Saskia Kropf
Herrmann Einsele
Andreas K. Buck
Hans-Jürgen Wester
Stefan Knop
Katharina Lückerath
eng
uncontrolled
medicine
eng
uncontrolled
multiple myeloma
eng
uncontrolled
FDG
eng
uncontrolled
molecular imaging
eng
uncontrolled
CXCR4
eng
uncontrolled
PET
eng
uncontrolled
radionuclide therapy
eng
uncontrolled
theranostics
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Medizinische Klinik und Poliklinik II
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/17210/Lapa_v07p0205.pdf