TY  - JOUR
A1  - Lapa, Constantin
A1  - Schreder, Martin
A1  - Schirbel, Andreas
A1  - Samnick, Samuel
A1  - Kortüm, Klaus Martin
A1  - Herrmann, Ken
A1  - Kropf, Saskia
A1  - Einsele, Herrmann
A1  - Buck, Andreas K.
A1  - Wester, Hans-Jürgen
A1  - Knop, Stefan
A1  - Lückerath, Katharina
T1  - [\(^{68}\)Ga]Pentixafor-PET/CT for imaging of chemokine receptor CXCR4 expression in multiple myeloma - comparison to [\(^{18}\)F]FDG and laboratory values
JF  - Theranostics
N2  - 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.
KW  - medicine
KW  - multiple myeloma
KW  - FDG
KW  - molecular imaging
KW  - CXCR4
KW  - PET
KW  - radionuclide therapy
KW  - theranostics
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172106
VL  - 7
IS  - 1
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  -