TY  - JOUR
A1  - Buck, Andreas K.
A1  - Serfling, Sebastian E.
A1  - Lindner, Thomas
A1  - Hänscheid, Heribert
A1  - Schirbel, Andreas
A1  - Hahner, Stefanie
A1  - Fassnacht, Martin
A1  - Einsele, Hermann
A1  - Werner, Rudolf A.
T1  - CXCR4-targeted theranostics in oncology
JF  - European Journal of Nuclear Medicine and Molecular Imaging
N2  - A growing body of literature reports on the upregulation of C-X-C motif chemokine receptor 4 (CXCR4) in a variety of cancer entities, rendering this receptor as suitable target for molecular imaging and endoradiotherapy in a theranostic setting. For instance, the CXCR4-targeting positron emission tomography (PET) agent [\(^{68}\)Ga]PentixaFor has been proven useful for a comprehensive assessment of the current status quo of solid tumors, including adrenocortical carcinoma or small-cell lung cancer. In addition, [\(^{68}\)Ga]PentixaFor has also provided an excellent readout for hematological malignancies, such as multiple myeloma, marginal zone lymphoma, or mantle cell lymphoma. PET-based quantification of the CXCR4 capacities in vivo allows for selecting candidates that would be suitable for treatment using the theranostic equivalent [\(^{177}\)Lu]/[\(^{90}\)Y]PentixaTher. This CXCR4-directed theranostic concept has been used as a conditioning regimen prior to hematopoietic stem cell transplantation and to achieve sufficient anti-lymphoma/-tumor activity in particular for malignant tissues that are highly sensitive to radiation, such as the hematological system. Increasing the safety margin, pretherapeutic dosimetry is routinely performed to determine the optimal activity to enhance therapeutic efficacy and to reduce off-target adverse events. The present review will provide an overview of current applications for CXCR4-directed molecular imaging and will introduce the CXCR4-targeted theranostic concept for advanced hematological malignancies.
KW  - CXCR4
KW  - theranostics
KW  - C-X-C motif chemokine receptor 4
KW  - [68Ga]PentixaFor
KW  - [177Lu]PentixaTher
KW  - [90Y]PentixaTher
KW  - endoradiotherapy
KW  - adrenocortical carcinoma
KW  - multiple myeloma
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324545
VL  - 49
IS  - 12
ER  - 
TY  - JOUR
A1  - Lapa, Constantin
A1  - Herrmann, Ken
A1  - Schirbel, Andreas
A1  - Hänscheid, Heribert
A1  - Lückerath, Katharina
A1  - Schottelius, Margret
A1  - Kircher, Malte
A1  - Werner, Rudolf A.
A1  - Schreder, Martin
A1  - Samnick, Samuel
A1  - Kropf, Saskia
A1  - Knop, Stefan
A1  - Buck, Andreas K.
A1  - Einsele, Hermann
A1  - Wester, Hans-Juergen
A1  - Kortüm, K. Martin
T1  - CXCR4-directed endoradiotherapy induces high response rates in extramedullary relapsed multiple myeloma
JF  - Theranostics
N2  - 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.
KW  - medicine
KW  - multiple myeloma
KW  - PET
KW  - CXCR4
KW  - theranostics
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172095
VL  - 7
IS  - 6
ER  -