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  - Werner, Rudolf A.
A1  - Sayehli, Cyrus
A1  - Hänscheid, Heribert
A1  - Higuchi, Takahiro
A1  - Serfling, Sebastian E.
A1  - Fassnacht, Martin
A1  - Goebeler, Maria-Elisabeth
A1  - Buck, Andreas K.
A1  - Kroiss, Matthias
T1  - Successful combination of selpercatinib and radioiodine after pretherapeutic dose estimation in RET-altered thyroid carcinoma
JF  - European Journal of Nuclear Medicine and Molecular Imaging
N2  - No abstract available.
KW  - papillary thyroid carcinoma (PTC)
KW  - selpercatinib
KW  - radioiodine
KW  - combination
KW  - thyroid carcinoma (TC)
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324435
VL  - 50
IS  - 6
ER  - 
TY  - JOUR
A1  - Marquardt, André
A1  - Hartrampf, Philipp
A1  - Kollmannsberger, Philip
A1  - Solimando, Antonio G.
A1  - Meierjohann, Svenja
A1  - Kübler, Hubert
A1  - Bargou, Ralf
A1  - Schilling, Bastian
A1  - Serfling, Sebastian E.
A1  - Buck, Andreas
A1  - Werner, Rudolf A.
A1  - Lapa, Constantin
A1  - Krebs, Markus
T1  - Predicting microenvironment in CXCR4- and FAP-positive solid tumors — a pan-cancer machine learning workflow for theranostic target structures
JF  - Cancers
N2  - (1) Background: C-X-C Motif Chemokine Receptor 4 (CXCR4) and Fibroblast Activation Protein Alpha (FAP) are promising theranostic targets. However, it is unclear whether CXCR4 and FAP positivity mark distinct microenvironments, especially in solid tumors. (2) Methods: Using Random Forest (RF) analysis, we searched for entity-independent mRNA and microRNA signatures related to CXCR4 and FAP overexpression in our pan-cancer cohort from The Cancer Genome Atlas (TCGA) database —  representing n = 9242 specimens from 29 tumor entities. CXCR4- and FAP-positive samples were assessed via StringDB cluster analysis, EnrichR, Metascape, and Gene Set Enrichment Analysis (GSEA). Findings were validated via correlation analyses in n = 1541 tumor samples. TIMER2.0 analyzed the association of CXCR4 / FAP expression and infiltration levels of immune-related cells. (3) Results: We identified entity-independent CXCR4 and FAP gene signatures representative for the majority of solid cancers. While CXCR4 positivity marked an immune-related microenvironment, FAP overexpression highlighted an angiogenesis-associated niche. TIMER2.0 analysis confirmed characteristic infiltration levels of CD8+ cells for CXCR4-positive tumors and endothelial cells for FAP-positive tumors. (4) Conclusions: CXCR4- and FAP-directed PET imaging could provide a non-invasive decision aid for entity-agnostic treatment of microenvironment in solid malignancies. Moreover, this machine learning workflow can easily be transferred towards other theranostic targets.
KW  - machine learning
KW  - tumor microenvironment
KW  - immune infiltration
KW  - angiogenesis
KW  - mRNA
KW  - miRNA
KW  - transcriptome
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-305036
SN  - 2072-6694
VL  - 15
IS  - 2
ER  -