TY  - JOUR
AU  - Martin, Sebastian
AU  - Viertl, David
AU  - Janz, Anna
AU  - Habringer, Stefan
AU  - Keller, Ulrich
AU  - Schottelius, Margret
TI  - Influence of corticosteroid treatment on CXCR4 expression in DLBCL.
JO  - EJNMMI Research
VL  - 13
IS  - 1
SN  - 2191-219X
CY  - Heidelberg
PB  - Springer
M1  - DKFZ-2023-00956
SP  - 40
PY  - 2023
N1  - Short Communication
AB  - CXCR4-targeted radioligand therapy (RLT) with [177Lu]Lu/[90Y]Y-PentixaTher has recently evolved as a promising therapeutic option for patients with advanced hematological cancers. Given their advanced disease stage, most patients scheduled for PentixaTher RLT require concomitant or bridging chemotherapy to prevent intermittent tumor progression. These (mostly combination) therapies may cause significant downregulation of tumoral CXCR4 expression, challenging the applicability of PentixaTher RLT. This study therefore aimed at investigating the influence of corticosteroids, a central component of these chemotherapies, on CXCR4 regulation in diffuse large B cell lymphoma (DLBCL).Different DLBCL cell lines (Daudi, OCI-LY1, SUDHL-4, -5-, -6 and -8) as well as the human T-cell lymphoma cell line Jurkat were incubated with Dexamethasone (Dex; 0.5 and 5 µM, respectively) and Prednisolone (Pred; 5 and 50 µM, respectively) for different time points (2 h, 24 h). Treatment-induced modulation of cellular CXCR4 surface expression was assessed via flow cytometry (FC) and compared to untreated cells. A radioligand binding assay with [125I]CPCR4.3 was performed in parallel using the same cells. To quantify potential corticosteroid treatment effects on tumoral CXCR4 expression in vivo, OCI-LY1 bearing NSG mice were injected 50 µg Dex/mouse i.p. (daily for 6 days). Then, a biodistribution study (1 h p.i.) using [68Ga]PentixaTher was performed, and tracer biodistribution in treated (n = 5) vs untreated mice (n = 5) was compared.In the in vitro experiments, a strongly cell line-dependent upregulation of CXCR4 was observed for both Dex and Pred treatment, with negligible differences between the high and low dose. While in Jurkat, Daudi and SUDHL-8 cells, CXCR4 expression remained unchanged, a 1.5- to 3.5-fold increase in CXCR4 cell surface expression was observed for SUDHL-5 < SUDHL-4 /-6 < OCI-LY1 via FC compared to untreated cells. This increase in CXCR4 expression was also reflected in correspondingly enhanced [125I]CPCR4.3 accumulation in treated cells, with a linear correlation between FC and radioligand binding data. In vivo, Dex treatment led to a general increase of [68Ga]PentixaTher uptake in all organs compared to untreated animals, as a result of a higher tracer concentration in blood. However, we observed an overproportionally enhanced [68Ga]PentixaTher uptake in the OCI-LY1 tumors in treated (21.0 ± 5.5
KW  - CXCR4 (Other)
KW  - Chemokine receptor regulation (Other)
KW  - Corticosteroids (Other)
KW  - Cortisol (Other)
KW  - PentixaTher (Other)
KW  - Radioligand therapy (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:37162652
DO  - DOI:10.1186/s13550-023-00993-4
UR  - https://inrepo02.dkfz.de/record/275976
ER  -