Nuklearmedizin 2021; 60(02): 167
DOI: 10.1055/s-0041-1726770
WIS-Vortrag
Präklinische Bildgebung

Enhanced PSMA expression in three prostate cancer cell lines after treatment with enzalutamide: implications for Lu-177-PSMA617 radioligand therapy

M Staniszewska
1   Universitätsklinikum Essen, Klinik für Nuklearmedizin, Essen
,
JM Klose
1   Universitätsklinikum Essen, Klinik für Nuklearmedizin, Essen
,
J Wosniack
1   Universitätsklinikum Essen, Klinik für Nuklearmedizin, Essen
,
P Fragoso Costa
1   Universitätsklinikum Essen, Klinik für Nuklearmedizin, Essen
,
M Nader
1   Universitätsklinikum Essen, Klinik für Nuklearmedizin, Essen
,
B Hadaschik
2   Universitätsklinikum Essen, Klinik und Poliklinik für Urologie, Kinderurologie und Uroonkologie, Essen
,
KM Lückerath
3   University of California, Los Angeles (UCLA), Institute of Urologic Oncology, Los Angeles, USA
,
K Herrmann
1   Universitätsklinikum Essen, Klinik für Nuklearmedizin, Essen
,
WP Fendler
1   Universitätsklinikum Essen, Klinik für Nuklearmedizin, Essen
,
J Iking
1   Universitätsklinikum Essen, Klinik für Nuklearmedizin, Essen
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    Ziel/Aim Lu-177-PSMA617 radioligand therapy (RLT) binding to prostate-specific membrane antigen (PSMA), is a new therapeutic option for prostate cancer. However, in about one third of patients, prostate cancer does not express sufficient amounts of PSMA. Here, we assess androgen receptor (AR) blockade and its potential to induce PSMA expression in different prostate cancer models in vitro and in vivo.

    Methodik/Methods Immunohistochemistry to confirm PSMA and AR expression was performed in three different PC cell lines (22Rv1, C4-2, LNCaP). Cells were treated with 10 µmol enzalutamide twice a week and evaluated weekly for their PSMA expression by flow cytometry over the course of 3 weeks. Male NSG mice bearing 22Rv1 tumours were treated with enzalutamide for 2 weeks and Ga-68-PSMA PET/CT scans were performed before and after treatment.

    Ergebnisse/Results Semi-quantitative analysis of immunohistochemistry showed highest PSMA expression in C4-2 and LNCaP cells (22Rv1/C4-2/LNCaP: 20 %/100 %/100 % PSMA+ cells) and highest AR expression in 22Rv1 and C4-2 cells (22Rv1/C4-2/LNCaP: 90 %/90 %/80 % AR+ cells). Flow cytometry revealed more than two-fold PSMA induction after treatment with enzalutamide in vitro in LNCaP cells after 3 weeks (mean ± SD: 5.2 ± 1.9 fold increase) and in C4-2 and 22Rv1 cells after 2 weeks (C4-2: 3.0 ± 1.8; 22Rv1: 2.6 ± 0.19). 22Rv1 tumours demonstrated significantly increased PSMA expression in vivo on baseline to follow-up Ga-68-PSMA PET after 2 weeks of enzalutamide treatment in male NSG mice (n = 7, mean %IA/g ± SD: 1.3 ± 0.5 vs. 2.7 ± 1.2; p = 0.03).

    Schlussfolgerungen/Conclusions Enzalutamide treatment increases PSMA expression in different PC cell lines in vitro and in vivo. Enhanced PSMA expression and RLT radiation delivery by short-term enzalutamide pre-treatment warrants further translational assessment.


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    Publication History

    Article published online:
    08 April 2021

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