Enzalutamide Enhances PSMA Expression of PSMA-Low Prostate Cancer
Prostate-specific membrane antigen (PSMA)-directed radioligand therapy (RLT) prolongs overall survival in men with metastatic castration-resistant prostate cancer (mCRPC). However, men with low PSMA expression are excluded from RLT. We explored the effect of androgen receptor blockade with enzalutam...
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doaj-6fdf68cba98543ceb1fadd8a9f1964ad2021-07-23T13:45:51ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-07-01227431743110.3390/ijms22147431Enzalutamide Enhances PSMA Expression of PSMA-Low Prostate CancerMagdalena Staniszewska0Pedro Fragoso Costa1Matthias Eiber2Jasmin M. Klose3Jasmin Wosniack4Henning Reis5Tibor Szarvas6Boris Hadaschik7Katharina Lückerath8Ken Herrmann9Wolfgang P. Fendler10Janette Iking11Department of Nuclear Medicine, University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, Hufelandstraße 55, D-45147 Essen, GermanyDepartment of Nuclear Medicine, University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, Hufelandstraße 55, D-45147 Essen, GermanyDepartment of Nuclear Medicine, Klinikum Rechts der Isar, Technical University of Munich, Ismaninger Straße 22, D-81675 Munich, GermanyDepartment of Nuclear Medicine, University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, Hufelandstraße 55, D-45147 Essen, GermanyDepartment of Nuclear Medicine, University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, Hufelandstraße 55, D-45147 Essen, GermanyInstitute of Pathology, University of Duisburg-Essen, University Hospital Essen, Hufelandstraße 55, D-45147 Essen, GermanyDepartment of Urology, University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, Hufelandstraße 55, D-45147 Essen, GermanyDepartment of Urology, University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, Hufelandstraße 55, D-45147 Essen, GermanyDepartment of Nuclear Medicine, University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, Hufelandstraße 55, D-45147 Essen, GermanyDepartment of Nuclear Medicine, University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, Hufelandstraße 55, D-45147 Essen, GermanyDepartment of Nuclear Medicine, University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, Hufelandstraße 55, D-45147 Essen, GermanyDepartment of Nuclear Medicine, University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, Hufelandstraße 55, D-45147 Essen, GermanyProstate-specific membrane antigen (PSMA)-directed radioligand therapy (RLT) prolongs overall survival in men with metastatic castration-resistant prostate cancer (mCRPC). However, men with low PSMA expression are excluded from RLT. We explored the effect of androgen receptor blockade with enzalutamide on PSMA expression. Assessment of PSMA and androgen receptor (AR) expression on the human PC cell lines 22Rv1, C4-2, and LNCaP by immunohistochemistry and flow cytometry revealed low (22Rv1) and high (C4-2 and LNCaP) PSMA expression, and high, comparable AR positivity. Treatment with enzalutamide increased PSMA levels in 22Rv1, C4-2, and LNCaP (2.2/2.3/2.6-fold, <i>p</i> = 0.0005/0.03/0.046) after one week compared to DMSO-treated controls as assessed by flow cytometry. NOD/Scid mice bearing 22Rv1 tumors were treated with enzalutamide for two weeks. Positron emission tomography/computed tomography (PET/CT) demonstrated higher tumor uptake of <sup>68</sup>Ga-PSMA after enzalutamide treatment (<i>p</i> = 0.004). Similarly, a clinical case with low baseline PSMA avidity demonstrated increased uptake of <sup>68</sup>Ga-PSMA after enzalutamide on PET/CT and post-therapeutic <sup>177</sup>Lu-PSMA scintigraphy in a patient with mCRPC. Enzalutamide induced PSMA expression in the 22Rv1 xenograft model and in an mCRPC patient, both with low baseline tumoral PSMA levels. Therefore, enzalutamide pre-treatment might render patients with low PSMA expression eligible for <sup>177</sup>Lu-PSMA RLT.https://www.mdpi.com/1422-0067/22/14/7431PSMAprostate cancerenzalutamideandrogen receptor blockadePETCT |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Magdalena Staniszewska Pedro Fragoso Costa Matthias Eiber Jasmin M. Klose Jasmin Wosniack Henning Reis Tibor Szarvas Boris Hadaschik Katharina Lückerath Ken Herrmann Wolfgang P. Fendler Janette Iking |
spellingShingle |
Magdalena Staniszewska Pedro Fragoso Costa Matthias Eiber Jasmin M. Klose Jasmin Wosniack Henning Reis Tibor Szarvas Boris Hadaschik Katharina Lückerath Ken Herrmann Wolfgang P. Fendler Janette Iking Enzalutamide Enhances PSMA Expression of PSMA-Low Prostate Cancer International Journal of Molecular Sciences PSMA prostate cancer enzalutamide androgen receptor blockade PET CT |
author_facet |
Magdalena Staniszewska Pedro Fragoso Costa Matthias Eiber Jasmin M. Klose Jasmin Wosniack Henning Reis Tibor Szarvas Boris Hadaschik Katharina Lückerath Ken Herrmann Wolfgang P. Fendler Janette Iking |
author_sort |
Magdalena Staniszewska |
title |
Enzalutamide Enhances PSMA Expression of PSMA-Low Prostate Cancer |
title_short |
Enzalutamide Enhances PSMA Expression of PSMA-Low Prostate Cancer |
title_full |
Enzalutamide Enhances PSMA Expression of PSMA-Low Prostate Cancer |
title_fullStr |
Enzalutamide Enhances PSMA Expression of PSMA-Low Prostate Cancer |
title_full_unstemmed |
Enzalutamide Enhances PSMA Expression of PSMA-Low Prostate Cancer |
title_sort |
enzalutamide enhances psma expression of psma-low prostate cancer |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2021-07-01 |
description |
Prostate-specific membrane antigen (PSMA)-directed radioligand therapy (RLT) prolongs overall survival in men with metastatic castration-resistant prostate cancer (mCRPC). However, men with low PSMA expression are excluded from RLT. We explored the effect of androgen receptor blockade with enzalutamide on PSMA expression. Assessment of PSMA and androgen receptor (AR) expression on the human PC cell lines 22Rv1, C4-2, and LNCaP by immunohistochemistry and flow cytometry revealed low (22Rv1) and high (C4-2 and LNCaP) PSMA expression, and high, comparable AR positivity. Treatment with enzalutamide increased PSMA levels in 22Rv1, C4-2, and LNCaP (2.2/2.3/2.6-fold, <i>p</i> = 0.0005/0.03/0.046) after one week compared to DMSO-treated controls as assessed by flow cytometry. NOD/Scid mice bearing 22Rv1 tumors were treated with enzalutamide for two weeks. Positron emission tomography/computed tomography (PET/CT) demonstrated higher tumor uptake of <sup>68</sup>Ga-PSMA after enzalutamide treatment (<i>p</i> = 0.004). Similarly, a clinical case with low baseline PSMA avidity demonstrated increased uptake of <sup>68</sup>Ga-PSMA after enzalutamide on PET/CT and post-therapeutic <sup>177</sup>Lu-PSMA scintigraphy in a patient with mCRPC. Enzalutamide induced PSMA expression in the 22Rv1 xenograft model and in an mCRPC patient, both with low baseline tumoral PSMA levels. Therefore, enzalutamide pre-treatment might render patients with low PSMA expression eligible for <sup>177</sup>Lu-PSMA RLT. |
topic |
PSMA prostate cancer enzalutamide androgen receptor blockade PET CT |
url |
https://www.mdpi.com/1422-0067/22/14/7431 |
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