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Enzalutamide Enhances PSMA Expression of PSMA-Low Prostate Cancer

1
Department of Nuclear Medicine, University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, Hufelandstraße 55, D-45147 Essen, Germany
2
Department of Nuclear Medicine, Klinikum Rechts der Isar, Technical University of Munich, Ismaninger Straße 22, D-81675 Munich, Germany
3
Institute of Pathology, University of Duisburg-Essen, University Hospital Essen, Hufelandstraße 55, D-45147 Essen, Germany
4
Department of Urology, University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, Hufelandstraße 55, D-45147 Essen, Germany
5
Department of Urology, Semmelweis University, Ulloi ut 78/b, 1082 Budapest, Hungary
6
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California Los Angeles, 650 Charles E Young Drive S, Los Angeles, CA 90095, USA
*
Authors to whom correspondence should be addressed.
Authors contributed equally to this study.
Academic Editor: Finn Edler von Eyben
Int. J. Mol. Sci. 2021, 22(14), 7431; https://doi.org/10.3390/ijms22147431
Received: 20 May 2021 / Revised: 2 July 2021 / Accepted: 8 July 2021 / Published: 11 July 2021
(This article belongs to the Special Issue PSMA in 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 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, p = 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 68Ga-PSMA after enzalutamide treatment (p = 0.004). Similarly, a clinical case with low baseline PSMA avidity demonstrated increased uptake of 68Ga-PSMA after enzalutamide on PET/CT and post-therapeutic 177Lu-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 177Lu-PSMA RLT. View Full-Text
Keywords: PSMA; prostate cancer; enzalutamide; androgen receptor blockade; PET; CT; radioligand therapy; 22Rv1; C4-2; LNCaP PSMA; prostate cancer; enzalutamide; androgen receptor blockade; PET; CT; radioligand therapy; 22Rv1; C4-2; LNCaP
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MDPI and ACS Style

Staniszewska, M.; Fragoso Costa, P.; Eiber, M.; Klose, J.M.; Wosniack, J.; Reis, H.; Szarvas, T.; Hadaschik, B.; Lückerath, K.; Herrmann, K.; Fendler, W.P.; Iking, J. Enzalutamide Enhances PSMA Expression of PSMA-Low Prostate Cancer. Int. J. Mol. Sci. 2021, 22, 7431. https://doi.org/10.3390/ijms22147431

AMA Style

Staniszewska M, Fragoso Costa P, Eiber M, Klose JM, Wosniack J, Reis H, Szarvas T, Hadaschik B, Lückerath K, Herrmann K, Fendler WP, Iking J. Enzalutamide Enhances PSMA Expression of PSMA-Low Prostate Cancer. International Journal of Molecular Sciences. 2021; 22(14):7431. https://doi.org/10.3390/ijms22147431

Chicago/Turabian Style

Staniszewska, Magdalena, Pedro Fragoso Costa, Matthias Eiber, Jasmin M. Klose, Jasmin Wosniack, Henning Reis, Tibor Szarvas, Boris Hadaschik, Katharina Lückerath, Ken Herrmann, Wolfgang P. Fendler, and Janette Iking. 2021. "Enzalutamide Enhances PSMA Expression of PSMA-Low Prostate Cancer" International Journal of Molecular Sciences 22, no. 14: 7431. https://doi.org/10.3390/ijms22147431

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