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GRPR versus PSMA: expression profiles during prostate cancer progression demonstrate the added value of GRPR-targeting theranostic approaches

INTRODUCTION: Central to targeted radionuclide imaging and therapy of prostate cancer (PCa) are prostate-specific membrane antigen (PSMA)-targeting radiopharmaceuticals. Gastrin-releasing peptide receptor (GRPR) targeting has been proposed as a potential additional approach for PCa theranostics. The...

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Detalles Bibliográficos
Autores principales: Verhoeven, Marjolein, Ruigrok, Eline A. M., van Leenders, Geert J. L. H., van den Brink, Lilian, Balcioglu, Hayri E., van Weerden, Wytske M., Dalm, Simone U.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10502172/
https://www.ncbi.nlm.nih.gov/pubmed/37719014
http://dx.doi.org/10.3389/fonc.2023.1199432
Descripción
Sumario:INTRODUCTION: Central to targeted radionuclide imaging and therapy of prostate cancer (PCa) are prostate-specific membrane antigen (PSMA)-targeting radiopharmaceuticals. Gastrin-releasing peptide receptor (GRPR) targeting has been proposed as a potential additional approach for PCa theranostics. The aim of this study was to investigate to what extent and at what stage of the disease GRPR-targeting applications can complement PSMA-targeting theranostics in the management of PCa. METHODS: Binding of the GRPR- and PSMA-targeting radiopharmaceuticals [(177)Lu]Lu-NeoB and [(177)Lu]Lu-PSMA-617, respectively, was evaluated and compared on tissue sections of 20 benign prostatic hyperplasia (BPH), 16 primary PCa and 17 progressive castration-resistant PCa (CRPC) fresh frozen tissue specimens. Hematoxylin-eosin and alpha-methylacyl-CoA racemase stains were performed to identify regions of prostatic adenocarcinoma and potentially high-grade prostatic intraepithelial neoplasia. For a subset of primary PCa samples, RNA in situ hybridization (ISH) was used to identify target mRNA expression in defined tumor regions. RESULTS: The highest median [(177)Lu]Lu-NeoB binding was observed in primary PCa samples, while median and overall [(177)Lu]Lu-PSMA-617 binding was highest in CRPC samples. The highest [(177)Lu]Lu-NeoB binding was observed in 3/17 CRPC samples of which one sample showed no [(177)Lu]Lu-PSMA-617 binding. RNA ISH analyses showed a trend between mRNA expression and radiopharmaceutical binding, and confirmed the distinct GRPR and PSMA expression patterns in primary PCa observed with radiopharmaceutical binding. CONCLUSION: Our study emphasizes that GRPR-targeting approaches can contribute to improved PCa management and complement currently applied PSMA-targeting strategies in both early and late stage PCa.