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

Marjolein Verhoeven; Eline A M Ruigrok; Geert J L H van Leenders; Lilian van den Brink; Hayri E Balcioglu; Wytske M van Weerden; Simone U Dalm

doi:10.3389/fonc.2023.1199432

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

Front Oncol. 2023 Aug 31:13:1199432. doi: 10.3389/fonc.2023.1199432. eCollection 2023.

Authors

Marjolein Verhoeven¹, Eline A M Ruigrok¹, Geert J L H van Leenders², Lilian van den Brink¹, Hayri E Balcioglu³, Wytske M van Weerden⁴, Simone U Dalm¹

Affiliations

¹ Department of Radiology & Nuclear Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands.
² Department of Pathology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, Netherlands.
³ Department of Medical Oncology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands.
⁴ Department of Experimental Urology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands.

Abstract

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 [¹⁷⁷Lu]Lu-NeoB and [¹⁷⁷Lu]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 [¹⁷⁷Lu]Lu-NeoB binding was observed in primary PCa samples, while median and overall [¹⁷⁷Lu]Lu-PSMA-617 binding was highest in CRPC samples. The highest [¹⁷⁷Lu]Lu-NeoB binding was observed in 3/17 CRPC samples of which one sample showed no [¹⁷⁷Lu]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.

Keywords: NeoB; PSMA-617; gastrin-releasing peptide receptor (GRPR); prostate cancer; prostate-specific membrane antigen (PSMA).

Grants and funding

This research was funded by the Erasmus MC Mrace Grant and the Dutch Cancer Society (KWF; grant number 10317).