Early changes of PSMA PET expression after initiation of androgen receptor signaling inhibitors in CRPC: an international multicenter retrospective study

Lena M Unterrainer; Andrea Farolfi; Tristan Grogan; Masatoshi Hotta; Loïc Djaileb; Andrei Gafita; Ida Sonni; Matthew B Rettig; Florian Rosar; Samer Ezziddin; Chloé S Denis; Ivan de Kouchkovsky; Rahul Aggarwal; Louise Emmett; Thomas A Hope; Johannes Czernin; Jeremie Calais

doi:10.1007/s00259-025-07178-2

Early changes of PSMA PET expression after initiation of androgen receptor signaling inhibitors in CRPC: an international multicenter retrospective study

Eur J Nucl Med Mol Imaging. 2025 Aug;52(10):3700-3708. doi: 10.1007/s00259-025-07178-2. Epub 2025 Mar 26.

Authors

Lena M Unterrainer^{1

2

3}, Andrea Farolfi^{4

5}, Tristan Grogan⁶, Masatoshi Hotta^{4

7}, Loïc Djaileb^{4

8}, Andrei Gafita^{4

9}, Ida Sonni^{4

10

11}, Matthew B Rettig^{12

13}, Florian Rosar¹⁴, Samer Ezziddin¹⁴, Chloé S Denis¹⁵, Ivan de Kouchkovsky^{16

17}, Rahul Aggarwal^{16

17}, Louise Emmett¹⁸, Thomas A Hope¹⁹, Johannes Czernin⁴, Jeremie Calais⁴

Affiliations

¹ Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, USA. Lena.unterrainer@med.uni-muenchen.de.
² Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany. Lena.unterrainer@med.uni-muenchen.de.
³ Bavarian Cancer Research Center (BZKF), Partner Site Munich, Munich, Germany. Lena.unterrainer@med.uni-muenchen.de.
⁴ Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, USA.
⁵ Division of Nuclear Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
⁶ Department of Medicine Statistics Core, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
⁷ Division of Nuclear Medicine, Department of Radiology, National Center for Global Health and Medicine, Tokyo, Japan.
⁸ Department of Nuclear Medicine, Grenoble Alpes University Hospital, Grenoble, France.
⁹ Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, USA.
¹⁰ Department of Radiological Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, USA.
¹¹ Department of Experimental and Clinical Medicine, University Magna Graecia, Catanzaro, Italy.
¹² Departments of Medicine and Urology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
¹³ Department of Medicine, VA Greater Los Angeles, Los Angeles, CA, USA.
¹⁴ Department of Nuclear Medicine, Saarland University, Homburg, Germany.
¹⁵ Department of Medical Oncology, University Hospital of Liège, Liège, Belgium.
¹⁶ Hellen Diller Family Comprehensive Cancer Center, UCSF, San Francisco, USA.
¹⁷ Department of Medicine, Division of Hematology and Oncology, UCSF, San Francisco, USA.
¹⁸ Department of Theranostics and Nuclear Medicine, St Vincent's Hospital, Sydney, Australia.
¹⁹ Department of Radiology and Biomedical Imaging, UCSF, San Francisco, USA.

PMID: 40137974
DOI: 10.1007/s00259-025-07178-2

Abstract

Background: An increase of PSMA expression under androgen receptor signaling inhibitors (ARSi) measured on PSMA PET was reported: However, results were inconsistently reproduced clinically and the frequency and timing of the PSMA expression modulation by ARSi remains unknown.

Methods: In this multicenter retrospective study, we aimed at assessing in patients with CRPC the influence of ARSi early after initiation (≤ 30 days) on PSMA expression at the whole-body (WB) level by using WB PSMA PET quantitative parameters. (m)CRPC patients from 5 international sites who underwent a PSMA PET prior to (PET1) and early (< 30 days) after (PET2) ARSi initiation were included. WB-PSMA PET quantitative parameters (PSMA-positive WB-tumor volume (TV), WB-SUV_max, WB-SUV_mean) and PSA changes between PET1 and PET2 (PSA1/PSA2) were evaluated. Changes of WB-TV / WB-SUVmax/mean between PET1 and PET2 were considered significant if ≥ 30% of increase or decrease.

Results: Fifty-six patients who initiated ARSi treatment were included. 30/56 (53.6%) were treated with an ARSi for the first time, 26/56 (41.1%) were previously treated with another ARSi agent and 29/56 (51.9%) received prior chemotherapy. 10/56 (17.9%) had a significantly increasing PSA of ≥ 25% between PET1 and PET2. 15/56 (27%), 14/56 (25%) and 1/56 (1.8%) patients had a significantly increasing WB-TV, WB-SUV_max or WB SUV_mean of ≥ 30% between PET1 and PET2, respectively. The patients with significant WB-TV increase (n = 15) and with significant WB SUV_max increase (n = 14) did not differ significantly from the ones with stable or decreased WB-TV (n = 41) or WB-SUV_max (n = 42) in their clinical characteristics or their PSA responses.

Conclusions: In this analysis of patients with early PSMA PET follow-up after ARSi initiation, we observed a PSMA-upregulation by WB-PET imaging in 25% of the patients. Further studies are needed to better understand the potential synergistic and / or additive effects of AR- and PSMA-targeted approaches.

Clinical trial number: Not applicable.

Keywords: (m)CRPC; ARSi; PET; PSMA.

Publication types

Multicenter Study

MeSH terms

Aged
Aged, 80 and over
Androgen Receptor Antagonists* / pharmacology
Androgen Receptor Antagonists* / therapeutic use
Antigens, Surface* / metabolism
Gene Expression Regulation, Neoplastic* / drug effects
Glutamate Carboxypeptidase II* / metabolism
Humans
Male
Middle Aged
Positron-Emission Tomography*
Prostatic Neoplasms, Castration-Resistant* / diagnostic imaging
Prostatic Neoplasms, Castration-Resistant* / drug therapy
Prostatic Neoplasms, Castration-Resistant* / metabolism
Receptors, Androgen* / metabolism
Retrospective Studies
Signal Transduction* / drug effects

Substances

Glutamate Carboxypeptidase II
FOLH1 protein, human
Androgen Receptor Antagonists
Antigens, Surface
Receptors, Androgen