This preclinical study aims to evaluate the extent to which a change in prostate-specific membrane antigen (PSMA) expression of castration-resistant prostate cancer (CRPC) following standard treatment is reflected in [18F]JK-PSMA-7 PET/CT.
Castrated mice supplemented with testosterone implant were xenografted with human LNCaP CRPC. After appropriate tumour growth, androgen deprivation therapy (ADT) was carried out by the removal of the implant followed by a single injection of docetaxel (400 μg/20-g mouse) 2 weeks later. [18F]JK-PSMA-7 PET/CT were performed before ADT, then before and at days 12, 26, 47 and 69 after docetaxel administration. The [18F]JK-PSMA-7 PET data were compared to corresponding unspecific metabolic [18F]FDG PET/CT and ex vivo quantification of PSMA expression estimated by flow cytometry on repeated tumour biopsies.
ADT alone had no early effect on LNCaP tumours that pursued their progression. Until day 12 post-docetaxel, the [18F]JK-PSMA7 uptake was significantly higher than that of [18F]FDG, indicating the persistence of PSMA expression at those time points. From day 26 onwards when the tumours were rapidly expanding, both [18F]JK-PSMA7 and [18F]FDG uptake continuously decreased although the decrease in [18F]JK-PSMA uptake was markedly faster. The fraction of PSMA-positive cells in tumour biopsies decreased similarly over time to reach a non-specific level after the same time period.
Applying PSMA-based imaging for therapy monitoring in patients with CRPC should be considered with caution since a reduction in [18F]JK-PSMA-7 PET uptake after successive ADT and chemotherapy may be related to downregulation of PSMA expression in dedifferentiated and rapidly proliferating tumour cells.
European journal of nuclear medicine and molecular imaging. 2021 Jan 04 [Epub ahead of print]
Gaetan Van Simaeys, Gilles Doumont, Coraline De Maeseneire, Nicolas Passon, Simon Lacroix, Cédric Lentz, Arnaud Horion, Corentin Warnier, David Torres, Corentin Martens, Irina Vierasu, Dominique Egrise, Serge Goldman
Center for Microscopy and Molecular Imaging, Université libre de Bruxelles, Charleroi, Belgium. ., Center for Microscopy and Molecular Imaging, Université libre de Bruxelles, Charleroi, Belgium., Trasis SA, Liège, Belgium., Institute for Medical Immunology, Université libre de Bruxelles, Charleroi, Belgium., Service de médecine nucléaire, Hôpital Érasme, Université libre de Bruxelles, Brussels, Belgium.