PSMA-Directed Theragnostics: Transforming Prostate Cancer Landscape

Abstract

Early diagnosis and the detection of distant metastases and recurrences in patients with prostate cancer (PCa) have been notably improved in recent decades through advances in imaging techniques. More recently, positron emission tomography (PET) hybrid imaging (PET/computed tomography [CT] and PET/magnetic resonance imaging [MRI]) using small molecule radio-pharmaceuticals to selectively bind targets unique to PCa has permitted more accurate staging of patients with localized, locally advanced and metastatic disease. Prostate-specific membrane antigen (PSMA), a transmembrane glycoprotein overexpressed in most PCa cells, has emerged as one of many specific targets for PCa imaging. Since its introduction in Switzerland in 2016, PSMA-targeted PET/CT with 68Gallium (68Ga)-labeled and, less commonly, 18Flourine (18F)-labelled radiotracers, has shown unparalleled precision in detecting metastatic PCa compared with conventional imaging techniques. Furthermore, radioligand therapies such as lutetium-177 (177Lu)-PSMA-617 can selectively deliver β-radiation to PSMA-expressing cells. The phase III VISION trial showed that this treatment significantly improved survival outcomes in patients with heavily pretreated metastatic castration-resistant prostate cancer (mCRPC). This article discusses the value and impact of 68Ga/18F-PSMA PET/CT imaging compared with conventional imaging modalities for accurately detecting PCa lesions in a primary setting and for local recurrence or metastases. In addition, an overview of the PSMA ligand therapy, a treatment modality for patients with advanced PCa is presented.