Current and Emerging Clinical Applications of PSMA PET Diagnostic Imaging for Prostate Cancer

Abstract

Prostate-specific membrane antigen (PSMA) is highly expressed on most prostate cancer (PCa) cells, and several PSMA ligands for PET imaging are now available worldwide. 68 Ga-PSMA-11 has already received U.S. Food and Drug Administration approval, and use of PSMA PET is currently suggested by several international guidelines for investigating PCa in different clinical settings. In primary PCa, PSMA PET has been shown to be superior to cross-sectional imaging for the detection of pelvic lymph nodes and distant metastases with subsequent clinical management changes. Additionally, it might also have a role in intraprostatic tumor localization, especially when combined with multiparametric MRI. In a setting of PCa recurrence, higher detection rates have been observed than for any other available imaging techniques, especially at low prostate-specific antigen values. Furthermore, PSMA PET consistently led to a shift in clinical management, thus increasing the proportion of radiotherapy, surgery, or other focal therapies at the expense of systemic options or no treatment. In oligometastatic disease after radical surgery, PSMA PET may be relevant in guiding a metastasis-directed therapy approach, as preliminary data seem to suggest a benefit in terms of progression-free survival after treatment of PSMA PET-positive lesions. As a staging and gatekeeping technique, PSMA PET represents a reliable wholebody imaging procedure in combination with second-line therapy of castration-resistant PCa, as well as being pivotal when assessing patients eligible for radioligand therapy such as 177 Lu-PSMA. This critical review aims at providing a comprehensive overview of the latest literature on the current or emerging main indications, as well as a general outlook on the recommended interpretation criteria for PSMA PET imaging.

Comparison between 18F‐DCFPyL PET and MRI for the detection of transition zone prostate cancer

“…PSMA PET has shown high accuracy in diagnosing and staging PCa, and is currently suggested by several international guidelines to investigate PCa in different clinical settings. [17][18][19][20] Several PSMA ligands for PET imaging are now available worldwide. Among them, 68 Ga-PSMA-11 has been approved by the American Food and Drug Administration.…”

Early molecular imaging response assessment based on determination of total viable tumor burden in [68Ga]Ga-PSMA-11 PET/CT independently predicts overall survival in [177Lu]Lu-PSMA-617 radioligand therapy

“…However, new parameters and imaging techniques are currently being investigated to assess response to treatment, especially in patients undergoing PSMA-RLT, as conventional imaging may be inappropriate in mCRPC [20,21]. In recent years, PSMA-targeted PET/CT (using, e.g., [ 68 Ga] Ga-PSMA-11) has gained increasing importance in the management of prostate cancer for initial staging, biochemical recurrence, and screening for PSMA-RLT [22][23][24]. The use of PSMA-targeted PET/CT for therapy monitoring and molecular imaging-based response assessment is currently the subject of ongoing research [25,26].…”

Value of Combined PET Imaging with [18F]FDG and [68Ga]Ga-PSMA-11 in mCRPC Patients with Worsening Disease during [177Lu]Lu-PSMA-617 RLT

“…PSMA-RLT using [ 177 Lu]Lu-PSMA-617 showed impressive results (with only moderate side effects) in various retrospective studies [8][9][10][11], in prospective phase II trials [12,13], and in a recently published phase III trial [14]. An adequate PSMA expression is essential for the success of PSMA-targeted radioligand therapy (PSMA-RLT), and is verified by PSMA-targeted positron emission tomography (PET)/computed tomography (CT) with radiolabeled PSMA ligands, such as [ 68 Ga]Ga-PSMA-11, before and during therapy [15]. Despite the promising results of PSMA-RLT, some patients do not exhibit a sufficient response, and others with initially good responses experience a worsening disease in the course of PSMA-RLT [16,17].…”