New Prostate Cancer Targets for Diagnosis, Imaging, and Therapy: Focus on Prostate-Specific Membrane Antigen

Abstract

The rising incidence rate of the cancer in the prostate gland has increased the demand for improved diagnostic, imaging, and therapeutic approaches. Prostate-specific membrane antigen (PSMA), with folate hydrolase and carboxypeptidase and, internalization activities, is highly expressed in the epithelial cells of the prostate gland and is strongly upregulated in prostatic adenocarcinoma, with elevated expression correlating with, metastasis, progression, and androgen independence. Recently, PSMA has been an active target of investigation by several approaches, including the successful utilization of small molecule inhibitors, RNA aptamer conjugates, PSMA-based immunotherapy, and PSMA-targeted prodrug therapy. Future investigations of PSMA in prostate cancer (PCa) should focus in particular on its intracellular activities and functions. The objective of this contribution is to review the current role of PSMA as a marker for PCa diagnosis, imaging, and therapy.

Fractionated stereotactic body radiotherapy for up to five prostate cancer oligometastases: Interim outcomes of a prospective clinical trial

“…These patients had a lower rate of treatment escalation at 2 years following initial SBRT and slightly longer TE‐FS compared to patients who were not initially staged with PSMA‐PET, however, these differences were not statistically significant. PSMA‐PET has excellent sensitivity and specificity and is a superior modality for detecting PCa lesions compared to choline‐based PET imaging . Based on the responses of a multidisciplinary panel of international experts, PSMA‐PET has become the preferred modality for staging biochemically recurrent and advanced PCa .…”

“…These patients had a lower rate of treatment escalation at 2 years following initial SBRT and slightly longer TE-FS compared to patients who were not initially staged with PSMA-PET, however, these differences were not statistically significant. PSMA-PET has excellent sensitivity and specificity 14 and is a superior modality for detecting PCa The median (IQR) time between last recorded PSA and treatment escalation was 22 (10-40) days. Abbreviations: ADT, androgen deprivation therapy; PSA, prostate-specific antigen; RT, radiotherapy; TE, treatment escalation.…”

Preparation of the alpha‐emitting prostate‐specific membrane antigen targeted radioligand [212Pb]Pb‐NG001 for prostate cancer

“…The prostate‐specific membrane antigen (PSMA) is highly expressed in metastatic castrate‐resistant prostate cancer (mCRPC) with limited expression in healthy tissues and correlates with a dismal prognosis . The majority of bone, visceral, and lymph‐node metastases highly express PSMA, making PSMA an ideal target for radioligand therapy (RLT) of mCRPC . A variety of low molecular weight PSMA‐targeting ligands have been synthesized, labelled with radionuclides, and tested in both preclinical and clinical trials .…”

“…1,2 The majority of bone, visceral, and lymph-node metastases highly express PSMA, 1,2 making PSMA an ideal target for radioligand therapy (RLT) of mCRPC. 3,4 A variety of low molecular weight PSMA-targeting ligands have been synthesized, labelled with radionuclides, and tested in both preclinical and clinical trials. [3][4][5] In general, PSMA-targeting ligands have a PSMA-binding region (motif), a linker (spacer), and a chelator (moiety for radiolabelling).…”

“…3,4 A variety of low molecular weight PSMA-targeting ligands have been synthesized, labelled with radionuclides, and tested in both preclinical and clinical trials. [3][4][5] In general, PSMA-targeting ligands have a PSMA-binding region (motif), a linker (spacer), and a chelator (moiety for radiolabelling). 5 The linker region is used to adjust molecular size and polarity to impact the in vivo distribution properties.…”