Recent Advances in Prostate-Specific Membrane Antigen-Based Radiopharmaceuticals

Abstract

Background: Prostate cancer (PCa) is the most common sex-related malignancy with high mortality in men worldwide. Prostate-specific membrane antigen (PSMA) is overexpressed on the surface of most prostate tumor cells and considered a valuable target for both diagnosis and therapy of prostate cancer. A series of radiolabeled agents have been developed based on the featured PSMA ligands in the previous decade and have demonstrated promising outcomes in clinical research of primary and recurrent PCa. Furthermore, the inspiring response and safety of lutetium-177-PSMA-617 (177Lu-PSMA-617) radiotherapy represent the potential for expanded therapeutic options for metastatic castration-resistant PCa. Retrospective cohort studies have revealed that radiolabeled PSMA agents are the mainstays of the current success, especially in detecting prostate cancer with metastasis and biochemical recurrence. </P><P> Objective: This review is intended to present a comprehensive overview of the current literature on PSMA ligand-based agents for both radionuclide imaging and therapeutic approaches, with a focus on those that have been clinically adopted. </P><P> Conclusion: PSMA-based diagnosis and therapy hold great promise for improving the clinical management of prostate cancer.

Targeted Radionuclide Therapy of Prostate Cancer—From Basic Research to Clinical Perspectives

“…Ideal targets for prostate cancer therapy would include structures that are exclusively expressed in normal prostate tissue, which are highly expressed in metastatic disease, and that are accessible to therapeutic modalities at the cell surface. So far, several cell-surface proteins, glycoproteins, receptors, enzymes and peptides have been tested as targets for the treatment of prostate cancer [10][11][12] (Figure 1). associated with the progression of this disease, there is an urgent need for new and targeted treatments.…”

“…Although monovalent scFv fragments exhibit efficient tumor penetration, they are cleared rapidly from blood and can demonstrate poor antigen binding [38]. Recently, a comprehensive overview of the current literature on PSMA-targeted monovalent scFv fragments for radionuclide PET and SPECT imaging was presented by Diao et al [12]. The highly promising preclinical results in vitro were reported for scFv constructs developed from the D2B antibody and radiolabeled with 131 I ( 131 I-scFvD2B), 111 In ( 111 In-scFvD2B), 123 I ( 123 I-scFvD2B) and 124 I ( 124 I-scFvD2B) [90][91][92][93].…”

Targeted 64Cu‐labeled gold nanoparticles for dual imaging with positron emission tomography and optical imaging

“…We designed a cell viability assay with PC3 (prostate adenocarcinoma cell line, 44,000 receptors per cell, 43 GRPR positive, 44 and PSMA negative 45 ) and LNCaP (metastatic prostate carcinoma cell line, 46 approximately 1 × 10 6 PSMA/cell, 47 PSMA positive, 48 and GRPR negative 45 ) cells in four 6-well plates. The cells were incubated for 24 hours at 37°C with 13 ± 0.2 MBq of [ 64 Cu]CuCl 2 , GRPR-targeting [ 64 Cu]Cu-1 AuNPs, or PSMA-targeting [ 64 Cu]Cu-2 AuNPs.…”

“…This could lead to a slower uptake of [ 64 Cu]Cu-1 by PC3 The aim of the experiments was to reach a therapeutic effect with the β − radiation of 64 Cu without the disturbance of cytotoxic free 64 Cu 2+ , which would infiltrate into the cell nuclei and accumulate there. Free 64 Cu 2+ is much more cytotoxic because of elemental copper binding to the DNA 46 ; however, bound 64 Cu should cause its toxic effects exclusively by β − radiation. The 64 Cu-AuNPs accumulated in the cell plasma but not in the cell nuclei; hence, the bound 64 Cu could not form complexes with the DNA of the cell nuclei.…”

Progress in Delivery of siRNA-Based Therapeutics Employing Nano-Vehicles for Treatment of Prostate Cancer

“…Since PCa lacks clinical symptoms in early stages, its definitive detection depends on prostate biopsy, alterations in PSA levels, and/or digital rectal examinations (DRE) [ 17 ]. Research so far shows that cell-surface proteins, glycoproteins, receptors, enzymes, and peptides are considered as targets in PCa therapy [ 18 , 19 , 20 ].…”