Comparison of prostate‐specific membrane antigen ligands in clinical translation research for diagnosis of prostate cancer

Abstract

Background Prostate‐specific membrane antigen (PSMA), overexpressed on prostate cancer (PCa), is a well‐characterized cell surface protein to selectively diagnose PCa. PSMA's unique characteristics and its 1000‐fold higher expression in PCa compared with other tissues renders it as a suitable biomarker for detection of PCa in its early stage. In this report, we critically analyze and recommend the requirements needed for the development of variety of PSMA‐targeted molecular imaging agents based on antibodies, small molecule ligands, peptides, and aptamers. The targeting moieties are either conjugated to radionuclear isotopes or near‐infrared agents for efficient diagnosis of PCa. Recent findings From the analysis, it was found that several small molecule–derived PCa imaging agents are approved for clinical trials in Europe and the United States, and few are already in the clinical use for diagnosis of PCa. Even though 111In‐labeled capromab pendetide was approved by the Food and Drug Administration (FDA) and other engineered antibodies are available for detection of PCa, but high production cost, low shelf life (less than 1 month at 4°C), possibility of human immuno reactions, and low blood clearance rate necessitated a need for developing new imaging agents, which are serum stable, cost‐effective, and possesses longer shelf life (6 months), have fast clearance rate from nontargeted tissues during the diagnosis process. It is found that small molecule ligand‐derived imaging agents possesses most of the desired properties expected for an ideal diagnostic agent when compared with other targeting moieties. Conclusion This report discusses in detail the homing moieties used in the development of targeted diagnostic tools for detection of PCa. The merits and demerits of monoclonal antibodies, small molecule ligands, peptides, and aptamers for imaging of PCa and intraoperative guided surgery are extensively analyzed. Among all, urea‐based ligands were found to be most successful in preclinical and clinical trials and show a major promise for future commercialization.

Diagnostic Role of 18F-PSMA-1007 PET/CT in Prostate Cancer Staging: A Systematic Review

“…PSMA is a transmembrane cell surface protein that is overexpressed in 95% of PCa cells; on the other hand, the overexpression of PSMA has not been found in benign prostatic diseases. However, PSMA is not prostate specific and is also found within other tissues than prostate and other tumors beyond PCa [ 11 ].…”

“…To date, several PSMA ligands slightly different in chemical structure are commercially available for diagnosis and therapy of PCa [ 11 , 12 , 13 , 14 , 15 , 16 , 17 ]. These molecules may be radiolabeled with different positron-emitters isotopes as Gallium-68 ( 68 Ga), Fluorine-18 ( 18 F), or Copper-64 ( 64 Cu) to obtain PET radiopharmaceuticals, which can be used in the clinical practice or in clinical trials [ 11 , 12 , 13 , 14 , 15 , 16 , 17 ]. Currently, PSMA-targeted agents radiolabeled with 68 Ga are the most used PSMA-based radiopharmaceuticals for PCa detection using PET imaging.…”

“…Currently, PSMA-targeted agents radiolabeled with 68 Ga are the most used PSMA-based radiopharmaceuticals for PCa detection using PET imaging. More recently, PSMA ligands have been radiolabeled with other isotopes with more favorable physical characteristics compared with 68 Ga, such as 18 F or 64 Cu [ 11 , 12 , 13 , 14 , 15 , 16 , 17 ].…”

“…Radiolabeling PSMA-targeted agents with 18 F may provide several advantages compared with 68 Ga radiolabeling for PET imaging, including a longer half-life of the radiopharmaceuticals and an improved resolution of PET images [ 11 , 12 , 13 , 14 , 15 , 16 , 17 ]. Among the different PSMA-targeted agents radiolabeled with 18 F, 18 F-PSMA-1007 has been recently introduced into the clinical practice [ 18 ] after successful preclinical studies [ 19 ].…”

Small Molecule, Multimodal, [18F]-PET and Fluorescence Imaging Agent Targeting Prostate-Specific Membrane Antigen: First-in-Human Study

“…Because the same receptor is targeted by multiple agents, this can lead to PSMA receptor saturation and reduced signal, which may cause false negatives and result in inadequate intervention. [8][9][10][11][12][13][14] In contrast to a single-modality agent approach, a multimodality agent approach combining PET and fluorescence into a single molecule is proposed. 14 , 15 In this vein, our group has developed [ 18 F]-BF3-Cy3-ACUPA, a prostate-specific membrane antigen positive (PSMA + ) PCa-specific multimodal positron-emitting ( 18 F) and fluorescence imaging agent.…”