Sagnik Sengupta1, Mena Asha Krishnan2, Sudeshna Chattopadhyay2,3,4, Venkatesh Chelvam1,2. 1. Discipline of Chemistry, School of Basic Sciences, Indian Institute of Technology Indore, Indore, India. 2. Discipline of Biosciences and Biomedical Engineering, School of Engineering, Indian Institute of Technology Indore, Indore, India. 3. Discipline of Physics, School of Basic Sciences, Indian Institute of Technology Indore, Indore, India. 4. Discipline of Metallurgy Engineering and Material Science, School of Engineering, Indian Institute of Technology Indore, Indore, India.
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.
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.
Authors: Zsolt Szabo; Esther Mena; Steven P Rowe; Donika Plyku; Rosa Nidal; Mario A Eisenberger; Emmanuel S Antonarakis; Hong Fan; Robert F Dannals; Ying Chen; Ronnie C Mease; Melin Vranesic; Akrita Bhatnagar; George Sgouros; Steve Y Cho; Martin G Pomper Journal: Mol Imaging Biol Date: 2015-08 Impact factor: 3.488
Authors: Mindy I Davis; Melanie J Bennett; Leonard M Thomas; Pamela J Bjorkman Journal: Proc Natl Acad Sci U S A Date: 2005-04-18 Impact factor: 11.205
Authors: G L Wright; B M Grob; C Haley; K Grossman; K Newhall; D Petrylak; J Troyer; A Konchuba; P F Schellhammer; R Moriarty Journal: Urology Date: 1996-08 Impact factor: 2.649
Authors: Ronnie C Mease; Crystal L Dusich; Catherine A Foss; Hayden T Ravert; Robert F Dannals; Jurgen Seidel; Andrew Prideaux; James J Fox; George Sgouros; Alan P Kozikowski; Martin G Pomper Journal: Clin Cancer Res Date: 2008-05-15 Impact factor: 12.531
Authors: A P Kiess; S R Banerjee; R C Mease; S P Rowe; A Rao; C A Foss; Y Chen; X Yang; S Y Cho; S Nimmagadda; M G Pomper Journal: Q J Nucl Med Mol Imaging Date: 2015-07-24 Impact factor: 2.346