title: PSMA-targeted dendrimers: a patent evaluation (WO2012078534).
abstract: Prostate-specific membrane antigen (PSMA) is a cell surface protein expressed primarily in prostate cancer and solid tumor neovasculature. PSMA has been a target for both imaging and therapeutic investigations due to its increased expression in advanced disease and in prostate cancer patients receiving hormonal therapy. The recent approval of new androgen receptor pathway targeted drugs for prostate cancer has sharply increased this interest in creating novel probes to measure this disease-specific biomarker. Monoclonal antibodies and small molecules targeting PSMA, however, have been investigated for diagnostic and therapeutic purposes, with only limited success. In fact, only one agent (monoclonal antibody agent - capromab pendetide) has been FDA-approved for human use. PSMA-targeting dendrimers may provide a targeting method that might maintain the specificity of monoclonal antibodies, achieve high levels of tumor concentration (similar to small molecule antagonist ligands) and avoid accumulation in non-target sites of PSMA expression (such as renal tubules). The current patent application provides theoretical evidence for the advantage of PSMA-targeting dendrimers with in vitro data for PSMA binding, but lacks sufficient preclinical animal binding, dosimetry and toxicology data.
authors.affiliation: Weill Cornell Medical College, Division of Hematology and Medical Oncology, Department of Medicine, New York, NY 10065, USA.
authors.forename: Naveed H
authors.initials: NH
authors.lastname: Akhtar
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Osborne
authors.forename: Shoaib B
authors.initials: SB
authors.lastname: Fareedy
authors.forename: Scott T
authors.initials: ST
authors.lastname: Tagawa
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000493:pharmacokinetics; D000954:Antigens, Surface / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D014408:Biomarkers, Tumor / Q000378:metabolism; D050091:Dendrimers / Q000737:chemistry*; D016503:Drug Delivery Systems; D015195:Drug Design; D043425:Glutamate Carboxypeptidase II / Q000378:metabolism*; D006801:Humans; D008297:Male; D010330:Patents as Topic; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000473:pathology*; D014018:Tissue Distribution
chemical_list: D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D050091:Dendrimers; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II