title: [(18)F]Fluorobenzoyllysinepentanedioic Acid Carbamates: New Scaffolds for Positron Emission Tomography (PET) Imaging of Prostate-Specific Membrane Antigen (PSMA).
abstract: Radiolabeled urea-based low-molecular weight inhibitors of the prostate-specific membrane antigen (PSMA) are under intense investigation as imaging and therapeutic agents for prostate and other cancers. In an effort to provide agents with less nontarget organ uptake than the ureas, we synthesized four (18)F-labeled inhibitors of PSMA based on carbamate scaffolds. 4-Bromo-2-[(18)F]fluorobenzoyllysineoxypentanedioic acid (OPA) carbamate [(18)F]23 and 4-iodo-2-[(18)F]fluorobenzoyllysine OPA carbamate [(18)F]24 in particular exhibited high target-selective uptake in PSMA+ PC3 PIP tumor xenografts, with tumor-to-kidney ratios of >1 by 4 h postinjection, an important benchmark. Because of its high tumor uptake (90% injected dose per gram of tissue at 2 h postinjection) and high tumor-to-organ ratios, [(18)F]23 is promising for clinical translation. Prolonged tumor-specific uptake demonstrated by [(18)F]24, which did not reach equilibrium during the 4 h study period, suggests carbamates as alternative scaffolds for mitigating dose to nontarget tissues.
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions , Baltimore, Maryland 21287, United States.
authors.forename: Xing
authors.initials: X
authors.lastname: Yang
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions , Baltimore, Maryland 21287, United States.
authors.forename: Ronnie C
authors.initials: RC
authors.lastname: Mease
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions , Baltimore, Maryland 21287, United States.
authors.forename: Mrudula
authors.initials: M
authors.lastname: Pullambhatla
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions , Baltimore, Maryland 21287, United States.
authors.forename: Ala
authors.initials: A
authors.lastname: Lisok
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions , Baltimore, Maryland 21287, United States.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions , Baltimore, Maryland 21287, United States.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Foss
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions , Baltimore, Maryland 21287, United States.
authors.forename: Yuchuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions , Baltimore, Maryland 21287, United States.
authors.forename: Hassan
authors.initials: H
authors.lastname: Shallal
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions , Baltimore, Maryland 21287, United States.
authors.forename: Hannah
authors.initials: H
authors.lastname: Edelman
authors.affiliation: Avid Radiopharmaceuticals, Inc. , Philadelphia, Pennsylvania 19104, United States.
authors.forename: Adam T
authors.initials: AT
authors.lastname: Hoye
authors.affiliation: Avid Radiopharmaceuticals, Inc. , Philadelphia, Pennsylvania 19104, United States.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Attardo
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions , Baltimore, Maryland 21287, United States.
authors.forename: Sridhar
authors.initials: S
authors.lastname: Nimmagadda
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions , Baltimore, Maryland 21287, United States.
authors.forename: Martin G
authors.initials: MG
authors.lastname: Pomper
mesh_terms: D000818:Animals; D002219:Carbamates / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004355:Drug Stability; D005260:Female; D005462:Fluorine Radioisotopes; D006801:Humans; D007668:Kidney / Q000000981:diagnostic imaging; D008297:Male; D051379:Mice; D016513:Mice, SCID; D062105:Molecular Docking Simulation; D009928:Organ Specificity; D010421:Pentanoic Acids / Q000138:chemical synthesis* / Q000494:pharmacology*; D049268:Positron-Emission Tomography / Q000379:methods*; D011467:Prostate / Q000000981:diagnostic imaging; D017430:Prostate-Specific Antigen / Q000378:metabolism*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D002219:Carbamates; D005462:Fluorine Radioisotopes; D010421:Pentanoic Acids; D019275:Radiopharmaceuticals; D017430:Prostate-Specific Antigen