[(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	Xing Yang, Ronnie C Mease, Mrudula Pullambhatla, Ala Lisok, Ying Chen, Catherine A Foss, Yuchuan Wang, Hassan Shallal, Hannah Edelman, Adam T Hoye, Giorgio Attardo, Sridhar Nimmagadda, Martin G Pomper
Journal	Journal of medicinal chemistry (J Med Chem) Vol. 59 Issue 1 Pg. 206-18 (Jan 14 2016) ISSN: 1520-4804 [Electronic] United States
PMID	26629713 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References	Carbamates Fluorine Radioisotopes Pentanoic Acids Radiopharmaceuticals Prostate-Specific Antigen
Topics	Animals Carbamates (chemical synthesis, pharmacokinetics, pharmacology) Cell Line, Tumor Drug Stability Female Fluorine Radioisotopes Humans Kidney (diagnostic imaging) Male Mice Mice, SCID Molecular Docking Simulation Organ Specificity Pentanoic Acids (chemical synthesis, pharmacology) Positron-Emission Tomography (methods) Prostate (diagnostic imaging) Prostate-Specific Antigen (metabolism) Radiopharmaceuticals (chemical synthesis, pharmacokinetics, pharmacology) Tissue Distribution Xenograft Model Antitumor Assays

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