| Literature DB >> 26629713 |
Xing Yang1, Ronnie C Mease1, Mrudula Pullambhatla1, Ala Lisok1, Ying Chen1, Catherine A Foss1, Yuchuan Wang1, Hassan Shallal1, Hannah Edelman1, Adam T Hoye2, Giorgio Attardo2, Sridhar Nimmagadda1, Martin G Pomper1.
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.Entities:
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Year: 2015 PMID： 26629713 PMCID： PMC4856055 DOI： 10.1021/acs.jmedchem.5b01268
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446