Discovery of Furanone-Based Radiopharmaceuticals for Diagnostic Targeting of COX-1 in Ovarian Cancer

Md Jashim Uddin, Andrew J. Wilson, Brenda C. Crews, Paola Malerba, Md Imam Uddin, Philip J. Kingsley, Kebreab Ghebreselasie, Cristina K. Daniel, Michael L. Nickels, Mohammed N. Tantawy, Elma Jashim, H. Charles Manning, Dineo Khabele, Lawrence J. Marnett

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


In vivo targeting and visualization of cyclooxygenase-1 (COX-1) using multimodal positron emission tomography/computed tomography imaging represents a unique opportunity for early detection and/or therapeutic evaluation of ovarian cancer because overexpression of COX-1 has been characterized as a pathologic hallmark of the initiation and progression of this disease. The furanone core is a common building block of many synthetic and natural products that exhibit a wide range of biological activities. We hypothesize that furanone-based COX-1 inhibitors can be designed as imaging agents for the early detection, delineation of tumor margin, and evaluation of treatment response of ovarian cancer. We report the discovery of 3-(4-fluorophenyl)-5,5-dimethyl-4-(p-tolyl)furan-2(5H)-one (FDF), a furanone-based novel COX-1-selective inhibitor that exhibits adequate in vivo stability, plasma half-life, and pharmacokinetic properties for use as an imaging agent. We describe a novel synthetic scheme in which a Lewis acid-catalyzed nucleophilic aromatic deiodo[18F]fluorination reaction is utilized for the radiosynthesis of [18F]FDF. [18F]FDF binds efficiently to COX-1 in vivo and enables sensitive detection of ovarian cancer in subcutaneous and peritoneal xenograft models in mice. These results provide the proof of principle for COX-1-targeted imaging of ovarian cancer and identify [18F]FDF as a promising lead compound for further preclinical and clinical development. ©

Original languageEnglish
Pages (from-to)9251-9261
Number of pages11
JournalACS Omega
Issue number5
StatePublished - May 24 2019


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