Detection of apoptosis by PET/CT with the diethyl ester of [18F]ML-10 and fluorescence imaging with a dansyl analogue

• Published in: Bioorganic & medicinal chemistry Vol. 22; no. 1; pp. 341 - 349
• Main Authors: Kadirvel, Manikandan, Fairclough, Michael, Cawthorne, Christopher, Rowling, Emily J., Babur, Muhammad, McMahon, Adam, Birkket, Paul, Smigova, Alison, Freeman, Sally, Williams, Kaye J., Brown, Gavin
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 01.01.2014; Elsevier
• Subjects: Animals; Apoptosis; Biochemistry & Molecular Biology; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Esters; Fluorine Radioisotopes; Fluorine-18; Halogenation; Humans; Life Sciences & Biomedicine; Male; Mice; ML-10; Nucleophilic fluorination; PET/CT; Pharmacology & Pharmacy; Physical Sciences; Positron-Emission Tomography - methods; Radiochemistry; Radiopharmaceuticals; Science & Technology; Tomography, X-Ray Computed - methods; XtalFluor-E; Fluorine-18; XtalFluor-E; Nucleophilic fluorination; ML-10; PET/CT; Apoptosis; ALCOHOLS; ANNEXIN-V; CELL-DEATH
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2013.11.019

The diethyl ester of [18F]ML-10 is a small molecule apoptotic PET probe for cancer studies. Here we report a novel multi-step synthesis of the diethyl ester of ML-10 in excellent yields via fluorination using Xtal-Fluor-E. In addition, a one-pot radiosynthesis of the diethyl ester of [18F]ML-10 from nucleophilic [18F]fluoride was completed in 23% radiochemical yield (decay corrected). The radiochemical purity of the product was ⩾99%. The diethyl ester of [18F]ML-10 was used in vivo to detect apoptosis in the testes of mice. In parallel studies, the dansyl-ML-10 diethyl ester was prepared and used to detect apoptotic cells in an in vitro cell based assay.