title: Synthesis of [18F]Xeloda as a novel potential PET radiotracer for imaging enzymes in cancers.
abstract: Xeloda (Capecitabine), a prodrug of antitumor agent 5-fluorouracil, is the first and only oral fluoropyrimidine to be approved for use as second-line therapy in metastatic breast cancer, colorectal cancer, and other solid malignancies. Fluorine-18 labeled Xeloda may serve as a novel radiotracer for positron emission tomography (PET) to image enzymes such as thymidine phosphorylase and uridine phosphorylase in cancers. The precursor 2',3'-di-O-acetyl-5'-deoxy-5-nitro-N(4)-(pentyloxycarbonyl)cytidine (11) was synthesized from D-ribose and cytosine in 8 steps with approximately 18% overall chemical yield. The reference standard 5'-deoxy-5-fluoro-N(4)-(pentyloxycarbonyl)cytidine (Xeloda; 1) was synthesized from D-ribose and 5-fluorocytosine in eight steps with approximately 28% overall chemical yield. The target radiotracer 5'-deoxy-5-[(18)F]fluoro-N(4)-(pentyloxycarbonyl)cytidine ([(18)F]Xeloda; [(18)F]1) was prepared by nucleophilic substitution of the nitro-precursor with K(18)F/Kryptofix 2.2.2 followed by a quick deprotection reaction and purification with the HPLC method in 20-30% radiochemical yields.
authors.affiliation: Department of Radiology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Xiangshu
authors.initials: X
authors.lastname: Fei
authors.forename: Ji-Quan
authors.initials: JQ
authors.lastname: Wang
authors.forename: Kathy D
authors.initials: KD
authors.lastname: Miller
authors.forename: George W
authors.initials: GW
authors.lastname: Sledge
authors.forename: Gary D
authors.initials: GD
authors.lastname: Hutchins
authors.forename: Qi-Huang
authors.initials: QH
authors.lastname: Zheng
mesh_terms: D000818:Animals; D000069287:Capecitabine; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D005462:Fluorine Radioisotopes / Q000737:chemistry* / Q000493:pharmacokinetics; D005472:Fluorouracil / Q000031:analogs & derivatives; D006801:Humans; D007553:Isotope Labeling / Q000379:methods; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000201:enzymology*; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics
chemical_list: D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil