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-N4- (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-N4-(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-[18F]fluoro-N4-(pentyloxycarbonyl) cytidine ([18F]Xeloda; [18F]1) was prepared by nucleophilic substitution of the nitro-precursor with K18F/Kryptofix 2.2.2 followed by a quick deprotection reaction and purification with the HPLC method in 20-30% radiochemical yields.
ASJC Scopus subject areas
- Cancer Research
- Molecular Medicine
- Radiology Nuclear Medicine and imaging