Synthesis of [18F]Xeloda as a novel potential PET radiotracer for imaging enzymes in cancers.

Research paper by Xiangshu X Fei, Ji-Quan JQ Wang, Kathy D KD Miller, George W GW Sledge, Gary D GD Hutchins, Qi-Huang QH Zheng

Indexed on: 21 Dec '04Published on: 21 Dec '04Published in: Nuclear Medicine and Biology


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.