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

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...

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Bibliographic Details
Published in:Nuclear medicine and biology 2004-11, Vol.31 (8), p.1033-1041
Main Authors: Fei, Xiangshu, Wang, Ji-Quan, Miller, Kathy D., Sledge, George W., Hutchins, Gary D., Zheng, Qi-Huang
Format: Article
Language:English
Subjects:
[ 18F]Xeloda
Animals
Cancer
Capecitabine
Deoxycytidine - analogs & derivatives
Deoxycytidine - chemical synthesis
Deoxycytidine - pharmacokinetics
Enzyme
Fluorine Radioisotopes - chemistry
Fluorine Radioisotopes - pharmacokinetics
Fluorine-18
Fluorouracil - analogs & derivatives
Humans
Isotope Labeling - methods
Neoplasms - diagnostic imaging
Neoplasms - enzymology
PET
Positron-Emission Tomography - methods
Radiopharmaceuticals - chemical synthesis
Radiopharmaceuticals - pharmacokinetics
Radiotracer
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Summary: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-[ 18F]fluoro-N 4-(pentyloxycarbonyl)cytidine ([ 18F]Xeloda; [ 18F] 1) was prepared by nucleophilic substitution of the nitro-precursor with K 18F/Kryptofix 2.2.2 followed by a quick deprotection reaction and purification with the HPLC method in 20–30% radiochemical yields.
ISSN:0969-8051
1872-9614
DOI:10.1016/j.nucmedbio.2004.02.006