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

Xiangshu Fei, Ji Quan Wang, Kathy Miller, George W. Sledge, Gary Hutchins, Qi-Huang Zheng

Research output: Contribution to journalArticle

35 Citations (Scopus)

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-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.

Original languageEnglish
Pages (from-to)1033-1041
Number of pages9
JournalNuclear Medicine and Biology
Volume31
Issue number8
DOIs
StatePublished - Nov 2004

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Positron-Emission Tomography
Cytidine
Enzymes
Ribose
Neoplasms
Uridine Phosphorylase
Thymidine Phosphorylase
Flucytosine
Fluorine
Cytosine
Prodrugs
Fluorouracil
Antineoplastic Agents
Colorectal Neoplasms
High Pressure Liquid Chromatography
Capecitabine
Breast Neoplasms
Therapeutics

Keywords

  • [F]Xeloda
  • Cancer
  • Enzyme
  • Fluorine-18
  • PET
  • Radiotracer

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging

Cite this

Synthesis of [18F]Xeloda as a novel potential PET radiotracer for imaging enzymes in cancers. / Fei, Xiangshu; Wang, Ji Quan; Miller, Kathy; Sledge, George W.; Hutchins, Gary; Zheng, Qi-Huang.

In: Nuclear Medicine and Biology, Vol. 31, No. 8, 11.2004, p. 1033-1041.

Research output: Contribution to journalArticle

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