Synthesis and biodistribution of 3'-fluoro-5-[(131)I]iodo-2'-deoxyuridine: a comparative study of [(131)I]FLIdU and [(18)F]FLT

Nucl Med Biol. 2007 Apr;34(3):273-81. doi: 10.1016/j.nucmedbio.2006.12.010. Epub 2007 Feb 22.

Abstract

The radioiodinated 3'-fluorothymidine (FLT) analogue 3'-fluoro-5-[(131)I]iodo-2'-deoxyuridine ([(131)I]FLIdU) was synthesized, with iodine mimicking the methyl group of pyrimidine. [(131)I]FLIdU was accessible by direct electrophilic iodination using Iodogen as oxidant. Optimized amounts of the oxidant allowed radiochemical yields of about 70% after a reaction time of 10 min in an aqueous buffer medium at 90 degrees C. The uptake of [(131)I]FLIdU in a DoHH2 leukemia xenograft mouse model and in healthy mice revealed moderate FLIdU accumulation, followed by a significant washout of activity in proliferating tissues such as splenic and tumor tissues. In contrast, intraperitoneal coinjection with [(18)F]FLT showed high uptake and high activity retention up to 2 h, in both splenic and tumor tissues. Uptake in stomach tissues and increasing fractions of [(131)I]iodide in urine indicated metabolic instability of [(131)I]FLIdU due to rapid deiodination. Therefore, [(131)I]FLIdU alone does not seem to be a promising compound, neither for diagnostic imaging nor for potential therapeutic applications.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Deoxyuridine / analogs & derivatives*
  • Deoxyuridine / chemistry
  • Deoxyuridine / pharmacokinetics
  • Dideoxynucleosides / chemistry
  • Dideoxynucleosides / pharmacokinetics*
  • Drug Evaluation, Preclinical
  • Humans
  • Isotope Labeling / methods
  • Lymphoma / diagnostic imaging
  • Lymphoma / metabolism*
  • Metabolic Clearance Rate
  • Mice
  • Mice, SCID
  • Organ Specificity
  • Radionuclide Imaging
  • Radiopharmaceuticals / chemical synthesis
  • Radiopharmaceuticals / pharmacokinetics
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Tissue Distribution

Substances

  • 3'-fluoro-5-iodo-2'-deoxyuridine
  • Dideoxynucleosides
  • Radiopharmaceuticals
  • alovudine
  • Deoxyuridine