Facile stereospecific synthesis and biological evaluation of (S)- and (R)-2-amino-2-methyl-4-[123I]iodo-3-(E)-butenoic acid for brain tumor imaging with single photon emission computerized tomography

J Med Chem. 2007 Dec 27;50(26):6718-21. doi: 10.1021/jm070476u. Epub 2007 Dec 4.

Abstract

Both enantiomers of 2-amino-2-methyl-4-iodo-3-(E)-butenoic acid (IVAIB, 5) were radioiodoinated in 65-72% yield. (S)-IVAIB entered 9L gliosarcoma cells primarily via A-type transport in vitro with higher uptake than (R)-IVAIB. Biodistribution studies in rats with 9L gliosarcoma brain tumors demonstrated higher tumor to brain ratios with (S)-IVAIB (75:1 at 1 h) than (R)-IVAIB (7.7:1). In this model, (S)-IVAIB is superior to (R)-IVAIB and is a promising radiotracer for brain tumor imaging.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine / analogs & derivatives*
  • Alanine / chemical synthesis
  • Alanine / chemistry
  • Alanine / pharmacokinetics
  • Amino Acids / chemical synthesis*
  • Amino Acids / chemistry
  • Amino Acids / pharmacokinetics
  • Animals
  • Biological Transport
  • Brain / diagnostic imaging*
  • Brain Neoplasms / diagnostic imaging*
  • Fatty Acids, Monounsaturated / chemical synthesis*
  • Fatty Acids, Monounsaturated / chemistry
  • Fatty Acids, Monounsaturated / pharmacology
  • Gliosarcoma / diagnostic imaging*
  • Iodine Radioisotopes*
  • Male
  • Neoplasm Transplantation
  • Radiopharmaceuticals / chemical synthesis*
  • Radiopharmaceuticals / chemistry
  • Radiopharmaceuticals / pharmacokinetics
  • Rats
  • Rats, Inbred F344
  • Stereoisomerism
  • Structure-Activity Relationship
  • Tissue Distribution
  • Tomography, Emission-Computed, Single-Photon
  • Transplantation, Heterologous
  • Tumor Cells, Cultured

Substances

  • 2-amino-2-methyl-4-iodo-3-butenoic acid
  • Amino Acids
  • Fatty Acids, Monounsaturated
  • Iodine Radioisotopes
  • Radiopharmaceuticals
  • Alanine