Synthesis and Biological Evaluation of (S)-Amino-2-methyl-4-[(76)Br]bromo-3-(E)-butenoic Acid (BrVAIB) for Brain Tumor Imaging

J Med Chem. 2015 Nov 12;58(21):8542-52. doi: 10.1021/acs.jmedchem.5b01035. Epub 2015 Oct 20.

Abstract

The novel compound, (S)-amino-2-methyl-4-[(76)Br]bromo-3-(E)-butenoic acid (BrVAIB, [(76)Br]5), was characterized against the known system A tracer, IVAIB ([(123)I]8). [(76)Br]5 was prepared in a 51% ± 19% radiochemical yield with high radiochemical purity (≥98%). The biological properties of [(76)Br]5 were compared with those of [(123)I]8. Results showed that [(76)Br]5 undergoes mixed amino acid transport by system A and system L transport, while [(123)I]8 had less uptake by system L. [(76)Br]5 demonstrated higher uptake than [(123)I]8 in DBT tumors 1 h after injection (3.7 ± 0.4% ID/g vs 1.5 ± 0.3% ID/g) and also showed higher uptake vs [(123)I]8 in normal brain. Small animal PET studies with [(76)Br]5 demonstrated good tumor visualization of intracranial DBTs up to 24 h with clearance from normal tissues. These results indicate that [(76)Br]5 is a promising PET tracer for brain tumor imaging and lead compound for a mixed system A and system L transport substrate.

Publication types

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

MeSH terms

  • Alanine / analogs & derivatives
  • Alanine / pharmacokinetics
  • Amination
  • Animals
  • Biological Transport
  • Brain / metabolism
  • Brain / pathology*
  • Brain Neoplasms / diagnosis*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Bromine Radioisotopes / chemistry*
  • Bromine Radioisotopes / pharmacokinetics
  • Crotonates / chemical synthesis
  • Crotonates / chemistry*
  • Crotonates / pharmacokinetics
  • Glioma / diagnosis*
  • Glioma / metabolism
  • Glioma / pathology
  • Iodine Radioisotopes / pharmacokinetics
  • Male
  • Mice, Inbred BALB C
  • Positron-Emission Tomography / methods*
  • Radiopharmaceuticals / chemical synthesis
  • Tissue Distribution

Substances

  • 2-amino-2-methyl-4-iodo-3-butenoic acid
  • Bromine Radioisotopes
  • Crotonates
  • Iodine Radioisotopes
  • Radiopharmaceuticals
  • 3-bromosenecioic acid
  • Alanine