Synthesis and radiolabelling of DOTA-linked glutamine analogues with ⁶⁷,⁶⁸Ga as markers for increased glutamine metabolism in tumour cells

Molecules. 2013 Jun 19;18(6):7160-78. doi: 10.3390/molecules18067160.

Abstract

DOTA-linked glutamine analogues with a C₆- alkyl and polyethyleneglycol (PEG) chain between the chelating group and the L-glutamine moiety were synthesised and labelled with ⁶⁷,⁶⁸Ga using established methods. High yields were achieved for the radiolabelling of the molecules with both radionuclides (>90%), although conversion of the commercially available ⁶⁷Ga-citrate to the chloride species was a requirement for consistent high radiochemical yields. The generator produced ⁶⁸Ga was in the [⁶⁸Ga(OH)₄]⁻ form. The ⁶⁷Ga complexes and the ⁶⁷Ga complexes were demonstrated to be stable in PBS buffer for a week. Uptake studies were performed with longer lived ⁶⁷Ga analogues against four tumour cell lines, as well as uptake inhibition studies against L-glutamine, and two known amino acid transporter inhibitors. Marginal uptake was exhibited in the PEG variant radio-complex, and inhibition studies indicate this uptake is via a non-targeted amino acid pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / metabolism
  • Cell Line, Tumor
  • Gallium Radioisotopes / chemistry*
  • Glutamine / analogs & derivatives
  • Glutamine / chemical synthesis
  • Glutamine / chemistry*
  • Glutamine / metabolism*
  • Heterocyclic Compounds, 1-Ring / chemistry*
  • Humans
  • Isotope Labeling
  • Neoplasms / metabolism*
  • Positron-Emission Tomography
  • Radioactive Tracers
  • Radiopharmaceuticals / chemical synthesis
  • Radiopharmaceuticals / chemistry
  • Radiopharmaceuticals / metabolism

Substances

  • Biomarkers
  • Gallium Radioisotopes
  • Heterocyclic Compounds, 1-Ring
  • Radioactive Tracers
  • Radiopharmaceuticals
  • Glutamine
  • 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid