title: Synthesis and radiolabelling of DOTA-linked glutamine analogues with ⁶⁷,⁶⁸Ga as markers for increased glutamine metabolism in tumour cells.
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.
authors.affiliation: Australian Nuclear Science and Technology Organisation, Locked Bag 2001, Kirrawee DC, NSW 2234, Australia. Paul.Pellegrini@ansto.gov.au
authors.forename: Paul A
authors.initials: PA
authors.lastname: Pellegrini
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Howell
authors.forename: Rachael K
authors.initials: RK
authors.lastname: Shepherd
authors.forename: Nigel A
authors.initials: NA
authors.lastname: Lengkeek
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Oehlke
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Katsifis
authors.forename: Ivan
authors.initials: I
authors.lastname: Greguric
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D045744:Cell Line, Tumor; D005710:Gallium Radioisotopes / Q000737:chemistry*; D005973:Glutamine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry*; D006801:Humans; D007553:Isotope Labeling; D009369:Neoplasms / Q000378:metabolism*; D049268:Positron-Emission Tomography; D011849:Radioactive Tracers; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism
chemical_list: D015415:Biomarkers; D005710:Gallium Radioisotopes; D006573:Heterocyclic Compounds, 1-Ring; D011849:Radioactive Tracers; D019275:Radiopharmaceuticals; D005973:Glutamine; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid