Synthesis and Radiolabelling of DOTA-Linked Glutamine Analogues with (67,68)Ga as Markers for Increased Glutamine Metabolism in Tumour Cells

DOTA-linked glutamine analogues with a C(6)- alkyl and polyethyleneglycol (PEG) chain between the chelating group and the l-glutamine moiety were synthesised and labelled with (67,68)Ga using established methods. High yields were achieved for the radiolabelling of the molecules with both radionuclides (>90%), although conversion of the commercially available (67)Ga-citrate to the chloride species was a requirement for consistent high radiochemical yields. The generator produced (68)Ga was in the [(68)Ga(OH)4](−) form. The (67)Ga complexes and the (67)Ga complexes were demonstrated to be stable in PBS buffer for a week. Uptake studies were performed with longer lived (67)Ga 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.