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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 (&gt;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.

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