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.
Keywords: PET; 67,68gallium; glutamine; amino acid transporter; radiochemistry; DOTA
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Pellegrini, P.A.; Howell, N.R.; Shepherd, R.K.; Lengkeek, N.A.; Oehlke, E.; Katsifis, A.G.; Greguric, I. Synthesis and Radiolabelling of DOTA-Linked Glutamine Analogues with 67,68Ga as Markers for Increased Glutamine Metabolism in Tumour Cells. Molecules 2013, 18, 7160-7178.
Pellegrini PA, Howell NR, Shepherd RK, Lengkeek NA, Oehlke E, Katsifis AG, Greguric I. Synthesis and Radiolabelling of DOTA-Linked Glutamine Analogues with 67,68Ga as Markers for Increased Glutamine Metabolism in Tumour Cells. Molecules. 2013; 18(6):7160-7178.
Pellegrini, Paul A.; Howell, Nicholas R.; Shepherd, Rachael K.; Lengkeek, Nigel A.; Oehlke, Elisabeth; Katsifis, Andrew G.; Greguric, Ivan. 2013. "Synthesis and Radiolabelling of DOTA-Linked Glutamine Analogues with 67,68Ga as Markers for Increased Glutamine Metabolism in Tumour Cells." Molecules 18, no. 6: 7160-7178.