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

Molecules

Paul A. Pellegrini¹  Nicholas R. Howell²  Rachael K. Shepherd²  Nigel A. Lengkeek²  Elisabeth Oehlke²  Andrew G. Katsifis² 

[1] id="af1-molecules-18-07160">Australian Nuclear Science and Technology Organisation, Locked Bag 2001 Kirrawee DC, NSW 2234, Austral

关键词: PET;    ⁶⁷;    68gallium;    glutamine;    amino acid transporter;    radiochemistry;    DOTA;   

DOI  :  10.3390/molecules18067160

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.