Microwave accelerated 68Ga‐labelling of oligonucleotides

Oligonucleotides are extensively used for characterization of gene expression in vitro and have now been studied as inhibitors of gene expression in vivo in various diseases. Labelled antisense oligonucleotides are therefore of potential interest for possible in vivo imaging of gene expression, considering the biology of tumors and applications in designing novel molecule‐targeted therapies. In the present work a method of microwave accelerated ⁶⁸Ga‐labelling of oligonucleotides and analysis of the resulting tracers are described. Four modified and functionalized 17‐mer oligonucleotides with a hexylamine group in the 3′‐ or 5′‐position were studied. The oligonucleotides were conjugated to the bifunctional chelator, 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid (DOTA), and then labelled with ⁶⁸Ga(T_1/2=68 min) using microwave activation. The isolated decay‐corrected radiochemical yields ranged from 30 to 52%. Labelled products were stable in water and ethanol for more than 4 h. The impact of the labelling procedure on the oligonucleotide probes was investigated using hybridization to a complementary 17‐mer sense oligonucleotide in solution. Chemical modification did not influence either the labelling or hybridization ability of the oligonucleotides. The radiolabelled oligonucleotides will be used for the further in vitro and in vivo biology studies. Copyright © 2003 John Wiley & Sons, Ltd.