In vitro stability of 188Re-labeled morpholino oligonucleotide and its distribution in mice

Objective To study the possibility of rhenium-188(188Re)-labeled morpholino oligonucleotide as a therapeutic drug.Methods Mercaptoacetyltriglycine(MAG3) was used as a bifunctional chelater to test the effect of 188Re-labelled morpholino oligonucleotide on labeling rate.Biological activity,in vitro stability and distribution of 188Re-labeled morpholino oligonucleotide in normal mice were detected.Results The labeling rate of 188Re-labeled morpholino oligonucleotide was 65%±12% with a radiochemical purity of over 93% and a specific activity of(2.37±0.32)MBq/μg.Re-oxidation of markers occurred in vitro,which caused disassociation of 188Re-labeled morpholino oligonucleotide.Addition of anti-oxidant and ascorbic acid into 188Re-labeled morpholino oligonucleotide could significantly improve its in vitro stability.188Re-labelled morpholino oligonucleotide was mainly excreted through the kidneys.Its uptake was significantly higher in thyroid and stomach.Conclusion MAG3 can label 188Re-labeled morpholino oligonucleotide with a poor in vitro stability.Addition of anti-oxidant into 188Re-labeled morpholino oligonucleotide can improve its in vitro stability,but the markers will disassociate in vivo.Thus,188Re-labeled morpholino oligonucleotide cannot be used as a therapeutic drug.