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.