Radiolabeling morpholino oligonucleotide with ~(111)In and its biodistribution in normal mice

Objective To observe the biodistribution of ~(111)In labeled oligonucleotides in normal mice.Methods A 25 mer morpholinos (MORF) with a primary amine on the 3′equivalent end attached via a 10 member linker was conjugated with an isothiocyanate backbone derivative of p-isothiocyanatobenzyl-1,4, 7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA).The ~(111)In labeled MORF was investigated for bioaetivity stability and then biodistribution in normal mice.Results By size exclusion high performance liq- uid chromatograph (HPLC) analysis,the DOTA conjugated MORF was successfully labeled,the labeling effi- ciency ranged from 51%～67%,the specific activity after purification was 2.52×10~7 MBq/mmol.Labeled compound kept in saline (room temperature) and in serum under 37℃ for 48 h was still stable and main- tained good hybridization.The biodistribution at 1 and 3 h in normal mice showed low radioactivity levels in all tissues other than in kidney,and demonstrated no difference with ~(99)Tc~m labeling.Conclusions MORF can be labeled successfully via DOTA as chelate,and it is excreted rapidly through the kidney.