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

Objective: To observe the biodistribution of 111In 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 111In labeled MORF was investigated for bioactivity stability and then biodistribution in normal mice. Results: By size exclusion high performance liquid chromatograph (HPLC) analysis, the DOTA conjugated MORF was successfully labeled, the labeling efficiency ranged from 51%-67%, the specific activity after purification was 2.52 x107 MBq/mmol. Labeled compound kept in saline (room temperature) and in serum under 37 degree C for 48 h was still stable and maintained 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 99Tcm labeling. Conclusions: MORF can be labeled successfully via DOTA as chelate, and it is excreted rapidly through the kidney. (authors)