One-step synthesis of a radioiodinated anti-microRNA-21 oligonucleotide for theranostics in prostate tumor xenografts

Abstract

Anti-miRNA oligonucleotide (AMO) has been used most widely to inhibit miRNA for loss-of-function studies and function as therapeutic agents. Iodine-131 (131I) radiolabeled AMO may have multiple functions for specific imaging, genetic inhibition, and radiotherapy. This study is to prepare a radioiodinated anti-miRNA-21 AMO by one-step synthesis for preliminary imaging in tumor xenografts and in vitro radiotherapy. A tyrosine was conjugated at the 3’ end of AMO via a C6 linker for labeling with 131I. After the molecular mass of AMO was confirmed by mass spectrometry, AMO was labeled with 131I by the chloramine-T method with high labeling yield (95.5% ± 3.1%). By gel electrophoresis, the radioactive distribution of 131I-AMO was located exactly where was AMO, verifying the successful radiolabeling. 131I-AMO presented high stability during 24 h of incubation in fresh human serum. The cellular uptake of 131I or FAM-labeled AMO in DU145 was significantly higher than that in PC-3 cells. After i.v. administration in mice, single-photon emission tomography (SPECT) imaging showed that increased 131I-AMO was found in DU145 tumor from 4 h to 24 h gradually. H&E staining of major organs validated the biocompatibility of 131I-AMO in vivo. Furthermore, the ability of 131I-AMO to inhibit cell growth is superior to that of 131I, along with stronger apoptosis in DU145 cells than in PC-3 cells. Therefore, AMO can be labeled with 131I via one-step synthesis after tyrosine conjugation in this study. Its high labeling yield, stability, inhibitory effect, and tumor distribution provide the potential value in the targeted theranostic role.