Application and Evaluation of [ 99m Tc]-Labeled Peptide Nucleic Acid Targeting MicroRNA-155 in Breast Cancer Imaging.

It has been reported that dysregulation ofmicroRNA-155expression and function is associated with tumorigenesis, growth, tumor subtypes, invasion, and poor survival rates. Peptide nucleic acid (PNA), an artificially synthesized nucleic acid mimic, has been applied for molecular diagnosis. In this study, a PNA sequence that undergoes complementary binding tomiR-155was labeled with(99m)Tc to evaluate whether the tracer could visualize the expression ofmiR-155in breast cancer. Both antisense PNA (anti-PNA, fully complementary bound to human maturemiR-155, referred to as "anti-PNA-155") and mismatched PNA (referred to as "mis-PNA") single strands containing 23-mer were synthesized. The relative expression ofmiR-155in MCF-7 cells and tumors was higher than that in MDA-MB-231 cells and tumors. Single-photon emission computed tomography (SPECT) scan showed that radioactivity mainly accumulated in kidney. MCF-7 tumors, but not MDA-MB-231 tumors, were clearly visualized after [Tc-99m]anti-PNA-155 injection. MCF-7 tumors were less visible when coinjected with 100-fold excess of anti-PNA-155 or injected with [Tc-99m]mis-PNA, which suggested specific binding. Biodistribution study results were consistent with SPECT imaging. We successfully demonstrated that [Tc-99m]anti-PNA-155 could visualizemiR-155expression in vivo, suggesting it may be a promising probe applied in breast cancer.