Application and Evaluation of [^99mTc]-Labeled Peptide Nucleic Acid Targeting <i>MicroRNA-155</i> in Breast Cancer Imaging

Abstract

It has been reported that dysregulation of <i>microRNA-155</i> expression 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 to <i>miR-155</i> was labeled with ^99mTc to evaluate whether the tracer could visualize the expression of <i>miR-155</i> in breast cancer. Both antisense PNA (anti-PNA, fully complementary bound to human mature <i>miR-155</i>, referred to as "anti-PNA-155") and mismatched PNA (referred to as "mis-PNA") single strands containing 23-mer were synthesized. The relative expression of <i>miR-155</i> in 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 [^99mTc]anti-PNA-155 injection. MCF-7 tumors were less visible when coinjected with 100-fold excess of anti-PNA-155 or injected with [^99mTc]mis-PNA, which suggested specific binding. Biodistribution study results were consistent with SPECT imaging. We successfully demonstrated that [^99mTc]anti-PNA-155 could visualize <i>miR-155</i> expression in vivo, suggesting it may be a promising probe applied in breast cancer.