Abstract

The objective of this study is to investigate the signal changes and optimal scanning concentration of MRI in tumor tissues of tumor-bearing nude mice by SPIO-shRNA molecular probes. 30 BALB/c tumor-bearing nude mice were randomly divided into 5 groups with 6 mice in each group. At the given scanning time (before and 27 h after injection), the caudal vein was respectively injected with iron content of 6 mg·kg−1, 12 mg·kg−1, 18 mg·kg−1, 24 mg·kg−1, and 30 mg·kg−1, and MR examination was simultaneously performed to measure signal intensity changes of tumor tissue and contralateral muscle tissue in each concentration group. After each examination above, the nude mice were sacrificed immediately, and the tumor and muscle tissues were removed for HE and Prussian blue staining,and observed under light microscope. Nude mice in 6 mg, 12 mg and 18 mg groups all survived after probe injection, but some nude mice died in 24 mg and 30 mg groups after probe injection or during scanning. The signal changes of T2WI and T2*WI sequences were the most obvious in MR scanning sequences. Compared with other groups, the signal intensity of the tumor tissue in 18 mg, 24 mg and 30 mg groups were most obvious (P < 0.05), while the 18 mg, 24 mg and 30 mg groups reached no statistical difference (P > 0.05 ); HE staining indicated that structural disorder of tumor tissue as well as increase of nuclear atypia. Prussian Blue staining showed that blue-stained iron particles were present in each experimental group,and the most densely distributed were in 18 mg,24 mg and 30 mg groups. Tumor tissue could be well labeled with SPIO-shRNA molecular probes, and the optimal MR scanning concentration (iron content) is 18 mg·kg−1.

Highlights

  • Emerging molecular imaging is a technique for imaging the pathology and physiological changes of the body from the molecular or cellular level

  • One mouse immediately died in the 30 mg group

  • According to the RNA interference theory, endonuclease cleaves the dsRNA fragments produced during cell transcription into several small fragments of short hairpin RNA (shRNA), and binds to the ribozyme complexes to silence the targeted mRNA homologous to shRNA, thereby inhibiting the expression of ovarian cancer protein and causing tumor cell ­death[22,23]

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Summary

Introduction

Emerging molecular imaging is a technique for imaging the pathology and physiological changes of the body from the molecular or cellular level. Based on the theory of RNA interference (RNAi)[2,3,4], the present study combined molecular imaging and gene therapy with SPIO as the MRI negative contrast agent, PLL as the gene carrier, and ovarian cancer EGFR as the gene target, in order to design the shRNA (short hairpin RNA), and construct the specific SPIO-sh RNA molecules probe (SPIO-shRNA, hereinafter referred to as probe). This was a dual-functional molecular probe that integrated the diagnosis and treatment. These were compared with the pathological results to obtain the best concentration of MR

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