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Imaging CXCR4 Expression with 99mTc-Radiolabeled Small-Interference RNA in Experimental Human Breast Cancer Xenografts

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Abstract

Purpose

Noninvasive quantification of chemokine receptor 4 (CXCR4) expression could serve as a prognostic indicator and may be of value for the design of personalized therapies and posttreatment monitoring. The objective of the present study was to assess the use of 99mTc-radiolabeled small-interference RNA (siRNA) targeting CXCR4 to detect CXCR4 expression in vivo.

Procedures

CXCR4 siRNAs were radiolabeled with 99mTc using the bifunctional chelator hydrazinonicotinamide (HYNIC), and the labeling efficiency, specific activity and radiochemical purity were determined. The stability of the probe in serum was assessed by measuring its radiochemical purity and inhibitory activity by RT-PCR and western blotting. Biodistribution studies and static imaging were performed in MDA-MB-231 tumor-bearing mice.

Results

Radiochemical purity remained highly stable in PBS and fresh human serum at room temperature and at 37 °C. Radiolabeled siRNA1 showed strong inhibitory effects similar to those of unlabeled siRNA1 on both CXCR4 messenger RNA (mRNA) and protein in vitro. The excretion of the probe occurred mainly through the liver and kidneys. Tumors were clearly visualized at 1–10 h after injection of the probe, but not after injection of the control probe.

Conclusions

99mTc-labeled CXCR4 siRNA1 shows tumor-specific accumulation and could be a promising strategy for the visualization of CXCR4 expression in human breast cancer.

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Acknowledgments

This study was funded by the Natural Science Foundation of Heilongjiang Province (No. H2015066).

Conflict of Interest

The authors declare that they have no competing interests.

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Author notes

    Authors and Affiliations

    1. Department of Nuclear Medicine, 1st Hospital of Harbin Medical University, Harbin, China

      Peng Fu & Peng Xu

    2. Department of Pathology, 1st Hospital of Harbin Medical University, Harbin, China

      Lin Tian

    3. Department of Nuclear Medicine, 4th Hospital of Harbin Medical University, Harbin, China

      Xueliang Cao, Li Li & Changjiu Zhao

    4. Department of Nuclear Medicine, 4th Hospital of Harbin Medical University, Harbin, 150001, China

      Changjiu Zhao

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    1. Peng Fu
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    2. Lin Tian
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    3. Xueliang Cao
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    5. Peng Xu
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    Corresponding author

    Correspondence to Changjiu Zhao.

    Additional information

    Peng Fu and Lin Tian contributed equally to this work.

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    Fu, P., Tian, L., Cao, X. et al. Imaging CXCR4 Expression with 99mTc-Radiolabeled Small-Interference RNA in Experimental Human Breast Cancer Xenografts. Mol Imaging Biol 18, 353–359 (2016). https://doi.org/10.1007/s11307-015-0899-4

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    • DOI: https://doi.org/10.1007/s11307-015-0899-4

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