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  • Title: Imaging CXCR4 Expression with (99m)Tc-Radiolabeled Small-Interference RNA in Experimental Human Breast Cancer Xenografts.
    Author: Fu P, Tian L, Cao X, Li L, Xu P, Zhao C.
    Journal: Mol Imaging Biol; 2016 Jun; 18(3):353-9. PubMed ID: 26452556.
    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 (99m)Tc-radiolabeled small-interference RNA (siRNA) targeting CXCR4 to detect CXCR4 expression in vivo. PROCEDURES: CXCR4 siRNAs were radiolabeled with (99m)Tc 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: (99m)Tc-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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