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| The molecular imaging research of chemokine receptor 4(CXCR4) |
| CAO Xue-liang1, FU Peng2, JIANG Ting-jun1, LUAN Sha1, ZHAO Chang-jiu1 |
1.The Fourth Hospital of Harbin Medical University, Harbin 150001, China;
2.The First Hospital of Harbin Medical University, Harbin 150001, China) |
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Abstract Objective: To investigate the possibility of using small interference RNA(siRNA) targeting human chemokine receptor 4(CXCR4) radiolabeled with 99mTc for diagnosing human breast cancer. Methods: Small interference RNA targeted to CXCR4 mRNA and negative control siRNA were synthesized and radiolabeled by 99mTc with the bifunctional chelator HYNIC. The labeling efficiency, radiochemical purity and stability were investigated. Animal models of nude mice bearing human breast cancer MDA-MB-231 were established, divided them into three groups, 10 mice in each group. 99mTcO4-, 99mTc-HYNIC- siRNA(interference group), 99mTc-HYNIC-siRNA(negative control group) were separately injected through tail vein to the three groups. After 99mTcO4-, 99mTc-HYNIC-siRNA(interference group), 99mTc-HYNIC-siRNA(negative control group) were introduced into these animal models, tumor images were acquired with SPECT, the ratio of T/M was calculated. The data were analyzed by two-sample t test and analysis of variance. Results: The labeling efficiency of siRNA(interference group) and siRNA(negative control group) were (61.26±2.47)% and (60.85±2.76)% respectively. The radiochemical purities were both above 90%. Incubated in fresh human serum and PBS for 30 min and 120 min at 37℃, respectively, probes’ properties remained stable in 2 hours. At 1, 4 and 10 h after injection of different probes, the T/M ratios of 99mTc-HYNIC-siRNA(interference group) were 3.486±0.145, 4.574±0.222 and 6.608±0.366, and that of 99mTc-HYNIC-siRNA(negative control group) were 1.286±0.189, 1.348±0.204 and 1.354±0.238, with 99mTcO4- group 1.317±0.164, 1.322±0.159 and 1.401±0.145 respectively, and there were statistically significant differences in different groups at every time spots. The ratios of T/M in 99mTcO4- group and 99mTc-HYNIC-siRNA(negative control group) were significantly lower than those in 99mTc-HYNIC-siRNA(interference group) at 1, 4, 10 h respectively(tcontrol=29.20, 33.84 and 38.07, 99mTcO4-=31.29, 37.61 and 41.86, all P<0.01), and the T/M ratios at 1 h, 4 h, 10 h of 99mTc-HYNIC-siRNA(negative control group) and 99mTcO4- groups were not significantly different(t=0.392, 0.318 and 0.533, all P>0.05). Conclusions: The 99mTc-HYNIC-siRNA(interference group) could specificity accumulated in breast cancer tissue. The imaging with 99mTc-HYNIC-siRNA may be a promising method for diagnosis of breast cancer.
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Received: 28 July 2016
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2017, Vol. 28 
