Preliminary evaluation of a small interfering RNA molecular probe targeting murine double minute 2 in breast cancer
NUCLEAR MEDICINE COMMUNICATIONS(2022)
Abstract
Introduction Murine double minute 2 (MDM2) is an oncogene that is important in tumorigenesis, tumor metastasis and chemotherapy resistance. We aimed to synthesize a molecular imaging probe, Tc-99m-HYNIC-siRNA 1489, which could specifically bind to MDM2. The [Tc-99m]HYNIC-siRNA 1489 molecular probe provided an effective way of assessing MDM2 expression via single-photon emission computed tomography. Method Three siRNAs were designed, and their inhibitory efficiencies were determined using western blots and qRT-PCR. The selected siRNA was labeled with the radionuclide technetium-99m (Tc-99m) through the chelator HYNIC. The bioactivity and properties of [Tc-99m]HYNIC-siRNA 1489 were evaluated prior to imaging in mice. Imaging and biodistribution of the probe were used to assess its targeting ability. Results SiRNA 1489, which was labeled with Tc-99m, displayed a strong inhibitory effect in Michigan Cancer Foundation-7 cell lines. The radiochemical purity of [Tc-99m]HYNIC-siRNA 1489 was stable at various temperatures in phosphate-buffered serum and bovine serum. The tumor/muscle ratio in mice injected with [Tc-99m]HYNIC-siRNA 1489 was higher than that in those injected with the negative control, [Tc-99m]HYNIC-NC siRNA. The percentage injected dose per gram (%ID/g) of the tumors injected with Tc-99m-HYNIC-siRNA 1489 was greater than that of the control group. Conclusion The [Tc-99m]HYNIC-siRNA 1489 was taken up by the tumor, which had a high level of MDM2. The probe exhibited a sufficient retention time in the tumor. This probe may be an effective strategy for evaluating MDM2 expression and achieving early diagnosis in breast cancer.
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Key words
molecular imaging,murine double minute 2,small interfering RNA,technetium-99m
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