Preliminary evaluation of a small interfering RNA molecular probe targeting murine double minute 2 in breast cancer.

Abstract

IntroductionMurine 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, 99mTc-HYNIC-siRNA 1489, which could specifically bind to MDM2. The [99mTc]HYNIC-siRNA 1489 molecular probe provided an effective way of assessing MDM2 expression via single-photon emission computed tomography.MethodThree 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 (99mTc) through the chelator HYNIC. The bioactivity and properties of [99mTc]HYNIC-siRNA 1489 were evaluated prior to imaging in mice. Imaging and biodistribution of the probe were used to assess its targeting ability.ResultsSiRNA 1489, which was labeled with 99mTc, displayed a strong inhibitory effect in Michigan Cancer Foundation-7 cell lines. The radiochemical purity of [99mTc]HYNIC-siRNA 1489 was stable at various temperatures in phosphate-buffered serum and bovine serum. The tumor/muscle ratio in mice injected with [99mTc]HYNIC-siRNA 1489 was higher than that in those injected with the negative control, [99mTc]HYNIC-NC siRNA. The percentage injected dose per gram (%ID/g) of the tumors injected with 99mTc-HYNIC-siRNA 1489 was greater than that of the control group.ConclusionThe [99mTc]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.