Imaging of a siRNA molecular probe targeting MDM2 in breast cancer

Abstract Background Murine double minute 2 (MDM2) is an oncogene that is important for 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 provides an effective way to assess MDM2 expression via SPECT. Method: Three siRNAs were designed and their inhibitory efficiencies were tested using western blots and qRT-PCR. The selected siRNA was labeled with the radionuclide 99 m-technetium (99mTc) through the chelator HYNIC. The bioactivity and properties of [99mTc]HYNIC-siRNA 1489 were determined before mouse imaging. Imaging and the biodistribution of the probe were used to assess its targeting ability. Results SiRNA 1489, which was labeled with 99mTc, displayed a strong inhibitory effect in MCF-7 cell lines. The radiochemical purity of [99mTc]HYNIC-siRNA 1489 was stable at different temperatures in PBS and bovine serum. The T/M ratio of mice injected with [99mTc]HYNIC-siRNA 1489 was higher than that of those injected with the negative control, [99mTc]HYNIC-NC siRNA. The percentage injected dose per g (%ID/g) of the tumors injected with 99mTc-HYNIC-siRNA 1489 was greater than that of the control group. Conclusions The [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. It might afford an effective strategy for evaluating MDM2 expression and achieving earlier diagnosis in breast cancer.