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Updated: Sep 22, 2025
Monitoring of Nanodrug Accumulation in Murine Breast Cancer Metastases
Published on: August 23, 2024
Preliminary evaluation of a small interfering RNA molecular probe targeting murine double minute 2 in breast cancer
Xinyu Wang1, Peng Xu2, Yuying Jiao2
1Department of Nuclear Medicine, The Fourth Affiliated Hospital of Harbin Medical University.
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, 99m Tc-HYNIC-siRNA 1489, which could specifically bind to MDM2. The [ 99m Tc]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 ( 99m Tc) through the chelator HYNIC. The bioactivity and properties of [ 99m Tc]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 99m Tc, displayed a strong inhibitory effect in Michigan Cancer Foundation-7 cell lines. The radiochemical purity of [ 99m Tc]HYNIC-siRNA 1489 was stable at various temperatures in phosphate-buffered serum and bovine serum. The tumor/muscle ratio in mice injected with [ 99m Tc]HYNIC-siRNA 1489 was higher than that in those injected with the negative control, [ 99m Tc]HYNIC-NC siRNA. The percentage injected dose per gram (%ID/g) of the tumors injected with 99m Tc-HYNIC-siRNA 1489 was greater than that of the control group.
Conclusion:
The [ 99m Tc]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.
Insights
A novel molecular imaging probe, technetium-99m (99mTc)-HYNIC-siRNA 1489, effectively targets and visualizes MDM2 expression in tumors. This probe shows promise for early breast cancer diagnosis and assessing MDM2 levels.
Area of Science:
- Oncology
- Molecular Imaging
- Radiochemistry
Background:
- Murine double minute 2 (MDM2) is an oncogene implicated in cancer development, metastasis, and treatment resistance.
- Targeting MDM2 is crucial for cancer therapy and diagnostics.
- Developing specific molecular probes for MDM2 is essential for in vivo assessment.
Purpose of the Study:
- To synthesize and evaluate a novel molecular imaging probe, 99mTc-HYNIC-siRNA 1489, for specific binding to MDM2.
- To assess the probe's efficacy in visualizing MDM2 expression using single-photon emission computed tomography (SPECT).
- To determine the potential of this probe for early breast cancer diagnosis.
Main Methods:
- Three small interfering RNAs (siRNAs) were designed and their inhibitory effects on MDM2 were validated.
- The selected siRNA (siRNA 1489) was radiolabeled with 99mTc using the HYNIC chelator.
- The bioactivity, stability, and targeting ability of the 99mTc-HYNIC-siRNA 1489 probe were assessed in vitro and in vivo using SPECT imaging and biodistribution studies in mice.
Main Results:
- siRNA 1489 demonstrated significant MDM2 inhibition in MCF-7 cell lines.
- The 99mTc-HYNIC-siRNA 1489 probe exhibited excellent radiochemical purity and stability in biological matrices.
- In vivo studies showed higher tumor uptake and retention of 99mTc-HYNIC-siRNA 1489 compared to a negative control, indicated by increased tumor/muscle ratios and %ID/g in tumors.
Conclusions:
- The 99mTc-HYNIC-siRNA 1489 probe is effectively taken up by MDM2-expressing tumors.
- The probe demonstrates adequate retention within the tumor microenvironment.
- This molecular imaging probe represents a promising tool for evaluating MDM2 expression and facilitating early breast cancer detection.
