Imaging of a siRNA molecular probe targeting MDM2 in breast cancer
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.
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.
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.
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.
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Posted 29 Sep, 2020
Received 18 Jan, 2021
On 18 Jan, 2021
On 26 Dec, 2020
Received 12 Dec, 2020
On 24 Nov, 2020
Invitations sent on 12 Oct, 2020
On 14 Sep, 2020
On 13 Sep, 2020
On 13 Sep, 2020
Posted 27 Jul, 2020
Imaging of a siRNA molecular probe targeting MDM2 in breast cancer
Posted 29 Sep, 2020
Received 18 Jan, 2021
On 18 Jan, 2021
On 26 Dec, 2020
Received 12 Dec, 2020
On 24 Nov, 2020
Invitations sent on 12 Oct, 2020
On 14 Sep, 2020
On 13 Sep, 2020
On 13 Sep, 2020
Posted 27 Jul, 2020
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.
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.
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.
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.
Figure 1
Figure 2
Figure 3