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Research article
Imaging of a siRNA molecular probe targeting MDM2 in breast cancer
Peng Fu
The First Affiliated Hospital of Harbin Medical University
Corresponding Author
ORCiD: https://orcid.org/0000-0002-9860-9150
License:
This work is licensed under a CC BY 4.0 License. Read Full License
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.
Keywords
MDM2, siRNA, molecular imaging, 99mTc
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CURRENT STATUS: Under Review
Version 1
Posted 29 Sep, 2020
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Review #2 received
Received 18 Jan, 2021
Editorial decision: Minor revision
On 18 Jan, 2021
Reviewer #2 agreed
On 26 Dec, 2020
Review #1 received
Received 12 Dec, 2020
Reviewer #1 agreed
On 24 Nov, 2020
Reviewers invited
Invitations sent on 12 Oct, 2020
Editor assigned
On 14 Sep, 2020
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On 13 Sep, 2020
Editor invited
On 13 Sep, 2020
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This preprint is under consideration at BMC Medical Imaging. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Imaging of a siRNA molecular probe targeting MDM2 in breast cancer
Peng Fu
The First Affiliated Hospital of Harbin Medical University
Corresponding Author
ORCiD: https://orcid.org/0000-0002-9860-9150
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 29 Sep, 2020
No community comments so far
Review #2 received
Received 18 Jan, 2021
Editorial decision: Minor revision
On 18 Jan, 2021
Reviewer #2 agreed
On 26 Dec, 2020
Review #1 received
Received 12 Dec, 2020
Reviewer #1 agreed
On 24 Nov, 2020
Reviewers invited
Invitations sent on 12 Oct, 2020
Editor assigned
On 14 Sep, 2020
Submission checks complete
On 13 Sep, 2020
Editor invited
On 13 Sep, 2020
Version (no preprint)
Posted 27 Jul, 2020
This version was not preprinted
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
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.
Figure 1
Figure 2
Figure 3