See the published version of this preprint at EJNMMI Research.
This is a preprint, 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
A new preprint design is coming!
We have improved readability, clarity, accessibility, and opportunities for engagement.
Original research
Min Yang
Corresponding Author
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Human epidermal growth factor receptor-2 (HER2) is an essential biomarker for tumor treatment. Affibody is an ideal vector for preparing HER2 specific probes because of high affinity and rapid clearance from normal tissues etc. Zirconium-89 is a PET imaging isotope with a long half-life and suitable for monitoring biological processes for more extended periods. In this study, a novel 89 Zr-labeled HER2 affibody, 89 ZrZr-DFO-MAL-Cys-MZHER2, was synthesized, and its imaging characters were also assessed. Results: The precursor, DFO-MAL-Cys-MZHER2, was obtained with a yield of nearly 50%. The radiochemical yield of 89 ZrZr -DFO-MAL-Cys-MZHER2 was 90.2±1.9% , and the radiochemical purity was higher than 95%. The total synthesis time was only 30 minutes. The probe was stable in PBS and serum. The tracer accumulated in HER2 overexpressing human ovarian cancer SKOV-3 cells. In vivo studies in mice bearing tumors showed that the probe highly retained in SKOV-3 xenografts even for 48 hours. The tumors were visualized with good contrast to normal tissues. ROI analysis revealed that the average uptake values in the tumor were greater than 5%IA/g during 48 hours postinjection. On the contrary, the counterparts of MCF-7 tumors kept low levels（~1%IA/g）. The outcome was consistent with the immunohistochemical analysis and ex vivo autoradiography. The probe quickly cleared from the normal organs except kidneys and mainly excreted through the urinary system. Conclusion: The novel HER2 affibody for PET imaging was easily prepared with satisfactory labeling yield and radiochemical purity. 89 ZrZr-DFO-MAL-Cys-MZHER2 is a potential candidate for detecting HER2 expression. It may play specific roles in clinical cancer theranostics.
Keywords
Human epidermal growth factor receptor-2, PET, affibody, 89Zr
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
This is a list of supplementary files associated with this preprint. Click to download.
Loading...
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: Published
View the published article at EJNMMI Research.
No community comments so far
Editorial decision: Accept
On 22 May, 2020
Version 3
Posted 28 Jun, 2020
No comments provided
Editorial decision: Minor revision
On 20 May, 2020
Editor assigned
On 19 May, 2020
Submission checks complete
On 18 May, 2020
Editor invited
On 18 May, 2020
No comments provided
Editorial decision: Minor Revision
On 08 May, 2020
Reviewer #2 agreed
On 07 May, 2020
Review #2 received
Received 07 May, 2020
Reviewer #1 agreed
On 01 May, 2020
Review #1 received
Received 01 May, 2020
Editor assigned
On 01 May, 2020
Reviewers invited
Invitations sent on 01 May, 2020
Submission checks complete
On 30 Apr, 2020
Editor invited
On 30 Apr, 2020
No comments provided
Review #2 received
Received 10 Apr, 2020
Editorial decision: Major Revision
On 10 Apr, 2020
Review #1 received
Received 27 Mar, 2020
Reviewer #2 agreed
On 26 Mar, 2020
Reviewer #1 agreed
On 24 Mar, 2020
Editor assigned
On 23 Mar, 2020
Reviewers invited
Invitations sent on 23 Mar, 2020
Editor invited
On 22 Mar, 2020
Submission checks complete
On 19 Mar, 2020
First submitted
On 13 Mar, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Learn more about our company.
A new preprint design is coming!
We have improved readability, clarity, accessibility, and opportunities for engagement.
See the published version of this preprint at EJNMMI Research.
This is a preprint, 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
Original research
Min Yang
Corresponding Author
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: Published
View the published article at EJNMMI Research.
No community comments so far
Editorial decision: Accept
On 22 May, 2020
Version 3
Posted 28 Jun, 2020
No comments provided
Editorial decision: Minor revision
On 20 May, 2020
Editor assigned
On 19 May, 2020
Submission checks complete
On 18 May, 2020
Editor invited
On 18 May, 2020
No comments provided
Editorial decision: Minor Revision
On 08 May, 2020
Reviewer #2 agreed
On 07 May, 2020
Review #2 received
Received 07 May, 2020
Reviewer #1 agreed
On 01 May, 2020
Review #1 received
Received 01 May, 2020
Editor assigned
On 01 May, 2020
Reviewers invited
Invitations sent on 01 May, 2020
Submission checks complete
On 30 Apr, 2020
Editor invited
On 30 Apr, 2020
No comments provided
Review #2 received
Received 10 Apr, 2020
Editorial decision: Major Revision
On 10 Apr, 2020
Review #1 received
Received 27 Mar, 2020
Reviewer #2 agreed
On 26 Mar, 2020
Reviewer #1 agreed
On 24 Mar, 2020
Editor assigned
On 23 Mar, 2020
Reviewers invited
Invitations sent on 23 Mar, 2020
Editor invited
On 22 Mar, 2020
Submission checks complete
On 19 Mar, 2020
First submitted
On 13 Mar, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at EJNMMI Research.
Background: Human epidermal growth factor receptor-2 (HER2) is an essential biomarker for tumor treatment. Affibody is an ideal vector for preparing HER2 specific probes because of high affinity and rapid clearance from normal tissues etc. Zirconium-89 is a PET imaging isotope with a long half-life and suitable for monitoring biological processes for more extended periods. In this study, a novel 89 Zr-labeled HER2 affibody, 89 ZrZr-DFO-MAL-Cys-MZHER2, was synthesized, and its imaging characters were also assessed. Results: The precursor, DFO-MAL-Cys-MZHER2, was obtained with a yield of nearly 50%. The radiochemical yield of 89 ZrZr -DFO-MAL-Cys-MZHER2 was 90.2±1.9% , and the radiochemical purity was higher than 95%. The total synthesis time was only 30 minutes. The probe was stable in PBS and serum. The tracer accumulated in HER2 overexpressing human ovarian cancer SKOV-3 cells. In vivo studies in mice bearing tumors showed that the probe highly retained in SKOV-3 xenografts even for 48 hours. The tumors were visualized with good contrast to normal tissues. ROI analysis revealed that the average uptake values in the tumor were greater than 5%IA/g during 48 hours postinjection. On the contrary, the counterparts of MCF-7 tumors kept low levels（~1%IA/g）. The outcome was consistent with the immunohistochemical analysis and ex vivo autoradiography. The probe quickly cleared from the normal organs except kidneys and mainly excreted through the urinary system. Conclusion: The novel HER2 affibody for PET imaging was easily prepared with satisfactory labeling yield and radiochemical purity. 89 ZrZr-DFO-MAL-Cys-MZHER2 is a potential candidate for detecting HER2 expression. It may play specific roles in clinical cancer theranostics.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
This is a list of supplementary files associated with this preprint. Click to download.
Loading...