This preprint is under consideration at EJNMMI Research. 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
Original research
A Microdose Clinical Trial to Evaluate 64Cu-NOTA-Trastuzumab as a Positron Emission Tomography Imaging Agent in Patients with Breast Cancer
Ilhan Lim
Korea Institute of Radiological and Medical Sciences
Corresponding Author
ORCiD: https://orcid.org/0000-0002-5903-1659
License:
This work is licensed under a CC BY 4.0 License. Read Full License
The most recent version of this article is available here.
Background: The purpose of this study was to evaluate the biodistribution and safety of 64Cu-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA)-Trastuzumab, a novel 64Cu-labelled positron emission tomography (PET) tracer for human epidermal growth factor receptor 2 (HER2) in patients with breast cancer.
Methods: PET images at 1, 24, and 48 hours after injection of 296 MBq of 64Cu-NOTA-Trastuzumab were obtained on seven patients with breast cancer. The maximum standardized uptake value (SUVmax) was evaluated in the tumors, including the primary tumor and metastatic lesions. The mean SUVmax (SUVmean) was evaluated in the normal organs including the blood pool, liver, kidney, muscle, spleen, bladder, lung, and bone. In addition, the internal radiation dosimetry was calculated using the OLINDA/EXM software. Safety was assessed by gathering the feedback of adverse reactions and safety-related issues within 1 month after 64Cu-NOTA-Trastuzumab administration.
Results: The overall values of SUVmean in each normal organ decreased with time on 64Cu-NOTA-Trastuzumab PET images. The average values of SUVmean of the liver were measured at 5.3 ± 0.7, 4.8 ± 0.6, and 4.4 ± 0.5 on 1 hour, 24 hours, and 48 hours after injection. The average values of SUVmean of the blood were evaluated as 13.1 ± 0.9, 9.1 ± 1.2, and 7.1 ± 1.9 on 1 hour, 24 hours, and 48 hours after injection. The SUVmax of HER2-positive tumors showed relatively higher than that of HER2-negative tumors (8.6 ± 5.1 and 5.2 ± 2.8 on 48 hours after injection, respectively). Tumor to background ratios were calculated higher in the HER2-positive tumors than those of HER2-negative tumors. No adverse events related to 64Cu-NOTA-Trastuzumab were reported. The calculated effective dose with a 296 MBq injection of 64Cu-NOTA-Trastuzumab was 2.96 mSv. The highest absorbed dose was observed in the liver (0.076 mGy/MBq), followed by the spleen (0.063 mGy/MBq), kidney (0.044 mGy/MBq), and heart wall (0.044 mGy/MBq).
Conclusions: 64Cu-NOTA-Trastuzumab showed specific uptake at the HER2-expressing tumors. It suggests that 64Cu-NOTA-Trastuzumab can be a feasible monitoring tool for HER2 tumor status in the patients with breast cancer with safe.
Trial registration: CRIS, KCT0002790. Registered 02 February 2018, https://cris.nih.go.kr
Keywords
HER-2, 64Cu-NOTA-trastuzumab, breast cancer, positron emission tomography, computed tomography
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
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
No community comments so far
Editor assigned
On 21 Dec, 2020
Submission checks complete
On 21 Dec, 2020
Editor invited
On 21 Dec, 2020
No comments provided
Editorial decision: Minor Revision
On 11 Dec, 2020
Review #1 received
Received 10 Dec, 2020
Editor assigned
On 16 Nov, 2020
Reviewers invited
Invitations sent on 16 Nov, 2020
Reviewer #1 agreed
On 16 Nov, 2020
Submission checks complete
On 16 Nov, 2020
Editor invited
On 16 Nov, 2020
Version 1
Posted 04 Aug, 2020
No comments provided
Editorial decision: Minor Revision
On 21 Oct, 2020
Review #3 received
Received 30 Sep, 2020
Reviewer #3 agreed
On 28 Sep, 2020
Review #1 received
Received 08 Sep, 2020
Review #2 received
Received 08 Sep, 2020
Reviewer #2 agreed
On 01 Sep, 2020
Reviewer #1 agreed
On 17 Aug, 2020
Reviewers invited
Invitations sent on 31 Jul, 2020
Editor assigned
On 29 Jul, 2020
Submission checks complete
On 28 Jul, 2020
Editor invited
On 28 Jul, 2020
First submitted
On 27 Jul, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Learn more about our company.
This preprint is under consideration at EJNMMI Research. 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
Original research
A Microdose Clinical Trial to Evaluate 64Cu-NOTA-Trastuzumab as a Positron Emission Tomography Imaging Agent in Patients with Breast Cancer
Ilhan Lim
Korea Institute of Radiological and Medical Sciences
Corresponding Author
ORCiD: https://orcid.org/0000-0002-5903-1659
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
No community comments so far
Editor assigned
On 21 Dec, 2020
Submission checks complete
On 21 Dec, 2020
Editor invited
On 21 Dec, 2020
No comments provided
Editorial decision: Minor Revision
On 11 Dec, 2020
Review #1 received
Received 10 Dec, 2020
Editor assigned
On 16 Nov, 2020
Reviewers invited
Invitations sent on 16 Nov, 2020
Reviewer #1 agreed
On 16 Nov, 2020
Submission checks complete
On 16 Nov, 2020
Editor invited
On 16 Nov, 2020
Version 1
Posted 04 Aug, 2020
No comments provided
Editorial decision: Minor Revision
On 21 Oct, 2020
Review #3 received
Received 30 Sep, 2020
Reviewer #3 agreed
On 28 Sep, 2020
Review #1 received
Received 08 Sep, 2020
Review #2 received
Received 08 Sep, 2020
Reviewer #2 agreed
On 01 Sep, 2020
Reviewer #1 agreed
On 17 Aug, 2020
Reviewers invited
Invitations sent on 31 Jul, 2020
Editor assigned
On 29 Jul, 2020
Submission checks complete
On 28 Jul, 2020
Editor invited
On 28 Jul, 2020
First submitted
On 27 Jul, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
The most recent version of this article is available here.
Background: The purpose of this study was to evaluate the biodistribution and safety of 64Cu-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA)-Trastuzumab, a novel 64Cu-labelled positron emission tomography (PET) tracer for human epidermal growth factor receptor 2 (HER2) in patients with breast cancer.
Methods: PET images at 1, 24, and 48 hours after injection of 296 MBq of 64Cu-NOTA-Trastuzumab were obtained on seven patients with breast cancer. The maximum standardized uptake value (SUVmax) was evaluated in the tumors, including the primary tumor and metastatic lesions. The mean SUVmax (SUVmean) was evaluated in the normal organs including the blood pool, liver, kidney, muscle, spleen, bladder, lung, and bone. In addition, the internal radiation dosimetry was calculated using the OLINDA/EXM software. Safety was assessed by gathering the feedback of adverse reactions and safety-related issues within 1 month after 64Cu-NOTA-Trastuzumab administration.
Results: The overall values of SUVmean in each normal organ decreased with time on 64Cu-NOTA-Trastuzumab PET images. The average values of SUVmean of the liver were measured at 5.3 ± 0.7, 4.8 ± 0.6, and 4.4 ± 0.5 on 1 hour, 24 hours, and 48 hours after injection. The average values of SUVmean of the blood were evaluated as 13.1 ± 0.9, 9.1 ± 1.2, and 7.1 ± 1.9 on 1 hour, 24 hours, and 48 hours after injection. The SUVmax of HER2-positive tumors showed relatively higher than that of HER2-negative tumors (8.6 ± 5.1 and 5.2 ± 2.8 on 48 hours after injection, respectively). Tumor to background ratios were calculated higher in the HER2-positive tumors than those of HER2-negative tumors. No adverse events related to 64Cu-NOTA-Trastuzumab were reported. The calculated effective dose with a 296 MBq injection of 64Cu-NOTA-Trastuzumab was 2.96 mSv. The highest absorbed dose was observed in the liver (0.076 mGy/MBq), followed by the spleen (0.063 mGy/MBq), kidney (0.044 mGy/MBq), and heart wall (0.044 mGy/MBq).
Conclusions: 64Cu-NOTA-Trastuzumab showed specific uptake at the HER2-expressing tumors. It suggests that 64Cu-NOTA-Trastuzumab can be a feasible monitoring tool for HER2 tumor status in the patients with breast cancer with safe.
Trial registration: CRIS, KCT0002790. Registered 02 February 2018, https://cris.nih.go.kr
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5