Reviewer’s report
Title: 
68Ga-NOTA PET imaging for gastric emptying assessment in mice
Version: 
0 
Date: 
26 Jun 2020
Reviewer's report:
It is an interesting and novel study proposing the use of PET imaging for the
non-invasive evaluation of GE in mice, including a large study for the follow-up
of therapies in a constipation model. Nevertheless, although the authors
demonstrated the feasibility of the technique, the design of the study is unclear
and unstructured, including redundant information and many useless tests. 
Finally, the reading of the article is cumbersome and unclear and we highly
recommend a professional english-editing service for the improvement of the
revised paper.
Major changes:
The Introduction section has to be revised for including additional cites to papers
focused on the use of preclinical imaging for gastrointestinal tracking and
mention the advantages of PET with respect to scintigraphy.
The comparison between ROI-based method and PMOD is poorly described and
the need to do it is not understood.
Scintigraphy scans were included in this study but the results are only included
in the Supplementary Data. We recommend removing scintigraphy scans from
the paper.
The correlation study between TAC, GER, and T1/2, %ID/g etc is absurd as the
high linear correlation obtained is expected from the definition.
Can the authors evaluate the use of CT-images for quantify GE from this study?
Required minor changes:
Page 2, L51: The authors state GE evaluation is challenging in mice, is it also in
humans?
Page 3, L55-56: Why MRI is limited? specify more
Page 3, L56: Computed Tomography can be also considered as alternative. Some
works have been carried out but they are uncited:
Gomez-Lado et al. Gastrointestinal Tracking and Gastric Emptying of Coated
Capsules in Rats with or without Sedation Using CT imaging. Pharmaceutics
2020 12(1):81
Page 3, L64: " have the advantages of scintigraphy" which??
Page 3, L68: Some works are uncited, for example:
Goyanes et al. PET/CT imaging of 3D printed devices in the gastrointestinal tract
of rodents. Int J Pharm 2018 536(1):158-164 
Page 4, L93: ICR??
Page 6, L133. How the conscious animal was immobilized? 
Page 6, L145. Manual ROIs were 3D or 2D?
Page 6, L156. 
Which type of "manual correction" was applied?
Page 11, L260. Part of the parameters TAC, GER, and T1/2 of %ID/g etc are
redundant, it would be convenient a simplification of the results in this sense. 
Page 12, L287. The authors state that "ROIs could substitute the volume or total
activity calculated by PMOD to reflect the GE process." but the reasons why it is
interesting are unknown
Page 14, L320-335 Again, redundant information is presented here, please
simplify
Page 15, L352 Further analysis are required for including the statement: "PET
owns more superior quantification capability and image quality" 
Furthermore, this study is not a face-to-face comparison between scintigraphy
and PET, because clinical gammacamera is used instead of a dedicated scan for
rodents. 
Page 15, L355 The authors states that "%ID/g, GER, and T1/2 provides similar
information" & "had high correlations with each other" as a result of the work,
but it is completely expected from the definition.
Publons Reviewer Recognition
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Publons’ privacy policy 
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Yes
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
Yes
Does the work include the necessary controls?
If not, please specify which controls are required in your comments to the
authors.
Yes
Are the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
Yes
Are you able to assess any statistics in the manuscript or would you
recommend an additional statistical review?
If an additional statistical review is recommended, please specify what aspects
require further assessment in your comments to the editors.
I am able to assess the statistics
Quality of written English
Please indicate the quality of language in the manuscript:
Not suitable for publication unless extensively edited
Declaration of competing interests
Please complete a declaration of competing interests, considering the following
questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
I declare that I have no competing interests
Reviewer Publication Consent.
 I agree for my report to be made available
under an Open Access Creative Commons CC-BY License (
http://creativecommons.org/licenses/by/4.0
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the editorial
office before completing the review.
If you wish, you can include your name in your published report. Please note
you must decide whether to include your name at the start of the process and
confirm this decision whenever prompted. If you change your decision later, we
will not be able to publish your name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
Reviewer’s report
Title: 
68Ga-NOTA PET imaging for gastric emptying assessment in mice
Version: 
0 
Date: 
26 Jun 2020
Reviewer's report:
It is an interesting and novel study proposing the use of PET imaging for the
non-invasive evaluation of GE in mice, including a large study for the follow-up
of therapies in a constipation model. Nevertheless, although the authors
demonstrated the feasibility of the technique, the design of the study is unclear
and unstructured, including redundant information and many useless tests. 
Finally, the reading of the article is cumbersome and unclear and we highly
recommend a professional english-editing service for the improvement of the
revised paper.
Major changes:
The Introduction section has to be revised for including additional cites to papers
focused on the use of preclinical imaging for gastrointestinal tracking and
mention the advantages of PET with respect to scintigraphy.
The comparison between ROI-based method and PMOD is poorly described and
the need to do it is not understood.
Scintigraphy scans were included in this study but the results are only included
in the Supplementary Data. We recommend removing scintigraphy scans from
the paper.
The correlation study between TAC, GER, and T1/2, %ID/g etc is absurd as the
high linear correlation obtained is expected from the definition.
Can the authors evaluate the use of CT-images for quantify GE from this study?
Required minor changes:
Page 2, L51: The authors state GE evaluation is challenging in mice, is it also in
humans?
Page 3, L55-56: Why MRI is limited? specify more
Page 3, L56: Computed Tomography can be also considered as alternative. Some
works have been carried out but they are uncited:
Gomez-Lado et al. Gastrointestinal Tracking and Gastric Emptying of Coated
Capsules in Rats with or without Sedation Using CT imaging. Pharmaceutics
2020 12(1):81
Page 3, L64: " have the advantages of scintigraphy" which??
Page 3, L68: Some works are uncited, for example:
Goyanes et al. PET/CT imaging of 3D printed devices in the gastrointestinal tract
of rodents. Int J Pharm 2018 536(1):158-164 
Page 4, L93: ICR??
Page 6, L133. How the conscious animal was immobilized? 
Page 6, L145. Manual ROIs were 3D or 2D?
Page 6, L156. 
Which type of "manual correction" was applied?
Page 11, L260. Part of the parameters TAC, GER, and T1/2 of %ID/g etc are
redundant, it would be convenient a simplification of the results in this sense. 
Page 12, L287. The authors state that "ROIs could substitute the volume or total
activity calculated by PMOD to reflect the GE process." but the reasons why it is
interesting are unknown
Page 14, L320-335 Again, redundant information is presented here, please
simplify
Page 15, L352 Further analysis are required for including the statement: "PET
owns more superior quantification capability and image quality" 
Furthermore, this study is not a face-to-face comparison between scintigraphy
and PET, because clinical gammacamera is used instead of a dedicated scan for
rodents. 
Page 15, L355 The authors states that "%ID/g, GER, and T1/2 provides similar
information" & "had high correlations with each other" as a result of the work,
but it is completely expected from the definition.
Publons Reviewer Recognition
. Springer Nature can send verification of this
review directly to Publons (a subsidiary of Clarivate Analytics). If you would
like to take advantage of this service, please click on the “Yes” option below.
Your name, email address, title of the reviewed manuscript, name of the journal,
and date of your review submission (the “Review Data”) will then be transmitted
to Publons upon publication of the manuscript. If you have already registered at
Publons, they will notify you of the receipt of this review and update your profile
as per your settings and their policy. If you are not registered with Publons, you
will receive an email from them asking you to register in order for them to be
able to recognize your review on your new profile page. Publons may use the
Review Data to generate derivative metadata for the benefit of Publons and you
as a reviewer, carefully considering the sensitivity of such information. For
example, Publons may verify your record as a reviewer by updating your profile
published on its webservice if you have registered for such service or help
editors to identify candidate reviewers. Please find the details of processing in
Publons’ privacy policy 
https://publons.com/about/terms
Yes
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
Yes
Does the work include the necessary controls?
If not, please specify which controls are required in your comments to the
authors.
Yes
Are the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
Yes
Are you able to assess any statistics in the manuscript or would you
recommend an additional statistical review?
If an additional statistical review is recommended, please specify what aspects
require further assessment in your comments to the editors.
I am able to assess the statistics
Quality of written English
Please indicate the quality of language in the manuscript:
Not suitable for publication unless extensively edited
Declaration of competing interests
Please complete a declaration of competing interests, considering the following
questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
I declare that I have no competing interests
Reviewer Publication Consent.
 I agree for my report to be made available
under an Open Access Creative Commons CC-BY License (
http://creativecommons.org/licenses/by/4.0
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the editorial
office before completing the review.
If you wish, you can include your name in your published report. Please note
you must decide whether to include your name at the start of the process and
confirm this decision whenever prompted. If you change your decision later, we
will not be able to publish your name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
Please review this paper.
user
Reviewer’s report
Title: 
68Ga-NOTA PET imaging for gastric emptying assessment in mice
Version: 
0 
Date: 
26 Jun 2020
Reviewer's report:
It is an interesting and novel study proposing the use of PET imaging for the
non-invasive evaluation of GE in mice, including a large study for the follow-up
of therapies in a constipation model. Nevertheless, although the authors
demonstrated the feasibility of the technique, the design of the study is unclear
and unstructured, including redundant information and many useless tests. 
Finally, the reading of the article is cumbersome and unclear and we highly
recommend a professional english-editing service for the improvement of the
revised paper.
Major changes:
The Introduction section has to be revised for including additional cites to papers
focused on the use of preclinical imaging for gastrointestinal tracking and
mention the advantages of PET with respect to scintigraphy.
The comparison between ROI-based method and PMOD is poorly described and
the need to do it is not understood.
Scintigraphy scans were included in this study but the results are only included
in the Supplementary Data. We recommend removing scintigraphy scans from
the paper.
The correlation study between TAC, GER, and T1/2, %ID/g etc is absurd as the
high linear correlation obtained is expected from the definition.
Can the authors evaluate the use of CT-images for quantify GE from this study?
Required minor changes:
Page 2, L51: The authors state GE evaluation is challenging in mice, is it also in
humans?
Page 3, L55-56: Why MRI is limited? specify more
Page 3, L56: Computed Tomography can be also considered as alternative. Some
works have been carried out but they are uncited:
Gomez-Lado et al. Gastrointestinal Tracking and Gastric Emptying of Coated
Capsules in Rats with or without Sedation Using CT imaging. Pharmaceutics
2020 12(1):81
Page 3, L64: " have the advantages of scintigraphy" which??
Page 3, L68: Some works are uncited, for example:
Goyanes et al. PET/CT imaging of 3D printed devices in the gastrointestinal tract
of rodents. Int J Pharm 2018 536(1):158-164 
Page 4, L93: ICR??
Page 6, L133. How the conscious animal was immobilized? 
Page 6, L145. Manual ROIs were 3D or 2D?
Page 6, L156. 
Which type of "manual correction" was applied?
Page 11, L260. Part of the parameters TAC, GER, and T1/2 of %ID/g etc are
redundant, it would be convenient a simplification of the results in this sense. 
Page 12, L287. The authors state that "ROIs could substitute the volume or total
activity calculated by PMOD to reflect the GE process." but the reasons why it is
interesting are unknown
Page 14, L320-335 Again, redundant information is presented here, please
simplify
Page 15, L352 Further analysis are required for including the statement: "PET
owns more superior quantification capability and image quality" 
Furthermore, this study is not a face-to-face comparison between scintigraphy
and PET, because clinical gammacamera is used instead of a dedicated scan for
rodents. 
Page 15, L355 The authors states that "%ID/g, GER, and T1/2 provides similar
information" & "had high correlations with each other" as a result of the work,
but it is completely expected from the definition.
Publons Reviewer Recognition
. Springer Nature can send verification of this
review directly to Publons (a subsidiary of Clarivate Analytics). If you would
like to take advantage of this service, please click on the “Yes” option below.
Your name, email address, title of the reviewed manuscript, name of the journal,
and date of your review submission (the “Review Data”) will then be transmitted
to Publons upon publication of the manuscript. If you have already registered at
Publons, they will notify you of the receipt of this review and update your profile
as per your settings and their policy. If you are not registered with Publons, you
will receive an email from them asking you to register in order for them to be
able to recognize your review on your new profile page. Publons may use the
Review Data to generate derivative metadata for the benefit of Publons and you
as a reviewer, carefully considering the sensitivity of such information. For
example, Publons may verify your record as a reviewer by updating your profile
published on its webservice if you have registered for such service or help
editors to identify candidate reviewers. Please find the details of processing in
Publons’ privacy policy 
https://publons.com/about/terms
Yes
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
Yes
Does the work include the necessary controls?
If not, please specify which controls are required in your comments to the
authors.
Yes
Are the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
Yes
Are you able to assess any statistics in the manuscript or would you
recommend an additional statistical review?
If an additional statistical review is recommended, please specify what aspects
require further assessment in your comments to the editors.
I am able to assess the statistics
Quality of written English
Please indicate the quality of language in the manuscript:
Not suitable for publication unless extensively edited
Declaration of competing interests
Please complete a declaration of competing interests, considering the following
questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
I declare that I have no competing interests
Reviewer Publication Consent.
 I agree for my report to be made available
under an Open Access Creative Commons CC-BY License (
http://creativecommons.org/licenses/by/4.0
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the editorial
office before completing the review.
If you wish, you can include your name in your published report. Please note
you must decide whether to include your name at the start of the process and
confirm this decision whenever prompted. If you change your decision later, we
will not be able to publish your name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
assistant