Research and Development for Cyclotron Production of 225Ac from 226Ra—The Challenges in a Country Lacking Natural Resources for Medical Applications
Round 1
Reviewer 1 Report
The manuscript describes the development of cyclotron production of Ac-225 from Ra-226 mainly in Japan. The situation abroad is also discussed. This is not a scientific article in the strict sense. It is more or less an essay. In this respect, the manuscript cannot be evaluated according to the usual criteria such as working hypothesis, conclusions, experimental work, methodology. Nevertheless, the paper contains some information on the international status of Ac-225 production that is interesting for insiders.
Author Response
Answer:　Thank you for your positive comments. We believe that this manuscript contains important and interesting information on the Japanese and the international status of Ac-225 production. As you said, this manuscript is not in the form of a scientific original paper, but is similar to a review article. However, this manuscript is a leading manuscript of the special issue of your journal named “Production of Ac-255 for Targeted Alpha Therapy” and I, Tatsuya Higashi, is one of the two Guest Editors of this special issue. Therefore, we believe that our manuscript is completely suitable as a review article to decorate the special issue.
Reviewer 2 Report
This manuscript summarized the past effort in Japan to secure the supply of the alpha-particle-emitting radionuclide actinium-225 and how its development fit into the global effort. It also covered the current situation and the probable cause of it in different parts of the world, and offered possible solutions to the current situation as recommendations. The information reported in this manuscript is of high importance and interests to readers in the radiopharmaceutical sciences, across academia and industry. I recommend this manuscript to be published with minor revisions. Here are the comments:
1. Line 38, please refer to targeted alpha therapy;
2. Line 39, please correct alpha-ray; I suggest using alpha particle emitting radionuclide therapy;
3. Line 45, "complete cure" be changed to remarkable regression, as complete cure would not be a clinically accurate description;
4. Line 47: alpha-particle-emitting radionuclide therapy;
5. Line 141: same as Line 47;
6. Line 240: please cite the sources of the number 33 GBq;
7. Line 248: please cite the sources of the number 1850 GBq;
8. Line 296: please use uniform unit Bq for describing radioactivity, and please make this correction throughout the manuscript;
9. Line 325: please use uniform font sizes;
10. Please double check table 1 and table 2 to ensure the complete list of activities.
Author Response
This manuscript summarized the past effort in Japan to secure the supply of the alpha-particle-emitting radionuclide actinium-225 and how its development fit into the global effort. It also covered the current situation and the probable cause of it in different parts of the world, and offered possible solutions to the current situation as recommendations. The information reported in this manuscript is of high importance and interests to readers in the radiopharmaceutical sciences, across academia and industry. I recommend this manuscript to be published with minor revisions. Here are the comments:
Answer:　Thank you for your valuable comments. I would like to answer your comments and questions, as follows.
- Line 38, please refer to targeted alpha therapy;
Answer:　Thank you for your comment. The part you pointed out has been corrected and I have added ref #1 (JNM Radchenko et al.; this ref was #3 before my modification.) here.
- Line 39, please correct alpha-ray; I suggest using alpha particle emitting radionuclide therapy;
Answer:　Thank you for your comment. The part you pointed out has been corrected.
- Line 45, "complete cure" be changed to remarkable regression, as complete cure would not be a clinically accurate description;
Answer:　Thank you for your comment. The part you pointed out has been corrected as complete remission (CR).
- Line 47: alpha-particle-emitting radionuclide therapy;
Answer:　Thank you for your comment. The part you pointed out has been corrected.
- Line 141: same as Line 47;
Answer:　Thank you for your comment. I deleted the word “alpha-emitter” and modified the sentence as follows;
On the other hand, QST has set itself apart from other domestic research institutes by conducting full-scale research on the production of 225Ac as well as 211At.
- Line 240: please cite the sources of the number 33 GBq;
Answer:　Thank you for your comment. I would like to add a reference of JNM 2018 paper written by Dr. Sophie Poty.
- Line 248: please cite the sources of the number 1850 GBq;
Answer:　Thank you for your comment. I would like to add a reference as follows:
https://science.osti.gov/Isotope-Research-Development-and-Production/Resources/Workshops/2008-Workshop-on-The-Nations-Needs-for-Isotopes-Present-and-Future
- Line 296: please use uniform unit Bq for describing radioactivity, and please make this correction throughout the manuscript;
Answer:　Thank you for your comment and I am sorry for my inappropriate terminology. All the parts you pointed out have been corrected.
- Line 325: please use uniform font sizes;
Answer:　Thank you for your comment. I found two points in my article and these have been corrected.
- Please double check table 1 and table 2 to ensure the complete list of activities.
Answer:　Thank you for your comment. I have added the two tables and I confirmed that there were no mistakes.
Reviewer 3 Report
This is an interesting and timely review describing the past, present and future directions of worldwide 225Ac production with a particular focus on the supply issues faced by Japanese researchers and industry.
A couple of minor comments that needed to be addressed before the manuscript is ready for publication:
Line 122 and line 127 – The radiopharmaceutical nomenclature should follow the rules outlined in Nucl. Med. Biol. 55, 2017, Pages v-xi.
Line 135 – What other countries are developing 211At? Please provide examples and references. How will the increasing focus on 225Ac affect 211Ac development and use in Japan?
Line 152 and throughout the manuscript – the phrase ‘resource poor’ is over-used.
Section 4 – more sub-headings are required to make this section easier to read and follow.
Where is Table 1, Table 2 and Figure 1? I couldn’t find them in the manuscript and therefore cannot comment on their suitability.
Throughout the manuscript the use of both Bq and Ci should be avoided. Can the authors stick with Bq?
Line 369 – Which isotope of Th is being referred to?
The references contain a lot of links to websites and press releases. It is particularly difficult for non-Japanese audiences because many are in Japanese. Are there more peer-reviewed articles that could be used? Reference 58 refers to a ‘New article’- please update.
Author Response
This is an interesting and timely review describing the past, present and future directions of worldwide 225Ac production with a particular focus on the supply issues faced by Japanese researchers and industry.
Answer:　Thank you for your valuable comments. I would like to answer your comments and questions, as follows.
A couple of minor comments that needed to be addressed before the manuscript is ready for publication:
1/ Line 122 and line 127 – The radiopharmaceutical nomenclature should follow the rules outlined in Nucl. Med. Biol. 55, 2017, Pages v-xi.
Answer:　Thank you for your comment. The part you pointed out has been corrected.
Line 135 – What other countries are developing 211At? Please provide examples and references. How will the increasing focus on 225Ac affect 211Ac development and use in Japan?
Answer:　Thank you for your comment. I have added ref #1 (JNM Radchenko et al.; this ref was #3 before my modification.) here. I have modified the sentence as follows;
“In general, the physical half-life of 211At is relatively short at 7.2 hours, which is inconvenient for commercial supply and logistics, so it is not currently regarded as the highest priority for the future development of TRT/TAT development worldwide, and only a few countries, such as, the United States, Sweden, Denmark, and Canada, are under development (1). ”
Line 152 and throughout the manuscript – the phrase ‘resource poor’ is over-used.
Answer:　Thank you for your comment. I deleted the word in one sentence in Line 541-542, as follows:
In summary, the diversification of domestic 225Ac production capacity is good news for Japan, but the fact that all 225Ac production platforms need 226Ra as the target indicates that securing a good supply of 226Ra is a very important issue for Japan.
Section 4 – more sub-headings are required to make this section easier to read and follow.
Answer:　Thank you for your comment. The parts you pointed out have been corrected.
Where is Table 1, Table 2 and Figure 1? I couldn’t find them in the manuscript and therefore cannot comment on their suitability.
Answer:　I am sorry for your inconvenience, probably due to some malfunction at the time of submission or editing of my manuscript. I have added the two tables and Figure1, and I confirmed that there were no mistakes.
Throughout the manuscript the use of both Bq and Ci should be avoided. Can the authors stick with Bq?
Answer:　Thank you for your comment. All the parts you pointed out have been corrected.
Line 369 – Which isotope of Th is being referred to?
Answer:　That is Th-232. I have modified this part.
The references contain a lot of links to websites and press releases. It is particularly difficult for non-Japanese audiences because many are in Japanese. Are there more peer-reviewed articles that could be used? Reference 58 refers to a ‘New article’- please update.
Answer:　Thank you for your comment. I really agree with you and I am sorry for your inconvenience at your reviewing work. I have already tried to find out appropriate English references but in fail. So, there is no article written in English you suggested as peer-reviewed one. Therefore, I would like to make this paper as the one you suggested as the appropriate peer-reviewed article.
Concerning ref # 58, at the time of my submission of my article, I have already asked the Editorial Office of your journal to add the paper written by Prof. Takaki, my collaborating Guest Editors of this special issue “Production of Ac-255 for Targeted Alpha Therapy”, but I am sorry to know that it seems that no information was brought to you. At that time, the Editorial Office of your journal told me that the name of the paper of Prof Takaki is as follows;
Iwahashi D, Kawamoto K, Sasaki Y, Takaki N. Neutronic study on production of Ac-225 for cancer therapy by (n,2n) reaction of Ra-226 or Th-230 using fast reactor Joyo. Processes, Under processing.
I would like to add this paper in ref #59.
