Nanoceria as Safe Contrast Agents for X-ray CT Imaging

Round 1

Reviewer 1 Report

This short paper reports on the first attempt of using cerium oxide nanoparticles as contrast agents for computed tomography. The subject of the paper fits well the scope of Nanomaterials journal. The results presented are new and worth of being published.

Before acceptance, the following issues should be addressed:

1. Recently, several papers were published concerning the use of gadolinium-doped cerium oxide nanoparticles as contrast agents in magnetic resonance imaging. A comparative analysis of the possible use of ceria-assisted MRT and CT would be useful for the readers.

2. In the Introduction section of the manuscript, only few papers are considered concerning radioprotective properties of nano-ceria. Please provide a more comprehensive review of the state-of-the-art.

3. In the Materials and Methods section, some typos need to be corrected.

4. Please replace "hexahydrated" with "hexahydrate" (twice).

5. In the title of the paper as well as in the Conclusions section, high solubility of CeO2 NPs is mentioned. Actually, no solubility measurements were performed in this paper. Similarly, existing paper demonstrating extremely low solubility of nano-ceria are ignored (see e.g. doi 10.1021/acs.jpcc.6b05650). Moreover, ob day 7, no traces of cerium were detected in mouse organs or blood plasma that confirms low solubility of ceria preparation used in this paper. Please comment on this issue and make the necessary corrections.

Author Response

see document attached

Author Response File: Author Response.pdf

Reviewer 2 Report

I think that the authors have used various experiments to obtain clear data, but I think that the content of this article is a little difficult to read for researchers who are not in the same field as authors. I think it's better to include explanations of the technical terms as much as possible (or include references).

Line 1

It seems the template. You might not fill in this section which you should be filled in.

Please confirm whether it is “Tumor” or “Tumour” with the publisher.

I think it would be better to standardize the notation to either "h" or "hour".

I think it would be better to standardize the notation to either "d" or "day".

I think it would be better to standardize the notation to either "min" or "minute".

If you do not put a space between the % and the number, please use the same notation both in the text and in the supplementary materials.

I think the notation for the magnification rate is ×(multiplication) instead of "x(éks)".

If you want to write the notation of "in vivo" italicized, please make it consistent throughout this article.

Line 22 

in the removal of 　excessive → in the removal of excessive

There seems to be an extra space after the “of”.

Line 29 and 30

% of injected dose can be abbreviated as %ID. 

Line 33 and 34

It seems the template. You might not fill in this section which you should be filled in.

Line 78-79

Please explain what is meant by the "Z number" in this article where it first appears. It's hard to understand.

Line 112, 128, 222, 229, 232

CeO2NP → CeO₂NP

Line 190

36μg Ce → 36 μg Ce

Line 143

T^a　→　temperature ??

I'm not very familiar with it, but is this style of writing major in this field of study?

Line 251

50mM → 50 mM

It seems that the space between the unit and the number is not standardized, so please check if it is consistent for each unit.

<Table 1>

In table 1 column Ce of Kidney, strange space is there.

3.2± 0.2 →3.2±0.2

<Table 1 and Table S3>

What is the value of "2-2.5ml" in the Plasma (μg/mL) column?

<Figure 2>

It is difficult to understand which CT image the time notation in Figure 2 corresponds to, so please correct it.

<Table S2>

Please check the number of spaces between all numbers.

In supplemental information, it is easier to see if inserted one line is under the title of section 5, 6, 7 and 8.

In section 5, 

CeO2NP → CeO₂NP

In section 7

714 ± 36μg Ce → 714 ± 36 μg Ce

Why is the legend in Figure S7 italicized?

Please edit the legend of Figure S10 so that the figure and the legend are combined.

(Those are in the different pages.)

Author Response

see document attached

Author Response File: Author Response.pdf