Imaging Inflammation in Atherosclerosis with CXCR4-Directed [68Ga]PentixaFor PET/MRI—Compared with [18F]FDG PET/MRI
, Wolfgang Wadsak 1,4, Alexander R. Haug 1, Marius Mayerhöfer 5,6, Markus Raderer 7, Xiaoli Zhang 3, Jingle Li 1, Marcus Hacker 1 and Xiang Li 1,3,*Round 1
Reviewer 1 Report
The file containing comments is attached.
Comments for author File: 
Comments.docx
Author Response
Reviewer 1
Comments 1: The present study majorly lacks in highlighting the novelty of their work over their previously published work. However, the present work can be accepted once authors provide and elaborate a bit more about the new findings in their work compared to their older study (Li X et al. Eur J Nucl Med Mol Imaging 2019,46,1616‐1625) in the manuscript (Discussion section).
Response: Thank you. In discussion section particularly, page 7, line 176-181. In this study we analyzed much more active lesions and confirmed that [68Ga]PentixaFor PET/MRI could identify more active arterial segments as compared to [18F]FDG. Patients with high-risk cardiovascular factors illustrated higher [68Ga]PentixaFor activity in PET/MR imaging. What’s more, we firstly analyzed the relationship of [68Ga]PentixaFor uptake in active arterial segments and cardiac uptake. This finding indicated a symmetric CXCR4 immune-signaling along with the cardiovascular system. These results highlight the novelty work of this study over previously published work.
(page 7, line 203-208)
Comments 2: In results section, for all active lesions, SUVmax does not appear to be significantly different for [18F]-FDG and 68Ga-Pentixafor, kindly review.
Response: Thanks. In results section, based on lesion analysis, SUVmax and TBR of all active lesions, [68Ga]PentixaFor displayed a significantly higher value than [18F]FDG (SUVmax: 2.88 ± 0.64 versus 2.36 ± 0.36; P < 0.001; TBR:1.90 ± 0.36 versus 1.63 ± 0.29; P < 0.001) (Figure 3). And patient-based analysis, the mean SUVmax (2.84 ± 0.82 versus 1.85 ± 0.30; P < 0.001) and mean TBR (1.85 ± 0.20 versus 1.42 ± 0.19; P < 0.001) of [68Ga]PentixaFor was also significantly higher than that of [18F]FDG. But as far as risk stratification analysis, SUVmax does not appear to be significantly different from [18F]-FDG and [68Ga]-PentixaFor but TBR was different between the high-risk group and low-risk group of [68Ga]PentixaFor. TBR value adjusted by blood background and was more correct in risk stratification research based on patient analysis than SUVmax and descripted in result section.
(page 4, line 158-160; page 6, line 172-175)
Comments 3: Authors can kindly re-read the manuscript and modify the sentences so as to offer better clarification to the readers, some of those have been pointed out and are mentioned below in the tabular format.
Response: Thank you! The writing errors had been revised one by one in manuscript and marked in red.
Reviewer 2 Report
Dear authors,
I think that your study is interesting and with promising results. The manuscript is well written down and easy to read. The methods and the discussion are sufficiently argued. I appreciated the clarification of the limitations.
I suggest the authors to consider and to specify the possible cost-effectiveness ot the use of 68Ga-Pentixafor PET/MRI and to more investigate the eventual clinical impact of this method for everyday use. Furthermore, even if it is a comparison of two tracers to make one stand out, I would still better specify the well-known merits of the 18F-FDG. in addition I think that the correlation with the cardiac uptake has to be more clarified because of the heterogeneous cardiac uptake with 18F-FDG.
Well down, best wishes
Author Response
Comments 1: I suggest the authors to consider and to specify the possible cost-effectiveness ot the use of 68Ga-Pentixafor PET/MRI and to more investigate the eventual clinical impact of this method for everyday use. Furthermore, even if it is a comparison of two tracers to make one stand out, I would still better specify the well-known merits of the 18F-FDG. in addition I think that the correlation with the cardiac uptake has to be more clarified because of the heterogeneous cardiac uptake with 18F-FDG.
Response: Thank you very much. I agree with you. Actually, [68Ga]PentixaFor PET/MRI was not much expensive than [18F]FDG PET/MRI. But it could indicate the valuable information on inflammation, so [68Ga]PentixaFor PET/MRI has good cost-effectiveness in some special clinical practice when the diagnosis of vulnerable plaque is essential for therapy strategy for the patients. We added the contents of cost-effectiveness on discussion section as well as clarified the correlation with cardiac uptake in discussion section.
(page 8, line 282-284)
Reviewer 3 Report
Authors carried out interesting and voluble research on CXCR4 directed Atherosclerosis imaging using 68GA-Pentixafor and 18F-FDG by PET/MRI. few comments and typo mistakes as pointed out below
-Title of figure 1 and 2 seems same, author has to rewrite the titles in detail so the readers can easily follow the results from figure.
-Page 4, line 143-144, “positive detection….(Figures 2),(Figure 2), or positive…only”. The sentence needs to revise as “Individually positive detection of 68Ga-Pentixafor and 18F-FDG uptake results depicted in figure 2.”
- A interesting review article on 18F-FDG by O. Prante et al.,Pharamceuticals, 2021, 14, 1175. need to cite for support the introduction section particularly, page 2, line 52-53.
Author Response
Comments 1: -Title of figure 1 and 2 seems same, author has to rewrite the titles in detail so the readers can easily follow the results from figure.
-Page 4, line 143-144, “positive detection….(Figures 2),(Figure 2), or positive…only”. The sentence needs to revise as “Individually positive detection of 68Ga-Pentixafor and 18F-FDG uptake results depicted in figure 2.”
- A interesting review article on 18F-FDG by O. Prante et al.,Pharamceuticals, 2021, 14, 1175. need to cite for support the introduction section particularly, page 2, line 52-53.
Response: Thank you very much. I had revised the title of figure 1. And rewrite the sentence as “Individually positive detection of [68Ga]PentixaFor and [18F]FDG uptake results depicted in figure 2” in page 4, line 152-154 marked in red. I also added the interesting review article on 18F-FDG by O.Prante et al to support the introduction section.
Author Response File: Author Response.docx
