Comparison of [68Ga]-FAPI PET/CT and [18F]-FDG PET/CT in Multiple Myeloma: Clinical Experience

Round 1

Reviewer 1 Report

Overall comments:
The authors present a clinical study towards the evaluation of [Ga-68]Ga-FAPI as a potential diagnostic tracer for staging and detection of multiple myeloma. The hypothesis and study design is logical and addresses a quick and potentially directly applicable solution towards the diagnosis and detection of bone cancers. The outcome of the study and discussion of the results is clear, however the description of the methodology and results is significantly lacking in detail and clarity. This is partly due to convoluted writing but also a lack of explanation on core elements of the experiment. 

With respect to writing, portions of the results section are difficult to follow. For example, the paragraph starting on line 183 is very difficult to follow. It appears to just be repeating the values from tables. It is not clear what the differences are between FDG and FAPI as it is written as the text goes back and forth between the two multiple times with many different comparisons.

Another key area that requires more explanation is how the staging system works with respect to CT scans. How are the CT scans used in conjunction with the serum assays of ß₂-microglobulin to generate a staging system, specifically?

Another area that requires more detail ins the methods section for image acquisition (What are the PET/CT acquisition parameters?) and radiochemistry. There are a few more specific comments below that also relate to this.

Finally there are a number of typos and formatting issues that need to be addressed, some of which are mentioned in the specific comments below.

Overall the work is of merit to publish and the authors are commended for their honest conclusions from the data. These types of studies which do not
contain the desired outcome openly are highly important and sorely needed to aid the development of improved methods in future studies. It would
strengthen the manuscript if the authors mentioned future opportunities and areas of future study, other than increased patient numbers. 

However, in its current state I cannot recommend the manuscript for review again after significant changes are made to the manuscript. 

Specific comments:
    ▪    The nomenclature for radioisotopes is is either with superscripted number before element (¹⁸F) or written after element with a dash between the element and the number (F-18). Formally the isotope should be included in the name as well in brackets preceding the tracer name ([¹⁸F]FDG or [F-18]FDG).This can be changed if desired through the use of an acronym if the authors prefer but it is highly recommend this is fixed throughout the manuscript.
    ▪    Multiple other places throughout document where superscripting and subscripting need to be used (eg. H2O).
    ▪    Space needed between “that” and “68Ga…” on line 77 and other places throughout document. Check spacing, especially between periods (“.”) and next sentence.
    ▪    Line 129: Acetonitrile is not commonly abbreviated to AcCN. Convention is typically MeCN or ACN. Formally all abbreviations need to be defined at their first use in a manuscript, but at the very least if an unconventional abbreviation is being used, they definitely need to be defined in the text. This line is one example of many which need to be fixed throughout the manuscript.
    ▪    What are the specific parameters used for PET/CT acquisitions. None are mentioned, only dosages and scan times. 
    ▪    Table 1 headings need to be spaced out more. Single words are spread out across multiple lines. Consider putting the table in landscape format across a single page, if possible. It is difficult to read as it is now.
    ▪    Table 2 is messy and large amounts of text make it difficult to read. Consider putting last two columns as footnotes. Also, this table is probably better for the supplementary information. Figure 1 is better for discussion in the manuscript.

Author Response

Dear reviewer, thank you for your valuable comments and suggestions. We have made the necessary arrangements and present it to you in the attachment. Please see the attachment.

Author Response File: Author Response.docx

Reviewer 2 Report

Thank you very much for selecting me as a reviewer for the manuscript entitled “Comparison of [68Ga]-FAPI PET/CT and [18F]-FDG PET/CT in Multiple Myeloma: Clinical Experience”.

I’ve read the manuscript with great interest, and I am really grateful to learn about the promising possibility of 68Ga-FAPI PET/CT as a complementary imaging to 18FDG PET/CT in some settings from this study.

My comments are shown below, and I hope my comments would be of help to make the study more sophisticated;

Through the entire manuscript, the authors use the abbreviations, for example, 68Ga-FAPI PET/CT, 18FDG PET/CT, SUV etc. Those meanings are taken for granted for specialists. However, authors are strongly encouraged to provide a list of those abbreviations, or to spell out the full forms at first mention.

The way of describing the statistics in the manuscript such as “median age, 58±10, 7 years” might not be appropriate. That should be “mean ± standard deviation (SD)” or “median, (interquartile range)”.

The additional detailed comments below in bold letters:

1. What are the main disadvantages with the passage?          I think the main disadvantages with the passage might be the strength of the evidence drawn from the study and the clinical usefulness.     2. Do you consider the topic original or relevant in the field, and if so, why?        I strongly consider that the topic of this study is original. Because the authors  address the promising possibility and importance of the imaging (68Ga-FAPI  PET/CT)  in assessing bone involvement in multiple myeloma (MM).    3. What does it add to the subject area compared with other published material?        The study adds the clinical usefulness of 68Ga-FAPI  PET/CT as an imaging modality in bone assessment in MM patients because the publications regarding 68Ga-FAPI PET/CT in bone assessment in MM patients are scarce.    4. What specific improvements could the authors consider regarding the methodology?       The methodology is well planned and structured mainly because of its prospective nature. I suppose this is a big if, but, if the number of patients enrolled in the study had been larger,  the evidence drawn from the study would have been stronger. But I have to add that I, as a reviewer, am not a specialist of statistics and that I am afraid I am not an appropriate person to suggest the appropriate number of cases which should have been enrolled.    5. Are the conclusions consistent with the evidence and arguments presented and do they address the main question posed?        The conclusions are consistent with the results presented. The authors well address the promising possibility of 68Ga-FAPI PET/CT by comparison.    6. Are the references appropriate?       All of the references cited in the manuscript are appropriate.    7. Please include any additional comments on the tables and figures.       The tables and figures are all well described and understandable. 

Author Response

Dear reviewer, thank you for your valuable comments and suggestions. We have made the necessary arrangements and present it to you in the attachment. Please see the attachment.

Author Response File: Author Response.docx