Radiopharmaceuticals for Pancreatic Cancer: A Review of Current Approaches and Future Directions
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsReviewer summary: Authors review radiopharmaceuticals for use in pancreatic cancers. Overall, review is well written and accessible to readers without expertise in this domain and warrants publication. However, several issues should be addressed beforehand. The most important of these, in this reviewer's opinion, is decoupling the discussion of "pancreatic cancer" to PDAC and NETs which are the two main types that authors describe, though, not often clearly. In addition, would recommend highlighting the imaging agents as well given that in theranostics dev, the imaging agent often precedes dev of the therapeutic.
Page 1: specify histological type: neuroendocrone neoplasm versus adenocarcinoma because very different management paradigms and outcomes.
Page 2, line 50: radiopharmaceuticals have been used for therapy since their discovery and radioiodine use in thyroid ca has been used since the late 1930s/early 1940s
Page 2, line 61+: Not all RPT requires labeling bc they include radionuclide salts (Ra, Sm, Sr) that can localize to areas of bone turnover (eg metastases). Radioiodine naturally localizes to thryoid tissues and some cancer types. What authors are referring to here are actively targeted radiopharmaceuticals, that have a biomolecule with specificity to tumor or tumor microenvironment target, versus others that intrinsically localize to therapeutically beneficial sites (eg bone turnover, thyroid ca)
Page 2, Figure 2: define PRRT in legend
Page 6, line 234: Authors have already defined RPT earlier in manuscript
Page 6, line 241, use RaCl2 as well as xofigo
Page 8, line 263: superscript for 177Lu
Page 8, 290: need to separate GEP-NETs from PDAC throughout review
Page 10: used generic name too DOTATATE
Page 10: authors should highlight clinical study of a6b6 PET imaging agent
10.1158/1078-0432.CCR-18-2665
Author Response
Please see the attachment.
Author Response File: 
Author Response.pdf
Reviewer 2 Report
Comments and Suggestions for AuthorsCalistri and co-worker presented an updated review on Radio-pharmaceuticals for Pancreatic Cancer: A Review of Current Approaches and Future Directions, which require further improvement following below given major comments before considering for publication.
1. Suggested to correct this by adding comma "treatment, compared to conventional treatments". Line no. 4.
2. Suggested to enhance clarity of manuscript by clearly delineating sections, including a more structured introduction that outlines the scope and objectives of the review.
3. Suggested to include a broader range of recent studies to provide a comprehensive overview of advancements in radio-pharmaceuticals specifically targeting pancreatic cancer (includes incorporating findings from the latest clinical trials and preclinical studies).
4. Suggested to improve the clarity of figure 3, which is very blurred.
5. The review should detail the methodologies used in the studies discussed, particularly in terms of how radiopharmaceutical efficacy and safety were evaluated to strengthen the review's scientific rigor.
6. Furthermore, It is crucial to address the limitations of current radiopharmaceutical approaches, including potential side effects, challenges in specificity, and issues related to tumor heterogeneity.
7. Emphasize the clinical implications of the findings discussed. How can these advancements translate into practice for treating pancreatic cancer?
8. Moreover, authors suggested to possibly discuss how patient-specific factors (e.g., genetic profiles) could influence the effectiveness of radiopharmaceutical therapies, suggesting a move towards personalized medicine in pancreatic cancer treatment.
These comments aim to enhance the quality and impact of the review by ensuring it is comprehensive, clear, and relevant to both researchers and clinicians in the field of pancreatic cancer treatment.
Author Response
Please see attachment.
Author Response File: Author Response.pdf
Round 2
Reviewer 2 Report
Comments and Suggestions for AuthorsThe authors have reflected all the said suggestions and comments, which made the manuscript enhanced with improved readability; Thus, I suggest for further consideration with acceptance.
