Radionuclide Delivery Strategies in Tumor Treatment: A Systematic Review

Round 1

Reviewer 1 Report

The manuscript of Giulia Poletto et al. is a review of the literature regarding delivery strategies of radionucleides for cancer treatment.

The manuscript is organized around three distinct strategies involving liposomes (a), avidin/biotin interactions (b) and molecular docking (c).

30 publishes articles are used for this review according to the filters applied during the selection, 16 on topic (a); 9 on topic (b); and 5 on topic (c).

These articles are deeply analysed and presented within the table 1 showing the reference, tracer disease and main outcomes.

Globally, the presented manuscript is well described and is reasonably well written.

This manuscript highlights some interesting considerations for the use of such strategies according to the specificity to the tumor cells.

I have nevertheless some comments for the improvement of this manuscript:

 (1) Pre-clinical and clinical studies should be analyzed separately since these strategies involve different scale and different endpoints

(2) Regarding the clinical studies, it is for me mandatory to ask the “clinical.gov” website in order to check all known studies. As an example, when asking this website for “cancer” and “radionuclide”, 326 clinical studies are found…(www.clinicaltrials.gov)

(3) The table 1s has to be modified to be readable

(4) The term “nanoparticle” is non-adapted for this manuscript, because it can be confusing with the use of “metallic nanoparticles” as radio-enhancer in radiotherapy

Considering all these comments, I recommend this manuscript for publication after major changes

Author Response

We are thankful to the Reviewer for his/her kind suggestions, please below the response to the queries, point by point.

The manuscript of Giulia Poletto et al. is a review of the literature regarding delivery strategies of radionucleides for cancer treatment.  The manuscript is organized around three distinct strategies involving liposomes (a), avidin/biotin interactions (b) and molecular docking (c). 30 publishes articles are used for this review according to the filters applied during the selection, 16 on topic (a); 9 on topic (b); and 5 on topic (c). These articles are deeply analysed and presented within the table 1 showing the reference, tracer disease and main outcomes. Globally, the presented manuscript is well described and is reasonably well written. This manuscript highlights some interesting considerations for the use of such strategies according to the specificity to the tumor cells.

 I have nevertheless some comments for the improvement of this manuscript:

Q1. Pre-clinical and clinical studies should be analyzed separately since these strategies involve different scale and different endpoints

R1. As suggested, specific sentences have been included to differentiate between clinical and preclinical studies. Moreover, also the Table 1 has been divided in Table 1a and Table 1b, respectively for preclinical and clinical studies.

Q2. Regarding the clinical studies, it is for me mandatory to ask the “clinical.gov” website in order to check all known studies. As an example, when asking this website for “cancer” and “radionuclide”, 326 clinical studies are found…(www.clinicaltrials.gov)

R2. A new Table (n=4) has been added with the available clinical trials.

Q3. The table 1s has to be modified to be readable

R3. The Table 1s has been modified.

Q4. The term “nanoparticle” is non-adapted for this manuscript, because it can be confusing with the use of “metallic nanoparticles” as radio-enhancer in radiotherapy

R4. The term nanoparticles have been replaced by liposomes, liposome vesicles, liposomal nanoparticles, as appropriate.

Considering all these comments, I recommend this manuscript for publication after major changes

Reviewer 2 Report

The review is generally good and I suggest it for publication after a revision. My comments are below:

1) It needs to address how to use the method to find a good solution to kill cancer resistant cells. Combination with photothermal therapy could be a good method, see papers like Nanomedicine (London), 2010, 5(8): 1161-1171

2) It needs to address how to solve the problem of hypoxia to enhance treatment, is it a good idea to combine with photodynamic therapy? see papers for more information: Journal of Nanoscience And Nanotechnology 2006, 6(4), 1159-1166;PNAS, 2019,116(34): 16823–16828; and  Scientific Reports, 2017, 7:9290 ; Signal Transduction and Targeted Therapy (Nature), 2020, 5:58 DOI: 10.1038/s41392-020-0156-4 and Bioactive Materials, 2021, 7:504-514

3) adding some figures or illustrations to make it more impressive 

Author Response

The authors are thankful to the Reviewer for his/her kind revisions and suggestions. Please below the response to your queries, point by point:

The review is generally good and I suggest it for publication after a revision. My comments are below:

Q5. It needs to address how to use the method to find a good solution to kill cancer resistant cells. Combination with photothermal therapy could be a good method, see papers like Nanomedicine (London), 2010, 5(8): 1161-1171.

R5. Some sentences have been added in the discussion section.

Q6. It needs to address how to solve the problem of hypoxia to enhance treatment, is it a good idea to combine with photodynamic therapy? see papers for more information: Journal of Nanoscience And Nanotechnology 2006, 6(4), 1159-1166;PNAS, 2019,116(34): 16823–16828; and  Scientific Reports, 2017, 7:9290 ; Signal Transduction and Targeted Therapy (Nature), 2020, 5:58 DOI: 10.1038/s41392-020-0156-4 and Bioactive Materials, 2021, 7:504-514

R6. Some sentences have been added in the discussion section.

Q7.  adding some figures or illustrations to make it more impressive 

Round 2

Reviewer 1 Report

The manuscript is now acceptable