First Live-Experience Session with PET/CT Specimen Imager: A Pilot Analysis in Prostate Cancer and Neuroendocrine Tumor

Round 1

Reviewer 1 Report (Previous Reviewer 1)

The manuscript is significcant improved after the revisions provided by the authors.

Now it is acceptable for the publication.

Reviewer 2 Report (Previous Reviewer 2)

Article is much improved with less ambitious claims.  I think it is ok to publish as is

This manuscript is a resubmission of an earlier submission. The following is a list of the peer review reports and author responses from that submission.

Round 1

Reviewer 1 Report

Interesting preliminary paper focused on the utility of a dedicated PET/CT camera for the use in the surgery room. The topic is interesting, but the very limitation of the study is the small sample size (only 3 patients). However, the content would be improved and consider for the publication after some major revisions:

1) The description of PET/CT results should be included for each patient

2) The decision for using a limited dosage of radiopharmaceutical agent should be further discussed

3) more details about the specimen acquisition should be included (the size of the specimen and how much great it could be for the FOV of the dedicated PET camera

4) in patients with prostate cancer, data about mpMRI before surgery should be inclueded, in order to understand the additional value of this methodology to the clinical practice

5) Also, as point 4, data about baseline biopsy should be included (for undestanding the presence of multifocal disease)

6) Table 1, please add the increase in SUVmax from WB PET to dedicated PET, in term of pecentage

7) discussion should be enriched by similar data with other dedicated techniques (although mainly based on gamma cameras or dedicated gamma probes) and also to include a limitation section.

8) future perspectives should be also reported.

Reviewer 2 Report

“First Live-Experience Session with PET/CT Specimen Imager. A pilot analysis in Prostate Cancer and Neuroendocrine Tumor” is a pilot study to explore micro PET/CT in explanted tissues.  This is an interesting concept but the authors do not really demonstrate a good understanding of why PET/CT is performed nor how semiquantitative analysis is appropriately utilized.  The authors seem to imply that PSMA/DOTATOC uptake is as valid a tool as histopathology when it has been proven to not be the case with known false positive and false negative examples.    I would like to see a better correlation of PET uptake to reference organs/tissues as the SUV values they provide do not correlate in any appreciable way to the baseline PET/CT.  Additionally, if the goal of this is to help define margins, there must be a more complete thresholding analysis beyond SUVmax.  Visual estimation of extent of disease based on PET is not appropriate due to blooming artifact and the ability to manually adjust the visual intensity.

Specific comments below:

Section 2.2 (line 90).  What is the time duration between administration of either the 68Ga-PSMA-11 68Ga-DOTA-TOC and the PET/CT.  Also, what is the time duration between radiopharmaceutical administration and the micro-CT/PET?  The authors state that the acquisition were perform 2.5 and 4.5 h post injection, but these scans were on tissues were explanted earlier (line 111).  It is more important to understand what is the time between administration of the radiopharmaceutical and surgical resection.  Also, how do the SUV values compare on the different time points (Table 1).  I would assume that the SUV values do not change and it would be good to list the different times to show that point and to justify any change that is observed.  I would like to see additional metrics such as SUVmean based on the histopatholofical extent of disease so that one could start understanding the thresholding drop-off that the micro-PET.

Section 2.3 (line 99).  What was the amount of radiopharmeautical injected and uptake time of the baseline PET/CT and how does this compare to the day of surgery.  It would be helpful to be able to have a better comparison to the baseline scan.

Line 108.  With PET imaging, you can vary the visual scale intensity to whatever you would like so an image without semiquantitative thresholding metrics is of only moderate utility.  To correlate uptake, it would be useful to compare SUV values to physiological tissues such as salivary glands, liver, and blood and determine that disease should have uptake greater than liver for example.  The SUVmax values have limited utility as presented as there is no real correlate to the baseline PET scan. 

“High-resolution PET/CT images (Figure 1: C,G) 130 showed higher spatial resolution compared to conventional PET images, allowing a precise assessment of the surgical margins. (line 130)”  This sentence is confusing and misleading.  PSMA uptake is not a pathological equivalent and benign tissues can have PSMA uptake, with high false positivities in the prostate itself.  In no way should PSMA PET uptake be suggested as an equivocal metric for histopathological analysis.

What is the slice thickness of the samples which is important as presumable you are getting photons from the entirety of the sample thickness.  Does this PET imaging provide a 3D imagine that can be rotated and manipulated by the surgeon?  I think that is the only real utility because a 2D analysis is done by histology.