Cyclic 68 Ga-Labeled Peptides for Specific Detection of Human Angiotensin-Converting Enzyme 2

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Abstract

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  1. SciScore for 10.1101/2020.12.15.412809: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementIACUC: Free gallium migrates to the solvent front (∼90 mm) and bound gallium remains at the origin (∼20 mm). μPET/CT imaging: All animal procedures were approved by the UCSF Institutional Animal Care and Use Committee, and all studies were performed in accordance with UCSF guidelines regarding animal housing, pain management, and euthanasia.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Experimental Models: Organisms/Strains
    SentencesResources
    Humanized ACE2 recombinant mice (B6.Cg-Tg(K18-ACE2)2Prlmn/J, 034860, Jackson Laboratory) were obtained from Jackson Labs, aged 6-10 weeks38–40.
    B6.Cg-Tg(K18-ACE2)2Prlmn/J
    suggested: RRID:IMSR_JAX:034860)
    Software and Algorithms
    SentencesResources
    All statistical analysis was performed using Microsoft Excel.
    Microsoft Excel
    suggested: (Microsoft Excel, RRID:SCR_016137)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).


    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    In other words, high background signal due to the normal excretion pathway of [68Ga]NOTA-PEP4 may represent a limitation of this method to detect ACE2 activity in the kidney. In the future, hACE2 expression-specific [68Ga]NOTA-PEP4 signals versus background excretion needs to be further clarified, perhaps using koACE2 animals50 in addition to the inhibitory studies described in this manuscript. The in vivo studies performed also reflect a limitation of most academic centers in the United States; specifically, few facilities have a biosafety level 3 (BSL-3) compatible μPET-CT imaging system. Future molecular imaging of live SARS-CoV-2 (a BSL-3 organism) and its host effects will therefore require collaborative work with those few centers able to accommodate these studies51. Given the history of ACE2 with respect to SARS-CoV (the 2003 SARS coronavirus) and ARDS, we expect that new ACE2-specific PET tools will be relevant beyond the current pandemic. We are partially motivated by data indicating that zoonotic infections especially coronavirus-related are on the rise52. The incidence of emerging and re-emerging zoonotic disease is increasing in many parts of the world, with animal viruses able to cross species barriers to infect humans; it appears likely that ACE2 will be relevant in future pandemics. Better understanding ACE2 suppression, and differential susceptibility to SARS-COV-2 will help us better treat COVID-19 and other diseases for which ACE2 plays a critical role.

    Results from TrialIdentifier: No clinical trial numbers were referenced.


    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.


    Results from JetFighter: Please consider improving the rainbow (“jet”) colormap(s) used on page 24. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.


    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.