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Review
. 2019 Sep 4;11(508):eaax8251.
doi: 10.1126/scitranslmed.aax8251.

Molecular imaging of bacterial infections: Overcoming the barriers to clinical translation

Alvaro A Ordonez  1   2   3 , Mark A Sellmyer  4   5 , Gayatri Gowrishankar  6 , Camilo A Ruiz-Bedoya  1   2   3 , Elizabeth W Tucker  1   3   7   8 , Christopher J Palestro  9 , Dima A Hammoud  10 , Sanjay K Jain  11   2   3   12
Affiliations
Review

Molecular imaging of bacterial infections: Overcoming the barriers to clinical translation

Alvaro A Ordonez et al. Sci Transl Med. .

Abstract

Clinical diagnostic tools requiring direct sample testing cannot be applied to infections deep within the body, and clinically available imaging tools lack specificity. New approaches are needed for early diagnosis and monitoring of bacterial infections and rapid detection of drug-resistant organisms. Molecular imaging allows for longitudinal, noninvasive assessments and can provide key information about infectious processes deep within the body.

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Conflict of interest statement

Competing interests: S.K.J. received consulting fees from Mediso Medical Imaging Systems Ltd., unrelated to this work. A.A.O. and S.K.J. are co-inventors on pending patent US20150250906A1 on bacteria-specific labeled substrates as imaging biomarkers, filed by Johns Hopkins University. M.A.S. is a co-inventor on pending patent US20180104365A1 filed by the University of Pennsylvania on radiotracer derivatives of TMP for medical imaging and is a cofounder of Vellum Biosciences. G.G. is an inventor on US20160303259A1 and US20140314671, both of which are held by Stanford University and cover the 6-18F-fluoromaltose and 6″−18F-fluoromaltotriose PET tracers.

Figures

Fig. 1.
Fig. 1.. Global burden of infections.
(A) Global years of life lost due to diseases in 2017. (B) The top 18 antimicrobial drug–resistant threats compiled by the U.S. Centers for Disease Control and Prevention (CDC). Extended spectrum β-lactamase (ESBL) producing Enterobacteriaceae. (C) Annual global mortality projected for 2050. Adapted from the Global Burden of Disease Study (1), U.S. CDC (5) and O’Neill (6).
Fig. 2.
Fig. 2.. Comparison of traditional methods with molecular imaging.
Traditional diagnostic tools for infectious diseases depend on available clinical samples (blood and urine), with most deep-seated infections requiring surgical biopsies to establish a definitive diagnosis. Microbiological or molecular assays are performed on surgical biopsies; however, some organisms are difficult to cultivate ex vivo or need a long time to grow, which can limit or delay the diagnosis. Clinically available imaging tests [radiographs, ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI)] incorporated into the diagnostic workup are not specific for infection and reflect a combination of infection and the host inflammatory response. Molecular imaging can provide spatial and temporal information about infections and can monitor response to treatment. An example of positron emission tomography (PET)/CT imaging in mice using a bacteria-specific imaging agent, 2-18F-fluorodeoxysorbitol, is shown. The radiopharmaceutical accumulates in the infected muscle but not in the inflamed sterile muscle. Repeat imaging before and after antibiotic treatment can also provide rapid efficacy monitoring, demonstrating a PET signal proportionate to the bacterial burden. Adapted from Weinstein et al. (23).
Fig. 3.
Fig. 3.. Bacteria-specific imaging tools.
PET and other molecular imaging modalities can detect the accumulation of an imaging agent at diseased sites with very high sensitivity. Fundamental biochemical differences between bacterial and human (mammalian) metabolism offer distinct targeting opportunities for developing bacteria-specific imaging tools. The relative volume of a single bacterium and the target density of the proposed agent need to be considered to achieve adequate target-to-background contrast.
Fig. 4.
Fig. 4.. Molecular imaging to complement traditional tools in select patient populations.
Molecular imaging can be useful for several patient populations and could be easily incorporated into the current clinical workflows to address the relevant clinical question(s) at hand.
See this image and copyright information in PMC

References

    1. GBD 2017 Causes of Death Collaborators, Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980–2017: A systematic analysis for the Global Burden of Disease Study 2017. Lancet 392, 1736–1788 (2018). - PMC - PubMed
    1. Dye C, After 2015: Infectious diseases in a new era of health and development. Philos. Trans. R. Soc. London B Biol. Sci 369, 20130426 (2014). - PMC - PubMed
    1. World Health Organization, Global Tuberculosis Report 2018 (World Health Organization, 2018); www.who.int/gho/tb/en/.
    1. Magill SS, Edwards JR, Bamberg W, Beldavs ZG, Dumyati G, Kainer MA, Lynfield R, Maloney M, McAllister-Hollod L, Nadle J, Ray SM, Thompson DL, Wilson LE, Fridkin SK; Emerging Infections Program Healthcare-Associated Infections; Antimicrobial Use Prevalence Survey Team, Multistate point-prevalence survey of health care–associated infections. N. Engl. J. Med 370, 1198–1208 (2014). - PMC - PubMed
    1. Centers for Disease Control and Prevention, The Direct Medical Costs of Healthcare-Associated Infections in U.S. Hospitals and the Benefits of Prevention (Centers for Disease Control and Prevention, 2009); www.cdc.gov/hai/pdfs/hai/scott_costpaper.pdf.

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