Radiotracers for in situ infection imaging: Experimental considerations for in vitro microbial uptake of gallium-68-labeled siderophores

Asma Akter; Maggie Cooper; Afnan Darwesh; Robert Hider; Philip Blower; Nicholas M. Price; Oliver Lyons; Silke Schelenz; Varun Mehra; Vincenzo Abbate

doi:10.1016/j.diagmicrobio.2024.116522

Radiotracers for in situ infection imaging: Experimental considerations for in vitro microbial uptake of gallium-68-labeled siderophores

Asma Akter, Maggie Cooper, Afnan Darwesh, Robert Hider, Philip Blower, Nicholas M. Price, Oliver Lyons, Silke Schelenz, Varun Mehra, Vincenzo Abbate^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

In vitro screening of gallium-68(⁶⁸Ga)-siderophores in pathogens relevant to infections is valuable for determining species specificity, their effect on cell viability, and potential clinical applications. As the recognition and internalization of siderophores relies on the presence of receptor- and/or siderophore-binding proteins, the level of uptake can vary between species. Here, we report in vitro uptake validation in Escherichia coli with its native siderophore, enterobactin (ENT) ([⁶⁸Ga]Ga-ENT), considering different experimental factors. Compared with other reporting methods of uptake, ‘% Added dose/109 CFU/mL (% AD/10⁹ CFU/mL),’ considering the total viable count, showed a better comparison among microbial species. Later, in vitro screening with [⁶⁸Ga]Ga-desferrioxamine B (DFO-B) showed high uptake by Staphylococcus aureus and S. epidermidis; moderate uptake by Pseudomonas aeruginosa; poor uptake by E. coli, Candida albicans, and Aspergillus fumigatus; and no uptake by Enterococcus faecalis and C. glabrata. Except for S. epidermidis, [⁶⁸Ga]Ga-DFO-B did not reduce the cell viability.

Original language	English
Article number	116522
Journal	Diagnostic Microbiology and Infectious Disease
Volume	110
Issue number	4
DOIs	https://doi.org/10.1016/j.diagmicrobio.2024.116522
Publication status	Published - 7 Sept 2024

Keywords

Diagnostics
PET tracers
DFO-B
Infection imaging
68Ga-siderophores
Uptake method

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Akter, A., Cooper, M., Darwesh, A., Hider, R., Blower, P., Price, N. M., Lyons, O., Schelenz, S., Mehra, V., & Abbate, V. (2024). Radiotracers for in situ infection imaging: Experimental considerations for in vitro microbial uptake of gallium-68-labeled siderophores. Diagnostic Microbiology and Infectious Disease, 110(4), Article 116522. https://doi.org/10.1016/j.diagmicrobio.2024.116522

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title = "Radiotracers for in situ infection imaging: Experimental considerations for in vitro microbial uptake of gallium-68-labeled siderophores",

abstract = "In vitro screening of gallium-68(68Ga)-siderophores in pathogens relevant to infections is valuable for determining species specificity, their effect on cell viability, and potential clinical applications. As the recognition and internalization of siderophores relies on the presence of receptor- and/or siderophore-binding proteins, the level of uptake can vary between species. Here, we report in vitro uptake validation in Escherichia coli with its native siderophore, enterobactin (ENT) ([68Ga]Ga-ENT), considering different experimental factors. Compared with other reporting methods of uptake, {\textquoteleft}% Added dose/109 CFU/mL (% AD/109 CFU/mL),{\textquoteright} considering the total viable count, showed a better comparison among microbial species. Later, in vitro screening with [68Ga]Ga-desferrioxamine B (DFO-B) showed high uptake by Staphylococcus aureus and S. epidermidis; moderate uptake by Pseudomonas aeruginosa; poor uptake by E. coli, Candida albicans, and Aspergillus fumigatus; and no uptake by Enterococcus faecalis and C. glabrata. Except for S. epidermidis, [68Ga]Ga-DFO-B did not reduce the cell viability.",

keywords = "Diagnostics, PET tracers, DFO-B, Infection imaging, 68Ga-siderophores, Uptake method",

author = "Asma Akter and Maggie Cooper and Afnan Darwesh and Robert Hider and Philip Blower and Price, {Nicholas M.} and Oliver Lyons and Silke Schelenz and Varun Mehra and Vincenzo Abbate",

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doi = "10.1016/j.diagmicrobio.2024.116522",

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Akter, A , Cooper, M , Darwesh, A , Hider, R , Blower, P, Price, NM, Lyons, O, Schelenz, S, Mehra, V & Abbate, V 2024, 'Radiotracers for in situ infection imaging: Experimental considerations for in vitro microbial uptake of gallium-68-labeled siderophores', Diagnostic Microbiology and Infectious Disease, vol. 110, no. 4, 116522. https://doi.org/10.1016/j.diagmicrobio.2024.116522

TY - JOUR

T1 - Radiotracers for in situ infection imaging: Experimental considerations for in vitro microbial uptake of gallium-68-labeled siderophores

AU - Akter, Asma

AU - Cooper, Maggie

AU - Darwesh, Afnan

AU - Hider, Robert

AU - Blower, Philip

AU - Price, Nicholas M.

AU - Lyons, Oliver

AU - Schelenz, Silke

AU - Mehra, Varun

AU - Abbate, Vincenzo

PY - 2024/9/7

Y1 - 2024/9/7

N2 - In vitro screening of gallium-68(68Ga)-siderophores in pathogens relevant to infections is valuable for determining species specificity, their effect on cell viability, and potential clinical applications. As the recognition and internalization of siderophores relies on the presence of receptor- and/or siderophore-binding proteins, the level of uptake can vary between species. Here, we report in vitro uptake validation in Escherichia coli with its native siderophore, enterobactin (ENT) ([68Ga]Ga-ENT), considering different experimental factors. Compared with other reporting methods of uptake, ‘% Added dose/109 CFU/mL (% AD/109 CFU/mL),’ considering the total viable count, showed a better comparison among microbial species. Later, in vitro screening with [68Ga]Ga-desferrioxamine B (DFO-B) showed high uptake by Staphylococcus aureus and S. epidermidis; moderate uptake by Pseudomonas aeruginosa; poor uptake by E. coli, Candida albicans, and Aspergillus fumigatus; and no uptake by Enterococcus faecalis and C. glabrata. Except for S. epidermidis, [68Ga]Ga-DFO-B did not reduce the cell viability.

AB - In vitro screening of gallium-68(68Ga)-siderophores in pathogens relevant to infections is valuable for determining species specificity, their effect on cell viability, and potential clinical applications. As the recognition and internalization of siderophores relies on the presence of receptor- and/or siderophore-binding proteins, the level of uptake can vary between species. Here, we report in vitro uptake validation in Escherichia coli with its native siderophore, enterobactin (ENT) ([68Ga]Ga-ENT), considering different experimental factors. Compared with other reporting methods of uptake, ‘% Added dose/109 CFU/mL (% AD/109 CFU/mL),’ considering the total viable count, showed a better comparison among microbial species. Later, in vitro screening with [68Ga]Ga-desferrioxamine B (DFO-B) showed high uptake by Staphylococcus aureus and S. epidermidis; moderate uptake by Pseudomonas aeruginosa; poor uptake by E. coli, Candida albicans, and Aspergillus fumigatus; and no uptake by Enterococcus faecalis and C. glabrata. Except for S. epidermidis, [68Ga]Ga-DFO-B did not reduce the cell viability.

KW - Diagnostics

KW - PET tracers

KW - DFO-B

KW - Infection imaging

KW - 68Ga-siderophores

KW - Uptake method

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U2 - 10.1016/j.diagmicrobio.2024.116522

DO - 10.1016/j.diagmicrobio.2024.116522

M3 - Article

SN - 0732-8893

VL - 110

JO - Diagnostic Microbiology and Infectious Disease

JF - Diagnostic Microbiology and Infectious Disease

IS - 4

M1 - 116522

ER -

Radiotracers for in situ infection imaging: Experimental considerations for in vitro microbial uptake of gallium-68-labeled siderophores

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