We present a new family of contrast agents, based on targeting the maltodextrin transporter termed maltodextrin based imaging probes (MDPs), which are designed to image infections associated with implanted medical devices by fluorescent imaging. The chemical structure of an MDP is composed of maltodextrins conjugated to the positron emitting radioelement fluorine-18. MDPs have the potential to offer significant advantages over existing methods for imaging bacteria, such as FDG, as a result of their high specificity and sensitivity for bacteria. MDPs target the maltodextrin transport pathway and are internalized as a major source of glucose by bacteria. MDPs can therefore deliver millimolar concentrations of imaging probes into bacteria, making it possible to image low numbers of bacteria. MDPs also have high specificity for bacteria because mammalian cells do not express the maltodextrin transporter and thus cannot internalize contrast agents conjugated to maltose. Finally, MDPs are composed of glucose oligomers, which are hydrophilic and membrane impermeable. MDPs are therefore efficiently cleared from un-infected tissues in vivo, leading to low background in organs such as the heart and muscle, which should lead to high sensitivity imaging of implanted device infections. These unique properties allow MDPs to accurately image small numbers of bacteria in vivo. MDPs thus have the unique properties allow MDPs to accurately image small numbers of bacteria in vivo. MDPs thus have the potential to detect implant device infections at an early stage and enable their treatment before they are challenging to eradicate.

Public Health Relevance

We present a new family of contrast agents, based on targeting the maltodextrin transporter termed maltodextrin based imaging probes (MDPs), which are designed to image infections associated with implanted medical devices by fluorescent imaging. The chemical structure of an MDP is composed of maltodextrins conjugated to the positron emitting radioelement fluorine-18. MDPs have the potential to offer significant advantages over existing methods for imaging bacteria, such as FDG, as a result of their high specificity and sensitivity for bacteria. MDPs target the maltodextrin transport pathway and are internalized as a major source of glucose by bacteria. MDPs can therefore deliver millimolar concentrations of imaging probes into bacteria, making it possible to image low numbers of bacteria. MDPs also have high specificity for bacteria because mammalian cells do not express the maltodextrin transporter and thus cannot internalize contrast agents conjugated to maltose. Finally, MDPs are composed of glucose oligomers, which are hydrophilic and membrane impermeable. MDPs are therefore efficiently cleared from un-infected tissues in vivo, leading to low background in organs such as the heart and muscle, which should lead to high sensitivity imaging of implanted device infections. These unique properties allow MDPs to accurately image small numbers of bacteria in vivo. MDPs thus have the unique properties allow MDPs to accurately image small numbers of bacteria in vivo. MDPs thus have the potential to detect implant device infections at an early stage and enable their treatment before they are challenging to eradicate.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
Project #
1R43EB021862-01A1
Application #
9141215
Study Section
Special Emphasis Panel (ZRG1-IDM-V (12)B)
Program Officer
Sastre, Antonio
Project Start
2016-07-01
Project End
2017-01-31
Budget Start
2016-07-01
Budget End
2017-01-31
Support Year
1
Fiscal Year
2016
Total Cost
$225,000
Indirect Cost
Name
Microbial Imaging, LLC
Department
Type
DUNS #
079111976
City
Lithia Springs
State
GA
Country
United States
Zip Code
30122