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Imaging InlC Secretion to Investigate Cellular Infection by the Bacterial Pathogen Listeria monocytogenes
Published on: September 19, 2013
Radiochemical Approaches to Imaging Bacterial Infections: Intracellular versus Extracellular Targets
Justin D Northrup1,2,3, Robert H Mach1, Mark A Sellmyer1,2
1Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Abstract:
The discovery of penicillin began the age of antibiotics, which was a turning point in human healthcare. However, to this day, microbial infections are still a concern throughout the world, and the rise of multidrug-resistant organisms is an increasing challenge. To combat this threat, diagnostic imaging tools could be used to verify the causative organism and curb inappropriate use of antimicrobial drugs. Nuclear imaging offers the sensitivity needed to detect small numbers of bacteria in situ. Among nuclear imaging tools, radiolabeled antibiotics traditionally have lacked the sensitivity or specificity necessary to diagnose bacterial infections accurately. One reason for the lack of success is that the antibiotics were often chelated to a radiometal. This was done without addressing the ramifications of how the radiolabeling would impact probe entry to the bacterial cell, or the mechanism of binding to an intracellular target. In this review, we approach bacterial infection imaging through the lens of bacterial specific molecular targets, their intracellular or extracellular location, and discuss radiochemistry strategies to guide future probe development.
Insights
Nuclear imaging can help diagnose bacterial infections and combat rising antimicrobial resistance. This review explores developing better radiolabeled probes by focusing on bacterial targets for improved diagnostic accuracy.
Area of Science:
- Medical Imaging
- Infectious Diseases
- Radiochemistry
Background:
- The advent of antibiotics revolutionized healthcare, but microbial infections and multidrug-resistant organisms remain significant global health challenges.
- Diagnostic imaging, particularly nuclear imaging, holds promise for detecting bacterial infections in situ and optimizing antimicrobial drug use.
- Current radiolabeled antibiotics often lack the necessary sensitivity and specificity due to issues with radiolabeling strategies impacting cellular uptake and target binding.
Purpose of the Study:
- To review the potential of nuclear imaging for diagnosing bacterial infections.
- To address the limitations of current radiolabeled antibiotic probes.
- To guide the development of novel probes by focusing on bacterial-specific molecular targets and radiochemistry.
Main Methods:
- Review of existing literature on nuclear imaging for bacterial infections.
- Analysis of the impact of radiolabeling on antibiotic probe efficacy.
- Exploration of bacterial molecular targets (intracellular and extracellular) and their suitability for imaging.
Main Results:
- Traditional radiolabeled antibiotics often fail due to inadequate consideration of how radiometal chelation affects bacterial cell penetration and target interaction.
- A strategic approach focusing on specific bacterial molecular targets and their locations is crucial for developing effective imaging probes.
- Radiochemistry strategies must be carefully considered to ensure probe functionality and diagnostic accuracy.
Conclusions:
- Developing sensitive and specific nuclear imaging probes for bacterial infections requires a deeper understanding of bacterial biology and molecular targets.
- Future probe development should prioritize strategies that enhance bacterial cell entry and target engagement.
- This approach, guided by radiochemistry principles, can lead to improved diagnostic tools for combating infectious diseases and antimicrobial resistance.
