Abstract
Currently, there are no non-invasive tools to accurately diagnose wound and surgical site infections before they become systemic or cause significant anatomical damage. Fluorescence and photoacoustic imaging are cost-effective imaging modalities that can be used to noninvasively diagnose bacterial infections when paired with a molecularly targeted infection imaging agent. Here, we develop a fluorescent derivative of maltotriose (Cy7-1-maltotriose), which is shown to be taken up in a variety of gram-positive and gram-negative bacterial strains in vitro. In vivo fluorescence and photoacoustic imaging studies highlight the ability of this probe to detect infection, assess infection burden, and visualize the effectiveness of antibiotic treatment in E. coli-induced myositis and a clinically relevant S. aureus wound infection murine model. In addition, we show that maltotriose is an ideal scaffold for infection imaging agents encompassing better pharmacokinetic properties and in vivo stability than other maltodextrins (e.g. maltohexose).
Highlights
There are no non-invasive tools to accurately diagnose wound and surgical site infections before they become systemic or cause significant anatomical damage
One primary reason for this epidemic is the overuse of antimicrobials, which enhanced the number of drug-resistant bacteria[1,2]
Azide-functionalized maltotriose intermediate at the anomeric carbon was synthesized to allow ease of functionalization with a variety of signaling agents using copperfree click chemistry
Summary
There are no non-invasive tools to accurately diagnose wound and surgical site infections before they become systemic or cause significant anatomical damage. In addition to increasing the duration of hospitalization, SSIs increase treatment cost as well as mortality risk by 2–11-fold[8] Many of these infections are only diagnosed after becoming systemic or having caused significant damage to key organs, making it harder and more costly to treat due to the high bacterial burden. A variety of radio-imaging agents or positron emission tomography (PET) tracers for whole-body bacterial imaging have been developed and several of these are currently under evaluation in clinical trials[10] These approaches are dependent on proximity to cyclotrons and generators (for isotope production or collection, respectively) and experienced radiochemists for tracer production, limiting their availability on demand. FLI of bacterial infections gained attention due to its many advantages such as high resolution, real-time imaging capabilities, ease of use, and low cost[11]
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