Fluorescent imaging of bacterial infections and recent advances made with multimodal radiopharmaceuticals

Abstract

Background Today, both radioactive SPECT and PET imaging radiopharmaceuticals are used for clinical diagnosis of bacterial infections. Due to the possible applications in image-guided surgery, fluorescent imaging of infections has gained interest. We here present the highlights and recent developments in the use of fluorescence imaging for bacterial infections. In this overview, we also include the latest developments in multimodal bacterial imaging strategies that combine radioactive and fluorescent imaging. Based on this literature, we present our future perspectives for the field including the translational potential. Methods In the current review, we complement earlier reports with the most recent fluorescent and multimodal radiopharmaceuticals for bacterial infection imaging. Where possible, in this review, the chemical structure of the compounds and clinical images were shown. Results A total of 35 out of 77 original articles on pre-clinical and clinical imaging of bacterial infections with fluorescent tracers and multimodality radiopharmaceuticals were included for reviewing. Conclusion In our view, the highest translational potential lies with compounds that are based on targeting vectors that are specific for bacteria: e.g., fluorescently labelled UBI 29-41 , polymyxin B, vancomycin, ZnDPA and a M. tuberculosis-specific β-lactamase-cleavable linker CNIP800. Multimodal concepts using dually labelled UBI 29-41 , vancomycin, and ZnDPA help connect optical imaging to the more traditional use of radiopharmaceuticals in infectious diseases. Multimodal bacterial imaging is a promising strategy not only to diagnose bacterial infections but also to evaluate the effectivity of surgical treatment for infections.

Hybrid Imaging of Aspergillus fumigatus Pulmonary Infection with Fluorescent, 68Ga-Labelled Siderophores

“…Different hybrid imaging approaches have already been developed for oncological applications [25,26], but are currently very limited in the field of infection. First steps have been made to establish this method for bacterial infections [27] but so far this approach has not been investigated for fungal infections. Based on the sophisticated TAFC-dependent mechanism of A. fumigatus to acquire iron from the human host, the exchange of iron by gallium-68 resulted in successful PET imaging in an IPA rat model [14,16,28], the overall approach of using radiolabelled siderophores for molecular imaging is described in [29].…”

Photodynamic treatment of pathogens

“…Moreover, simultaneous detection of both the photosensitizing compound and the carrier during the delivery process is readily achieved, for example by labeling the carrier with a spectrally distinct fluorophore [ 68 ]. Despite fluorescence emission is conveniently used for imaging, diverse theranostic constructs can be obtained by combining PSs with species that give other types of diagnostic readouts [ 288 , 289 ]. In spite of their potential, applications of fluorescence imaging techniques with subdiffraction resolution to investigate the interaction of the PS with their targets and the effect of photosensitization on the microbial structure are still just a few.…”

Imaging Inflammation – From Whole Body Imaging to Cellular Resolution

“…The most straightforward form of imaging bacteria in the clinical application is to use their endogenous fluorescence by exciting the bacteria with low-intensity violet light (405 nm) ( 158 , 159 ). In several pre-clinical and clinical bacterial imaging studies, dual radioactive and fluorescent imaging has proceeded mainly using endoscopic set up ( 160 ). In these studies, the fluorescent staining was primarily done using bacterial targeting molecules like antibiotics or antibiotic peptides ( 161 , 162 ), enzyme activated tracers ( 163 , 164 ), or bacterial lectins ( 165 ).…”