Targeting apoptosis for optical imaging of infection
Mathew L Thakur1, Kaijun Zhang, Bishnuhari Paudyal
1Department of Radiology, Thomas Jefferson University, Philadelphia, PA 19107, USA. mathew.thakur@jefferson.edu
Purpose:
Infection is ubiquitous and a major cause of morbidity and mortality. The most reliable method for localizing infection requires radiolabeling autologous white blood cells ex vivo. A compound that can be injected directly into a patient and can selectively image infectious foci will eliminate the drawbacks. The resolution of infection is associated with neutrophil apoptosis and necrosis presenting phosphatidylserine (PS) on the neutrophil outer leaflet. Targeting PS with intravenous administration of a PS-specific, near-infrared (NIR) fluorophore will permit localization of infectious foci by optical imaging.
Methods:
Bacterial infection and sterile inflammation were induced in separate groups (n = 5) of mice. PS was targeted with a NIR fluorophore, PSVue(®)794 (2.7 pmol). Imaging was performed (ex = 730 nm, em = 830 nm) using Kodak Multispectral FX-Pro system. The contralateral normal thigh served as an individualized control. Confocal microscopy of normal and apoptotic neutrophils and bacteria confirmed PS specificity.
Results:
Lesions, with a 10-s image acquisition, were unequivocally visible at 5 min post-injection. At 3 h post-injection, the lesion to background intensity ratios in the foci of infection (6.6 ± 0.2) were greater than those in inflammation (3.2 ± 0.5). Image fusions confirmed anatomical locations of the lesions. Confocal microscopy determined the fluorophore specificity for PS.
Conclusions:
Targeting PS presented on the outer leaflet of apoptotic or necrotic neutrophils as well as gram-positive microorganism with PS-specific NIR fluorophore provides a sensitive means of imaging infection. Literature indicates that NIR fluorophores can be detected 7-14 cm deep in tissue. This observation together with the excellent results and the continued development of versatile imaging devices could make optical imaging a simple, specific, and rapid modality for imaging infection.
Insights
A novel near-infrared (NIR) fluorophore targets phosphatidylserine (PS) on apoptotic neutrophils for sensitive optical imaging of infection. This method allows rapid, specific detection of infectious foci, improving upon traditional methods.
Area of Science:
- Medical Imaging
- Biotechnology
- Immunology
Background:
- Infection is a significant cause of illness and death globally.
- Current methods for localizing infection, such as radiolabeling white blood cells, are invasive and complex.
- Neutrophil apoptosis and necrosis expose phosphatidylserine (PS), a potential imaging target.
Purpose of the Study:
- To develop a non-invasive imaging method for infection detection.
- To evaluate a phosphatidylserine (PS)-specific, near-infrared (NIR) fluorophore for targeting infectious foci.
- To enable direct intravenous injection for simplified infection localization.
Main Methods:
- Bacterial infection and sterile inflammation models were established in mice.
- A PS-targeting NIR fluorophore (PSVue®794) was administered intravenously.
- Infection sites were imaged using multispectral optical imaging; specificity was confirmed via confocal microscopy.
Main Results:
- Infectious lesions were clearly visible within 5 minutes post-injection with short image acquisition times.
- Lesion-to-background ratios were significantly higher in infection sites compared to inflammatory sites at 3 hours.
- Confocal microscopy confirmed the fluorophore's specific binding to PS on apoptotic neutrophils and bacteria.
Conclusions:
- Targeting PS with a PS-specific NIR fluorophore offers a sensitive and specific method for optical imaging of infection.
- NIR fluorophores can penetrate deep tissues, enhancing imaging capabilities.
- Optical imaging holds promise as a rapid, simple, and specific modality for infection detection.
