Abstract
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.
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Acknowledgments
Dr. Mathew Thakur and Dr. Kaijun Zhang thank Dr. Donald Jungkind and Mr. David Lander for the supply of the microorganisms.
Research was supported by NIH/NCRR 1S10RR 026678–01 (MLT) and NIH 5P30 CA-56036.
Conflict of Interest
M.L. Thakur, K. Zhang, B. Paudyal, D. Devakumar, M.Y. Covarrubias, C. Cheng, and E. Wickstrom have no conflict of interest. Drs. Brian D. Gray and Koon Y. Pak are the employees of Molecular Targeting Technologies, Inc. which sells PSVue®794.
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An erratum to this article can be found at http://dx.doi.org/10.1007/s11307-011-0498-y.
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Thakur, M., Zhang, K., Paudyal, B. et al. Targeting Apoptosis for Optical Imaging of Infection. Mol Imaging Biol 14, 163–171 (2012). https://doi.org/10.1007/s11307-011-0490-6
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DOI: https://doi.org/10.1007/s11307-011-0490-6