Targeting apoptosis for optical imaging of infection

Objectives Infection is ubiquitous and a major cause of morbidity and mortality. The most reliable method for localizing infection is radiolabeling autologous white blood cells (WBC) ex-vivo. A molecule that can be injected into patients directly and image infection selectively, will eliminate the drawbacks and contribute to the patient management. Resolution of infection is associated with WBC apoptosis presenting phosphatidylserine (PS) on the cell outer leaflet. Targeting PS, with an i.v. administration of a PS-specific, near infrared (NIR) fluorophore, may permit localization of infectious foci by optical imaging.

Methods Bacterial infection and sterile inflammation were induced in separate groups (n=5 each) of Balb/C mice. PS was targeted with a PS-specific, NIR fluorophore, PSVueTM794, (2.7 pmol). Longitudinal imaging was performed (ex max = 730 nm, em max = 830 nm) using Kodak, Multispectral FX-Pro. The contralateral normal thigh, served as an individualized control. Confocal microscopy of normal and apoptotic WBC and bacteria, was carried out to assess PS-specificity.

Results Infection and inflammatory lesions were unequivocally visible at 5 min post-injection with a 10 second image acquisition. At 3 hr post injection, the lesion to background intensity ratios in infection (6.1±0.2), were greater than that in inflammation (2.9±0.5). Image fusions confirmed anatomical locations of lesions and confocal microscopy assured fluorophore specificity.

Conclusions Literature indicates that NIR fluorophores can detect lesions 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 of infection a simple, specific and rapid imaging modality.

Research Support NIH 1S10 RR026678-0