A synthetic, near-infrared, fluorescent probe, named PSS-794 was assessed for its ability to detect cell death in two animal models. The molecular probe contains a zinc(II)-dipicolylamine (Zn2+-DPA) affinity ligand that selectively targets exposed phosphatidylserine on the surface of dead and dying cells. The first animal model used rats that were treated with dexamethasone to induce thymic atrophy. Ex vivo fluorescence imaging and histological analysis of excised organs showed thymus uptake of PSS-794 was four times higher than a control fluorophore that lacked the Zn2+-DPA affinity ligand. In addition, the presence of PSS-794 produced a delayed and higher build up of dead and dying cells in the rat thymus. The second animal model employed focal beam radiation to induce cell death in tumor-bearing rats. Whole-body and ex vivo imaging showed that the amount of PSS-794 in a radiationtreated tumor was almost twice that in a non-treated tumor. The results indicate that PSS-794 may be useful for preclinical optical detection of tumor cell death due to therapy.
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Acknowledgments We thank Sarah Chapman for preparing the histology sections, and Chelsea Poschar and Samantha Korda for assistance in operating the accelerator. This work was supported by the Walther Cancer Foundation, the Notre Dame Integrated Imaging Facility, and NIH Grants R01GM059078 (B.D.S.), T32GM075762 (B.A.S.).
- Cell death
- Molecular probe
- Optical imaging
- Tumor therapy