These results combined with the resistance situation in other pathogens

Previous studies investigating paramagnetic labeled LIBS antibody with magnetic resonance imaging have already elucidated the unique binding qualities of this antibody to selectively target activated platelets with high specificity. Using an in vitro setup of activated human platelets we Org 24598 lithium salt confirmed this specific binding to activated platelets with nuclear autoradiographic imaging by showing a significant increase in ligand uptake that occurred exclusively after incubation with 111In-LIBS. Therefore, 111In-LIBS antibody can be used to selectively depict activated platelets and seems to be suitable for the detection of intravascular thrombosis with nuclear imaging techniques. To evaluate the potential of 111In-LIBS to detect activated platelets on the surface of intravascular arterial thrombosis in an in vivo situation, we transferred this contrast agent approach to a mouse model of wall-adherent non-occlusive thrombosis. Others have previously described the imaging of activated platelets with nuclear imaging OXSI 2 techniques in the low pressure venous system. However, imaging activated platelets under the high shear stress of arterial flow remains challenging. Ex vivo autoradiography allowed the direct assessment of 111In-LIBS target binding after exposure to arterial flow conditions and natural elimination from the blood pool with high sensitivity. To guarantee the presence of a relevant thrombosis and to ensure blood flow over its surface for the delivery of sufficient bioavailability of radiotracer, we chose specimens with a relevant but non-occlusive thrombosis as confirmed by histology. After injection of the contrast agent and incubation, both carotid vessels were resected and analyzed with autoradiography. The assessment of the contralateral non-injured side served for the measurement of the remnant background radiation. Non-specific uptake was expected due to the extremely high sensitivity of this autoradiographic approach and was minimized by perfusion of vessels with physiological saline solution. Uptake of the injured carotid artery was, hence, evaluated in the context of the present background radiation. The significant increase in ligand uptake after injection of 111In-LIBS compared to 111In-control proved a sufficient target binding of 111In-LIBS even under arterial flow conditions to allow a highly sensitive detection of activated platelets and intravascular thrombosis in the direct assessment of carotid specimens ex vivo. However, as in vitro and ex vivo studies are artificial constructs that are not likely to fully cover the complexity of an in vivo environment, we used a dedicated small-animal SPECT-CT scanner to evaluate the capability of 111In-LIBS to also detect platelet activation and intravascular thrombosis in vivo. Nuclear imaging techniques such as SPECT provide the possibility of functional analysis of in vivo processes, allowing the detection of even small amounts of bound ligands down to picomolar concentration. However the techniques suffer from unclear anatomical localization of the radioactive uptake.

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