P-selectin is an adhesion molecule translocated to the surface of endothelial cells and platelets under inflammatory stimuli, and its potential as a biomarker in inflammatory conditions has driven preclinical studies to investigate its application for molecular imaging of inflammation. lead to considerable and irreversible damage, increased pain, and a poorer prognosis (1). Reliably assessing inflammation early and throughout the disease course requires sensitive diagnostic methods (2). Noninvasive molecular imaging modalities, including ultrasound, MRI, SPECT, and PET, have been used as supportive diagnostic tools for physicians in evaluating inflammation (3). Traditional imaging techniques can be used to assess tissue morphology changes due to inflammation, whereas nuclear medicineCbased imaging methodsPET and SPECTare able to functionally and molecularly measure inflammation with high sensitivity. Nonetheless, clinical nuclear brokers currently utilized for inflammation imaging, such as MC 70 HCl 18F-FDG, which accumulates in tissues with increased cellular glycolytic activity, are limited in scope by high background levels or nonspecific uptake that can complicate analysis and interpretation (4,5). With more recent preclinical improvements, new contrast brokers developed for MRI and ultrasound are emerging as strong contenders to image at the molecular level for MC 70 HCl diagnosing and monitoring inflammation (6,7). The clinical demand for sensitive molecular imaging brokers for early and reliable characterization of inflammation has charged preclinical research with developing selective targeting strategies using PET, SPECT, ultrasound, and MRI. Experts are investigating hallmark biomarkers expressed in inflammation to develop targeted brokers for imaging specific aspects of inflammation. Among disease biomarker candidates, preclinical research has focused on brokers that bind cell adhesion molecules to characterize inflammatory responses across diseases. A recent review by Lee et al. discusses targeting of cell adhesion molecules in chronic inflammatory diseases, focusing on preclinical PET/SPECT imaging of integrins, the immunoglobulin superfamily (vascular cell adhesion molecule 1, intercellular adhesion molecule 1), and selectins (2). The adhesion molecule, P-selectin, has been the focus of intense investigation as a molecular imaging target for early inflammatory disease says and shows promise in assisting clinical disease staging, treatment planning, and monitoring. The focus of this evaluate is usually to highlight the pivotal role P-selectin plays among inflammatory says and its current preclinical application as a biomarker of inflammation across molecular imaging platforms. P-SELECTIN INVOLVEMENT IN INFLAMMATORY DISEASES: THE ROLE OF HYPERADHESION Although disease-specific factors Tnfrsf1b can elicit inflammation and produce diverse physiologic manifestations, the activation of the vascular endothelium remains a crucial part of the inflammatory process across pathologic says. The inflammatory response is initiated by cytokine signaling that activates the local blood vessel endothelium for recruitment, adhesion, and diapedesis of leukocytes. Leukocyte attachment to the vessel endothelium entails a regulated succession of specific adhesion molecules expressed at the cell surface to facilitate the multistep adhesion process of leukocyte tethering, rolling, and ultimately adherence and diapedesis. The activated endothelium mediates the first catching contacts with leukocytes through triggering cell surface expression of a cell adhesion molecule, P-selectin. Within minutes, readily available pools of P-selectin are trafficked to the endothelial cell surface from cytoplasmic storage granules. At the MC 70 HCl surface, P-selectin binds to its counterligand, P-selectin glycoprotein ligand 1 (PSGL-1), which is usually constitutively expressed on leukocytes. The P-selectin/PSGL-1 transient interactions slow leukocytes to roll along the vessel endothelium, allowing for stronger attachments to form with subsequently expressed or activated adhesion molecules (Figs. 1A and 1B) (8). Open in a separate window Physique 1. P-selectin role in endothelial MC 70 HCl activation (A) and in atherosclerosis and thrombus (B). Aberrant or prolonged vascular endothelial activation caused by inflammatory triggers can result in overexpression of adhesion molecules and in turn increase leukocyte attachment and infiltration, which can damage the vasculature and localized tissue (9). Damage to the vessel endothelium through destructive inflammation or injury can additionally activate local platelets to express P-selectin, facilitating aggregation and adhesive interactions between platelets, leukocytes, and endothelium. Like endothelial cells, platelets also have intracellular storage pools of P-selectin in the -granules that are quickly.