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Special Collection: Molecular Imaging
Development of a Translatable Ultrasound Molecular Imaging Agent for Inflammation
This study details the development, characterization and non-clinical efficacy of an ultrasound molecular imaging agent intended for molecular imaging of P-selectin in humans. A targeting ligand based on a recently discovered human selectin ligand was manufactured as fusion protein, and activity for human and mouse P- and E-selectin was evaluated by functional immunoassay. The targeting ligand was covalently conjugated to a lipophilic anchor inserted into a phospholipid microbubble shell. Three lots of the targeted microbubble drug product, TS-07-009, were produced, and assays for size distribution, zeta potential and morphology were established.Surface Modification with Lactadherin Augments the Attachment of Sonazoid Microbubbles to Glycoprotein IIb/IIIa
Arginine–glycine–aspartate (RGD)-carrying microbubbles (MBs) have been utilized as a specific contrast agent for glycoprotein IIb/IIIa (αIIbβ3 integrin)-expressing activated platelets in ultrasound molecular imaging. Recently, we found that surface modification with lactadherin provides the RGD motif on the surface of phosphatidylserine-containing clinically available MBs, Sonazoid. Here, we examined the potential of lactadherin-bearing Sonazoid MBs to be targeted MBs for glycoprotein IIb/IIIa using the custom-designed in vitro settings with recombinant αIIbβ3 integrin, activated platelets or erythrocyte-rich human clots.Ultrasound Molecular Imaging of Atherosclerosis Using Small-Peptide Targeting Ligands Against Endothelial Markers of Inflammation and Oxidative Stress
The aim of this study was to evaluate a panel of endothelium-targeted microbubble (MB) ultrasound contrast agents bearing small peptide ligands as a human-ready approach for molecular imaging of markers of high-risk atherosclerotic plaque. Small peptide ligands with established affinity for human P-selectin, VCAM-1, LOX-1 and von Willebrand factor (VWF) were conjugated to the surface of lipid-stabilized MBs. Contrast-enhanced ultrasound (CEUS) molecular imaging of the thoracic aorta was performed in wild-type and gene-targeted mice with advanced atherosclerosis (DKO).
