Targeting microparticles to select tissue via radiation induced upregulation of endothelial cell adhesion molecules

The up-regulation of certain endothelial cell adhesion molecules in tissue that has been irradiated for therapeutic purposes provides a potential avenue for targeting drugs to select tissue. Microspheres were coated with a mAb to ICAM-1 and the level of adhesion of the anti-ICAM-1 microspheres to irradiated tissue in vitro and in vivo was quantified. Under in vitro flow conditions, the number of adherent microspheres on irradiated human umbilical vein endothelial cells (HUVEC) was 4.5±0.9 times that of control; this ratio could be enhanced by increasing ligand density on the surface of the microspheres, adding RBC to the suspending media, or reducing shear rate. In vivo in a rat cranial window model, the number of adherent anti-ICAM-1 microspheres in irradiated cerebral tissue was 13 times that of IgG microspheres at 48 hr post-irradiation. In locally irradiated animals, the number of adhering microspheres in unirradiated tissue remained at the basal level.