In vivo ICAM-1 directed molecular imaging of tumor, inflamed milieu, and acute inflammation

We hypothesized that nanoparticles designed to mimic the molecular interactions occurring between inflamed leukocytes and endothelium may possess specificity toward diverse host inflammatory responses. Here, superparamagnetic iron oxide (SPIO) nanoparticles were conjugated with integrin lymphocyte function-associated antigen (LFA)-1 Inserted (I) domain, engineered to mimic activated LFA-1 in leukocytes. By whole body optical imaging and MRI, we found I domain-coated nanoparticles were localized specifically to the tumors with high ICAM-1 expression as well as to the vasculature with ICAM-1 induction within and in the invasive front of the tumor. Furthermore, with a newly developed MRI technique, we achieved quantitative mapping of nanoparticle distribution in vivo in a mouse model of acute inflammation. This study presents the first demonstration of in vivo detection of tumor-associated vasculature by targeting inflammation with systemically injected nanoparticles, offering a possibility of tumor detection not by tumor surface antigens but by an inflamed milieu present in the tumor microenvironment.