The goal of this project is to establish antibody or ligand conjugated liposomes as a versatile tool for diagnosis, treatment and treatment monitoring of inflammatory and neoplastic disease processes. Methods We have now produced antibody conjugated paramagnetic liposomes (ACPLs) with high affinity for the receptors found on the vascular endothelium upregulated during disease, low non-specific uptake in other tissues and high enough relaxivity so these receptors can be localized accurately to specific anatomic sites with high spatial and contrast resolution on in vivo MRI images. We have demonstrated the use of ACPLs for ex-vivo MR histology to visualize the expression of the cell adhesion molecule ICAM-l on the endothelial surface in the brains of mice with Experimental Autoimmune Encephalomyelitis (EAE), an animal model for multiple sclerosis (MS). We have also demonstrated the use of ACPLs for in vivo visualization of tumor angiogenesis using an anti-avb3 antibody. Since the development of new blood vessels (angiogenesis) plays a crucial role in rapid solid tumor growth and metastasis, ACPL enhanced MRI should improve the sensitivity and specificity of detecting various tumors. Results and Discussion In summary, we have demonstrated that ACPLs, a new target-specific MR contrast enhancing agent, can be successfully delivered to cell adhesion molecules upregulated in two different disease models. This result lays the groundwork for in vivo imaging studies of endothelial antigens involved in many different inflammatory and neoplastic diseases. We will also study the use of ACPLs for blocking the attachment of lymphocytes to endothelial receptors as a new means of immunotherapy.
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