Molecular MR Imaging with Paramagnetic Perfluorocarbon Nanoparticles

Abstract

Targeted contrast agents, such as perfluorocarbon (PFC) nanoparticles, have been developed to allow conventional imaging modalities, including MRI, to detect and characterize specific pathological biomarkers of early disease rather than simply observe the anatomical manifestations occurring at very late stages. PFC nanoparticles are typically 200–300 nm in diameter and are encapsulated in a phospholipid shell, which provides an ideal surface for the incorporation of targeting ligands and/or imaging agents. Through chemical modification of the paramagnetic chelates incorporated on the particle surface, nanoparticle relaxivity as well as stability can be increased to improve the efficacy of MR molecular imaging. PFC nanoparticles can be targeted to a number of different biological epitopes, including fibrin, an abundant marker of ruptured atherosclerotic plaques; αvβ3-integrin, an endothelial biomarker of angiogenesis associated with atherosclerosis, tumor growth, and vascular injury; collagen III, a component of the extracellular matrix that is exposed after balloon angioplasty; and tissue factor, a vascular smooth muscle cell (VSMC) marker that is overexpressed following vascular injury. In addition to paramagnetic nanoparticles for 1H MRI, the PFC core has a high fluorine content that can be detected with 19F MRI, providing unambiguous and quantitative mapping of the contrast agent distribution. Another distinctive advantage of PFC nanoparticles for molecular imaging applications is their compatibility with several imaging modalities, including MRI, ultrasound, nuclear imaging, and CT.