Characterization of early neovascular response to acute lung ischemia using simultaneous 19F/1H MR molecular imaging

Angiogenesis is an important constituent of many inflammatory pulmonary diseases, which has been unappreciated until recently. Early neovascular expansion in the lungs in preclinical models and patients is very difficult to assess noninvasively, particularly quantitatively. The present study demonstrated that F-19/H-1 MR molecular imaging with alpha(v)beta(3)-targeted perfluorocarbon nanoparticles can be used to directly measure neovascularity in a rat left pulmonary artery ligation (LPAL) model, which was employed to create pulmonary ischemia and induce angiogenesis. In rats 3 days after LPAL, simultaneous F-19/H-1 MR imaging at 3T revealed a marked F-19 signal in animals 2 h following alpha(v)beta(3)-targeted perfluorocarbon nanoparticles [F-19 signal (normalized to background) = 0.80 +/- A 0.2] that was greater (p = 0.007) than the non-targeted (0.30 +/- A 0.04) and the sham-operated (0.07 +/- A 0.09) control groups. Almost no F-19 signal was found in control right lung with any treatment. Competitive blockade of the integrin-targeted particles greatly decreased the F-19 signal (p = 0.002) and was equivalent to the non-targeted control group. Fluorescent and light microscopy illustrated heavy decorating of vessel walls in and around large bronchi and large pulmonary vessels. Focal segmental regions of neovessel expansion were also noted in the lung periphery. Our results demonstrate that F-19/H-1 MR molecular imaging with alpha(v)beta(3)-targeted perfluorocarbon nanoparticles provides a means to assess the extent of systemic neovascularization in the lung.