Dynamic microPET imaging of ultrasound contrast agents and lipid delivery

Interest in ultrasound contrast agents (lipid-shelled microbubbles) as delivery vehicles is increasing; however, the biodistribution of these agents remains uncharacterized, both with and without ultrasound. In this study, an F-18-labeled lipid ([F-18]fluorodipalmitin), incorporated in microbubble shells, was used as a dynamic microPET probe for quantitative 90-minute biodistribution measurements in male Fischer 344 rats (n=2). The spleen retained the highest concentration of radioactive lipid at similar to 2.6%-injected dose per cubic centimeter (% ID/cc) and the liver demonstrated the largest total accumulation (similar to 17% ID). The microbubble pharmacokinetic profile differed from free lipid, which is rapidly cleared from blood, and liposomes, which remain in circulation. Additionally, region of interest (ROI) analysis over 60 minutes (post-ultrasound treatment) quantified the delivery of lipid by therapeutic ultrasound from microbubbles to kidney tissue (n=8). The ultrasound sequence consisted of a 200 kPa, 5.3 MHz radiation force pulse followed by a 1.6 MPa, 1.4 MHz fragmentation pulse and was applied to one kidney, while the contralateral kidney served as a control. ROI-estimated activity in treated kidneys was slightly but significantly greater at 0 and 60 min than in untreated kidneys (p=0.0012 and 0.0035, respectively). This effect increased with the number of microbubbles injected (p=0.006). In summary, [F-18]fluorodipalmitin was used to characterize the biodistribution of contrast microbubble shells and the deposition of lipid was shown to be locally increased after insonation. (c) 2008 Elsevier B.V. All rights reserved.