The Use of Ultrasound-Targeted Microbubble Destruction in Mediated Delivery of a Gadolinium Magnetic Resonance Imaging Contrast Agent Into Fibroblast Cells In Vitro
Russell, C. Hunter, III
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A method for delivering Gd-based MRI contrast agents by ultrasound-targeted microbubble destruction into fibroblast cells in vitro is presented. First, MRI contrast agents Gd-F-DOTP-ME and Gd-DOTA-4iBA are shown to associate with liposome microbubbles used as ultrasound contrast agents. Repeated washings with phosphate buffered saline followed by T1 measurements at 20 MHz revealed Gd-DOTA-4iBA was retained more effectively by the liposome microbubbles. Secondly, ultrasound-targeted microbubble destruction using Optison(tm) microbubbles to deliver Gd-DOTA-4iBA into fibroblast cells displays negligible T1 shortening at 4.7T over controls. Further experiments are planned to validate these observations with other MRI contrast agents and other forms of microbubbles used for ultrasound image enhancement. The goal of these experiments is eventually combining MRI contrast agent delivery with ultrasound targeted microbubble destruction gene therapy to quantitatively determine the amount of DNA delivered into target tissues.