A method for the making and utility of gadolinium-labeled albumin microbubbles

Objective: Perfluorocarbon-exposed sonicated dextrose albumin microbubbles (PESDA) binds scavenger receptors and can be noninvasively imaged. To enhance imaging, gadolinium (Gd)-labeled PESDA was developed and tested in a model of vascular inflammation by magnetic resonance imaging (MRI). Methods and Results: Purified human serum albumin (HSA) (5%) was labeled with Gd via the covalent binding of diethylenetriaminepentacetic acid. Abdominal aortic tissues in Sprague-Dawley rats (n=5 per group) were analyzed by 7-T MRI and scanning electron microscopy to evaluate PESDA binding. Labeling-purified 5% human albumin resulted in an average of 16.1 Gd atoms per albumin molecule as determined by atomic absorption. Forty-eight hours after balloon angioplasty, aortic tissue was enhanced with Gd-PESDA as compared to control tissue. 7-T MRI of explanted tissues was sensitive to the detection of retained PESDA. Enhancement of aortic tissue in vivo was present albeit to a lesser extent than explanted tissue from the same animals. Conclusions: HSA was successfully labeled, and an albumin-based microbubble with Gd was synthesized. This contrast agent, Gd-PESDA, may serve as an additional agent for the MRI evaluation of innate inflammation and used to noninvasively image early vascular pathophysiologic processes. Condensed Abstract: In this study, Gd-PESDA microbubbles and were synthesized and shown to detect the binding of these microbubbles using MRI in injured aortic tissue. The method for synthesizing Gd-PESDA is detailed, and the proposed utility of this new contrast agent is discussed.