Long-residence-time nano-scale liposomal lohexol for X-ray-based blood pool imaging

Rationale and Objectives. Although soluble nonionic iodine compounds with low systemic toxic effects have been developed for use in computed tomography (CT), they have short residence times of a few minutes or mere seconds-insufficient time for blood pool imaging, even with high-speed multi-detector row spiral CT. Moreover, potential renal toxic effects preclude repeated administration of these contrast agents during imaging, as well as their use in patients with compromised renal function. The objective of this study was to develop and evaluate a CT contrast agent for blood pool imaging that remains in the blood for more than 3 hours and that is relatively nontoxic to the kidneys. Materials and Methods. The authors assessed a liposomal iohexol formulation for its encapsulation efficiency in terms of milligrams of iodine per milliliter of lipid formulation and for its stability in phosphate buffer solution and in human plasma in vitro. Using a rabbit model, they also assessed the formulation's in vivo stability, residence time, and enhancement of contrast on images of various organ systems. Results. The formulation, which contained 34.8 mg of iodine per milliliter of liposomal iohexol solution, remained stable in blood plasma both in vitro and in vivo, after injection into rabbit vasculature. An intravenous dose of 475 mg of iodine per kilogram of body weight produced contrast enhancement in the rabbit model of approximately 130 HU in the aorta and liver cortex and approximately 100 HU in the kidney cortex. Contrast enhancement was maintained for 3 hours after injection, and minimal clearance of the contrast agent via the kidneys was observed. Conclusion. The liposomal iohexol formulation tested in this study had a sufficient residence time for blood pool imaging in a rabbit model. Future experiments with long-residence-time iohexol formulations may lead eventually to applications in cardiac imaging and in early tumor detection.