Stable polymeric micelles: Lymphangiographic contrast media for gamma scintigraphy and magnetic resonance imaging

Abstract Rationale and Objectives Amphiphilc biocompatible polyoxyethylene (PEO)-based polymers form particles (micelles) that are 10-50 nm in diameter. In the current research, we successfully incorporated amphiphilic indium-111 ( 111 In) and gadolinium chelates into these particles and used them as particulate contrast media in percutaneous lymphography. Methods Micelles of amphiphilic PEO-lipid conjugates were loaded with 111 In and gadolinium diethylenetriamine pentaacetic acid-phosphatidylethanolamine (Gd-DTPA-PE) and were injected subcutaneously into the rabbit's paw. Corresponding images of local lymphatics were acquired using a gamma camera and a magnetic resonance (MR) imager. Results The entire lymphatic chain from the paw to the thoracic duct could be visualized using 111 In micelles after injection site massage. Tl-weighted MR images of the primary lymph node and collecting vessels were obtained within 4 min after administration of gadolinium micelles and massage. Conclusion Polymeric PEO-containing micelles can be loaded with diagnostic metals and, on subcutaneous injection, can visualize elements of lymphatic system. The major fraction of injected micelles stays within the lymph fluid, thus serving as lymphangiographic agents for indirect MR or gamma lymphography.