1H-CEST and 19F MRI of Temperature-Responsive Liposomal Contrast Agents for Image Guided Drug Delivery

Jochen Keupp¹, Sander Langereis², Inge de Roos², Dirk Burdinski², Jeroen Pikkemaat², Holger Gruell^2,3

Localized delivery of anti-cancer drugs by external stimulation of nanocarriers (temperature, pH) promises a larger therapeutic window with reduced side effects of the treatment. The present imaging study is based on a new type of temperature-responsive liposomes, which are dually labeled for ¹H-CEST and ¹⁹F MR imaging and release an encapsulated payload near the melting temperature (T_m) of their lipid membrane (38 C). In their lumen, a chemical shift agent for ¹H-lipoCEST imaging and NH₄PF₆ for ¹⁹F detection is contained. Inside the liposome, the ¹⁹F spectral lines are strongly broadened and not detectable. Upon reaching T_m, the lipoCEST contrast vanishes, due to the release of the chemical shift agent and, simultaneously, the ¹⁹F MR signal becomes visible. Hence, the ¹⁹F signal could be used to quantify the amount of released drug payload, while the CEST signal could measure the local nanocarrier concentration before the release. The study demonstrates the potential of the new liposomal nanocarriers for MRI-guided drug delivery in cancer therapy.