Diffusional mechanisms augment the fluorine MR relaxation in paramagnetic perfluorocarbon nanoparticles that provides a “relaxation switch” for detecting cellular endosomal activation

Purpose: To develop a physical model for the 19 F relaxation enhancement in paramagnetic perfluorocarbon nanoparticles (PFC NP) and demonstrate its application in monitoring cellular endosomal functionality through a “ 19 F relaxation switch” phenomenon. Materials and Methods: An explicit expression for 19 F longitudinal relaxation enhancement was derived analytically. Monte‐Carlo simulation was performed to confirm the gadolinium‐induced magnetic field inhomogeneity inside the PFC NP. Field‐dependent T 1 measurements for three types of paramagnetic PFC NPs were carried out to validate the theoretical prediction. Based on the physical model, 19 F and 1 H relaxation properties of macrophage internalized paramagnetic PFC NPs were measured to evaluate the intracellular process of NPs by macrophages in vitro. Results: The theoretical description was confirmed experimentally by field‐dependent T 1 measurements. The shortening of 19 F T 1 was found to be attributed to the Brownian motion of PFC molecules inside the NP in conjunction with their ability to permeate into the lipid surfactant coating. A dramatic change of 19 F T 1 was observed upon endocytosis, revealing the transition from intact bound PFC NP to processed constituents. Conclusion: The proposed first‐principle analysis of 19 F spins in paramagnetic PFC NP relates their structural parameters to the special MR relaxation features. The demonstrated “ 19 F relaxation switch” phenomenon is potentially useful for monitoring cellular endosomal functionality. J. Magn. Reson. Imaging 2011;. © 2011 Wiley‐Liss, Inc.