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 F-19 relaxation enhancement in paramagnetic perfluorocarbon nanoparticles (PFC NP) and demonstrate its application in monitoring cellular endosomal functionality through a "F-19 relaxation switch" phenomenon. Materials and Methods: An explicit expression for 19F 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, F-19 and H-1 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 F-19 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 F-19 T-1 was observed upon endocytosis, revealing the transition from intact bound PFC NP to processed constituents. Conclusion: The proposed first-principle analysis of F-19 spins in paramagnetic PFC NP relates their structural parameters to the special MR relaxation features. The demonstrated "F-19 relaxation switch" phenomenon is potentially useful for monitoring cellular endosomal functionality.