Magnetic Particle Imaging Reveals Heterogeneous Retention, Leakage, and Redistribution of Nanoparticles Following Intratumoral Injection.

Intratumoral (i.t.) delivery of nanoparticles (NPs) is widely used to achieve high local NP concentrations. However, the temporal and spatial fate of i.t.-injected NPs remains poorly understood. We present a quantitative approach using whole-body in vivo magnetic particle imaging (MPI) to track magnetic NPs (MNPs) following i.t. injection. Using fiducial-calibrated imaging, we quantified MNP mass over time in subcutaneous 4T1 breast tumors. Longitudinal imaging revealed progressive loss of i.t. MNP content and heterogeneous off-target redistribution across animals despite standardized delivery conditions. Ex vivo MPI confirmed off-target accumulation primarily in the liver and spleen, consistent with reticuloendothelial clearance pathways. Histological analysis demonstrated spatially heterogeneous i.t. MNP deposition, potentially associated with local vascular features and tumor microenvironmental heterogeneity that may influence i.t. MNP retention or clearance from the tumor. These findings highlight the importance of quantitative longitudinal whole-body in vivo MPI for understanding the fate of MNPs for informing localized nanotherapy.