Magnetic particle imaging of tumor retention and leakage of magnetic nanoparticles reveals high inter-subject variability

Intratumoral (i.t.) injection of magnetic nanoparticles (MNPs) is a clinically relevant strategy for localized therapy, including magnetic fluid hyperthermia (MFH). However, the fate of i.t.-injected MNPs remains poorly characterized. Here, we employed magnetic particle imaging (MPI) to quantitatively and longitudinally monitor MNP retention and leakage of i.t.-Synomag®-D70 in a mouse subcutaneous 4T1 breast tumor model. Mice (n=4) were scanned serially (15 min to 8 day) using 2D MPI with fiducial calibration. At day 8, 3D MPI and CT co-registration were performed, followed by ex vivo imaging. A strong linear calibration (R²=0.967) between MNP concentration and MPI signal enabled accurate iron quantification. All tumors showed strong initial MPI signal with an 1.8 to 3.0-fold signal reduction by day 8, indicating gradual tumor clearance. Liver and spleen uptake could only be observed in 2 out of 4 mice, while none of the other major organs showed uptake. The high inter-subject variability in MNP tumor retention calls for integrating MPI quantification for developing individualized MFH treatment plans.