Ultrasensitive Detection of Lung Inflammation Using Immuno-Magnetic Particle Imaging

Abstract Timely and sensitive detection of inflammatory and infectious lung diseases remains a major clinical challenge. Current diagnostics often detect pathology only at advanced stages, leaving gaps in acute triage, fibrotic activity assessment, transplant rejection monitoring, and inflammation follow-up. Real-time evaluation of lung inflammation status improves clinical decision-making. Magnetic Particle Imaging (MPI) offers a sensitive, background-free, whole-body imaging modality without ionizing radiation. Here, we present immuno-Magnetic Particle Imaging (immuno-MPI) using micron-sized iron oxide particles targeted to VCAM-1, a key endothelial inflammation marker. In two lung inflammation models, high-contrast images appear within 3 minutes after intravenous injection of only 1 mg/kg MPIO@αVCAM-1, showing rapid accumulation at inflamed endothelium and fast clearance of unbound particles. Confined to the vasculature, these particles selectively target VCAM-1, allowing clear biological interpretation. This optimized biodistribution, combined with MPI’s sensitivity, differentiates inflamed from healthy lungs at doses as low as 0.35 mg/kg (15 µg iron). Specificity for VCAM-1 is confirmed by the absence of signal with control antibodies (MPIO@IgG) and competitive blocking with free αVCAM-1 antibodies. Immuno-MPI provides a novel, non-invasive approach that avoids radiation risks of immuno-PET and is better suited for lung imaging than immuno-MRI, paving the way for promising clinical applications in pulmonary inflammation monitoring.