Intratracheal delivery of perfluorocarbon nanoparticles (PFCE NPs) enables 19F-MRI imaging of lung cancer via alveolar macrophage-mediated transport

Abstract

Early and specific imaging of lung cancer remains a major clinical challenge. Here we report that intratracheal delivery of perfluoro-15-crown-5-ether nanoparticles (PFCE NPs, ~200 nm) enables persistent, high-contrast ¹⁹F magnetic resonance imaging (MRI) of orthotopic lung tumors through alveolar macrophage (AM)-mediated transport. Compared with size-matched perfluorooctyl bromide (PFOB) nanoparticles, PFCE NPs generated significantly higher tumor signal-to-noise ratios that persisted for up to 7 days after a single intratracheal administration. Quantitative ¹⁹F-NMR, immunofluorescence, and transmission electron microscopy demonstrated efficient phagocytosis of PFCE NPs by AMs, followed by their migration to the tumor margin and concurrent translocation to lung-draining lymph nodes. The latter process reduced parenchymal background signal and further improved tumor contrast. Macrophage depletion abolished both tumor-margin enrichment and lymph-node accumulation, confirming the causal role of AMs. Ex vivo biodistribution revealed preferential retention of PFCE in the tumor-bearing lung and draining lymph nodes with minimal hepatic and splenic uptake. These findings establish AM-mediated hitchhiking as an effective mechanism for concentrating ¹⁹F-MRI contrast at lung tumor sites after local pulmonary delivery, providing a radiation-free strategy for sensitive visualization of lung cancer and a foundation for future inhalable theranostic applications.