Nearly real-time monitoring of magnetic nanoparticle-mediated photothermal therapy by MRI-based proton resonance frequency thermometry

Abstract

Iron oxide-based nanoparticles (NPs) have been used in the clinic for decades, making them strategic for clinical applications. Monitoring magnetic NP-mediated photothermal therapy (PTT) with MRI thermometry is challenging due to susceptibility effects, which might explain the limited progress in clinical translation. Here, we explore Mn-ferrite NPs for PTT and demonstrate ex vivo and in vivo noninvasive MRI thermometry using the proton resonance frequency shift (PRF) method. We observed a high external photothermal efficiency at 808 nm, 0.8 g·L–1·cm–1. Temperature-dependent NMR spectroscopy of the B16F10 tumor revealed a PRF coefficient of −0.0091 ppm·°C–1. The image artifact for this NP was quantified, which resulted in a radius increase distortion of 0.75 mm using 1 mg·mL–1 of NP. PRF thermometry was effectively monitored at the boundary regions of NP locations that guided the therapeutic procedure. In vivo experiments at a power density of 1.25 W·cm–2 using the melanoma model confirmed MRI-PRF thermometry and demonstrated that NP-mediated PTT improves the distribution of thermal doses within the tumor compared to laser therapy alone. Challenges for ablation application are discussed, suggesting opportunities for magnetic NP design. These results may pave the way for the clinical translation of PTT with magnetic NPs.