Multimodal imaging approach to track theranostic nanoparticle accumulation in glioblastoma with magnetic resonance imaging and intravital microscopy

Theranostic nanoparticles (NPs) have been designed for simultaneous therapeutic and diagnostic purposes, thereby enabling personalized cancer therapy and <i>in vivo</i> drug tracking. However, studies thus far have focused on imaging NP tumor accumulation at the macroscopic level and correlating results with <i>ex vivo</i> histology. Limited evidence exists on whether <i>in vivo</i> NP tumor contrast enhancement on magnetic resonance imaging (MRI) correlates with <i>in vivo</i> NP tumor accumulation at the microscopic level. To address this gap, the purpose of our study was to correlate quantitative MRI estimates of NP accumulation with <i>in vivo</i> NP signal quantification as measured through two-photon intravital microscopy (IVM) in an orthotopic murine glioblastoma multiforme model (GBM). To enable multimodal imaging, we designed dual-mode NPs, composed of a carbohydrate-coated magnetic core (Ferumoxytol) as an MRI contrast agent, and a conjugated fluorophore (FITC) for IVM detection. We administered these NPs with or without a conjugated vascular disrupting agent (VDA) to assess its effect on NP delivery to GBM. We correlated <i>in vivo</i> MRI contrast enhancement in tumors, quantified as <i>T</i>₂ relaxation time, with IVM fluorescence spatial decay rate. Results demonstrated a significantly lower tumor <i>T</i>₂ relaxation time and spatial decay rate in tumors targeted with VDA-conjugated NPs compared to unconjugated NPs. <i>Postmortem</i> histological analyses validated the <i>in vivo</i> observations. The presented multimodal imaging approach enabled a quantitative correlation between MRI contrast enhancement at the macroscopic level and NP accumulation in the tumor microenvironment. These studies lay the groundwork for the precise evaluation of the tumor targeting of theranostic NPs.